Changes in masseter muscle morphology after surgical-orthodontic treatment in patients with skeletal Class III malocclusion with mandibular asymmetry: The automatic masseter muscle segmentation model.

INTRODUCTION: This study evaluated the masseter muscle changes after surgical-orthodontic treatment in patients with a skeletal Class III malocclusion using automatic segmentation. METHODS: Images of 120 patients with skeletal Class III malocclusion were obtained and reconstructed at T0 (pretreatment), T1 (presurgery), and T2 (6-12-month postsurgery). The patients were divided into symmetrical and asymmetrical groups. The volume, major axis length, maximum cross-sectional area, horizontal cross-sectional area 5 mm above the mandibular foramen (CSAF), and orientation were calculated automatically. RESULTS: In the asymmetrical group, the volume and major axis length on the deviated side were lower than on the nondeviated side at T0, T1, and T2 (P <0.05). There were no significant differences in maximum cross-sectional area and CSAF bilaterally. The orientation was coronally more vertical and sagittally more forward on the deviated side (both P <0.001). In the symmetrical group, there were no significant bilateral differences at T0, T1, and T2. The volume, major axis length, and CSAF decreased, and the coronal orientation was more vertical on the nondeviated side at T2 than at T0 in both groups (P <0.05). The coronal plane orientation was more inclined on the deviated side at T2 than at T0 in the asymmetrical group (P <0.05). CONCLUSIONS: The smaller volume on the deviated side at T2 indicates the need for myofunctional training after surgery. The masseter muscle volume and the cross-sectional area did not recover to the preorthodontic levels. Studies with longer follow-up durations are needed to confirm these findings.

Improving photovoltaic performance of light-responsive double-heterojunction nanorod light-emitting diodes.

Double heterojunction nanorods enable both electroluminescence and light harvesting capabilities within the same device structure, providing a promising platform for energy-scavenging displays and related applications. However, the efficiency of the photovoltaic mode remains modest for useful power conversion and may be challenging to improve without sacrificing performance in electroluminescence. Through a facile on-film partial ligand exchange with benzenethiol integrated into the device fabrication step, we achieve an average of more than threefold increase in power conversion efficiency while maintaining the maximum external quantum efficiency and the maximum luminance in the LED mode. The improved photovoltaic performance is mainly due to the increase in the short circuit current, which we attribute to the enhanced charge separation afforded by the partial ligand exchange. The recovery of the photoluminescence lifetime under the forward bias suggests that the hole traps introduced by benzenethiols are filled prior to reaching the voltage at which light emission begins, allowing LED performance to be maintained and possibly improved.

Early and 1-year postsurgical stability and its factors in patients with complicated skeletal Class â ¢ malocclusion treated by conventional and surgery-first approach: A prospective cohort study.

INTRODUCTION: This study aimed to compare postsurgical stability between conventional (CSA) and surgery-first (SFA) approaches and investigate its prognostic factors in patients with a skeletal Class Ⅲ extraction. METHODS: Twenty and 19 patients treated with LeFort I osteotomy and bilateral sagittal split ramus osteotomy (BSSRO) with premolar extraction were enrolled in SFA and CSA groups, respectively. Serial cone-beam computed tomography images obtained before surgery, immediately after surgery (T1), 3 months after surgery, and 12 months after surgery were used for 3-dimensional quantitative analysis. The condyle was segmented for analyzing volumetric changes. Repeated measures analysis of variance, independent t test, and chi-square test were used to compare time-course and intergroup differences. Pearson and Kendall correlation and multivariate linear regression analyses were used to explore prognostic factors affecting skeletal stability. RESULTS: In both CSA and SFA, postsurgical relapse mainly occurred in the mandible sagittal and vertical dimensions and during the first 3 months after surgery. Stability in SFA was significantly less than that in CSA. Intraoperatively, inferolateral condylar displacement with proximal segment inwards, clockwise rotation, and return movements after surgery were observed regardless of the treatment approach. The condylar volume remained stable over time. Multivariate regression analysis showed that posterior vertical dimension (VD) at T1 (-1.63 mm), surgical amount of mandibular setback (-10.33 mm), surgical condylar downwards displacement (-1.28 mm), and anterior overjet at T1 (6.43 mm) were the most important predictors of early mandibular relapse (r2 = 0.593). CONCLUSIONS: The risk of early relapse could be reduced by controlling the anterior, middle, and posterior constraints provided by the prediction model.

