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Purpose In the Guidelines for the Prevention and Control of Type 2 Diabetes in China (2017 edition), intensive lifestyle interventions are recommended for preventing the progression of impaired glucose tolerance (IGT) to type 2 diabetes mellitus. Acarbose and metformin can also be considered if intensive lifestyle modification has been ineffective for 6 months. But the effects of intensive lifestyle modification and glucose-lowering drug interventions that work best in the population with IGT are unclear. This network meta-analysis assessed the effectiveness of intensive lifestyle modification, acarbose, and metformin in treating populations with IGT. Methods We systematically searched both Chinese- and English-language databases, including China Knowledge, the Cochrane Library, Embase, PubMed, VIP, and Wanfang, for articles published between database inception and September 2019. Randomized, controlled clinical trials in patients with IGT treated with acarbose, metformin, and intensive lifestyle modification were assessed for eligibility. The data from all included studies were evaluated by 2 reviewers independently in accordance with the Cochrane Handbook for Systematic Reviews of Intervention version 6.0. A network meta-analysis was performed by using R software version 3.6.1. Findings The data from 53 randomized controlled trials were included in the review, with a sample size of 21,208 patients. Compared with the control group, the use of acarbose, metformin, and/or intensive lifestyle modification was associated with reduced rates of progression to diabetes (relative risks [RRs] [95% credible intervals]: acarbose, 0.37 [0.29–0.47]; metformin, 0.39 [0.30–0.50]; intensive lifestyle modification, 0.61 [0.50–0.73]). The surface under the cumulative ranking (SUCRA) value of acarbose was 88.35%, supporting that acarbose was more effective in reducing the rate of progression to diabetes compared with controls. With acarbose, metformin, and intensive lifestyle modification, the rates of achieving a normal glucose level were increased by RR = 2.1, 1.7, and 1.2, respectively when compared with control group. The SUCRA value of acarbose was 99.69%, supporting the optimal effect of acarbose in achieving a normal blood glucose level. Implications In this meta-analysis in patients with IGT, compared with controls, acarbose and metformin were associated with decreased rates of progression to diabetes and increased rates of achieving a normal glucose level. Acarbose use was associated with an increased rate of achieving a normal glucose level, while intensive lifestyle modification was not.

Objectives: To assess the performance of elastography (ES) and ultrasound (US) in predicting the malignancy of breast lesions and to compare their combined diagnostic value with that of magnetic resonance imaging (MRI). Materials and Methods: The study prospectively enrolled 242 female patients with dense breasts treated in 35 heath care facilities in China between November 2018 and October 2019. Based on conventional US and elastography, radiologists classified the degree of suspicion of breast lesions according to the US Breast Imaging Reporting and Data System (BI-RADS) criteria. The diagnostic value was compared between US BI-RADS and MRI BI-RADS, with pathological results used as the reference standard. Results: The results demonstrated that irregular tumor shape, a nonparallel growth orientation, indistinct margins, angular contours, microcalcifications, color Doppler flow and ES score on US imaging were significantly related to breast cancer in dense breasts (P=0.001; P=0.001; P=0.008; P

Programmed death-1 receptor ligand 1 (PD-L1) is a promising therapeutic target in aggressive cancers. However, immune landscapes and cancer hallmarks of human PD-L1(+) tumors as well as their roles in determining therapeutic efficacies are unknown. Here, we showed, in detailed studies of gene data regarding 9769 patients of 32 types of human cancers, that PD-L1 could not exclusively represent the IFN-γ signature and potentially signified proinflammatory myeloid responses in a tumor. PD-L1 heterogeneity endowed by local immune landscapes controlled cancer hallmarks and clinical outcomes of patients. Mechanically, NF-κB signal elicited by macrophage inflammatory responses generated PD-L1(+) cancer cells exhibiting capabilities to aggressively survive, support angiogenesis, and metastasize, whereas STAT1 signal triggered by activated T cells induced PD-L1(+) cancer cells susceptive to apoptosis. Importantly, PD-L1(+) cancer cells generated by macrophages established great resistance to conventional chemotherapy, cytotoxicity of tumor-specific effector T cells, and therapy of immune-checkpoint blockade. Therapeutic strategy combining immune-checkpoint blockade with macrophage depletion or NF-κB inhibition in vivo effectively and successfully elicited cancer regression. Our results provide insight into the functional features of PD-L1(+) tumors and suggest that strategies to influence functional activities of inflammatory cells may benefit immune-checkpoint blockade therapy.

Citrate-capped gold nanoparticles (AuNPs) modified with thrombin-binding aptamer are often implemented for colorimetric, fluorescent, and electrochemical detection of thrombin in an aqueous solution. However, researchers have rarely explored the application of fibrinogen-modified AuNPs (F-AuNPs) for thrombin sensing. We present a simple, inexpensive, sensitive, and selective probe for colorimetric assay of thrombin through combining thrombin-induced inclusion of F-AuNPs into Fibrin and F-AuNPs-catalyzed reduction of 4-nitrophenol with an excess amount of NaBH4. Considering that fibrinogen stabilized citrate-capped AuNPs against a high-ionic-strength buffer, F-AuNPs efficiently catalyzed the NaBH4-mediated decrease of yellow 4-nitrophenol to colorless 4-aminophenol. The presence of thrombin converted fibrinogen into fibrin on the nanoparticle surface, leading to the inclusion of nanoparticles into fibrin. The formation of fibrin inhibited that the AuNPs catalyzed the NaBH4-mediated reduction of 4-nitrophenol. Consequently, the color of the solution gradually varied from colorless to yellow with increasing thrombin concentration. The proposed system was shown to be accurate in the quantification of small differences in the concentration of human thrombin over the range of 4–60 pM. The lowest detectable concentration of human thrombin by the naked eye was as low as 16 pM. We demonstrated the practical application of the proposed system in quantifying 1–15 nM human thrombin in human plasma.

Myocardial contrast echocardiography (MCE) and two-dimensional speckle tracking echocardiography (2D-STE) were used to detect left ventricular myocardial microcirculation perfusion and myocardial systolic function in dilated cardiomyopathy (DCM) and to explore the relationship between the two.Conventional ultrasound, MCE, and 2D-STE examinations were performed on 30 patients and 30 controls. Left ventricular microcirculation perfusion, left ventricular longitudinal strain (GLS), and circumferential strain (GCS) were analyzed to further compare the correlation between left ventricular perfusion and myocardial strain parameters.Regional myocardial perfusion was reduced in patients with DCM, manifesting as a decrease in the rising slope (A) of the mid-segment of the posterior septum, the peak intensity (PI) of the mid-segment of the anterior septum and the posterior septum, the apical segment of the lateral wall, the area under the curve (AUC) of the posterior septum, the basal segment of the posterior wall, the anterior septum, posterior septum, posterior wall, mid-segment of the lateral wall, and apical segment of the lateral wall and the overall average PI and AUC of the mid-segment, compared with that in the controls (P < 0.05). The left ventricular systolic function and the strain parameters GLS and GCS of DCM patients were lower than those of the controls (P < 0.001). Correlation analysis revealed a positive correlation between the A of the mitral valve and GCS (r = 0.372, P = 0.043), and MV-E/e' had a positive correlation with the AUC of the basal and intermediate segments (r = 0.379, P = 0.039; r = 0.404, P = 0.027).In patients with DCM, regional myocardial microcirculation perfusion is reduced, and myocardial strain is impaired. Myocardial perfusion has a good positive correlation with myocardial mechanics.

