The risk of concurrent malignancies in patients with multiple endocrine neoplasia type 1: insights into clinical characteristics of those with multiple endocrine neoplasia type 1.

OBJECTIVE: Summarize and analyze the characteristics of patients with Multiple Endocrine Neoplasia type 1 (MEN-1) who were diagnosed with malignant tumors that do not belong to MEN-1 components. METHODS: Clinical data from patients with MEN-1 who visited Peking Union Medical College Hospital between April 2012 and April 2022 were collected. We compared the clinical characteristics of patients with malignant tumors outside of their MEN-1 components to those without additional tumors. MEN-1 gene testing was performed on most of these patients using Sanger sequencing, whole-exome sequencing, or MLPA. RESULTS: A total of 221 MEN-1 patients were diagnosed, of which 23 (10.40%) were found to have malignant tumors that did not belong to MEN-1 components, including papillary thyroid carcinoma (PTC) (4.52%), breast cancer (1.81%), urologic neoplasms (1.35%), primary hepatic carcinoma (PCC) (0.09%), meningeal sarcoma (0.05%), glioblastoma (0.05%), cervical cancer (0.05%), and lung carcinoma (0.05%). MEN-1 gene mutations were identified in 11 patients, including missense mutations, frameshift mutations, and splice mutations. The prevalence of each endocrine neoplasm, particularly gastroenteropancreatic neuroendocrine tumor, was higher in MEN-1 patients with other malignant tumors compared to MEN-1 patients without malignant tumors. CONCLUSION: Our retrospective study revealed a higher incidence of non-MEN-1 component malignant tumors in MEN-1 patients, especially breast cancer, PTC, and urologic neoplasms. These patients also exhibit more severe clinical phenotypes of MEN-1.

Identification of U-shaped curve relation between proneurotensin and risk of coronary artery disease (CAD) in patients with premature CAD.

BACKGROUND AND AIMS: Neurotensin (NT) is a gut hormone with broad effects on the cardiovascular system. Recent data suggested that circulating proneurotensin (pro-NT)-the stable precursor fragment of NT-could independently predict cardiovascular artery disease (CAD) development. However, serum pro-NT levels in patients with premature cardiovascular artery disease (PCAD) are still unknown. This study aims to determine serum pro-NT levels in patients with PCAD and investigate its relationship with PCAD risk. METHODS AND RESULTS: A total of 490 subjects, including 364 with PCAD and 126 without PCAD (NPCAD), and 182 controls were enrolled in the study. Data of baseline clinical parameters and biochemical variables were collected. Serum pro-NT levels were measured by ELISA. Serum pro-NT levels were higher in patients with PCAD than in controls (59.42 ± 66.66 vs. 38.07 ± 48.48 pg/mL, P < 0.05), especially in patients with BMI<25 kg/m2. Serum pro-NT levels were independently related to PCAD (ß = 0.349, P < 0.001), and the association revealed a U-shaped curve characteristic between pro-NT tertiles and CAD risk in patients with premature CAD and controls. Subjects with low and high tertiles of pro-NT levels had 1.79-fold and 2.23-fold higher risks of PCAD, respectively, than subjects with median pro-NT levels (P < 0.05). After adjusting for age, gender, and BMI in Model 1 and other confounders in Model 2 and Model 3, the U-shaped relationship remained significant. CONCLUSION: Serum pro-NT levels were significantly increased in patients with PCAD. The association between pro-NT levels and PCAD risk presents a U-shaped curve characteristic, which demonstrated that subjects with lower and higher pro-NT levels both were more likely to have PCAD.

Type 3 iodothyronine deiodinase in neonatal goats: molecular cloning, expression, localization, and methylation signature.