KCNJ5 Mutation Contributes to Complete Clinical Success in Aldosterone-Producing Adenoma: A Study From a Single Center.

OBJECTIVE: The KCNJ5 mutation is the most frequent mutation in aldosterone-producing adenoma (APA). We aimed to illustrate the relationship between KCNJ5 and prognosis after adrenalectomy as a guide for further treatment. METHODS: Our study included 458 patients with APA. Tumor tissues were screened for somatic mutations in KCNJ5 hot-spot regions. We performed a retrospective analysis to identify correlations between KCNJ5 and clinical outcomes in 334 patients with adrenal venous sampling lateralization. RESULTS: Somatic KCNJ5 mutations were identified in 324 of 458 patients with APA (70.7%). Compared with the KCNJ5-wild type patients, patients with KCNJ5 mutations were younger, had a higher proportion of women, and had shorter durations of hypertension, lower body mass indexes (BMIs), and lower systolic blood pressure values (P < .05). During follow-up, among the 334 patients with APA with adrenal venous sampling lateralization, 320 (95.8%) presented complete biochemical success and 187 (56.0%) presented complete clinical success. One hundred eighty-seven patients with primary aldosteronism who achieved complete clinical success presented the following characteristics: age <40 years (78.7%), BMI <24 kg/m2 (71.0%), hypertension duration <5 years (78.4%), females (66.9%), and KCNJ5 mutation (65.5%). A multivariate logistic regression analysis identified BMI, hypertension duration, and KCNJ5 mutation as independent predictors of complete clinical success. CONCLUSION: The prevalence of KCNJ5 mutations was 70.7%. KCNJ5 mutation is a protective factor of complete clinical success, while BMI and hypertension duration were risk factors of incomplete clinical success.

The application and accuracy of feature matching on automated cephalometric superimposition.

BACKGROUND: The aim of this study was to establish a computer-aided automated method for cephalometric superimposition and to evaluate the accuracy of this method based on free-hand tracing. METHODS: Twenty-eight pairs of pre-treatment (T1) and post-treatment (T2) cephalograms were selected. Structural superimpositions of the anterior cranial base, maxilla and mandible were independently completed by three operators performing traditional hand tracing methods and by computerized automation using the feature matching algorithm. To quantitatively evaluate the differences between the two methods, the hand superimposed patterns were digitized. After automated and hand superimposition of T2 cephalograms to T1 cephalometric templates, landmark distances between paired automated and hand T2 cephalometric landmarks were measured. Differences in hand superimposition among the operators were also calculated. RESULTS: The T2 landmark differences in hand tracing between the operators ranged from 0.61 mm to 1.65 mm for the three types of superimposition. There were no significant differences in accuracy between hand and automated superimposition (p > 0.05). CONCLUSIONS: Computer-aided cephalometric superimposition provides comparably accurate results to those of traditional hand tracing and will provide a powerful tool for academic research.

A novel clinical nomogram to predict bilateral hyperaldosteronism in Chinese patients with primary aldosteronism.

CONTEXT: Adrenal venous sampling (AVS) is recommended as the gold standard for subtype classification in primary aldosteronism (PA); however, this approach has limited availability. OBJECTIVE: We aimed to develop a novel clinical nomogram to predict PA subtype based on routine variables, thereby reducing the number of candidates for AVS. PATIENTS AND METHOD: Patients were randomly divided into a training set (n = 185) and a validation set (n = 79). Risk factors for idiopathic hyperaldosteronism (IHA) differentiating from aldosterone-producing adenoma (APA) were identified using logistic regression analysis. A nomogram was constructed to predict the probability of IHA. A receiver operating characteristic (ROC) curve and a calibration plot were applied to assess the predictive value. Then, 115 patients were prospectively enrolled, and a nomogram was used to predict the subtypes before AVS. RESULTS: Body mass index (BMI), serum potassium and computed tomography (CT) finding were adopted in the nomogram. The nomogram presented an area under the ROC (AUC) of 0.924 (95% CI: 0.875-0.957), sensitivity of 86.59% and specificity of 87.38% in the training set and an AUC of 0.894 (95% CI: 0.804-0.952), sensitivity of 82.86% and specificity of 84.09% in the validation set. Predicted probability and actual probability matched well in the nomogram (Hosmer-Lemeshow test: P > 0.05). Using the nomogram as a surrogate to predict IHA in the prospective set before AVS, the specificity reached 100% when we increased the threshold to a probability of 90%. CONCLUSION: We have developed a tool that is able to predict IHA in patients with PA and potentially avoid AVS.

