Portable and miniature mercury analyzer using direct sampling inbuilt-metal ceramic electrothermal vaporization.

In this work, a small-size inbuilt-metal ceramic heater (IMCH) was for the first time utilized as a solid sampling electrothermal vaporizer (ETV), and then a novel direct sampling mercury analyzer coupled with a miniature atomic absorption spectrometer was thereby fabricated for sensitive determination of mercury in soil. The mercury analyzer is mainly composed of an IMCH-ETV, a catalytic pyrolysis furnace (CPF) using Al2O3 particles as a new filler, an atomic absorption spectrometer (AAS) and a miniature air pump for carrier gas; herein, the mostly used gold amalgamation was canceled. The IMCH with 30 W heating fulfills the 100% vaporization of mercury from up to 80 mg soil samples using 0.1 L min-1 air carrier. Under the optimized conditions, the method detection limit (LOD) was 0.4 ng g-1 for a 50 mg sample and the RSD of 11 repeated measurements of GSS-3a soil certified reference material (CRM) was 4%. Furthermore, the measured Hg values in various soil CRMs and real soil samples were within their certified values and consistent with that using the Chinese standard method (solid sampling catalytic pyrolysis AAS with gold amalgamation); and the recoveries were 85-113%, which proved favorable analytical accuracy and precision. This fabricated instrumentation only occupies 5 kg and 200 W power consumption vs. more than 25 kg and 1000 W for the traditional Hg analyzer. Therefore, the proposed IMCH-ETV-AAS method is very suitable for portable and rapid detection of mercury in soil.

Expression and clinical significance of Cathepsin K and MMPs in invasive non-functioning pituitary adenomas.

Background: Cathepsin K (CTSK) is a protease that degrades type I collagen and extracellular matrix, thereby contributing to bone resorption and tumor invasion. Some pituitary adenomas (PAs) could invade the sphenoid sinus (SS) and cavernous sinus (CS). Purpose: This retrospective cohort study aimed to study the expression of tumoral biomarkers (CTSK, MMP9, MMP2, TIMP2, and PTTG1) and evaluate their clinical significance in non-functioning pituitary adenomas (NFPAs) with different invasion patterns. Methods: We assessed the expression levels of candidate invasion-specific protein biomarkers CTSK, MMP9, MMP2, TIMP2, and PTTG1 by immunohistochemical staining in paraffin-embedded NFPA tumor tissues. Variations in staining intensity were analyzed in cases with SS and CS invasion and non-invasive NFPAs. Results: We found that the levels of CTSK were higher in PA cases with SS invasion than that in PA cases with CS invasion (95.57 ± 31.57 vs. 65.29 ± 29.64, P < 0.001), and the expression of MMP9 and MMP2 was higher in CS-invasive cases than that in SS-invasive cases (145.02 ± 49.25 vs. 111.80 ± 51.37, P = 0.002, and 138.67 ± 52.06 vs. 108.30 ± 41.70, P = 0.002). Multiple Cox regression demonstrated that higher CTSK expression (P=0.011), subtotal resection (P<0.001), invasion (P=0.037), and larger tumor diameter (P=0.001) were independent risk factors for recurrence. A positive correlation was observed between CTSK expression and tumor size (r=0.671, p<0.001). There was no significant difference in TIMP2 and PTTG1 levels between CS-and SS-invasive cases (97.42± 39.80 vs. 102.10± 43.22, P = 0.58 and 13.89 ± 4.59 vs. 12.56 ± 3.96, P = 0.14). Conclusion: Our data indicated that CTSK has the potential as a marker for SS invasion of PAs, whereas MMP9 and MMP2 may be markers for CS invasion. And CTSK may play an important role in tumor relapse.

Clinical Analysis of the Renal Protective Effect of GLP-1 on Diabetic Patients Based on Edge Detection.

With the rapid development of IoT technology, it is a new trend to combine edge computing with smart medicine in order to better develop modern medicine, avoid the crisis of information "sibling," and meet the requirements of timeliness and computational performance of the massive data generated by edge devices. However, edge computing is somewhat open and prone to security risks, so the security and privacy protection of edge computing systems for smart healthcare is receiving increasing attention. The two groups were compared before and after treatment for blood glucose, blood lipids, blood pressure, renal function, serum advanced glycosylation end products (AGEs) and cyclic adenosine monophosphate (cAMP), serum oxidative stress indicators, and levels of cAMP/PKA signalling pathway-related proteins in peripheral blood mononuclear cells. The results of this study show that the reduction of AGEs, the improvement of oxidative stress, and the regulation of the cAMP/PKA signalling pathway may be associated with a protective effect against early DKD. By introducing the edge computing system and its architecture for smart healthcare, we describe the security risks encountered by smart healthcare in edge computing, introduce the solutions proposed by some scholars to address the security risks, and finally summarize the security protection framework and discuss the specific solutions for security and privacy protection under this framework, which will provide some help for the credible research of smart healthcare edge computing.