Objectives. To assess the effectiveness and safety of ARW for vascular recanalization in CTO patients. Background. Chronic total occlusion (CTO) of coronary artery accompanied with large branch distal to the occluded segment (

The 1986 Food Research Institute-Tanaka et al. model predicts the safety of shelf-stable process cheese spread formulations using the parameters of moisture, pH, NaCl, and disodium phosphate (DSP) to inhibit toxin production by Clostridium botulinum. Although this model is very reliable for predicting safety for standard-of-identity spreads, the effects of additional factors have not been considered. The objective of this study was to create a predictive model to include the interactive effect of moisture, pH, fat, sorbic acid, and potassium-based replacements for NaCl and DSP to reflect modern reduced-sodium recipes. Eighty formulations were identified using a central composite design targeting seven factors: 50 to 60% moisture, pH 5.4 to 6.2, 0 to 0.2% sorbic acid, 10 to 30% fat, 1.7 to 2.4% NaCl, 0.8 to 1.6% DSP, and 0 to 50% potassium replacement for sodium salts. Samples were inoculated with proteolytic C. botulinum spores at 3 log spores per g, hot filled into sterile vials, and stored anaerobically at 27°C. Samples were assayed at 0, 1, 2, 3, 4, 8.5, 17.5, 26, and 40 weeks for the presence of botulinum toxin using the mouse bioassay. A parametric survival model was fit to the censored time-to-toxin data. All linear, quadratic, and pairwise effects were considered for model fit. As hypothesized, the effects of pH, sorbate, moisture, DSP, and NaCl were highly significant (P < 0.001). Fat concentration and potassium replacement effects were significant at P < 0.021 and P < 0.057, respectively. The model consistently predicted the safety failure of the toxic samples, but it also predicted failure for some samples that were not toxic. This model is an adjunct to existing models by adding the factors of potassium salts, fat, and sorbic acid to predict the botulinal safety of prepared process cheese products but is not intended to be a substitute for formulation evaluation by a competent process authority.

Calf Spleen Extractive Injection (CSEI), extracted from the spleen of healthy cows (within 24 hours of birth), is a small-peptide-enriched extraction and often used as an ancillary agent in cancer therapy. This study evaluated the hematopoietic function of CSEI and its underlying mechanisms, principally in CHRF, K562 cells, BMNCs and a mouse model of cyclophosphamide (CTX)-induced hematopoietic suppression. CSEI promoted the proliferation and differentiation of CHRF and K562 cells, activated hematopoietic- and proliferation-related factors RSK1p90, ELK1 and c-Myc, and facilitated the expression of differentiation- and maturation-related transcription factors GATA-1, GATA-2. In the mice with hematopoietic suppression, 3 weeks of CSEI administration enhanced the bodyweights and thymus indices, suppressed the spleen indices and strongly elevated the production of HSPCs, neutrophils and B cells in bone marrow, ameliorated bone marrow cellularity, and regulated the ratio of peripheral blood cells. Proteome profiling combined with ELISA revealed that CSEI regulated the levels of cytokines, especially G-CSF and its related factors, in the spleen and plasma. Additional data revealed that CSEI promoted phosphorylation of STAT3, which was stimulated by G-CSF in both mice spleen and cultured BMNCs. Taken together, CSEI has the potential to improve hematopoietic function via the G-CSF-mediated JAK2/STAT3 signaling pathway.

In September 2013, 2248 students from 36 junior high schools in Shaanxi Province underwent assessment of visual acuity (VA), completed a questionnaire about their spectacle use and were administered a standardized mathematics examination. Among 2,248 students (mean age 13.6 years, 52% male), visual impairment was present in 699 (31%, 95% Confidence Interval 29-33%). Spectacle wear was observed in 360 of 966 children needing glasses (37%). Ownership of spectacles among children needing glasses was associated with poorer uncorrected vision in the better-seeing eye (P

Infusion of mesenchymal stem cells (MSCs) has been identified in the rapid alleviation in hyperglycemia of diabetic individuals, but the mechanism involved has not been adequately explained by these cells' potential role in modulating system insulin sensitivity and islet regeneration. In this study, we demonstrated adipose-derived mesenchymal stem cells (ASCs) produced significantly lower blood glucose via promoting hepatic glycogen synthesis and inhibiting hepatic glucose production within 24 h after infusion in T2DM rats. In vitro, HepG2 cells treated with palmitate (PA) were used as a model of hepatic glucose metabolism disorder to confirm that ASCs stimulates the phosphorylation of hepatic AMP-activated protein kinase (AMPK) to restores hepatic glucose metabolism in type 2 diabetes. In summary, this study indicated that ASCs improve hyperglycemia via regulating hepatic glucose metabolism. Additionally, the effect of ASCs on hepatic glucose metabolism depended on the AMPK signaling pathway. Thus, this is the new research of the molecular mechanisms of MSCs administration to improve glucose metabolism, and it may indicate a new treatment target of MSCs in T2DM.

Cyclic diadenylate monophosphate (c-di-AMP) and P1,P5-diadenosine-5′ pentaphosphate (Ap5A) have been determined to play important roles in bacterial physiological processes and human metabolism, respectively. However, few, if any, methods have been developed that use fluorescent sensors to sense c-di-AMP and Ap5A in the real world. To address this challenge, this study presents a fast, convenient, selective, and sensitive assay for quantifying c-di-AMP and Ap5A fluorescence based on the competitive binding of diadenosine nucleotides and a polyadenosine probe to coralyne. The designed probe consists of a 20-mer adenosine base (A20), a fluorophore unit at the 5′-end, and a quencher unit at the 3′-end. Through A2–coralyne–A2 coordination, coralyne causes a change in the conformation of A20 from that of a random coil to a folded structure, thus enabling the fluorophore to be close to the quencher. As a result, fluorescence quenching occurs between the two organic dyes. When the A20·coralyne probe encounters t...

Aims Currently, available Doppler echocardiographic reference values are derived mainly from North American and European population studies, which may not applicable to the Chinese population. We aimed to establish normal reference values of Doppler echocardiographic parameters in a nationwide, population-based cohort of healthy Han Chinese adults. Methods and results A total of 1394 qualified healthy subjects (mean age 47.3 ± 16.0 years, 678 men) were enrolled at 43 collaborating laboratories, 37 transvalvular flow and tissue Doppler parameters were obtained, and the impacts of gender and age on each parameter were analysed. Significant differences were found between men and women in 48.6% (18/37) of the parameters analysed, and among different age groups in 83.8% (31/37) of the parameters in men and in 86.5% (32/37) of the parameters in women. Conclusions Normal reference values of Doppler echocardiographic parameters were established for the first time in a nationwide, population-based cohort of healthy Han Chinese adults. Since most of these parameters differed by gender and/or age, reference values specified for gender and age should be recommended in clinical practice. [10.1093/ehjci/jev353][1] [1]: /lookup/doi/10.1093/ehjci/jev353

A rapid, simple and sensitive method for the detection of piperazinyl phenothiazine drugs using dispersive liquid-liquid microextraction (DLLME) combined with field-amplified sample stacking (FASS) in CE was developed. Sensitivity parameters that affect the extraction and FASS efficiency, such as the type and volume of disperser solvent, extraction time, addition of salt, and efficiency of FASS, were investigated and optimized. Note that the conductivity ratio between BGE and sample zone was measured to be 2300. Under optimal extraction and stacking conditions, the calibration curve, which ranged from 0.3 to 160 ng/mL, demonstrated good linearity with a correlation coefficient r≧ 0.9900. The LODs of prochlorperazine (Pcp), trifluoperazine (Tfp), perphenazine (Ppa), and fluphenazine (Fpa) at an S/N of 3 were 0.1, 0.1, 0.07, and 0.08 ng/mL, respectively. An approximately 1000-fold to 2500-fold improvement in sensitivity was achieved for the four tested analytes compared to conventional CZE without DLLME. The recoveries of all phenothiazines in urine and plasma ranged from 85.7 to 107.6% and 95.6 to 105.4%, respectively. The proposed method was demonstrated to be a rapid and convenient method for the determination of four piperazinyl phenothiazine drugs in human urine and plasma.