Type 3 iodothyronine deiodinase (DIO3) is an important enzyme in the metabolism of thyroid hormones. It plays critical roles in fetal development and neonatal growth and is especially important for brain development in mammals. In the present study, we profiled the expression pattern and methylation signature of the DIO3 gene in goats. The complete coding sequence of caprine DIO3 encoded a protein of 301 amino acids and harbored an internal selenocysteine-encoding TGA codon. The DIO3 messenger RNA (mRNA) was predominantly expressed in the neonatal goat liver (P < 0.01), while expression in other tissues was quite low, with the lowest levels in the lung. In in situ hybridization, the DIO3 mRNA was predominantly localized in the liver and the lowest content was detected in the lung. The DIO3 transcript was widely localized in neurons and the neuropil. Methylation profiling of the DIO3 CpG island showed a significant difference between the 5' region (CpGs_1∼24) and the 3' region (CpG_25∼51) of the coding region. Furthermore, no significant difference in methylation status was observed among the six tested tissues with levels in the range of 29.11-33.12 %. The CpG islands in the intergenic-differentially methylated region (IG-DMR) showed significantly different methylated levels among tissues, and the highest methylated level was observed in lung (CpG island 1, 69.34 %) and longissimus dorsi (LD) (CpG island 2, 52.62 %) tissues. Our study lays a foundation for understanding DIO3 function and the diseases caused by altered methylation profiles of the DIO3 gene.

Extensive female-mediated gene flow and low phylogeography among seventeen goat breeds in southwest China.

Indigenous Chinese goat mtDNA is highly diverse but lacks geographic specificity; however, whether gene flow or gene exchange contributed to this remains unknown. We reanalyzed a consensus fragment of 481 bp in the D-loop region from 339 individuals. The network and neighbor-joining tree revealed three divergent maternal haplogroups (A, B1, and B2) in 17 local breeds. Although high polymorphism resulting in 198 different haplotypes was observed (h = 0.984 ± 0.002; π = 0.0336 ± 0.0008), neither the distribution of haplotypes nor PCA analysis revealed any obvious geographic structure in the local breeds. Extensive gene flow was widely detected among breeds from southwest China. High levels of gene exchange were detected between Qianbei Brown goats and the other breeds, indicating either more contribution or introgression to their gene pools. This study will be helpful in understanding the phylogeography and gene flow among the goat breeds of southwest China.

Correlation of health literacy, health management self-efficacy, and attitude in elderly patients with schizophrenia: A cross-sectional study.

AIM: The study investigated the relationship between chronic diseases and health problems, emotional health status, health literacy, health self-management attitude, and health management self-efficacy in older patients with schizophrenia. It is expected to provide multiple health perspectives in the care of older patients with schizophrenia and improve their health literacy and self-management. DESIGN: A cross-sectional study. METHODS: Data collection from 2020/09 to 2021/10, the study of older patients with schizophrenia who were diagnosed with schizophrenia and were over 50 years, live in residential mental rehabilitation institutions in eastern Taiwan as older people. Data were collected on demographic variables, chronic diseases, health problems, health literacy, healthy management self-efficacy, and attitudes. RESULTS: The study results show 61.49 years (SD = 6.57), the gender, health literacy, and health management self-efficacy can effectively explain the variance of health self-management state by 18.5% (F(3,116) = 10.01, p < 0.000), in which health literacy (ß = 0.28, t = 3.07, p = 0.003) and health management self-efficacy (ß = 0.19, t = 2.03, p = 0.04) that in the analysis of predictors, emotional health status, and health literacy not only have significant explanatory power on health management self-efficacy and the performance of physical functions but are also important factors affecting the quality of life among the elderly; the important influencing factor of health management self-efficacy and health self-management behaviour is health literacy. Therefore, health literacy is crucial to the health attitudes of older patients with schizophrenia. CONCLUSION: This study found that increased health literacy among older patients with schizophrenia can enhance their attitude and ability to manage their health. IMPLICATIONS FOR THE PROFESSION AND NO PATIENT OR PUBLIC CONTRIBUTION: Nursing can provide nursing measures related to individual health literacy to help patients improve their health literacy, maintain the health of chronic older patients with schizophrenia, reduce elderly schizophrenia disability, enhance patients' ability to manage their self-efficacy and health self-management attitude, and improving the health and quality of life of patients.

Direct shear behaviors of excavated clay reinforced with geocomposite drainage layer encapsulated in thin sand layers.