Human umbilical cord-derived mesenchymal stem cells alleviate insulin resistance in diet-induced obese mice via an interaction with splenocytes.

BACKGROUND: Previous research has demonstrated that the spleen plays an important role in mesenchymal stem cell (MSC)-mediated alleviation of acute inflammation, as MSC infusion increases the spleen-derived anti-inflammatory cytokine interleukin 10 (IL-10) levels. However, studies on splenic involvement in MSC-induced protection against chronic inflammatory diseases are limited. Obesity is characterized by chronic low-grade inflammation, a key driver of insulin resistance. This study aims to evaluate the effects of MSCs on obesity-related insulin resistance and explore the underlying mechanism, particularly regarding splenic involvement. METHODS: We induced obesity in mice by feeding them high-fat diets for 20 weeks. Human umbilical cord-derived MSCs (UC-MSCs) were systemically infused into the obese mice once per week for 6 weeks. Systemic glucose metabolic homeostasis and insulin sensitivity in epididymal adipose tissue (EAT) were evaluated. Then, we conducted in vivo blockade of IL-10 during UC-MSC infusion by intraperitoneally administrating an IL-10-neutralizing antibody twice per week. We also investigated the therapeutic effects of UC-MSCs on obese mice after removal of the spleen by splenectomy. RESULTS: UC-MSC infusions improved systemic metabolic homeostasis and alleviated insulin resistance in EAT but elicited no change in weight. Despite rare engraftment of UC-MSCs in EAT, UC-MSC infusions attenuated insulin resistance in EAT by polarizing macrophages into the M2 phenotype, coupled with elevated serum IL-10 levels. In vivo blockade of IL-10 blunted the effects of UC-MSCs on obese mice. Furthermore, UC-MSCs overwhelmingly homed to the spleen, and the ability of UC-MSCs to elevate serum IL-10 levels and alleviate insulin resistance was impaired in the absence of the spleen. Further in vivo and in vitro studies revealed that UC-MSCs promoted the capacity of regulatory T cells (Treg cells) to produce IL-10 in the spleen. CONCLUSIONS: Our results demonstrated that UC-MSCs elevated serum IL-10 levels and subsequently promoted macrophage polarization, leading to alleviation of insulin resistance in EAT. The underlying mechanism was that UC-MSCs improved the capacity of Treg cells to produce IL-10 in the spleen. Our findings indicated that the spleen played a critical role in amplifying MSC-mediated immunomodulatory effects, which may contribute to maximizing MSC efficacy in clinical applications in the future.

Characteristics of Interferon-Associated Diabetes Mellitus in Past 30 Years: A Review.

Interferon (IFN) is a broad-spectrum antiviral agent that activates cell surface receptors and causes cells to produce antiviral proteins, inhibiting viral replication. Interferon use has long been associated with diabetes. The PubMed database was searched for articles related to diabetes and interferon from March 30, 2020. Patients were divided into type 1 diabetes group and type 2 diabetes group. We reviewed the relevant literature to compare interferon-associated T1D and interferon-associated T2D differences. Interferon treatment shortened the incubation period of T2D and changed the original T2D to T1D. The onset of interferon-associated T1D required longer periods of IFN treatment than interferon-associated T2D, and the interferon-associated T1D group had higher GADA positive rates, lower BMI, lower fasting blood glucose, and greater insulin dependence (p<0.05). More patients in the T1D group were positive for HLA-DRB1*04, DRB1*03, DRB1*09, DRB1*14, HLA-DQB1*04, HLA-DQB1*02, HLA-DQB1*03, and HLA-DQB1*05. The combined detection of GAD antibodies and HLA alleles may be an effective method to predict the incidence of T1D after IFN treatment.

A retrospective analysis of endocrinopathy manifestations in 136 Chinese patients with POEMS syndrome.