Background The aim of this study is to evaluate the safety and feasibility of laparoscopic common bile duct exploration and primary closure of choledochotomy for the patients with common bile duct stones (CBDS) who failed in endoscopic sphincterotomy (EST). Methods Between January 2007 and June 2012, a total of 78 patients who subjected to endoscopic retrograde cholangiopancreatography (ERCP) and EST, but failed in endoscopic stone extraction, were referred to us. The following day, laparoscopic cholecystectomy, laparoscopic common bile duct exploration (LCBDE) and primary closure of choledochotomy were performed in all patients. Results No intraoperative complications were experienced in the patients. 6 patients required conversion to open cholecystectomy due to impacted stones. The mean operative time was 145 min. The mean postoperative hospital stay was 6d. All the patients achieved successful stone clearance. 13 cases had slight bile leaks, which resolved spontaneously. None of the patients experienced biliary peritonitis, biliary fistula, pancreatitis, or cholangitis. Conclusion If it is performed by experienced laparoscopic surgeons, primary closure following immediate laparoscopic common bile duct exploration (LCBDE) is safe and feasible for patients with CBDS who fail in endoscopic stone extraction.

China is the largest antibiotic producer, producing a large amount of antibiotic bacterial residues classified to hazard wastes in 2008. It is urgent to find suitable techniques to dispose antibiotic bacterial residues for pharmaceutical enterprises. In this paper, the characteristics of antibiotic bacterial residues are discussed and the current situation and treatment and disposal techniques are summarized, including the technology of composting, incineration, feed stuff, landfill and energy regeneration and so on. In the last, the future development trend of dealing with antibiotic bacterial residues is prospected.

In this study, we aimed to study the role of growth factor receptor-bound protein 2 (Grb2) in palmitic acid-induced steatosis and other "fatty liver" symptoms in vitro. HepG2 cells, with or without stably suppressed Grb2 expression, were incubated with palmitic acid for 24 h to induce typical clinical "fatty liver" features, including steatosis, impaired glucose metabolism, oxidative stress, and apoptosis. MTT and Oil Red O assays were applied to test cell viability and fat deposition, respectively. Glucose uptake assay was used to evaluate the glucose utilization of cells. Quantitative polymerase chain reaction and Western blot were used to measure expressional changes of key markers of insulin signaling, lipid/glucose metabolism, oxidative stress, and apoptosis. After 24-h palmitic acid induction, increased fat accumulation, reduced glucose uptake, impaired insulin signaling, enhanced oxidative stress, and increased apoptosis were observed in HepG2 cells. Suppression of Grb2 in HepG2 significantly reduced fat accumulation, improved glucose metabolism, ameliorated oxidative stress, and restored the activity of insulin receptor substrate-1/Akt and MEK/ERK pathways. In addition, Grb2 deficiency attenuated hepatic apoptosis shown by reduced activation of caspase-3 and fluorescent staining. Modulation of Bcl-2 and Bak1 also contributed to reduced apoptosis. In conclusion, suppression of Grb2 expression in HepG2 cells improved hepatic steatosis, glucose metabolism, oxidative stress, and apoptosis induced by palmitic acid incubation partly though modulating the insulin signaling pathway.

KMT5A (known as PR-Set7/9, SETD8 and SET8), a member of the SET domain containing methyltransferase family specifically targeting H4K20 for methylation, has been implicated in multiple biological processes. In the present study, we identified that KMT5A was elevated in 50 pairs of papillary thyroid cancer tissue samples and in cell lines K1 and TPC-1 by qRT-PCR and western blotting, as well as by immunohistochemical staining. CCK-8 assay and flow cytometric analysis revealed that inhibition of KMT5A attenuated proliferation and induced apoptosis. Transwell assays revealed that cell migration and invasion were suppressed in KMT5A-knockdown cells. Moreover, the inhibition of KMT5A arrested the cell cycle in the G1/S phase of papillary thyroid cancer cells. The TCGA data revealed that elevated KMT5A expression was significantly correlated with extrathyroidal extension, lymph node metastasis and advanced pathological stage of papillary thyroid cancer. Furthermore, we observed that inhibition of KMT5A suppressed the expression of SREBP1, SCD, FASN and ACC, key molecules involved in lipid metabolism and decreased the level of malondialdehyde in papillary thyroid cancer cells. In conclusion, KMT5A may be a novel oncogenic factor, specifically a regulator for lipid metabolism in papillary thyroid carcinoma.

In this study, we present a case of a 52-year-old male with a chondrosarcoma of the left lamina of the thyroid cartilage. Pre-operative evaluations detected typical calcifications and delineated the extent of the tumor. The patient underwent a total laryngectomy to ensure the complete resection of the tumor. The tumor was histopathologically found to consist of chondrocytes in a hyaline cartilage matrix. The patient's post-operative course has been successful apart from the permanent tracheostomy. Herien, we discuss the methods and rationales for the diagnosis and management of and recovery from this rare tumor, and also provide a review of the literature.

We describe an elderly male patient who presented with fever of unknown origin and refractory hyponatraemia. Following (18) fluorine-fluorodeoxyglucose positron emission tomography/computed tomography scan and core adrenal biopsy, the diagnosis of diffuse large B-cell non-Hodgkin lymphoma with pituitary and bilateral adrenal involvement was confirmed. After chemotherapy, his symptoms resolved, and all the lesions shrank significantly.

Asia bears the world's greatest burden of type 2 diabetes (T2DM) and prevalence is increasing rapidly. Compared to other races, Asians develop T2DM younger, at a lower degree of obesity, suffer longer from its complications and die earlier. Curbing this epidemic requires an integrated, risk-based, and multidisciplinary approach. Inadequately managed T2DM has macrovascular and microvascular sequelae, Asians with T2DM being particularly susceptible to diabetic nephropathy. Earlier and more intensive monitoring and management of risk factors are required, especially for patients with, or at risk of, renal impairment. Particular challenges of T2DM management in Asia include: lack of access to specialist healthcare, insufficient clinical evaluation and delayed diagnosis. As in Caucasians, conventional treatment modalities are limited by deteriorating glycaemic control with disease progression and there is an unmet need for efficacious, safe, cost-effective and convenient pharmacotherapies for treating different stages of T2DM and preventing its complications, particularly in high-risk patients. There is a trend towards increasing use of DPP-IV inhibitors, which are no less efficacious and safe in Asians than Caucasians and may have some advantages over existing oral antidiabetic agents, particularly for certain high-risk groups. Such agents may play a significant future role in the management of T2DM.