The objective of this study is to assess the effectiveness of a novel structure comprising a geocomposite drainage layer and a thin sand layer (GDL + sand) in mitigating the rapid dumping of excavated clay and its associated issues, such as landslides. Two sets of direct shear tests were conducted to investigate the influence of sand layer thickness and compaction degree on the interface shear behavior of the GDL + sand structure. As the sand layer thickness increased, both the interface shear strength and friction angle gradually increased, first more sharply and then at a slower rate toward stability, while the interface cohesion decreased gradually. The optimal sand layer thickness for achieving the most effective reinforcement in stabilizing the clay was identified as 10 mm. A higher sand layer compaction degree was found to result in increased interface shear strength, interface friction angle, and interface cohesion. Building on these findings, the reinforcing efficiency of the GDL + sand structure was investigated through mechanism analysis in comparison to that of a geogrid + sand structure and GDL structure as per the interface friction coefficient. The ranking of interface friction coefficients among the three structures emerged as: geogrid + sand > GDL + sand > GDL. These results suggests that the GDL + sand structure exhibits superior reinforcement efficiency compared to the GDL structure and offers better drainage efficiency than the geogrid + sand structure.

Genetic phylogeography and maternal lineages of 18 Chinese black goat breeds.

To understand the origin and genetic phylogeography of Chinese black goats, variations of mitochondrial DNA were characterised with 394 goats from 18 breeds, including 91 new individuals from regions poorly studied until now. Comparison of a 481-bp segment revealed a total of 192 haplotypes with 141 variable sites. The haplotype and nucleotide diversities ranged from 0.782 ± 0.079 to 1.000 ± 0.020 and from 0.009 ± 0.001 to 0.045 ± 0.006, respectively, indicating a relatively high genetic diversity in Chinese black goats. Phylogenetic analyses identified five haplogroups (A, B1, B2, C and D). The dominant haplogroups A, B1 and B2 were distributed in most of breeds, while the haplogroups C and D were only presented in the breeds located in north or northwest of China. Analysis of molecular variance and multidimensional scaling plot of F ST analyses indicated no obvious geographic structure among breeds. Furthermore, the migration rates revealed that a wide range of gene flow or gene exchange occurred among breeds, which may result in the weak geographic structure of Chinese black goats. Population expansion analysis based on mismatch distribution indicated that two expansion events in Chinese black goats occurred at 10 and 28 mutational time units. Finally, our findings indicate the multiple maternal origins of Chinese black goats and more gene flow (female-mediated) which occurred during their domestic and breeding histories.

Blood Lipid Disorders in Post-Operative Craniopharyngioma Children and Adolescents and the Improvement with Recombinant Human Growth Hormone Replacement.

Context: The high prevalence of hypothalamic obesity (HO) and dyslipidemia in individuals with craniopharyngioma (CP) following surgery is a cause for increasing concern. However, few studies have explored the lipid profile in pediatric CP patients, with inconsistent findings. In addition, the role of recombinant human growth hormone (rhGH) replacement remains unclear in these patients. Objective: To compare the blood lipid profile among post-operative craniopharyngioma children and adolescents with that among healthy controls and to reveal the effects of rhGH replacement. Methods: Data of 79 post-operative craniopharyngioma children and adolescents in our center were retrospectively collected. Sixty patients underwent rhGH replacement during the follow-ups. We selected 36 patients who received rhGH replacement therapy, while 20 patients received rhGH replacement for at least 1 year and had complete lipid data before and after treatment and compared them with 19 patients who did not receive rhGH replacement therapy. Results: Craniopharyngioma patients had higher total cholesterol (TC) (5.17 vs 3.77 mmol/L), triglyceride (TG) (1.51 vs 0.73 mmol/L), and low-density lipoprotein cholesterol (LDL-C) (3.14 vs 2.10 mmol/L), and lower high-density lipoprotein cholesterol (HDL-C) (1.06 vs 1.39 mmol/L) than controls (all p < 0.001). The lipid profile of obese and non-obese patients was not significantly different. After rhGH replacement, TC was 0.90 mmol/L lower (p = 0.002) and LDL-C was 0.73 mmol/L lower (p = 0.010) than baseline. Although the baseline LDL-C was higher, patients with rhGH replacement had lower LDL-C (-0.73 mmol/L adjusted for age and sex, p = 0.045) after the initiation of replacement compared with patients without rhGH replacement. Conclusion: The lipid profile of obese and non-obese children and adolescents with craniopharyngioma was unfavorable, and rhGH replacement could improve their lipid profile.

Appendiceal Neuroendocrine Tumor Is a Rare Cause of Ectopic Adrenocorticotropic Hormone Syndrome With Cyclic Hypercortisolism: A Case Report and Literature Review.