OBJECTIVE: POEMS syndrome is a rare multisystemic disease, with a wide spectrum of clinical endocrinopathies. Patients with POEMS syndrome may present with one or more hormone disorders during the disease course, but such phenomenon has usually been underestimated. In this report, we analyzed the prevalence and clinical characteristics of endocrine abnormalities in a large Chinese cohort with POEMS syndrome. METHODS: This retrospective review was performed in patients with a definite diagnosis of POEMS syndrome who were hospitalized in our hospital between January 2000 and January 2020. The clinical data about endocrine abnormalities were extracted from their medical records and analyzed. RESULTS: This study comprised 136 patients (95 male, 41 female) with a median age of 48(40-56) years old. Endocrine abnormalities were frequent (127 cases, 93.38%) in patients with POEMS syndrome. The prevalence of single endocrinopathy and multiple endocrinopathies were 12.60% (16/127 cases) and 87.40% (111/127), respectively. The most frequent endocrinopathy was hypogonadism (98/136, 72.06%), followed by hypothyroidism (83/136, 61.03%), hypocalcemia (50/136, 36.76%), hyperprolactinemia (47/136, 34.56%), abnormal glucose metabolism (41/136, 30.15%) and adrenal insufficiency (41/136, 30.15%). In patients with multiple endocrinopathies, the prevalence of 2, 3, 4, 5, and 6 kinds of endocrine axes involved were 29.92% (38/127), 30.71% (39/127), 17.32% (22/127), 7.09% (9/127) and 2.36% (3/127), respectively. Such hormone disorders cause complex clinical presentations, including overt or subclinical situations. CONCLUSION: Endocrinopathy manifestations in POEMS syndrome are more frequent, and its clinical complicacy should be emphasized in differential diagnosis. For patients with a definite diagnosis of POEMS syndrome, an early and thorough endocrine evaluation should be performed.

Case Report: Three Rare Cases of Ectopic ACTH Syndrome Caused by Adrenal Medullary Hyperplasia.

Ectopic ACTH syndrome (EAS) accounts for 10-20% of endogenous Cushing's syndrome (CS). Hardly any cases of adrenal medullary hyperplasia have been reported to ectopically secrete adrenocorticotropic hormone (ACTH). Here we describe a series of three patients with hypercortisolism secondary to ectopic production of ACTH from adrenal medulla. Cushingoid features were absent in case 1 but evident in the other two cases. Marked hypokalemia was found in all three patients, but hyperglycemia and osteoporosis were present only in case 2. All three patients showed significantly elevated serum cortisol and 24-h urinary cortisol levels. The ACTH levels ranged from 19.8 to 103.0pmol/L, favoring ACTH-dependent Cushing's syndrome. Results of bilateral inferior petrosal sinus sampling (BIPSS) for case 1 and case 3 confirmed ectopic origin of ACTH. The extremely high level of ACTH and failure to suppress cortisol with high dose dexamethasone suppression test (HDDST) suggested EAS for patient 2. However, image studies failed to identify the source of ACTH secretion. Bilateral adrenalectomy was performed for rapid control of hypercortisolism. After surgery, cushingoid features gradually disappeared for case 2 and case 3. Blood pressure, blood glucose and potassium levels returned to normal ranges without medication for case 2. The level of serum potassium also normalized without any supplementation for case 1 and case 3. The ACTH levels of all three patients significantly decreased 3-6 months after surgery. Histopathology revealed bilateral adrenal medullary hyperplasia and immunostaining showed positive ACTH staining located in adrenal medulla cells. In summary, our case series reveals the adrenal medulla to be a site of ectopic ACTH secretion. Adrenal medulla-originated EAS makes the differential diagnosis of ACTH-dependent Cushing's syndrome much more difficult. Control of the hypercortisolism is mandatory for such patients.

Comparative efficacy and dysmenorrhea score of 6 object-separated moxibustions for the treatment of Chinese patients with dysmenorrhea: A systematic review and network meta-analysis.