Laparoscopic approach has been increasingly used in the treatment of pancreatic benign diseases. This report evaluates our experience with laparoscopic surgery for pancreatic insulinomas.Between July 2000 and December 2007, laparoscopic pancreatectomy was attempted in 29 consecutive patients with insulinomas. The localization of tumors, operating characteristics, and clinical outcomes were analyzed.Tumors were precisely localized in 28 of 29 (96.6%) patients by a combination of preoperative imaging techniques and intraoperative ultrasonography. Laparoscopic pancreatectomy was successfully performed in 26 patients, including enucleation (n = 14), hand-assisted enucleation (n = 2), and distal pancreatectomy with (n = 9) or without (n = 1) spleen preservation. Two conversions to open procedure were required because of unfavorable locations of the tumors. The pancreatic fistula occurred in four patients who underwent tumor enucleation. The median hospital stay was 5.5 days (range, 3-18 days) after laparoscopic procedure. Twenty-eight patients with pancreatic resection were free of symptoms and remained normoglycemic after a median follow-up period of 19 months (range, 10-36 months).Laparoscopic pancreatic resection is a feasible and safe procedure for patients with insulinomas. Further studies are required to evaluate the potential application of the hand-assisted approach for tumors located at anatomically unfavorable positions.

LRP16 was previously identified as an estrogen-induced gene in breast cancer cells. The responsiveness of LRP16 to estrogen and its functional effects in endometrial cancer (EC) cells are still unclear. Here, we show that the mRNA level and promoter activity of the LRP16 gene were significantly increased by 17beta-estradiol (E2) in estrogen receptor alpha (ER alpha)-positive Ishikawa human EC cells. Although the growth rate of Ishikawa cells was not obviously affected by ectopic expression of LRP16, the results of a Transwell assay showed an approximate one-third increase of the invasive capacity of LRP16-overexpressing cells. As a result of molecular screening, we observed that the expression of E-cadherin, an essential adhesion molecule associated with tumor metastasis, was repressed by LRP16. Further promoter analyses demonstrated that LRP16 inhibited E-cadherin transactivation in a dose-dependent manner. However, the inhibition was abolished by estrogen deprivation, indicating that the downregulation of E-cadherin transcription by LRP16 requires ER alpha mediation. Chromatin immunoprecipitation analyses revealed that the binding of ER alpha to the E-cadherin promoter was antagonized by LRP16, suggesting that LRP16 could interfere with ER alpha-mediated transcription. These results suggest that the upregulation of LRP16 by estrogen could be involved in invasive growth by downregulating E-cadherin in human ECs.

Angiotensin II type 1 receptor (AT1R) blockers (ARBs) have been shown to reduce the incidence of type 2 diabetes mellitus; however, the underlying molecular mechanism is unknown. Peroxisome proliferator-activated receptor γ (PPARγ) is the central regulator of insulin and glucose metabolism, which improves insulin sensitivity. Whether candesartan cilexetil, as a prodrug of the AT1R blocker candesartan, has PPARγ-activating properties remains to be elucidated. The aim of the present study was to investigate the effects of oral administration of candesartan cilexetil on glucose tolerance and the actions of PPARγ on liver and adipose tissue in the insulin-resistant obese rat induced by high-fat diet. Animals treated with candesartan cilexetil showed an improved glucose tolerance after oral glucose challenge. Whole-body insulin sensitivity was evaluated using the hyperinsulinemic-euglycemic clamp technique. During high-fat feeding in high-fat diet (HF) rats, the glucose infusion rate (GIR) was 52.3% lower than that in normal chow (NC) rats. However, the GIR was significantly enhanced following candesartan cilexetil treatment. Angiotensin II receptor antagonism also resulted in significant increases in PPARγ protein expression in adipose and liver tissue. These results indicate that PPARγ activation by candesartan cilexetil may provide novel therapeutic options in the treatment of patients with metabolic syndrome.

To investigate the effects of saturated free fatty acid, palmitic acid (PA), on hepatocytes, we administered PA to rat hepatocytes. We demonstrated that PA inhibited the cell growth as a dose- and time-dependent manner in rat hepatocytes. PA-induced morphological changes including swelling, membrane dissolution and formation of debris, and apoptosis with appearance of sub-G1 fraction determined by cell cycle analysis after treatment for 4 days. The level of Bcl-2 was slightly decreased, in contrast, the level of Bax elevated markedly, which resulted in a significant decrease of Bcl-2/Bax ratio after PA treatment on HepG2 cells. These findings demonstrated that PA induces cell death on hepatocytes, perhaps via mitochondria-mediated apoptosis. Furthermore, the present study indicates that PA's cell toxicity may play important roles in the transition from steatosis to steatohepatitis in human especially with obesity.

Pituitary tumor transforming gene (PTTG) is a proto-oncogene cloned from rat GH4 cells. This gene was able to induce cell transformation in vitro and is also associated with p53-dependent and -independent apoptosis. In this study, we cloned human PTTG (hPTTG) from a pituitary tumor and then stably transfected the hPTTG into HeLa and A549 cells. An overexpression of hPTTG significantly inhibited cell growth, which was determined by the adherent cell growth properties, colony formation in soft agar and [3H] thymidine incorporation, respectively, in HeLa and A549 cells. The inhibitory effect on cell growth was associated with the activation of p21WAF1/CIP1 in A549 cells, but not in HeLa cells. The hPTTG overexpression increased both the p21WAF1/CIP1 mRNA and protein expression levels as determined by both Northern and Western blot analysis, respectively, in A549 cells. The increased expression of p21WAF1/CIP1 mRNA was regulated at the transcription level and was independent on p53 expression because the luciferase activity increased after the co-transfection of hPTTG and p21WAF1/CIP1 promoter fragments with and without a p53 binding sequence. The subcellular distribution of hPTTG was dependent on cell type, and was predominantly in the nucleus in HeLa, Cos-7 and DU145 cells, but showed a diffuse distribution in both the nucleus and cytoplasm in A549, DLD-1 and NIH3T3 cells. These results indicate that an overexpression of hPTTG inhibits the cell growth due to different mechanisms, which are p21WAF1/CIP1 -dependent and -independent.

A partially filling technique for the analysis of DNA markers and polymerase chain reaction (PCR) products by capillary electrophoresis in the presence of electroosmotic flow using polymer solutions is presented. Either after or prior to the sample injection, a plug of salts at high pH was hydrodynamically injected. During the separation, poly(ethylene oxide) (PEO) solution entered the capillary. We have found that the position, length, and composition of the plugs affect the sensitivity, resolution, and speed on the analysis of PhiX-174/HaeIII DNA restriction fragments or a DNA mixture (pBR 322/HaeIII digest, pBR 328/BglI digest and pBR 328/HinfI digest) with different degrees. Through careful evaluation of the impact of anions and cations on the analysis of DNA, we have suggested that the optimal condition is applying a plug consisting of 32 mM NaCl and 0.01 M NaOH at 30 cm height for 60 s after sample injection. In the presence of such a plug, PEO adsorption reduces, and thus the separation is faster, as well as the sensitivity improves. Using this condition, the analysis of a DNA mixture (injected at 30 cm for 360 s) containing ten different PCR products amplified after 17 cycles was complete in 25 min. About a 2000-fold improvement in the sensitivity was achieved when compared to that by a conventional method (10 s injection) without applying a plug.

