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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 Al 2 O 3 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Zhang, Wu, Lv, Ba, Gu and Mu.)

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., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Jing Wang et al.)

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., (© 2022. The Author(s).)

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., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

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.

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 (β = 1.75) and risk of future hyperuricemia (p trend  < 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.

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., Competing Interests: The authors declare that they have no conflicts of interest in this paper., (Copyright © 2020 Yuqing Qu et al.)

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±0.73×10 9 /l, p=0.004), platelet (249±56.6 vs. 111±68.0×10 9 /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., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

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., Competing Interests: The authors have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

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.

The aim of present study was to explore the relationships between osteopenia and dyslipidemia, glycemic levels or blood pressure in postmenopausal Chinese women. A total of 4080 women aged 42-85 years were enrolled in this cross-sectional study, which was nested in an ongoing longitudinal (REACTION) study. Calcaneus quantitative ultrasound (QUS) was performed and QUS T score was calculated to assess bone mineral density. Osteopenia was defined as a T score ≤-1.0. The relationship between osteopenia and dyslipidemia, glycemic levels or blood pressure was investigated. The prevalence of osteopenia was significantly lower in subjects with systolic blood pressure (SBP) ≥140 mmHg, fasting blood glucose (FBG) ≥8.0 mmol/L, postprandial blood glucose (PBG) ≥15.0 mmol/L, hemoglobin A1c (HbA1C) 6.5-7.5 %, HbA1C ≥7.5 %. These relationships remained significant after controlling for multiple factors. Moreover, significant trend between osteopenia and SBP, FBG, PBG and HbA1C was observed in women. In contrast, no significant associations between osteopenia and diastolic blood pressure (DBP), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) were found, and no significant trend relationship between osteopenia and DBP, TC, TG, HDL-C, LDL-C was found in postmenopausal Chinese women. The present study showed a relationship between SBP, FBG, PBG, HbA1C and osteopenia in postmenopausal Chinese women, while no significant relationship was observed between dyslipidemia, DBP and osteopenia, even after controlling for multiple confounding factors.

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.

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.

The DEK oncogene is overexpressed in various cancers and overexpression of DEK correlates with poor clinical outcome. Vascular endothelial growth factor (VEGF) is the most important regulator of tumor angiogenesis, a process essential for tumor growth and metastasis. However, whether DEK enhances tumor angiogenesis remains unclear. Here, we show that DEK is a key regulator of VEGF expression and tumor angiogenesis. Using chromatin immunoprecipitation assay, we found that DEK promoted VEGF transcription in breast cancer cells (MCF7, ZR75-1 and MDA-MB-231) by directly binding to putative DEK-responsive element (DRE) of the VEGF promoter and indirectly binding to hypoxia response element (HRE) upstream of the DRE through its interaction with the transcription factor hypoxia-inducible factor 1α (HIF-1α), a master regulator of tumor angiogenesis and growth. DEK is responsible for recruitment of HIF-1α and the histone acetyltransferase p300 to the VEGF promoter. DEK-enhanced VEGF increases vascular endothelial cell proliferation, migration and tube formation as well as angiogenesis in the chick chorioallantoic membrane. DEK promotes tumor angiogenesis and growth in nude mice in HIF-1α-dependent and -independent manners. Immunohistochemical staining showed that DEK expression positively correlates with the expression of VEGF and microvessel number in 58 breast cancer patients. Our data establish DEK as a sequence-specific binding transcription factor, a novel coactivator for HIF-1α in regulation of VEGF transcription and a novel promoter of angiogenesis., Competing Interests: The authors declare no conflicts of interest.