PITUITARY STALK THICKENING IN A LARGE COHORT: TOWARD MORE ACCURATE PREDICTORS OF PITUITARY DYSFUNCTION AND ETIOLOGY.

Objective: To summarize the characteristics of patients with pituitary stalk thickening, analyze the association between pituitary stalk width and hypopituitarism, and develop a diagnostic model to differentiate neoplastic and inflammatory origins. Methods: A total of 325 patients with pituitary stalk thickening in a tertiary teaching hospital between January 2012 and February 2018 were enrolled. Basic characteristics and hormonal status were evaluated. Indicators to predict etiology in patients with histologic diagnoses were analyzed. Results: Of the 325 patients, 62.5% were female. Deficiency in gonadotropin was most common, followed by corticotropin, growth hormone, and thyrotropin. The increase in pituitary stalk width was associated with a risk of central diabetes insipidus (odds ratio [OR], 3.57; P<.001) and with a combination of central diabetes insipidus and anterior pituitary deficiency (OR, 2.28; P = .029). The cut-off pituitary stalk width of 4.75 mm had a sensitivity of 69.2% and a specificity of 71.4% for the presence of central diabetes insipidus together with anterior pituitary deficiency. Six indicators (central diabetes insipidus, pattern of pituitary stalk thickening, pituitary stalk width, neutrophilic granulocyte percentage, serum sodium level, and gender) were used to develop a model having an accuracy of 95.7% to differentiate neoplastic from inflammatory causes. Conclusion: Pituitary stalk width could indicate the presence of anterior pituitary dysfunction, especially in central diabetes insipidus patients. With the use of a diagnostic model, the neoplastic and inflammatory causes of pituitary stalk thickening could be preliminarily differentiated. Abbreviations: APD = anterior pituitary dysfunction; AUC = area under the curve; CDI = central diabetes insipidus; GH = growth hormone; MRI = magnetic resonance imaging; OR = odd ratio; PHBS = posterior hypophyseal bright spots; PST = pituitary stalk thickening; PSW = pituitary stalk width.

Reliability and validity of miniscrews as references in cone-beam computed tomography and intraoral scanner digital models: study on goat heads.

BACKGROUND: Miniscrews have been used to superimpose three-dimensional (3D) craniofacial images as well as explore stable structures in jaws. Our purpose was to evaluate the reliability and validity of linear and angular measurements made with miniscrews on a 3D cone-beam computed tomography (CBCT) at two voxel sizes and compared to models created by an intraoral scanner (IOS). METHODS: Altogether, 64 miniscrews were placed in 12 goat jaws. The jaws were scanned by CBCT machine at 0.12 mm and 0.3 mm voxels and by the IOS. Linear and angular measurements between miniscrews on CBCT at the two voxel settings and the IOS were compared with actual measurements and with each other. RESULTS: An intra-and inter-class correlation of 0.961-1.000 were obtained by each method. Linear measurements showed significant overestimations of 0.27 ± 0.24, 0.14 ± 0.22 and 0.15 ± 0.26 mm, and angular measurements showed non-significant differences of 0.11 ± 1.97°, 0.15 ± 2.79° and 0.41 ± 2.34° for the CBCT at 0.12-mm, 0.3-mm voxels and the IOS, respectively. Equal magnification of linear measurements was on homolateral and contralateral sides using CBCT, whereas significantly greater magnification on the homolateral side than on the opposite was observed using the IOS. There was no significant difference with angular measurements between digital CBCT models at two voxels and IOS. In addition, all angular measurements were comparable to actual measurement results. CONCLUSIONS: Miniscrews in CBCT and IOS are reliable and clinical valid when used as a reference measuring tooth movement. However, when miniscrews are involved in high precision measurement in CBCT or IOS image, systematic error should be taken into consideration. When comparing CBCT images, using the same voxel size is recommended for miniscrew related measurements to reduce error.