White blood cell (WBC) count has been associated with diabetic risk, but whether the correlation is independent of other risk factors has hardly been studied. Moreover, very few such studies with large sample sizes have been conducted in Chinese. Therefore, we investigated the relationship between WBC count and glucose metabolism in China. We also examined the relevant variables of WBC count. A total of 9,697 subjects (mean age, 58.0 ± 9.1 years) were recruited. The subjects were classified into four groups, including subjects with normal glucose tolerance, isolated impaired fasting glucose, impaired glucose tolerance and type 2 diabetes mellitus (T2DM). We found that WBC count increased as glucose metabolism disorders exacerbated. WBC count was also positively correlated with waist hip ratio, body mass index, smoking, triglycerides, glycosylated haemoglobin A1c (HbA1c) and 2-h postprandial glucose. In addition, high density lipoprotein and the female gender were inversely correlated with WBC levels. In patients with previously diagnosed T2DM, the course of T2DM was not correlated with WBC count. Our findings indicate that elevated WBC count is independently associated with worsening of glucose metabolism in middle-aged and elderly Chinese. In addition, loss of weight, smoking cessation, lipid-modifying therapies, and control of postprandial plasma glucose and HbA1c may ameliorate the chronic low-grade inflammation.

Background Currently available echocardiographic reference values are derived mainly from North American and European population studies, and no echocardiographic reference values are available for the Chinese population. The aim of this study was to establish normal values of echocardiographic measurements of the cardiac chambers and great arteries in a nationwide, population-based cohort of healthy Han Chinese adults. Methods A total of 1,586 healthy Han Chinese volunteers aged 18 to 79 years were screened at 43 collaborating laboratories throughout China. Standard M-mode and two-dimensional echocardiography was performed to obtain measurements of the cardiac chambers and great arteries. The impacts of gender and age on all echocardiographic measurements were analyzed. Results A total of 1,394 qualified healthy subjects (mean age, 47.3 ± 16.0 years; 678 men) were ultimately enrolled. Except for left ventricular ejection fraction, values of cardiac chamber and great arterial dimensions were significantly higher in men than in women. Most measurements of the atrial and great arterial dimensions, left ventricular wall thickness, and left ventricular mass increased with age in both men and women. Conclusions Normal reference values of cardiac dimensional parameters were established for the first time in a nationwide, population-based cohort of healthy Han Chinese adults. Because most of these parameters were found to vary with gender and age, reference values stratified for gender and age should be used in clinical practice.

We report concentration and separation of DNA in the presence of electroosmotic flow (EOF) using poly(ethylene oxide) (PEO) solution. DNA fragments migrating against EOF stacked between the sample zone and PEO solution. To maximize the injection volume, several factors, such as concentrations of Tris-borate (TB) buffer and PEO solution, capillary size, and matrix, were carefully evaluated. The use of 25 mM TB buffers, pH 10.0, containing suitable amounts (less than 10 mM) of salts, such as sodium chloride, sodium phosphate, and sodium acetate, to prepare DNA is essential for the concentration of large-volume samples. In the presence of salts, the peaks also became sharper and the fluorescence intensity of DNA complexes increased. Using 2.5% PEO and a 150 microm capillary filled with 400 mM TB buffer, pH 10.0, up to 5 microL DNA samples (phiX 174 RF DNA-HaeIII digest or the mixture of pBR 322/HaeIII, pBR 328/Bg/I, and pBR 328/HinfI digests) have been analyzed, resulting in more than 400-fold improvements in the sensitivity compared to that by conventional injections (ca. 36 nL). Moreover, this method allows the analysis of 3.5 microL PCR products amplified after 17 cycles without any sample pretreatment.

We investigated the effects of a nuclear receptor system constituted by retinoid X receptor (RXR) and its heterodimer partner on the aromatase activity in a cultured MCF-7 human breast cancer cell line and also in human ovarian granulosa cells, using each selective ligand for retinoic acid receptor, RAR (TTNPB), retinoid X receptor, RXR (LG100268), PPARgamma (troglitazone), and vitamin D3 receptor (cholecalciferol). In MCF-7 cells, the combined treatment with TTNPB and LG100268 caused a dramatic stimulation of the aromatase activity. The combined treatment with other ligand and LG100268 had little or no effect on the aromatase activity. The increase in the aromatase activity by TTNPB plus LG100268 was accompanied by an increase in the P450arom mRNA levels, which was also found to be related to the specific usage of promoter 1a of the CYP19 gene. These results suggest that a nuclear receptor system constituted by a RAR:RXR heterodimer is involved in the regulation of aromatase activity in MCF-7 breast cancer cells. In cultured human ovarian granulosa cells obtained from patients who underwent in vitro fertilization, troglitazone or LG100268 alone decreased the aromatase activity, while the combined treatment caused an even greater reduction in this activity. Little effect of other specific ligands for RXR heterodimer partners may support the notion that the effects of troglitazone and/or LG100268 in human granulosa cells may be mediated through the specific activation of PPARgamma:RXR heterodimer system. Since similar manners of effects of several PPARgamma ligands and/or LG100268 on the aromatase activity were observed in a newly established human ovarian granulosa cancer cell line, KGN, we performed the detailed analysis of the mechanisms of these effects using this cell line. As a result, the inhibitory effect of aromatase activity by troglitazone plus LG100268 was accompanied by the decrease of P450arom mRNA level. Furthermore, the loss of P450arom expression was considered to be due to both the decreased transcription and rapid degradation of its RNA based on the studies of nuclear run-on assay and RNA stability assay. In conclusion, RAR:RXR and PPARgamma:RXR heterodimer nuclear receptor systems may be other important modulators of estrogen production in human breast cancer cells and ovarian granulosa cells, respectively.

Obesity is associated with insulin resistance and some reproductive abnormalities. Circulating FFAs are often elevated in obese subjects and are also closely linked to insulin resistance. In this study, we demonstrated that saturated FFAs, such as palmitic acid and stearic acid, markedly suppressed the granulosa cell survival in a time- and dose-dependent manner. Polyunsaturated FFA, arachidonic acid, had no effect on the cell survival, even at supraphysiological concentrations. The suppressive effect of saturated FFAs on cell survival was caused by apoptosis, as evidenced by DNA ladder formation and annexin V-EGFP/propidium iodide staining of the cells. The apoptotic effects of palmitic acid and stearic acid were unrelated to the increase of ceramide generation or nitric oxide production and were also completely blocked by Triacsin C, an inhibitor of acylcoenzyme A synthetase. In addition, acylcoenzyme A, pamitoylcoenzyme A, and stearylcoenzyme A markedly suppressed granulosa cell survival, whereas arachidonoylcoenzyme A had no such effect, and this finding was consistent with the effect of the respective FFA form. Surprisingly, arachidonic acid instead showed a protective effect on palmitic acid- and stearic acid-induced cell apoptosis. A Western blot analysis showed the apoptosis of the granulosa cells induced by palmitic acid to be accompanied by the down-regulation of an apoptosis inhibitor, Bcl-2, and the up-regulation of an apoptosis effector, Bax. These results indicate that saturated FFAs induce apoptosis in human granulosa cells caused by the metabolism of the respective acylcoenzyme A form, and the actual composition of circulating FFAs may thus play a critical role in the apoptotic events of human granulosa cells. These effects of FFAs on granulosa cell survival may be a possible mechanism for reproductive abnormalities, such as amenorrhea, which is frequently observed in obese women.