OBJECTIVE: Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a condition of hypercortisolism caused by non-pituitary tumors secreting ACTH. Appendiceal neuroendocrine tumor as a rare cause of ectopic ACTH syndrome was reported scarcely. We aimed to report a patient diagnosed with EAS caused by an appendiceal neuroendocrine tumor and summarized characteristics of these similar cases reported before. CASE REPORT AND LITERATURE REVIEW: We reported a case with Cushing's syndrome who was misdiagnosed as pituitary ACTH adenoma at first and accepted sella exploration. Serum and urinary cortisol decreased, and symptoms were relieved in the following 4 months after surgery but recurred 6 months after surgery. The abnormal rhythm of plasma cortisol and ACTH presented periodic secretion and seemingly rose significantly after food intake. EAS was diagnosed according to inferior petrosal sinus sampling (IPSS). Appendiceal mass was identified by 68Ga-DOTA-Tyr3-octreotate (DOTATATE)-PET-CT and removed. The pathological result was consistent with appendiceal neuroendocrine tumor with ACTH (+). The literature review demonstrated 7 cases diagnosed with EAS caused by appendiceal neuroendocrine tumor with similarities and differences. CONCLUSION: The diagnosis of an ectopic ACTH-producing tumor caused by the appendiceal neuroendocrine tumor can be a challenging procedure. Periodic ACTH and cortisol secretion may lead to missed diagnosis and misdiagnosis. IPSS is crucial in the diagnosis of EAS and 68Ga-DOTATATE-PET-CT plays an important role in the identification of lesions.

Profiling of cybersickness and balance disturbance induced by virtual ship motion immersion combined with galvanic vestibular stimulation.

Profile of cybersickness and balance disturbance induced by virtual ship motion alone and in combination with galvanic vestibular stimulation (GVS) remained unclear. Subjects were exposed to a ship deck vision scene under simulated Degree 5 or 3 sea condition using a head-mounted virtual reality display with or without GVS. Virtual ship motion at Degree 5 induced significant cybersickness with symptom profile: nausea syndrome > central (headache and dizziness) > peripheral (cold sweating) > increased salivation. During a single session of virtual ship motion exposure, GVS aggravated balance disturbance but did not affect most cybersickness symptoms except cold sweating. Repeated exposure induced cybersickness habituation which was delayed by GVS, while the temporal change of balance disturbance was unaffected. These results suggested that vestibular inputs play different roles in cybersickness and balance disturbance during virtual reality exposure. GVS might not serve as a potential countermeasure against cybersickness induced by virtual ship motion.

The Negative Impacts of Acromegaly on Bone Microstructure Not Fully Reversible.

Purpose: This study aimed to evaluate the bone turnover markers and bone microarchitecture parameters derived from high-resolution peripheral quantitative computed tomography (HR-pQCT) in active and controlled acromegaly patients. Methods: This cross-sectional study involved 55 acromegaly patients from a tertiary hospital (23 males and 32 females, aged 45.0 ± 11.6 years). Firstly, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and markers for bone turnover were assessed. Next, we derived peripheral bone microstructure parameters and volumetric bone mineral density (vBMD) through HR-pQCT. These parameters were compared between acromegaly patients and 110 healthy controls, as well as between 27 active and 28 controlled acromegaly patients. Moreover, the relationship between GH/IGF-1 and bone microstructure parameters was analyzed through multiple linear regression. Results: As compared with healthy controls, acromegaly patients exhibited elevated cortical vBMD, reduced trabecular vBMD, and increased trabecular inhomogeneity in the distal radius and tibia. While controlled acromegaly patients had slower bone turnover, they did not necessarily have better bone microstructure relative to active patients in intergroup comparison. Nevertheless, multiple regression indicated that higher IGF-1 was associated with lower tibial stiffness and failure load. Additionally, males with higher IGF-1 typically had larger trabecular separation, lower trabecular number, and larger cortical pores in the radius. Moreover, patients with elevated GH typically had more porous cortical bone in the radius and fewer trabeculae in the tibia. However, the compromised bone strength in active patients was partially compensated by increased bone thickness. Furthermore, no significant linkage was observed between elevated GH/IGF-1 and the most important HR-pQCT parameters such as trabecular volumetric bone density. Conclusion: Acromegaly adversely affected bone quality, even in controlled patients. As the deterioration in bone microstructure due to prolonged GH/IGF-1 exposure was not fully reversible, clinicians should be aware of the bone fragility of acromegaly patients even after they had achieved biochemical remission.