Establishment and evaluation of a novel biomarker-based nomogram for malignant phaeochromocytomas and paragangliomas.

OBJECTIVE: No single histological or molecular marker is diagnostic for malignant phaeochromocytomas and paragangliomas (PPGLs). This study aimed to establish and evaluate a prognostic nomogram to improve the prediction of metastatic probability in individual PPGL patients. METHODS: Three hundred and 47 consecutive PPGL patients from January 2002 through December 2014 were randomly divided into a training set (n=208) and a validation set (n=139). A multivariate logistic regression analysis of selected prognostic features was performed, and a nomogram to predict metastasis was constructed. Discrimination and calibration were employed to evaluate the performance of the nomogram. Clinical usefulness was calculated using decision curve analysis. RESULTS: The overall metastatic rate was 10.6%. Primary tumour size, primary tumour location, vascular invasion, ERBB-2 overexpression, SDHB mutation and catecholamine type were associated with malignancy in the logistic analysis and were included in the nomogram. The nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.872 (95% confidence interval [CI], 0.819-0.914) in the training set. The validation set showed good discrimination, with an AUC of 0.870 (95% CI, 0.803-0.921). The nomogram was well calibrated, with no significant difference between the predicted and the observed probabilities (Hosmer-Lemeshow test: P=.510 for the training set; .314 for the validation set). Decision curve analysis revealed that molecular markers (ERBB-2 overexpression and SDHB mutation) could increase the clinical benefit of the nomogram. CONCLUSION: Our results support the use of the present biomarker-based nomogram, which has good discriminative ability, to predict the metastatic probability of PPGLs.

Intensive insulin therapy combined with metformin is associated with reduction in both glucose variability and nocturnal hypoglycaemia in patients with type 2 diabetes.

BACKGROUND: The effect on glucose variability in patients with intensive insulin therapy has not been fully understood. This observational study investigated the different glucose variability and hypoglycaemia patterns in type 2 diabetes patients treated with continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) with or without metformin administration. METHODS: During hospitalization, a total of 501 patients with poor glycaemic control and in initial treatment with either CSII alone (n = 187), CSII + Metformin (n = 81), MDI alone (n = 146), or MDI + Metformin (n = 87) were involved in the final analysis. Data obtained from continuous glucose monitoring were used to assess blood glucose fluctuation and nocturnal hypoglycaemia. RESULTS: Among the 4 groups, no difference was found in mean blood glucose levels. Results in parameters reflecting glucose fluctuation: continuous overlapping net glycaemic action in CSII + Metformin and mean amplitude of glycaemic excursions in MDI + Metformin were significantly lower than those in either CSII alone or MDI alone, respectively, even after adjustment (P = .031 and .006). Frequency of nocturnal hypoglycaemia was significantly decreased in CSII + Metformin as compared with CSII alone (0.6% vs 1.8%) and in MDI + Metformin as compared with MDI alone (1.6% vs 2.3%), with the highest frequency observed in MDI alone and the lowest in CSII + Metformin (all between group P < .001). Consistent results were obtained in between-group comparisons for hypoglycaemia duration. Subgroup analysis matched with baseline body mass index, and glycated haemoglobin and fasting blood glucose further confirmed these findings. CONCLUSION: Metformin added to initial CSII or MDI therapy is associated with a reduction in both glucose fluctuation and nocturnal hypoglycaemic risk in patients with type 2 diabetes.

Factors affecting parathyroid hormone levels in different types of primary aldosteronism.