We have demonstrated on-line concentration and separation of DNA in the presence of electroosmotic flow (EOF) using poly(ethylene oxide) (PEO) solutions. After injecting large-volumes DNA samples, PEO solutions entered a capillary filled with 400 mM Tris-borate (TB) buffers by EOF and acted as sieving matrices. DNA fragments stacked between the sample zone and PEO solutions. Because sample matrixes affected PEO adsorption on the capillary wall, leading to changes in EOF, migration time, concentration, and resolving power varied with the injection length. When injecting phiX174 RF DNA-HaeIII digest prepared in 5 mM Tris-HCl buffer, pH 7.0, at 250 V/cm, peak height increased linearly as a function of injection volume up to 0.9 microl (injection time 150 s). The sensitivity improvement was 100-fold compare to that injected at 25 V/cm for 10 s (0.006 microl). When injecting 1.54 microl of GeneScan 1000 ROX, the sensitivity improvement was 265-fold. The sensitivity improvement was 40-fold when injecting 0.17 microl DNA sample containing pBR 322/HaeIII, pBR 328/BglI, and pBR 328/HinfI digests prepared in phosphate-buffered saline. This method allows the analysis of polymerase chain reaction (PCR) products amplified after 17 cycles when injecting 0.32 microl (at 30 cm height for 300 s). The total analysis time was shorter (91.6 min) than that (119.6 min) obtained from injecting PCR products after 32 cycles for 10 s.

Our previous study demonstrated that PPARγ specific ligand troglitazone (TGZ) or RXR specific ligand LG100268 (LG) alone decreased the aromatase activity in cultured human ovarian granulosa cells from pre-ovulatory follicles, and combined treatment caused an even greater reduction in this activity. Since similar manners of effects of TGZ or/and LG on the aromatase activity in human ovarian granulosa cancer cell line were observed, we performed the detailed analysis of the mechanisms of these effects using this cell line. The changes in the aromatase activity were associated with comparable changes in the P450arom mRNA levels based on a RNase protection assay. A nuclear run-on assay indicated the P450arom transcript to decrease by 40 and 66% at 24 and 48 h, respectively, after TGZ plus LG treatment. An RNA stability analysis showed the half-life of P450arom mRNA to decrease from 13 to 9 h after the TGZ plus LG treatment. The inhibitory effect of TGZ plus LG on the aromatase activity and P450arom mRNA may not be mediated by the cAMP-PKA pathway that is usually implicated in the regulation of aromatase activity in granulosa cells: because (1) the aromatase activity stimulated by forskolin was not inhibited by TGZ plus LG; (2) the specific PKA inhibitor H89 could not block the inhibitory effect of TGZ plus LG on the aromatase activity; and (3) the luciferase activity of P450arom promoter II did not decrease by the addition of TGZ and LG in transfected cells either at a basic state or in the states stimulated by forskolin or PGE2, respectively. Taken together, these results indicate that TGZ plus LG inhibited the aromatase activity and also decreased the P450arom mRNA level in granulosa cancer cells, and the loss of P450arom mRNA expression was considered to be due to both the decreased transcription and rapid degradation of its RNA.

We established a steroidogenic human ovarian granulosa-like tumor cell line, designated KGN, from a patient with invasive ovarian granulosa cell carcinoma. KGN had a relatively long population doubling time of about 46.4 h and had an abnormal karyotype of 45,XX, 7q-, -22. A steroid analysis of the cultured medium by RIA performed 5 yr after the initiation of culture showed that KGN was able to secrete pregnenolone and progesterone, and both dramatically increased after stimulation with (Bu)(2)cAMP. However, little or no secretion of 17alpha-hydroxylated steroids, dehydroepiandrosterone, androstenedione, or estradiol was observed. The aromatase activity of KGN was relatively high and was further stimulated by (Bu)(2)cAMP or FSH. These findings showed a pattern similar to that of steroidogenesis in human granulosa cells, thus allowing analysis of naturally occurring steroidogenesis in human granulosa cells. Fas-mediated apoptosis of KGN was also observed, which mimicked the physiological regulation of apoptosis in normal human granulosa cells. Based on these findings, this cell line is considered to be a very useful model for understanding the regulation of steroidogenesis, cell growth, and apoptosis in human granulosa cells.

Estrogen is the most important endocrine hormone that stimulates the growth of hormone-dependent breast cancer. The biosynthesis of estrogens in breast tissue is catalyzed by cytochrome P450 aromatase (P450arom). The expression of P450arom is controlled by the tissue- or cell-specific promoters of CYP 19 gene. The roles of nuclear receptor systems for the aromatase activity in breast cancer cells have not yet been fully investigated. In the present study, we investigated the effects of a nuclear receptor system constituted by retinoid X receptor (RXR) and its heterodimer partner on the aromatase activity in a cultured MCF-7 human breast cancer cell line, using each selective ligand for retinoic acid receptor (RAR) (TTNPB), RXR (LG100268), PPARgamma (troglitazone), and vitamin D(3) receptor (vitamin D(3)). The treatment of the cells with TTNPB or LG100268 alone for 2 days increased slightly the aromatase activity, but the increases were not statistically significant in comparison to the control. However, the combined treatment with TTNPB (10(-7) M) and LG100268 (10(-7) M) caused a dramatic stimulation of the aromatase activity. The treatment with other ligands had little or no effect on the aromatase activity. The stimulation of the aromatase activity by TTNPB plus LG100268 was dose-dependent, and a maximum stimulation was observed at 10(-7) M in both compounds. In addition, the increase in the aromatase activity was accompanied by an increase in the P450arom mRNA levels determined by RT-PCR in MCF-7 cells. The increase in the P450arom transcript was also found to be related to the specific usage of promoter 1a of the CYP 19 gene based on the analysis using RT-PCR. This is the first demonstration that a nuclear receptor system constituted by a RAR:RXR heterodimer is involved in the regulation of aromatase activity in MCF-7 breast cancer cells.

Ovarian granulosa cells synthesize estrogens from androgens, which are catalyzed by aromatase cytochrome P450 (P450arom). Troglitazone (Tro), one of the insulin-sensitizing compounds, thiazolidinediones (TZDs), is a ligand for peroxisome proliferator activated receptor gamma (PPARgamma) and is effective in the treatment of both non-insulin-dependent diabetes mellitus (NIDDM) as well as polycystic ovary syndrome (PCOS). PPARgamma exerts a transcriptional activity as a PPARgamma:RXR heterodimer. In this study, we investigated the effects of Tro and/or RXR ligand, LG100268 (LG) on the aromatase activity in cultured human ovarian granulosa cells obtained from patients who underwent in vitro fertilization. Human ovarian granulosa cells expressed PPARgamma mRNA assessed by RT-PCR. The treatment of the granulosa cells with Tro for 24 h resulted in a dramatic inhibition of the aromatase activity in a dose-dependent manner. While the treatment with LG alone also inhibited the aromatase activity, the combined treatment with both Tro and LG caused a much more reduction in the aromatase activity. The changes in the aromatase activity by Tro and/or LG were associated with comparable changes in P450arom mRNA assessed by RT-PCR. These results suggest that Tro directly inhibit the aromatase activity in human granulosa cells probably via nuclear receptor system PPARgamma:RXR heterodimer. The findings may provide a biochemical basis for the decrease in the blood concentrations of estrogens which is observed after the in vivo administration of Tro and may also possibly be useful as a novel therapy for estrogen-dependent diseases.