BACKGROUND: Primary dysmenorrhea (PD), one of the most common diseases in women, is known to be effective with object-separated moxibustion. However, because there is no large sample size for comparison, it is difficult to choose the best method for the clinical treatment of these different treatments. Therefore, our aim was to compare and rank different moxibustion methods to determine the most effective treatment method for PD. MATERIALS AND METHODS: A systematic search was carried out in PubMed, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, and Chinese Biomedical Literature, to identify the randomized controlled trials (RCTs) investigated the object-separated moxibustion is associated with dysmenorrhea, as well as we also manually checked the bibliographies of eligible studies and topic-related reviews, RCTs from their inception to May 1, 2020. Three investigators read the citations and excluded quasi-randomized trials and trials that were incomplete. We extracted data following a predefined hierarchy. We assessed the studies' risk of bias in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The primary outcomes were efficacy (response rate) and dysmenorrhea scores. We estimated the summary odds ratio (OR) and mean difference (MD) using pairwise and network meta-analyses with random effects. STATA software version 16.0, ADDIS software version 1.16.5, and R software version 3.6.1 were used to statistically analyze all data. RESULTS: Fifty-six RCTs with 5550 patients were included, comparing 6 object-separated moxibustion therapies with acupuncture or oral medicine. All moxibustions were more effective than ibuprofen, with OR ranging between 6.75 (95%CI: 3.58 to 13.22) for moxibustion at the navel. For relieving pain which uses dysmenorrhea score to evaluate, mild moxibustion (MD = -1.42, -4.24 to 0.85) was more effective than others. A total of 24 (42.8%) of 56 trials were rated as having a high risk of bias, 31(55.4%) as moderate, and 1(1.8%) as low, and the certainty of the evidence was moderate. CONCLUSIONS: Mild moxibustion cannot only effectively treat PD but also relieve pain in comparison with ibuprofen. Although GRADE evidence indicate low to moderate for most comparisons, mild moxibustion seems to be an advisable option for PD treatment to relieve symptoms.

Clinical Characteristics and Management of Functional Pancreatic Neuroendocrine Neoplasms: A Single Institution 20-Year Experience with 286 Patients.

BACKGROUND: Functional pancreatic neuroendocrine neoplasms (PanNENs) are very rare disorders but have complex spectrum, including insulinoma, gastrinoma, glucagonoma, somatostatinoma, and VIPoma. Patients with PanNENs usually present with characteristic symptoms caused by corresponding hormone hypersecretion. It has always been challenging in dealing with such rare but complicated disorders. In this report, we analyzed the clinical characteristics of functional PanNENs in a large cohort of Chinese patients and summarized our clinical experience in diagnosis and treatment. METHODS: The retrospective analysis was performed in patients with a definite diagnosis of functional PanNENs hospitalized in Chinese PLA General Hospital between 2000 and 2020. The clinical characteristics, surgical information, and pathological findings were extracted from their medical records and were analyzed. RESULTS: Totally, 286 patients (gender: male 103 and female 183; age: 45.55 ± 15.23 years old) were diagnosed with definite functional PanNENs. The most frequent functional PanNENs were insulinoma (266/286) followed by glucagonoma (10/286), somatostatinoma (3/286), adrenocorticotropic hormone- (ACTH-) producing tumor (3/286), gastrinoma (2/286), and VIPoma (2/286). Nine patients were diagnosed with multiple endocrine neoplasia type 1 (MEN1) in which all the associated functional PanNENs were insulinomas. The duration from symptoms' onset to confirmed diagnosis was 3.67 ± 4.28 years. Two hundred and eighty patients with tumor localized in pancreatic or with limited metastasis underwent surgery. The symptoms associated with hormonal oversecretion were improved significantly after surgery. Five patients with unresectable metastases or tumor recurrence after surgery were administrated with systemic chemotherapy or other targeted therapies. With these various therapies, the symptoms were also partially relieved. According to findings in pathological and immunochemical examination, all the functional PanNENs were categorized into NEN-G1 (41.95%), NEN-G2 (54.90%), NEN-G3 (3.15%), and NEC-G3 (0%). CONCLUSION: Patients with suspected functional PanNENs should have a systematic endocrine examination at diagnosis. Multidisciplinary collaborations are essential for precise diagnosis and tumor localization. A successful surgery or other targeted therapies can improve the prognosis of patients with such rare but complex disorders.

Neck circumference is an independent risk factor for hyperuricemia within 3 years in women: a longitudinal study.