BACKGROUND: Recent studies have found that mild secondary hyperparathyroidism might be another clinical feature of patients with primary aldosteronims (PA), but whether serum parathyroid hormone level (PTH) is correlated with subtypes of PA and what contributes to the elevated PTH level remains unclear. OBJECTIVE: To illustrate the changes of PTH in PA and to partly explain the mechanism of how the effects of aldosterone regulating the secretion of PTH in PA. METHODS: We enrolled a total of 120 patients with primary hypertension (PH) and 242 patients with PA, which included 89 APAs (aldosterone-producing adenoma), 119 IHAs (idiopathic hyperaldosteronism) and 34 UAHs (unilateral adrenal hyperplasia). The plasma levels of aldosterone, renin activity, parathyroid hormone and markers associated with calcium metabolism were measured. RESULTS: We found serum PTH level was significantly elevated in patients with PA compared with primary hypertension [9·0 (6·6, 11·7) vs 5·7 (4·4, 7·0)] pmol/l, P < 0·001]. However, no difference was found between the three PA subtypes (P > 0·05). Stepwise multiple regression analysis showed that in patients with PA, serum levels of K(+) and Ca(2+) were independently associated with serum PTH level. More importantly, elevated PTH level could be corrected either by unilateral adrenalectomy [9·9 (7·5, 12·8) vs 5·2 (4·4, 7·0) pmol/l, P < 0·001] or mineralocorticoid receptor (MR) antagonists treatment [11·7 (9·1, 13·4) vs 6·3 (5·1, 7·8) pmol/l, P < 0·001]. CONCLUSIONS: PTH level is elevated in PA patients and irrelevant with subtypes of PA. Serum K(+) and serum Ca(2+) level are main factors influence the plasma PTH level in PA patients. After medical or surgical treatment, PTH levels return to normal.

ERBB-2 overexpression as a risk factor for malignant phaeochromocytomas and paraganglinomas.

OBJECTIVE: There are currently no good histological or molecular markers to differentiate benign from malignant phaeochromocytomas and paraganglinomas (PPGLs). Our previous cross-sectional study observed that ERBB-2 overexpression was associated with malignant PPGLs. This study aimed to evaluate the predictive value of ERBB-2 overexpression for metastasis in PPGLs in a large population. METHODS: A total of 262 patients diagnosed as PPGLs in our institution between 2002 and 2012 were included. We analysed ERBB-2 protein expression in the primary PPGL tumours by immunohistochemistry (IHC) and ERBB-2 amplification by fluorescence in situ hybridization (FISH). Direct Sanger sequencing was performed to examine ERBB-2 exon 20 mutations. The occurrence of malignant PPGLs was documented in the follow-up period. Kaplan-Meier analysis and Cox proportional hazard models were used to evaluate the association between ERBB-2 overexpression and metastasis of PPGLs. RESULTS: Twenty-six (9·9%) patients had ERBB-2 overexpression in their primary PPGL tumours, which was significantly associated with ERBB-2 amplification (17/25, 68%). No ERBB-2 mutation was found. At a median follow-up of 4·5 years, a total of 23 malignant PPGLs were documented, including eight (30·8%) patients in the ERBB-2 overexpression group and 15 (6·4%) patients in the ERBB-2-negative group. The incidence rate of metastasis was 5·3 per 100 person-years vs 1·4 per 100 person-years in the ERBB-2 overexpression and ERBB-2-negative groups (P < 0·001), respectively. Kaplan-Meier analysis showed that ERBB-2 overexpression was associated with decreased metastasis-free survival (P = 0·001, log-rank test). After adjusting for primary tumour size and location, Cox regression analysis revealed that ERBB-2 overexpression was independently associated with risk of malignant PPGLs (HR = 2·78; 95% CI, 1·12-6·90; P = 0·028). CONCLUSION: Patients harbouring tumours with ERBB-2 overexpression have a significantly higher risk of developing malignant PPGLs.

Downregulation of miR-375 in aldosterone-producing adenomas promotes tumour cell growth via MTDH.

OBJECTIVE: Previous studies have investigated the genetic and molecular basis of primary aldosteronism (PA), a common cause of human hypertension, but the effects of microRNAs (miRNAs) on the adrenocortical cell proliferation and aldosterone production are largely obscure. Here, we characterized miRNA expression patterns in the subtypes of PA to gain a better understanding of its pathogenesis. METHODS: miRNA expression was assessed by microarray profiling analysis in aldosterone-producing adenoma (APA), unilateral adrenal hyperplasia (UAH) and normal adrenal cortex tissues. Selected differentially expressed miRNAs were further validated in a validation cohort by qRT-PCR. A gain-of-function approach was used to explore the functional role of the specific miRNA in vitro. RESULTS: Of 31 miRNAs including miR-375, miR-7 and miR-29b were found to be significantly differentially expressed among these three groups. miR-375 was the most downregulated one in adrenal cortex tissues from PA patients, and its expression level was inversely correlated with the tumour size in APA. Overexpression of miR-375 in a human adrenocortical cell line (H295R) reduced cell proliferation and suppressed the expression of MTDH (metadherin, also known as astrocyte elevated gene-1). Moreover, MTDH was verified as a direct target of miR-375 through luciferase reporter assays. Knock-down of MTDH in H295R cells attenuated Akt-Ser473 phosphorylation and inhibited cell viability. CONCLUSION: Our findings suggest that miR-375 exerts its tumour-suppressive function via targeting MTDH/Akt pathway and implicate a potential therapeutic target in PA.