The activation of PPARgamma:RXR nuclear system induces monocytic differentiation of some myelogeneous leukemia cell lines. The present study was undertaken to examine the effect of PPARgamma ligand, TZD (troglitazone or pioglitazone) and/or RXR selective ligand, LG100268 on the erythroleukaemia cell line K562 which has both an erythroid character and a potential for differentiation into megakaryocytes. TZD suppressed cell proliferation and the erythroid phenotype of K562 cells. The suppression of erythroid phenotype of K562 cells by TZD was synergistically enhanced by the combined treatment with LG100268. Moreover, the marked suppression of erythroid phenotype in K562 cells was also accompanied by the downregulation of the erythroid lineage-transcription factor, GATA-1. These novel actions of troglitazone may provide a biochemical basis for anemia occasionally which is observed after the in vivo administration of TZD.

The changes in carotid artery structure during the natural longevity of the Uighurs people were compared with other ethnic groups. The 419 subjects were divided into (1) longevity and (2) older groups as follows: Uighurs longevity group in Hotan (ULH); and Uighurs, Hans and Kazaks older groups in Hotan or Balikun (UOH, HOH, HOB and KOB). The wall thickness of the common carotid artery (CCA) was measured by ultrasonography. Risk factors were evaluated by measuring total cholesterol (T-C), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and fasting glucose, and by 24-h ambulatory blood pressure monitoring. Wall thickness and blood pressure were greater in the Balikun groups than in the Hotan groups. The CCA wall was thicker in Uighurs and Kazaks than in Hans, in the ULH than in the UOH. There was no significant difference in blood pressure among the Hotan groups. LDL-C and glucose were higher and HDL-C was lower in the Hotan groups than in the Balikun groups. T-C, LDL-C, TG and glucose were higher in the HOH than in the ULH and UOH. Systolic blood pressure and LDL-C were higher and TG was lower in the KOB than in the HOB. These results suggest that an increased CCA wall thickness can be attributed to age in Hotan, and to a higher blood pressure level in Balikun, and that the higher blood pressure affected the Balikun groups more than the Hotan groups.

The Uygur in Hotan (Xinjiang, China) are reported to have a long life expectancy. The purpose of this study was to clarify the relationship between variations in blood pressure (BP) and longevity. Cross-sectional surveillance was carried out in both Hotan and Barkol. The subjects were divided into five groups: 1. Uygur longevity subjects in Hotan (103 subjects, age >90 yr); 2. Uygur elderly subjects in Hotan (107 subjects, age 65-70 yr); 3. Han elderly subjects in Hotan (41 subjects, age 65-70 yr); 4. Kazakh elderly subjects in Barkol (117 subjects, age 65-70 yr); 5. Han elderly subjects in Barkol (50 subjects, age 65-70 yr). BP was monitored and analyzed using the fourteen devices of ambulatory BP monitoring. The prevalence of hypertension was lowest in the Uygur (16.2% in Uygur elderly subjects in Hotan; 23.7% in Uygur longevity subjects in Hotan; 27.0% in Han elderly subjects in Hotan; 42.0% in Han elderly subjects in Barkol; 50.0% in Kazakh elderly subjects in Barkol). The ratio of dips in BP was largest in the Han (57% in Han elderly subjects in Barkol; 50% in Han elderly subjects in Hotan; 50% in Uygur longevity subjects in Hotan, 49% in Uygur elderly subjects in Hotan; 17% in Kazakh elderly subjects in Barkol). The 24-h mean systolic BP in Uygur longevity subjects in Hotan was not different from those in Uygur elderly subjects and Han elderly subjects in Hotan, nor did the 24-h mean diastolic BP differ from those in Uygur elderly subjects and Han elderly subjects in Hotan respectively. In conclusion, Uygur subjects seem to be less hypertensive, compared to Kazakh subjects. Uygur longevity subjects had more dipping in their BP variation than did the Kazakh subjects in Xinjiang, China.

Thiazolidinedione (TZD) is known to be a potent activator of peroxisome proliferator-activated receptor γ (PPARγ), a nuclear receptor that constitutes a heterodimer with retinoid X receptor (RXR). Since a considerable amount of PPARγ is expressed in various hematopoietic cells, the present study was undertaken to examine the effect of TZD in the absence or presence of LG100268, an RXR-selective ligand, on a cultured promyelocytic leukemia cell line, HL60. Treatment with TZD (25–50 µM troglitazone or pioglitazone) markedly suppressed cell proliferation of HL60. A cell cycle analysis revealed that the suppressive effect of troglitazone on HL60 cell proliferations was caused by G0/G1 cell cycle arrest as well as by an apoptotic effect. Treatment with the same concentration of troglitazone also induced the monocytic differentiation of HL60 cells. The apoptotic or the differentiating effect of TZD on HL60 cells was synergistically enhanced by the combined treatment with 1 µM LG100268, while LG100268 alone neither had an apoptotic nor a differentiating effect on HL60 cells. These results suggest that these actions are mediated through the nuclear receptor system constituted by the PPARγ: RXR heterodimer.

OBJECTIVES The overnight 8-mg dexamethasone suppression test is often used to differentiate Cushing's disease, due to an oversecretion of ACTH from the pituitary gland, from other kinds of Cushing's syndrome. However, a few patients with ACTH-producing pituitary adenoma show no suppression of plasma cortisol after the administration of 8 mg of dexamethasone. To clarify the relationship between the level of glucocorticoid receptor (GR) in the pituitary adenoma and the sensitivity to dexamethasone in Cushing's disease, we thus examined the levels of GRα and GRβ mRNAs in the pituitary adenomas in six patients who were proven at surgery to have pituitary ACTH-producing adenomas. MATERIALS Total RNA was extracted from six pituitary adenomas and pituitary tissue adjacent to one of the adenomas, and the mRNA levels of GRα, GRβ, pro-opiomelanocortin (POMC) and β-actin in these samples were sampled by quantitative RT–PCR. RESULTS The GRα mRNA levels in the adenomas from the two patients who showed no response to the 8-mg dexamethasone suppression test were significantly lower than those in the adenomas of four patients who showed suppression. The GRβ mRNA level was much lower than that of GRα mRNA but not significantly different among the six adenomas. CONCLUSIONS These results suggest strongly that decreased expression of GRα in pituitary adenomas may be the major reason for the marked insensitivity to the 8-mg dexamethasone suppression test observed in two patients with Cushing's disease.

OBJECTIVES An orphan nuclear receptor, DAX-1, is known to be involved in the development and differentiation of anterior pituitary cells. The present study aimed to examine 1) whether DAX-1 is expressed in human pituitary adenomas, and 2) if it is expressed, what types of adenoma express the factor. MATERIALS AND METHODS Adenoma tissues examined included 18 clinically non-functioning adenomas, 14 GH-secreting adenomas and 7 PRL-secreting adenomas. The expression of the following genes were tested by reverse transcription-polymerase chain reaction (RT-PCR): DAX-1, Adrenal-4-binding protein/steroidogenic factor-1 (Ad4BP/SF-1), Pit-1, LHβ, FSHβ, gonadotrophin-releasing hormone receptor (GnRH-R), GH, PRL, and TSHβ, as well as β-actin as a control. RESULTS Eleven clinically non-functioning adenomas expressed DAX-1, 10 of which also expressed Ad4BP/SF-1. Nine out of the 11 DAX-1-expressing adenomas also expressed LHβ, FSHβ and GnRH-R as well, indicating that these adenomas possessed gonadotrophic properties. Nine clinically non-functioning adenomas expressed Pit-1 as well as GH, PRL and/or TSHβ, thus having somatomammotrophic or thyrotrophic properties, 3 of which overlapped with the above DAX-1-expressing adenomas. One non-functioning adenoma expressed Ad4BP/SF1 and FSHβ but not DAX-1, and another one expressed DAX-1 and Ad4BP/SF-1 with PRL. On the other hand, all GH-secreting and PRL-secreting adenomas expressed Pit-1 and GH and/or PRL, but neither DAX-1 nor Ad4BP/SF-1. CONCLUSIONS The results shown here indicate that DAX-1 is expressed in the majority of human pituitary adenomas of gonadotrophic origin in parallel with Adrenal-4-binding protein/steroidogenic factor-1.