INTRODUCTION: Our previous cross-sectional study revealed the association between neck circumference (NC) and hyperuricemia. This study aimed to further investigate the longitudinal association between NC and hyperuricemia and to compare the strengths of longitudinal association of NC and waist circumference (WC) with hyperuricemia. METHODS: A total of 4383 subjects without hyperuricemia at baseline were included. Multivariable linear regression was used to assess the association between baseline anthropometric indices and uric acid level at follow-up. Cox regression was used to assess the relationship between baseline anthropometric indices and the risk of future hyperuricemia. A receiver-operating characteristic curve was used to compare the predictive ability of baseline anthropometric indices for future hyperuricemia. RESULTS: Among women, only baseline NC was positively, linearly associated with uric acid level at follow-up (ß = 1.75) and risk of future hyperuricemia (ptrend < 0.05); risk of hyperuricemia in the third and fourth quartile groups of baseline NC significantly increased, compared with the first quartile group of baseline NC (HR = 1.48 and 1.81, respectively). Among men, neither NC nor WC was associated with hyperuricemia after adjusting for confounder factors. The area under the curve of baseline NC and WC for hyperuricemia was comparable in both genders (0.606 for NC and 0.599 for WC in women, 0.578 for NC and 0.602 for WC in men). CONCLUSIONS: For women, only baseline NC is an independent risk factor of hyperuricemia within 3 years. NC and WC have a similar 3-year predictive ability for hyperuricemia in both genders. Key Points • This is the first study to assess the longitudinal association between neck circumference and hyperuricemia. • According to the results of this study, we propose for the first time that neck circumference is an independent risk factor for hyperuricemia in women in the future, rather than waist circumference. • We found for the first time that neck circumference and waist circumference have similar predictive ability for future hyperuricemia in both genders.

Comparison of Two Autoimmune Dysglycemia Syndromes: Insulin Autoimmune Syndrome (IAS) and Type B Insulin Resistance Syndrome (B-IRS).

Insulin autoimmune syndrome (IAS) and type B insulin resistance syndrome (B-IRS) are rare autoimmune dysglycemia syndromes, but their treatment and prognosis are different. This study aimed to provide a basis for the clinical differential diagnosis of IAS and B-IRS. This was a retrospective study of the medical records of all patients diagnosed with IAS or B-IRS between January 2006 and March 2018 at the Chinese PLA General Hospital. Demographic, clinical, biochemistry, treatment, and follow-up data were examined. There were several different biochemical parameters between IAS (n=13) and B-IRS (n=6): white blood count (WBC, 7.05±3.06 vs. 2.70±0.73×109/l, p=0.004), platelet (249±56.6 vs. 111±68.0×109/l, p<0.001), serum creatine (59.0±17.8 vs. 43.1±7.05 µmol/l, p=0.013), serum albumin (42.3±5.17 vs. 33.6±3.40 g/l, p=0.002), triglyceride (median, 1.33 (1.01, 1.93) vs. 0.56 (0.50, 0.79) mmol/l, p=0.002), plasma IgG (1183±201 vs. 1832±469 mg/ml, p=0.018), IgA (328±140 vs. 469±150 mg/ml, p=0.018), and C3 (128±23.4 vs. 45.3±13.5 mg/l, p<0.001). Fasting insulin in the IAS and B-IRS patients was high (299-4708 vs. 118-851 mU/l, p=0.106), and there was a difference in 2 h oral glucose tolerance test insulin (4217-8343 mU/l vs. 274-1143 mU/l, p=0.012). Glycated hemoglobin (HbA1c) in the B-IRS patients was higher than in IAS patients (114±14.4. vs. 40.6±8.89 mmol/mol, p<0.001). Serum insulin-like growth factor-1 (IGF-1) was lower in all B-IRS patients (25±0.00 vs. 132±52.7 ng/ml, p<0.001). Although IAS and B-IRS are autoimmune hyperinsulinemic dysglycemic syndromes, several clinical parameters (body mass index, HbA1c, WBC, platelet, albumin, triglyceride, IgG, C3, and IGF-1) are different between these two syndromes.

Bilateral adrenocortical adenomas causing adrenocorticotropic hormone-independent Cushing's syndrome: A case report and review of the literature.