Relationship between pituitary stalk (PS) visibility and the severity of hormone deficiencies: PS interruption syndrome revisited.

CONTEXT: Pituitary stalk interruption syndrome (PSIS) is a rare cause of combined pituitary hormone deficiency characterized by a triad shown in pituitary imaging, yet it has never been evaluated due to the visibility of pituitary stalk (PS) in imaging findings. OBJECTIVE: The major objective of the study was to systematically describe the disease including clinical presentations, imaging findings and to estimate the severity of anterior pituitary hormone deficiency based on the visibility of the PS. METHODS: This was a retrospective study including 74 adult patients with PSIS in Shanghai Clinical Center for Endocrine and Metabolic Diseases between January 2010 and June 2014. Sixty had invisible PS according to the findings on MRI, while the rest had a thin or intersected PS. Basic characteristics and hormonal status were compared. RESULTS: Of the 74 patients with PSIS, age at diagnosis was 25 (22-28) years. Absent pubertal development (97·3%) was the most common presenting symptom, followed by short stature. Insulin tolerance test (ITT) and gonadotrophin-releasing hormone (GnRH) stimulation test were used to evaluate the function of anterior pituitary. The prevalence of isolated deficiency in growth hormone (GH), gonadotrophins, corticotrophin and thyrotrophin were 100%, 97·2%, 88·2% and 70·3%, respectively. Although the ratio of each deficiency did not vary between patients with invisible PS and with visible PS, panhypopituitarism occurred significantly more frequent in patients with invisible PS. Patients with invisible PS had significantly lower levels of luteinizing hormone (LH), follicle stimulation hormone (FSH) and hormones from targeted glands including morning cortisol, 24-h urine free cortisol, free triiodothyronine (FT3), free thyroxine (FT4) and testosterone (T) in male than patients with visible PS. Moreover, patients with invisible PS had lower peak LH and FSH in GnRH stimulation test, and higher peak cortisol in ITT while peak GH remained unchanged between two groups. CONCLUSIONS: The prevalence of multiple anterior pituitary hormone deficiency was high in adult patients with PSIS. And more importantly, we found the visibility of PS shown on MRI might be an indication of the severity of PSIS.

Low serum potassium level is associated with nonalcoholic fatty liver disease and its related metabolic disorders.

CONTEXT: Subjects with nonalcoholic fatty liver disease (NAFLD) have a high risk of developing type 2 diabetes and cardiovascular diseases. Low serum potassium concentration or low dietary potassium intake can result in metabolic disorders. OBJECTIVE: Our objective was to evaluate the association between low serum potassium level and prevalence of NAFLD in a Chinese population. DESIGN: A population-based cross-sectional study. PATIENTS: We conducted a community-based study in 8592 subjects to investigate the association of serum potassium with the risk of prevalent NAFLD. NAFLD was diagnosed by hepatic ultrasonography. RESULTS: The prevalence rate of NAFLD was 30·3% in this population and gradually decreased across serum potassium quartiles. With the reduction in serum potassium level, participants have larger waist circumference (WC) and more severe insulin resistance. The correlations hold also in multivariate linear regression analysis. In logistic regression analysis, compared with subjects in the highest quartile of serum potassium level, the adjusted odds ratios (ORs) in the lowest quartile was 1·33 [95% confidence interval (CI), 1·11-1·60] for NAFLD, 1·81 (95% CI, 1·49-2·19) for insulin resistance and 1·58 (95% CI, 1·30-1·93) for central obesity. In subgroup analysis after multiple adjustments, significant relation between serum potassium level and prevalent NAFLD was detected in women, younger subjects, those with insulin resistance and those with central obesity, respectively. CONCLUSION: Low serum potassium level significantly associated with prevalence of NAFLD in middle-aged and elderly Chinese.