Fatty acid synthase and hormone-sensitive lipase expression in liver are involved in zinc-alpha2-glycoprotein-induced body fat loss in obese mice.

OBJECTIVE: To explore the effects of zinc-alpha2-glycoprotein (ZAG) on body weight and body fat in high-fat-diet (HFD)-induced obesity in mice and the possible mechanism. METHODS: Thirty-six male mice were fed with standard food (SF) (n = 9) and HFD (n = 27), respectively. Five weeks later, 9 mice fed with HFD were subjected to ZAG expression plasmid DNA transfection by liposome transfection method, and another 9 mice to negative control plasmid transfection. Two weeks later, serum ZAG level in the mice was assayed by Western blot, and the effects of ZAG over-expression on body weight, body fat, serum biochemical indexes, and adipose tissue of obese mice were evaluated. The mRNA expressions of fatty acid synthase (FAS) and hormone-sensitive lipase (HSL) in liver tissue were determined by reverse transcription-polymerase chain reaction. RESULTS: Serum ZAG level significantly lowered in simple HFD-fed mice in comparison to SF-fed mice (0.51 +/- 0.10 AU vs. 0.75 +/- 0.07 AU, P < 0.01). Further statistical analysis demonstrated that ZAG level was negatively correlated with body weight (r = -0.56, P < 0.001), epididymal fat mass (r = -0.67, P < 0.001), percentage of epididymal fat (r = -0.65, P < 0.001), and increased weight (r = -0.57, P < 0.001) in simple SF- and HFD-fed mice. ZAG over-expression in obese mice reduced body weight and the percentage of epididymal fat. Furthermore, FAS mRNA expression decreased (P < 0.01) and HSL mRNA expression increased (P < 0.001) in the liver in ZAG over-expressing mice. CONCLUSIONS: ZAG is closely related to obesity. Serum ZAG level is inversely correlated with body weight and percentage of body fat. The action of ZAG is associated with reduced FAS expression and increased HSL expression in the liver of obese mice.

Comparative Proteome Analysis of Epicardial and Subcutaneous Adipose Tissues from Patients with or without Coronary Artery Disease.

BACKGROUND AND AIMS: Owing to its unique anatomical structure and metabolism, epicardial adipose tissue (EAT) has attracted amount of attention in coronary artery disease (CAD) research. Here, we analyzed differences in proteome composition in epicardial (EAT) and subcutaneous adipose tissues (SAT) from patients with or without CAD. METHODS: EAT and SAT samples were collected from 6 CAD patients and 6 non-CAD patients. Isobaric Tagging for Relative and Absolute Quantitation (iTRAQ) analysis combined with liquid chromatography tandem-mass spectrometry (LC-MS/MS) was performed to identify the differentially expressed proteins. RESULTS: In total, 2348 proteins expressed in EAT and 2347 proteins expressed in SAT were separately identified. 385 differentially expressed proteins were found in EAT and 210 proteins were found in SAT in CAD patients compared to non-CAD patients. Many proteins differentially expressed in EAT of CAD patients were involved in biological functions associated with CAD development such as cell-to-cell signaling and interaction, inflammatory response, and lipid metabolism. Differential expressions of proteins (MMP9, S100A9, and clusterin) in EAT or SAT were involved in several signaling pathways such as mitochondrial dysfunction, acute phase inflammation, and LXR/RXR activation, which was confirmed by western blotting, and similar results were obtained. CONCLUSIONS: The largest profiles of differentially expressed proteins in EAT and SAT between CAD patients and non-CAD patients were identified. The significant signal pathways, mitochondrial dysfunction, and LXR/RXR activation, which differential proteins were involved in, were firstly found to play roles in EAT of CAD patients, and clusterin was firstly found to be upregulated in EAT of CAD patients.

Clinical characteristics of non-alcoholic fatty liver disease in Chinese adult hypopituitary patients.