In addition to their hypotensive properties, angiotensin receptor blockers (ARBs) have been shown to exert clinical antidyslipidemic effects. The mechanism underlying these ARB lipid metabolic effects remains unclear. Some ARBs, for example, telmisartan, activate peroxisome proliferator-activated activated receptor-gamma (PPAR-gamma). We hypothesized that PPAR-gamma-activating ARBs might exert antidyslipidemic effects via PPAR-alpha. In this study, we assessed the effect of telmisartan on the expression of PPAR-alpha and lipoprotein lipase (LPL). PPAR-alpha expression was detected by reverse-transcription polymerase chain reaction and Western blot in HepG2 hepatocytes as well as differentiated C2C12 myocytes treated with increasing concentrations of telmisartan (0.1-10 μmol/L) for 48 h. Results showed that 1 μmol/L and 10 μmol/L telmisartan significantly increased the expression of PPAR-alpha mRNA and protein in HepG2 cells (p 0.01). No effect was shown in differentiated C2C12 cells. Similarly, 1 µmol/L and 10 μmol/L telmisartan significantly increased the expression of LPL mRNA and protein in HepG2 cells (p 0.01), and this increase was significantly (p 0.01) inhibited by the PPAR-alpha-specific antagonist MK886. These results indicate that certain of the antidyslipidemic effects of telmisartan might be mediated via increased PPAR-alpha-dependent induction of LPL expression.

Thyroid nodules (TNs) have annual increasing trends worldwide, and large-scale investigations on the prevalence of TNs in Beijing communities have not been conducted since the introduction of salt iodization in 1995. We performed a cross-sectional study to determine the prevalence of TNs, their epidemiological characteristics, and their correlation with lifestyle factors. A total of 6324 permanent residents aged 18 years or older (mean age, 52.15 ± 11.58 years) from seven representative communities in Beijing were included in the analyses. Once informed consent was obtained, the subjects were asked to complete questionnaires, a physical examination, and thyroid ultrasound. A total of 3100 cases had TNs. The overall prevalence rate was 49.0%, and the age-standardized prevalence was 40.1%, which increased significantly as age increased (p < 0.001). The prevalence was significantly higher in females compared to males (p < 0.001), and it was significantly higher among female current smokers and former smokers compared to non-smokers (p = 0.007). There was no correlation between alcohol consumption and TNs, and there were no significant differences in the prevalence among different groups of taste preference. The prevalence decreased with an increased frequency of seafood intake (p = 0.015) and with higher literacy levels (p < 0.001). The Cochran–Armitage trend test showed that the prevalence significantly increased with decreased physical labor and exercise intensity (p < 0.001, p = 0.009). Logistic regression analysis showed that age (Odds ratio (OR) = 1.039 (1.034–1.044), p < 0.001), the female sex (OR = 1.789 (1.527–2.097)), Body mass index (BMI) (OR = 1.019 (1.005–1.034)), and current smoking habits (OR = 1.246 (1.046–1.483)) were independent risk factors for TNs. Our findings indicate that there is a high prevalence of TNs in Beijing, with a higher prevalence in females than in males. Moreover, the prevalence increases as age increases. Smoking and BMI are independent risk factors for TNs. Therefore, intervention against smoking and weight loss might help reduce the risk of TN occurrence.

To the Editor: We reported 2 cases of ectopic thyroid gland (ETG) masquerading as pituitary adenoma (PA). The first case was a 15-year-old boy with growth, and mental retardation whose height was 121 cm and weight was 44 kg on admission. Bone age development index was 40, while bone age showed 6–10 years old. Magnetic resonance imaging (MRI) revealed pituitary hyperplasia [Figure 1a]. Thyroid ultrasonography did not found thyroid on the anterior aspect of the neck and the normal position of thyroid gland. The peak value of growth hormone experiments was 1.8 μg/L. Gonad function indicated testosterone (T) 0.55 nmol/L, luteotropic hormone 150 mU/L. After treatment with eltroxin, the patient was 21 cm higher than before in one year and his intelligence improved significantly comparatively. MRI after treatment showed pituitary hyperplasia significantly regressed [Figure 1b]. The second case was a 27-year-old female with galactorrhea, amenorrhea, and infertility. MRI showed the signal was obviously abnormal (uniform strengthening) in the saddle pituitary, the size was 1.0 cm × 1.5 cm × 1.6 cm, which indicated the PA was huge [Figure 1c]. Thyroid function showed FT4 9.07 pmol/L, TSH >150 mU/L, and 15 minutes serum prolactin was 2.66 μg/L. Gonad function, 8 after midnight (AM) serum adreno-cortico-tropic-hormone, and 8 AM serum cortisol were normal. Thyroid ultrasonography did not found thyroid at the normal position. History revealed that the patient was found thyroglossal cyst in 15 years old and accepted total excision of thyroglossal duct cyst in 18 years old. Then eltroxin was prescribed, and the patient was pregnant successfully in 7 months. Now, her menstruation is normal, and galactorrhea is rarely happen. These two cases were ectopic thyroid masquerading as PA. At present, classification of PA is based on plasma hormone levels or immunohistochemical staining, clinical features are always complex and confusing. In these two cases, retardation, infertility, and amenorrhea were not arising from PA, while the primary ectopic thyroid was the culprit. It caused primary hypothyroidism, TSH cell proliferation, and compensatory pituitary gland hyperplasis. Figure 1 (a) Magnetic resonance imaging of the 15-year-old teenager with ectopic thyroid before the treatment showed pituitary hyperplasia (black arrow), sagittal T1-weighed contrast enhanced image; (b) magnetic resonance imaging of the 15-year-old teenager with ... ETG, the most frequent form of thyroid dysgenesis, refers to the presence of thyroid tissue in locations other than the normal anterior neck region.[1] It remains a rare disease.[1,2] Moreover, females account for 65–80% of ETG cases.[3] Although ETG has been understood gradually, diagnostic delay in ETG remains common, and this delay compounded with inappropriate therapeutic methods is responsible for the poor outcome in affected patients, especially in adolescents and women with childbearing age. When aberrant thyroid was totally excised, thyroid function would be absent or inadequate permanently. Substitute therapy would be essential, cost unpleasantly high and therapeutic period, unfortunately, life-long time. Thereby, thyroid function test and color Doppler ultrasonography are necessary when PA is considered. If ETG is suspected, preoperative analysis is of particular significance. A high index of clinical awareness and education of clinical practitioners will help a great deal in improving the ultimate outcome in patients with ETG. Financial support and sponsorship The work was supported by grants from the Chinese National Natural Science Fund (No. 30900543), the Clinical Science Fund of PLA General Hospital (No. 2013FC-TSYS-1028) and the Beijing Natural Science Fund (No. 7152136). Conflicts of interest There are no conflicts of interest.