Diagnosis and therapy of giant epidermoid double cysts with infection on the buttock: A case report and literature review.

RATIONALE: Epidermoid cyst (EC) is a common clinical condition and it can be filled with keratinized material. EC often represents painless, slow progressive growth, and single cyst. The cyst is usually 1 to 5 cm in size. Giant epidermoid cysts on the buttock area are extremely rare, and reports of giant epidermoid double cysts on the buttock are even rarer. PATIENT CONCERNS: This paper reports a patient with a painless mass was on the left buttock. DIAGNOSIS: A giant epidermoid double cysts with infection in a left buttock paranal location. INTERVENTIONS: The mass was surgically removed. OUTCOMES: The patient recovered well after surgical treatment and currently has no recurrence. CONCLUSION: For patients with EC, MRI is recommended as a routine examination before surgery in order to detect the variation and extent of the cyst early. This lays a foundation for the complete resection of the lesion during the operation. The review of relevant literature will hopefully be helpful to clinicians.

The influence of cortisol co-secretion on clinical characteristics and postoperative outcomes in unilateral primary aldosteronism.

Context: The prevalence of unilateral primary aldosteronism (UPA) with cortisol co-secretion varies geographically. Objective: To investigate the prevalence and clinical characteristics of UPA with cortisol co-secretion in a Chinese population. Design: Retrospective cohort study. Methods: We recruited 580 patients with UPA who underwent cosyntropin stimulation test (CST) after the 1-mg dexamethasone suppression test (DST) and retrospectively analyzed the clinical characteristics and postoperative outcomes of UPA with and without cortisol co-secretion. Results: UPA with cortisol co-secretion (1 mg DST>1.8 ug/dL) was identified in 65 of 580 (11.2%) patients. These patients were characterized by older age, longer duration of hypertension, higher concentration of plasma aldosterone and midnight cortisol, lower adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS), larger tumor diameter, and more history of diabetes mellitus. Cortisol and aldosterone levels were higher and DHEAS level was lower in UPA with cortisol co-secretion at 0-120 min after CST. Among 342 UPA patients with KCNJ5 gene sequencing and follow-up results, the complete clinical success rate was lower in UPA with cortisol co-secretion (33.3% vs. 56.4%, P<0.05); the complete biochemical success rate and KCNJ5 mutation did not differ between the two groups. Age, tumor size, and ACTH were independent predictors of UPA with cortisol co-secretion. Sex, BMI, duration of hypertension, KCNJ5 mutation, and cortisol co-secretion were independent predictors for complete clinical success in UPA after surgery. Conclusions: UPA with cortisol co-secretion is not uncommon in China, but the clinical features were distinctly different from those without co-secretion. Cortisol co-secretion is an independent risk factor for incomplete clinical success after surgery in UPA.

NPC1 is required for postnatal islet ß cell differentiation by maintaining mitochondria turnover.

Rationale: NPC1 is a protein localized on the lysosome membrane regulating intracellular cholesterol transportation and maintaining normal lysosome function. GWAS studies have found that NPC1 variants in T2D was a pancreatic islet expression quantitative trait locus, suggesting a potential role of NPC1 in T2D islet pathophysiology. Methods: Two-week-old Npc1-/- mice and wild type littermates were employed to examine pancreatic ß cell morphology and functional changes induced by loss of Npc1. Single cell RNA sequencing was conducted on primary islets. Npc1-/- Min6 cell line was generated using CRISPR/Cas9 gene editing. Seahorse XF24 was used to analyze primary islet and Min6 cell mitochondria respiration. Ultra-high-resolution cell imaging with Lattice SIM2 and electron microscope imaging were used to observe mitochondria and lysosome in primary islet ß and Min6 cells. Mitophagy Dye and mt-Keima were used to measure ß cell mitophagy. Results: In Npc1-/- mice, we found that ß cell survival and pancreatic ß cell mass expansion as well as islet glucose induced insulin secretion in 2-week-old mice were reduced. Npc1 loss retarded postnatal ß cell differentiation and growth as well as impaired mitochondria oxidative phosphorylation (OXPHOS) function to increase mitochondrial superoxide production, which might be attributed to impaired autophagy flux particularly mitochondria autophagy (mitophagy) induced by dysfunctional lysosome in Npc1 null ß cells. Conclusion: Our study revealed that NPC1 played an important role in maintaining normal lysosome function and mitochondria turnover, which ensured establishment of sufficient mitochondria OXPHOS for islet ß cells differentiation and maturation.