BACKGROUND: Patients with hypothalamic-pituitary disease have the feature of central obesity, insulin resistance, and dyslipidemia, and there is increased prevalence of liver dysfunction consistent with non-alcoholic fatty liver disease (NAFLD) in this population. The causes of hypopituitarism in the reported studies varied and combined pituitary hormone deficiency including central diabetes insipidus is much common in this population. This retrospective cross-sectional study was performed to analyze the clinical characteristics and related factors with NAFLD and cirrhosis in Chinese adult hypopituitary/panhypopituitary patients. AIM: To analyze the clinical characteristics of and related risk factors for NAFLD in Chinese adult hypopituitary patients. METHODS: Adult Chinese patients with hypopituitarism and/or panhypopituitarism were enrolled at the Pituitary Center of Peking Union Medical College Hospital between August 2012 and April 2018. According to abdominal ultrasonography, these patients were divided into an NAFLD (-) group and an NAFLD (+) group, and the latter was further divided into an NAFLD group and a cirrhotic group. The data, such as patient characteristics, diagnosis, and treatment, were extracted from medical records, and statistical analysis was performed. RESULTS: A total of 36 male and 14 female adult Chinese patients with hypopituitarism were included in this retrospective study; 43 (87.0%) of these patients exhibited growth hormone (GH) deficiency, and 39 (78.3%) had diabetes insipidus. A total of 27 (54.0%) patients were diagnosed with NAFLD, while seven patients were cirrhotic. No significant differences were noted in serum GH or insulin-like growth factor 1 among patients with cirrhosis, subjects with NAFLD, and those without NAFLD. However, plasma osmolality and serum sodium concentration of the cirrhotic patients were 314.9 mOsm/kgH2O and 151.0 mmol/L, respectively, which were significantly higher than those of the NAFLD patients (P = 0.036 and 0.042, respectively). Overweight/obesity and insulin resistance were common metabolic disorders in this population. The body mass index (BMI) and homeostasis model assessment of insulin resistance parameters of the cirrhotic patients were 27.7 kg/m2 and 9.57, respectively, which were significantly higher than those of the patients without NAFLD (P = 0.011 and 0.044, respectively). A correlation analysis was performed, and fasting insulin concentration was positively associated with plasma osmolality in patients with NAFLD, after adjusting for gender, age, and BMI (r = 0.540, P = 0.046), but no correlation was noted in patients without NAFLD. CONCLUSION: NAFLD is common in patients with hypopituitarism. Plasma osmolality and serum sodium levels of hypopituitary patients with cirrhosis are higher than those of subjects with NAFLD, and fasting insulin concentration is positively associated with plasma osmolality in patients with NAFLD, which suggests that hyperosmolality might be a contributor to the worsening of NAFLD in hypopituitary patients.

Dysregulation of matrix metalloproteinases and their tissue inhibitors is related to abnormality of left ventricular geometry and function in streptozotocin-induced diabetic minipigs.

This study aimed to characterize matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in relation to changes in left ventricle (LV) geometry and function in a porcine model with streptozotocin (STZ)-induced diabetes. In 15 Chinese Guizhou minipigs with STZ-induced diabetes (diabetic group) and 15 age-matched normal controls (control group), Doppler tissue imaging was performed at 6 months of diabetes. Serum MMP-2, -9, TIMP-1, -4 and B-type natriuretic peptide (BNP) were determined. Expression of MMPs, TIMPs, urokinase type-plasminogen activator (uPA), its receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) in aortic intima and LV myocardium was evaluated, with gelatinolytic activities of tissue MMP-2, -9 accessed by zymography. Left ventricle end-diastolic septum thickness (P < 0.05) and mass (P < 0.05) were increased, whereas peak systolic mitral annulus velocity (Sm, P < 0.001), LV systolic (P = 0.01) and diastolic strain (P < 0.001) were significantly decreased in diabetic group than in controls. Diabetic group showed higher expression of TIMP-1, -4 in aortic intima and LV myocardium (P < 0.01 or P < 0.05), with increased collagen content and elevated serum BNP level (P = 0.004) and lower gelatinolytic activities of tissue MMP-2, -9 (all P < 0.05). Semi-quantitative RT-PCR of those diabetic tissues revealed elevated mRNA levels of major TIMPs, uPA, uPAR and PAI-1. Reduction of serum MMP-2 and -9 levels was observed in diabetic group vs. control group (both P < 0.05). This study features elevated levels of TIMP-1, -4, uPA, uPAR and PAI-1, and decreased activities of MMP-2, -9 in aorta and myocardium in STZ-induced diabetic minipigs, indicating that MMP-TIMP dysregulation is associated with LV hypertrophy, cardiac dysfunction and increased cardiovascular fibrosis in diabetes.