BACKGROUND: Adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome (CS) is mostly due to unilateral tumors, with bilateral tumors rarely reported. Its common causes include primary pigmented nodular adrenocortical disease, ACTH-independent macronodular adrenal hyperplasia, and bilateral adrenocortical adenomas (BAAs) or carcinomas. BAAs causing ACTH-independent CS are rare; up to now, fewer than 40 BAA cases have been reported. The accurate diagnosis and evaluation of BAAs are critical for determining optimal treatment options. Adrenal vein sampling (AVS) is a good way to diagnose ACTH-independent CS. CASE SUMMARY: A 31-year-old woman had a typical appearance of CS. The oral glucose tolerance test showed impaired glucose tolerance and obviously increased insulin and C-peptide levels. Her baseline serum cortisol and urine free cortisol were elevated and did not show either a circadian rhythm or suppression with dexamethasone administration. The peripheral 1-deamino-8-D-arginine-vasopressin (DDVAP) stimulation test showed a delay of the peak level, which was 1.05 times as high as the baseline level. Bilateral AVS results suggested the possibility of BAAs. Abdominal computed tomography showed bilateral adrenal adenomas with atrophic adrenal glands (right: 3.1 cm × 2.0 cm × 1.9 cm; left: 2.2 cm × 1.9 cm × 2.1 cm). Magnetic resonance imaging of the pituitary gland demonstrated normal findings. A left adenomectomy by retroperitoneoscopy was performed first, followed by resection of the right-side adrenal mass 3 mo later. Biopsy results of both adenomas showed cortical tumors. Evaluations of ACTH and cortisol showed a significant decrease after left adenomectomy but could still not be suppressed, and the circadian rhythm was absent. Following bilateral adenomectomy, this patient has been administered with prednisone until now, all of her symptoms were alleviated, and she had normal blood pressure without edema in either of her lower extremities. CONCLUSION: BAAs causing ACTH-independent CS are rare. AVS is of great significance for obtaining information on the functional state of BAAs before surgery.

Cardiovascular disease outcomes in metabolically healthy obesity in communities of Beijing cohort study.

OBJECTIVE: The objective of this study was to investigate the association between metabolically healthy obese (MHO) phenotype and the risk of cardiovascular disease (CVD). METHODS: A total of 9393 subjects aged ≥40 years were enrolled in the cohort study (2011-2015). The participants were stratified by body mass index category and metabolic risk at baseline, and incidence of CVD was ascertained at follow-up. RESULTS: The MHO accounted for 6.7%. Compared with the metabolically healthy normal weight (MHNW) group, MHO subjects demonstrated increased risk of CVD events (HR = 1.91; 95% CI, 1.13-3.24). In people with obesity, there was no significant difference on increasing risk of incidence of CVD in the metabolically unhealthy individuals compared with metabolically healthy individuals (HR = 1.19; 95% CI, 0.74-1.91). Female (OR = 1.97; 95% CI, 1.06-3.64), smoking (OR = 2.09; 95% CI, 1.06-4.10), a larger waist circumference (OR = 1.07; 95% CI, 1.03-1.10) and higher LDL cholesterol levels (OR = 1.55; 95% CI, 1.20-2.00) were independent risk factors of the development of the MHO to the metabolically unhealthy obese (MUO) phenotype. CONCLUSIONS: The risk of CVD events of MHO phenotypes is similar to MUO phenotypes; both are higher than the MHNW phenotypes.

A Craniopharyngioma Associated With Elevated Cerebrospinal Fluid HCG Concentrations Misdiagnosed as a Germinoma.

Craniopharyngiomas and germinomas are both rare cranial tumors that most commonly present during childhood or adolescence. Although these tumors have different origins, their clinical and radiological features may be similar. In this article, we report the case of a 35-year female patient with clinical and radiological findings and increased human chorionic gonadotrophin (HCG) levels in the cerebrospinal fluid (CSF) that were consistent with a germinoma. However, pathological analysis revealed a craniopharyngioma. This case report indicates that HCG, which is regarded as a specific tumor marker for germinomas in the differential diagnosis of intracranial lesions, is also detectable in other kinds of suprasellar tumors, such as craniopharyngiomas.

Thyrotrophic status in patients with pituitary stalk interruption syndrome.

Pituitary stalk interruption syndrome (PSIS) is associated with simultaneous or subsequent pituitary hormone deficiencies (PHDs). Although the clinical features of multiple PHDs are well known, the status of the thyrotrophic axis in PSIS has not been thoroughly investigated.The clinical data of 89 PSIS patients and 34 Sheehan syndrome (SS) patients were retrospectively analyzed.The prevalence of central hypothyroidism in the PSIS patients and the SS patients was 79.8% and 70.6%, respectively. The thyroid-stimulating hormone (TSH) levels in the PSIS patients were significantly higher in comparison with the SS patients (5.13 ±â€Š3.40 vs 1.67 ±â€Š1.20 mU/L, P < .05). TSH elevation (8.79 ±â€Š3.17 mU/L) was noticed in 29 of 71 (40.85%) hypothyroid PSIS patients but not in the 24 hypothyroid SS patients. The TSH levels in the hypothyroid PSIS patients were significantly higher in comparison with the euthyroid PSIS patients (5.42 ±â€Š3.67 vs 3.66 ±â€Š1.50 mU/L). Thyroid hormone replacement significantly reduced the TSH levels in the PSIS patients with elevated TSH levels from 7.24 ±â€Š0.98 to 1.67 ±â€Š1.51 mU/L (P < .05). The logistic regression analysis suggested that TSH level was not significantly associated with pituitary stalk status and height of the anterior pituitary gland.PSIS is a newly recognized cause of central hypothyroidism. The proportion and amplitude of TSH elevations are higher in PSIS than in other causes of central hypothyroidism.