In the present study, the case of a female patient with pseudo-hermaphrodism caused by an androgen-producing adrenocortical tumor is presented, and the possible mechanism is investigated. The expression of the luteinizing hormone/human chorionic gonadotrophin (LH/hCG) receptor in tumor tissues and normal adrenal tissues was analyzed using immunohistochemistry. Furthermore, the activities of 3β-hydroxysteroid dehydrogenase 2 (HSD2), cytochrome P450 17α-hydroxylase (CYP17) and 17β-hydroxysteroid dehydrogenase 3 (HSD3) enzymes were measured using enzyme-linked immunosorbent assay, and the expression levels of 3β-HSD2, 17β-HSD3, CYP17 and LH/hCG receptor mRNA were determined by quantitative polymerase chain reaction (qPCR). Immunohistochemical staining for the LH/hCG receptor was negative in the tumor tissue and positive in the normal adrenal tissue. The activities of 3β-HSD2 and CYP17 in the tumor tissue were higher than those in the normal tissue (P<0.01), whereas the activity of 17β-HSD3 was lower (P<0.01). The mRNA levels of 3β-HSD2 and CYP17 were higher (P<0.01) and the levels of 17β-HSD3 and LH/hCG receptor were lower (P<0.01) in the tumor tissue compared with those of the normal tissue. In conclusion, in the present study, a rare case of virilization by an androgen-producing adrenocortical tumor is present. The results indicate that it may be associated with increased activities of 3β-HSD2 and CYP17 but not with the expression of the LH/hCG receptor.

Osteogenesis imperfecta (OI) is a family of genetic disorders associated with bone loss and fragility. Mutations associated with OI have been found in genes encoding the type I collagen chains. People with OI type I often produce insufficient α1-chain type I collagen because of frameshift, nonsense, or splice site mutations in COL1A1 or COL1A2. This report is of a Chinese daughter and mother who had both experienced two bone fractures. Because skeletal fragility is predominantly inherited, we focused on identifying mutations in COL1A1 and COL1A2 genes. A novel mutation in COL1A1, c.700delG, was detected by genomic DNA sequencing in the mother and daughter, but not in their relatives. The identification of this mutation led to the conclusion that they were affected by mild OI type I. Open reading frame analysis indicated that this frameshift mutation would truncate α1-chain type I collagen at residue p263 (p.E234KfsX264), while the wild-type protein would contain 1,464 residues. The clinical data were consistent with the patients' diagnosis of mild OI type I caused by haploinsufficiency of α1-chain type I collagen. Combined with previous reports, identification of the novel mutation COL1A1-c.700delG in these patients suggests that additional genetic and environmental factors may influence the severity of OI.

Type 2 diabetes mellitus (T2DM) is a complex and heterogeneous disorder affecting >220 million individuals worldwide; this is projected to reach 366 million by 2030. Exenatide, a long‑acting glucagon‑like peptide 1 receptor agonist, exhibits potential in the treatment of T2MD due to its ability to increase β‑cell mass. However, the molecular mechanism by which exenatide increases β‑cell mass is yet to be elucidated. Exenatide function was explored in the INS‑1 rat pancreatic β‑cell line. Exenatide was found to increase adiponectin protein levels by 20% (P<0.05 versus the control group) and reduce the level of C‑reactive protein (CRP) by 50% (P<0.01 versus the control group) in INS‑1 cells, resulting in an increase in the INS‑1 rat pancreatic β‑cell mass by 20% (P<0.01 versus the control group). These findings suggest that exenatide may ameliorate T2DM by increasing adiponectin protein levels and reducing the level of CRP.