[The analysis of healthy adult male lens fibers proteome using tandem mass spectrometry].

OBJECTIVE: To establish the method for studying the proteome of the lens fibers of healthy adult male in order to provide a tool for further analysis of cataract-related protein using reverse tandem mass spectrometry. METHODS: Lens fibers proteins were separated and analyzed using sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by RPLC-MS/MS (SDS-PAGE-RPLC/MS/MS). The experiment was repeated three times. The tandem mass spectra of positive results were quality controlled by SEQUEST/AMASS softwares which were based on high abundance ion matching rate, continuity of matched ions and randomnicity score proteins were identified based on 2-hit criteria with reliability over 98% for each peptide. RESULTS: Total 60 lens fibers proteins were identified at least twice in three experiments. Among these proteins, 22 were identified in previous lens proteome study. CONCLUSION: The results in this study provided preliminary data on the composition of crystallin in the lens fibers of healthy adult male. The results can be used as a reference for future studies to detect the changes of human lens proteins during aging and cataract formation. Combination of SDS-PAGE and RPLC/MS/MS is a quick and simple method, it may be useful for large scale analysis of clinical samples.

[Distribution Characteristics of Water Temperature and Water Quality of Fuxian Lake During Thermal Stratification Period in Summer].

In order to explore the distribution characteristics and change rule in daytime of the water temperature and water quality of the deep plateau lake Fuxian Lake during the thermal stratification period in summer, a typical point location was selected respectively in the south, middle and north of Fuxian Lake in July 2014 to carry out investigation and observation after stratified sampling at each point location and continuous stratified sampling of the point location in the north during daytime. The result showed that ①The distribution of water temperature of Fuxian Lake in summer had the temperature distribution characteristics of deep lake during stratification period. The segment from the surface to a depth of 15 meters was epilimnion with a range of 25.51-22.81℃. The segment from the depth of 15m to 40m was thermocline with a range of 22.81-14.72℃. The segment below 40m was hypolimnion with a range of 14.72-13.70℃. The max temperature difference between the surface and the lakebed was 11.8℃, which was smaller than that of lakes in temperate zone during the same period. The temperature of the lakebed was about 14℃ which was higher than that of the lakes in temperate zone,which reflected the characteristics of water temperature stratification of the deep plateau lake Fuxian Lake; ②The water temperature stratification determined the characteristics of chemical stratification and the ecological stratification:the pH, DO and conductivity presented the same layered structure as the distribution of water temperature. What is noteworthy was that the DO concentration of the lakebed was as low as 2-3mg·L-1. As an oligotrophic lake, the DO became lower and lower at the lakebed of Fuxian Lake, which indicated that it possibly faced ecological risks. Due to the separation of thermocline, the nutritive salt accumulative effect appeared in the hypolimnion. Chlorophyll a and permanganate index had a corresponding response relation with the water temperature stratification and showed the max value at the upper layer of the lake. ③During the thermal stratification period, the water temperature stratification of Fuxian Lake had a change during daytime. The increased thermal radiation in the noon caused the thermocline to dive, the strength to increase and the depth to narrow, which significantly influenced the dynamic distribution of pH, DO, conductivity and chlorophyll a of the epilimnion and the thermocline. The change rule of TP, TN and permanganate index during the daytime was not significant.

The Changes of Serum Leptin and Kisspeptin Levels in Chinese Children and Adolescents in Different Pubertal Stages.