The Role of Cortisol/ACTH Ratio for Screening of Subclinical Hypercortisolism in Patients with Adrenal Incidentalomas.

INTRODUCTION: The cortisol/ACTH ratio was supposed to be helpful in the screening of subclinical hypercortisolism (SHC) in the published literatures. This study assessed the cortisol/ACTH ratio in patients with adrenal incidentaloma (AI) confirmed to have SHC and investigated its role for screening SCS in patients with AI. METHODS: This descriptive retrospective study included 183 patients with AIs [45 with SHC and 138 with non-functional adenoma (NFA)]. Cortisol and ACTH levels were measured at 8:00, 16:00, and 0:00, and the cortisol/ACTH ratio was calculated. ROC curve was used to evaluate efficacy of the cortisol/ACTH ratio, explore the best cut-off value and its corresponding sensitivity and specificity. RESULTS: The cortisol/ACTH ratios at all time points were significantly higher in the SHC group than the NFA group (P<0.05) and were significantly correlated with serum cortisol levels after the 1-mg dexamethasone suppression test (DST). Area Under the Curve (AUC) of the cortisol/ACTH ratio at 0:00 and midnight serum cortisol levels were 0.893 (0.843-0.943) and 0.831 (0.765-0.806), respectively. A cortisol/ACTH ratio at 0:00 cut-off of 32.18 nM/pM showed a sensitivity of 100% and specificity of 39.1%. The optimal cut-off was 68.83 nM/pM (sensitivity 86.7%, specificity 75.4%). CONCLUSIONS: Patients with SHC have a higher cortisol/ACTH ratio than those with NFAs. The cortisol/ACTH ratio is significantly correlated with serum cortisol after the 1-mg DST. The diagnostic performance of the cortisol/ACTH ratio at 0:00 is superior to midnight serum cortisol. Therefore, the cortisol/ACTH ratio at 0:00 may be a reliable parameter for SHC screening in patient with AI.

Whole-genome sequencing revealed armadillo repeat containing 5 (ARMC5) mutation in a Chinese family with ACTH-independent macronodular adrenal hyperplasia.

Primary macronodular adrenal hyperplasia (PMAH), also known in the past as bilateral macronodular adrenalhyperplasia or adrenocorticotropin (ACTH)-independent macronodular adrenal hyperplasia, is a rare type of Cushing's syndrome (CS) and is associated with bilateralenlargement of the adrenal glands. It accounts for <1% of all endogenous cases of CS. In order toidentify the pathogenic mutations in the causative gene of (AIMAH pedigrees, Whole-genome sequencing of three patients in family I was used to retrieve candidate causative genes. Meanwhile, the causative gene was identified by Sanger sequencing from the two pedigrees. Sequencing of ARMC5 exons of three patients was carried out to identify somatic mutations. Moreover, haploid clone of one tumor DNA sample was conducted. ARMC5 was the causative gene of two pedigrees confirmed by whole-genome sequencing (WGA) and Sanger sequencing. The variant sites of the two families were c.C943T (p.R315W) and c.C1960T (p.R654X), respectively. Autosomal dominant inheritance of AIMAH was confirmed by genotypes of one family member. Several somatic mutations were discovered in tumor DNA samples. In addition, haploid clone of tumor DNA was confirmed by germline mutation and somaticmutation, which suggested the pathogenic mechanism of "two-hit-model." ARMC5 was the causative gene of AIMAH pedigrees. This AIMAH in this study presented autosomal dominant inheritance, fitting to Mendelian inheritance law. However, the pathogenic mode of this disease showed as compound heterozygote.

Baseline Demographic and Clinical Characteristics of Patients with Adrenal Incidentaloma from a Single Center in China: A Survey.