Eye absent (Eya) proteins are involved in cell fate determination in a broad spectrum of cells and tissues. Aberrant expression of Eya2 has been documented in a variety of cancers and correlates with clinical outcome. However, whether microRNAs (miRNAs) can regulate Eya2 expression remains unknown. Here, we show that miR-30a represses Eya2 expression by binding to the 3'-untranslated region of Eya2. Overexpression of Eya2 in miR-30a-transfected breast cancer cells effectively rescued the inhibition of cell proliferation and migration caused by miR-30a. Knockdown of Eya2 by small-interfering RNA (siRNA) in breast cancer cells mimicked the effect induced by miR-30a and abolished the ability of miR-30a to regulate breast cancer cell proliferation and migration. The miR-30a/Eya2 axis could regulate G1/S cell cycle progression, accompanied by the modulation of expression of cell cycle-related proteins, including cyclin A, cyclin D1, cyclin E, and c-Myc. Moreover, miR-30a expression was downregulated in breast cancer patients, and negatively correlated with Eya2, which was upregulated in breast cancer patients. These data suggest that the miR-30a/Eya2 axis may play an important role in breast cancer development and progression and that miR-30a activation or Eya2 inhibition may be a useful strategy for cancer treatment., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Vascular endothelial growth factor (VEGF) plays an important role in many disease states, including ischemia, chronic and acute inflammation, and pathologies associated with angiogenesis such as tumors and wounds. A number of factors regulate VEGF promoter activity and VEGF expression such as four and a half LIM domains 1 (FHL1) and Smad4. FHL1 belongs to a family of LIM-only proteins that regulate gene transcription, cell proliferation, differentiation and apoptosis. Smad4 is a tumor suppressor gene, initially identified as deleted in pancreatic carcinoma locus 4 (DPC4). The aim of this study was to determine whether FHL1 and Smad4 inhibited VEGF signaling. HepG2 cells were transfected with the VEGF-Luc reporter, Smad4 and FHL1 or Smad4 and FHL1 siRNA. Results showed that the overexpression of FHL1 and Smad4 synergistically inhibited the promoter activity, mRNA expression and secretion of VEGF, whereas knockdown of endogenous Smad4 and FHL1 had opposite effects. Moreover, the reduction of endogenous Smad4 eliminated FHL1-mediated inhibition of the VEGF promoter activity. In conclusion, a cooperative regulation of VEGF signaling by FHL1 and Smad4 was evidenced, which may provide a novel regulation mechanism underlying cancer development and progression.

Objective: Pituitary stalk interruption syndrome (PSIS) is characterized by the absence of pituitary stalk, pituitary hypoplasia, and ectopic posterior pituitary. Due to the rarity of PSIS, clinical data are limited, especially in Chinese people. Herein, we analyzed the clinical characteristics of patients diagnosed with PSIS from our center over 10 years., Patients and Methods: We retrospectively analyzed the clinical manifestations and laboratory and MRI findings in 55 patients with PSIS., Results: Of the 55 patients with PSIS, 48 (87.3%) were male. The average age was 19.7±6.7 years and there was no familial case. A history of breech delivery was documented in 40 of 45 patients (88.9%) and 19 of 55 patients (34.5%) had a history of dystocia. Short stature was found in 47 of 55 patients (85.5%) and bone age delayed 7.26±5.37 years. Secondary sex characteristics were poor or undeveloped in most patients. The prevalence of deficiencies in growth hormone, gonadotropins, corticotropin, and thyrotropin were 100%, 95.8%, 81.8%, 76.3%, respectively. Hyperprolactinemia was found in 36.4% of patients. Three or more pituitary hormone deficiencies were found in 92.7% of the patients. All patients had normal posterior pituitary function and absent pituitary stalk on imaging. The average height of anterior pituitary was 28 mm, documented anterior pituitary hypoplasia. Midline abnormalities were presented in 9.1% of patients., Conclusions: The clinical features of our Chinese PSIS patients seem to be different from other reported patients in regarding to the higher degree of hypopituitarism and lower prevalence of midline defects. In addition, our patients were older at the time of case detection and the bone age was markedly delayed. We also had no cases of familial PSIS.

Background/aims: To assess the accuracy of combined preoperative localizations and analyze the change in management strategy of operation of insulinoma., Methodology: One hundred and seventy-two patients with a diagnosis of insulinoma at a tertiary hospital between 1985 and 2010 were reviewed, where accurate combined preoperative localization before surgical exploration was the primary management policy of insulinoma. Operation details for 147 patients were checked., Results: An average of 2.89 preoperative localization studies including 1.61 non-invasive studies and 1.28 invasive studies were utilized per patient. Contrast-enhanced ultrasonography (CEUS) was the most sensitive invasive modality (88.1%) whereas magnetic resonance imaging (MRI) was the most sensitive non-invasive modality (64.0%). All 147 patients underwent complete surgical resection which included 126 enucleations and 18 distal pancreatectomies with a cure rate of 95.2% (140/147) at a median follow-up of 45 months (range 1-248). The postoperative morbidity and long-term outcome of enucleation was similar to distal pancreatectomy despite a higher rate of microscopic margin involvement., Conclusions: Accurate combined preoperative localization of insulinomas is useful of the choice of enucleation, eliminates the need for blind distal pancreatectomy and avoids re-operation. Whenever possible, a pancreas-sparing approach such as enucleation should be adopted.