The aim of the study is to investigate the changes of serum leptin and kisspeptin levels in children and adolescents with different pubertal stages and nutritional states. A total of 647 Chinese children and adolescents were recruited, and serum estradiol, testosterone, pituitary gonadotropins, leptin, and kisspeptin levels were measured. The results showed that serum leptin levels of boys in T2 stage were the highest among the five stages, while they showed a gradual increase from T1 to T5 stage in girls and reached the highest in T5 stage (P < 0.05). Conversely, serum kisspeptin levels of boys were higher in T4 and T5 stages than those in T1 stage, while its levels of girls were the highest in T2 stage, 21.4% higher than those in T1 stage (P < 0.05). Both leptin and kisspeptin levels were positively correlated with BMI, WC, and weight in all boys and girls (all P < 0.05). In conclusion, kisspeptin levels were firstly found to be notably changed in pubertal stages and nutritional status in Chinese children and adolescents with a significant sexual dimorphism. Obese/overweight girls had higher kisspeptin levels, and there was a positive correlation between kisspeptin and FSH and LH and obesity-related parameters in all boys and girls.

The effect of myostatin on proliferation and lipid accumulation in 3T3-L1 preadipocytes.

Myostatin is a critical negative regulator of skeletal muscle development, and has been reported to be involved in the progression of obesity and diabetes. In the present study, we explored the effects of myostatin on the proliferation and differentiation of 3T3-L1 preadipocytes by using 3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyl tetrazolium bromide spectrophotometry, intracellular triglyceride (TG) assays, and real-time quantitative RT-PCR methods. The results indicated that recombinant myostatin significantly promoted the proliferation of 3T3-L1 preadipocytes and the expression of proliferation-related genes, including Cyclin B2, Cyclin D1, Cyclin E1, Pcna, and c-Myc, and IGF1 levels in the medium of 3T3-L1 were notably upregulated by 35.2, 30.5, 20.5, 33.4, 51.2, and 179% respectively (all P<0.01) in myostatin-treated 3T3-L1 cells. Meanwhile, the intracellular lipid content of myostatin-treated cells was notably reduced as compared with the non-treated cells. Additionally, the mRNA levels of Pparγ, Cebpα, Gpdh, Dgat, Acs1, Atgl, and Hsl were significantly downregulated by 22-76% in fully differentiated myostatin-treated adipocytes. Finally, myostatin regulated the mRNA levels and secretion of adipokines, including Adiponectin, Resistin, Visfatin, and plasminogen activator inhibitor-1 (PAI-1) in 3T3-L1 adipocytes (all P<0.001). Above all, myostatin promoted 3T3-L1 proliferation by increasing the expression of cell-proliferation-related genes and by stimulating IGF1 secretion. Myostatin inhibited 3T3-L1 adipocyte differentiation by suppressing Pparγ and Cebpα expression, which consequently deceased lipid accumulation in 3T3-L1 cells by inhibiting the expression of critical lipogenic enzymes and by promoting the expression of lipolytic enzymes. Finally, myostatin modulated the expression and secretion of adipokines in fully differentiated 3T3-L1 adipocytes.

Hydroxysafflor yellow A (HYSA) inhibited the proliferation and differentiation of 3T3-L1 preadipocytes.

Hydroxysafflor yellow A (HSYA), a main component of safflor yellow, has been demonstrated to prevent steroid-induced avascular necrosis of femoral head by inhibiting primary bone marrow-derived mesenchymal stromal cells adipogenic differentiation induced by steroid. In this study, we investigate the effect of HSYA on the proliferation and adipogenesis of mouse 3T3-L1 preadipocytes. The effects of HSYA on proliferation and differentiation of 3T3-L1 cells and its possible mechanism were studied by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide spectrophotometry, Oil Red O staining, intracellular triglyceride assays, real-time quantitative RT-PCR, transient transfection and dual luciferase reporter gene methods. HSYA inhibited the proliferation of 3T3-L1 preadipocytes and cell viability greatly decreased in a dose and time dependent manner. HSYA (1 mg/l) notably reduced the amount of intracellular lipid and triglyceride content in adipocytes by 21.3 % (2.13 ± 0.36 vs 2.71 ± 0.40, P < 0.01) and 22.6 % (1.33 ± 0.07 vs 1.72 ± 0.07, P < 0.01) on days 8 following the differentiation, respectively. HSYA (1 mg/l) significantly increased hormone-sensitive lipase (HSL) mRNA expression and promoter activities by 2.4- and 1.55-fold, respectively (P < 0.01), in differentiated 3T3-L1 adipocytes. HSYA inhibits the proliferation and adipogenesis of 3T3-L1 preadipocytes. The inhibitory action of HYSA on adipogenesis may be due to the promotion of lipolytic-specific enzyme HSL expression by increasing HSL promoter activity.