AIM: To investigate the clinical and endocrinological characteristics of patients with adrenal incidentaloma (AI). MATERIALS AND METHODS: This retrospective study enrolled 1941 AI patients hospitalized at the Department of Endocrinology, Chinese PLA General Hospital, Beijing, China, between January 1997 and December 2016. The patient gender, age at visits, imaging features, functional status, and histological results were analyzed. RESULTS: Of the 1941 patients, 984 (50.70%) were men. The median age was 52 years (interquartile range: 44-69 years). 140 cases had bilateral AI. Endocrine evaluation showed that 1411 (72.69%) patients had nonfunctional tumor, 152 (7.83%) had subclinical Cushing syndrome (SCS), and 82 (4.33%) had primary hyperaldosteronism. A total of 925 patients underwent operation for removal of 496 cortical adenomas (53.62%), 15 adrenal cortical carcinomas (1.62%), and 172 pheochromocytomas (18.59%). The bilateral group had a higher proportion of SCS (18.57% versus 7.10%, P < 0.001, P = 0.006). A mass size of 46 mm was of great value in distinguishing malignant tumors from the benign tumors, with sensitivity of 88.2% and specificity of 95.5%. CONCLUSIONS: We reported the baseline demographic and clinical characteristics of patients with AI in a large series from a single center in China.

Characteristics of glucose metabolism indexes and continuous glucose monitoring system (CGMS) in patients with insulinoma.

AIMS: Analyze the clinical applicability of glucose metabolism indexes and continuous glucose monitoring data on the qualitative diagnosis of insulinoma. METHODS: Involve 22 patients with insulinoma (insulinoma group), 11 patients with hypoglycemia (hypoglycemia group) and 31 people with normal glucose tolerance (control group). HbA1c, fasting blood glucose (FBG), insulin (FINS) and C-peptide (FCP) was tested. Using CGMS to monitor the blood glucose for three consecutive days and selecting the monitoring data of 24 h thereof, figuring out, with the aid of EasyGV Version 9.0, the mean glucose (MG), the standard deviation (SD) of blood glucose, CONGA (continuous overall net glycemic action), J-Index, LI (Lability Index), LBGI (Low Blood Glucose Index), HBGI (High Blood Glucose Index), GRADE (glycaemic risk assessment diabetes equation), MAGE (mean aplitude of glycaemic excursions), M value, MAG (mean absolute glucose). RESULTS: (1) FBG and LBG of insulinoma group are lower than those of control group and those of hypoglycemia group while FINS and FCP of insulinoma group are markedly higher than those of the other two groups; (2) the MG and CONGA of insulinoma group are lower than those of control group and its indexes like ST, LI, LBGI, GRADE, MAGE, M value and MAG are higher than those of control group; there are differences between the indexes of insulinoma group and those of hypoglycemia group in CONGA (lower than that of hypoglycemia group), LBGI (higher than that of hypoglycemia group), and M value (higher than that of hypoglycemia group). By drawing the ROC curve and calculating Youden index, the cut-off values of LBGI, M value, CONGA are respectively as 4.06, 7.79, 4.38, and the best index of differential diagnosis is LBGI. CONCLUSION: Continuous glucose monitoring data can be used to diagnose insulinoma and blood glucose fluctuation indicators such as LBGI, M value, CONGA might be useful to identify insulinoma.

A signature motif in LIM proteins mediates binding to checkpoint proteins and increases tumour radiosensitivity.

Tumour radiotherapy resistance involves the cell cycle pathway. CDC25 phosphatases are key cell cycle regulators. However, how CDC25 activity is precisely controlled remains largely unknown. Here, we show that LIM domain-containing proteins, such as FHL1, increase inhibitory CDC25 phosphorylation by forming a complex with CHK2 and CDC25, and sequester CDC25 in the cytoplasm by forming another complex with 14-3-3 and CDC25, resulting in increased radioresistance in cancer cells. FHL1 expression, induced by ionizing irradiation in a SP1- and MLL1-dependent manner, positively correlates with radioresistance in cancer patients. We identify a cell-penetrating 11 amino-acid motif within LIM domains (eLIM) that is sufficient for binding CHK2 and CDC25, reducing the CHK2-CDC25 and CDC25-14-3-3 interaction and enhancing CDC25 activity and cancer radiosensitivity accompanied by mitotic catastrophe and apoptosis. Our results provide novel insight into molecular mechanisms underlying CDC25 activity regulation. LIM protein inhibition or use of eLIM may be new strategies for improving tumour radiosensitivity.