Pharmacogenomic analysis in adrenocortical carcinoma reveals genetic features associated with mitotane sensitivity and potential therapeutics.

Background: Adrenocortical carcinoma (ACC) is an aggressive endocrine malignancy with limited therapeutic options. Treating advanced ACC with mitotane, the cornerstone therapy, remains challenging, thus underscoring the significance to predict mitotane response prior to treatment and seek other effective therapeutic strategies. Objective: We aimed to determine the efficacy of mitotane via an in vitro assay using patient-derived ACC cells (PDCs), identify molecular biomarkers associated with mitotane response and preliminarily explore potential agents for ACC. Methods: In vitro mitotane sensitivity testing was performed in 17 PDCs and high-throughput screening against 40 compounds was conducted in 8 PDCs. Genetic features were evaluated in 9 samples using exomic and transcriptomic sequencing. Results: PDCs exhibited variable sensitivity to mitotane treatment. The median cell viability inhibition rate was 48.4% (IQR: 39.3-59.3%) and -1.2% (IQR: -26.4-22.1%) in responders (n=8) and non-responders (n=9), respectively. Median IC50 and AUC were remarkably lower in responders (IC50: 53.4 µM vs 74.7 µM, P<0.0001; AUC: 158.0 vs 213.5, P<0.0001). Genomic analysis revealed CTNNB1 somatic alterations were only found in responders (3/5) while ZNRF3 alterations only in non-responders (3/4). Transcriptomic profiling found pathways associated with lipid metabolism were upregulated in responder tumors whilst CYP27A1 and ABCA1 expression were positively correlated to in vitro mitotane sensitivity. Furthermore, pharmacologic analysis identified that compounds including disulfiram, niclosamide and bortezomib exhibited efficacy against PDCs. Conclusion: ACC PDCs could be useful for testing drug response, drug repurposing and guiding personalized therapies. Our results suggested response to mitotane might be associated with the dependency on lipid metabolism. CYP27A1 and ABCA1 expression could be predictive markers for mitotane response, and disulfiram, niclosamide and bortezomib could be potential therapeutics, both warranting further investigation.

Cushing Syndrome Is Associated With Gut Microbial Dysbiosis and Cortisol-Degrading Bacteria.

CONTEXT: Cushing syndrome (CS) is a severe endocrine disease characterized by excessive secretion of cortisol with multiple metabolic disorders. While gut microbial dysbiosis plays a vital role in metabolic disorders, the role of gut microbiota in CS remains unclear. OBJECTIVE: The objective of this work is to examine the alteration of gut microbiota in patients with CS. METHODS: We performed shotgun metagenomic sequencing of fecal samples from 78 patients with CS and 78 healthy controls matched for age and body mass index. Furthermore, we verify the cortisol degradation capacity of Ruminococcus gnavus in vitro and identify the potential metabolite by LC-MC/MS. RESULTS: We observed significant differences in microbial composition between CS and controls in both sexes, with CS showing reduced Bacteroidetes (Bacteroides vulgatus) and elevated Firmicutes (Erysipelotrichaceae_bacterium_6_1_45) and Proteobacteria (Enterobacter cloacae). Despite distinct causes of hypercortisolism in ACTH-dependent and ACTH-independent CS, we found no significant differences in metabolic profiles or gut microbiota between the 2 subgroups. Furthermore, we identified a group of gut species, including R. gnavus, that were positively correlated with cortisol levels in CS. These bacteria were found to harbor cortisol-degrading desAB genes and were consistently enriched in CS. Moreover, we demonstrated the efficient capacity of R. gnavus to degrade cortisol to 11-oxygenated androgens in vitro. CONCLUSION: This study provides evidence of gut microbial dysbiosis in patients with CS and identifies a group of CS-enriched bacteria capable of degrading cortisol. These findings highlight the potential role of gut microbiota in regulating host steroid hormone levels, and consequently host health.