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1.
Endocrine ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31605362

RESUMO

PURPOSE: The purpose of this study is to assess the prevalence of heterozygous CYP21A2 mutation and analyze its correlation with clinical manifestation in patients with acne, hirsutism, or both. METHODS: Clinical evaluation, hormone testing, and genetic analysis of the CYP21A2 gene were performed in 60 female patients who visited department of endocrinology of Peking Union Medical College Hospital (PUMCH) for acne, hirsutism, or both from May to November of 2018. The average age of the patients was 26.72 ± 5.73 years. ACTH, Plasma cortisol, LH, FSH, PRL, estradiol, progesterone, testosterone, 17-hydroxyprogesterone (17-OHP), and dehydroepiandrosterone sulfate (DHEA-S) were measured in all participants. Polymerase chain reaction (PCR) combined with sequencing and multiplex ligation dependent probe amplification (MLPA) technique were used to detect the mutation of the CYP21A2 gene. The prevalence of CYP21A2 mutation was compared between the patients and 60 controls, as well as the data in different genetic variant database. RESULTS: A total of 8.3% (5/60) of individuals with acne, hirsutism, or both in this study were found to harbor heterozygotic CYP21A2 mutation, and the frequency was significantly higher than that in public databases. Identified mutations included V282L (n = 2), I173N (n = 1), E6 cluster [I237N, V238E, and M240K (n = 1)] and large deletion (n = 1). There was no significant difference in hormone levels between heterozygous carriers and subjects with normal CYP21A2 genes. CONCLUSIONS: The prevalence of heterozygous CYP21A2 mutation detected in patients with acne, hirsutism, or both was significantly higher than in the general population. Whether the heterozygous mutation of CYP21A2 is the cause of clinical symptoms needs further assessment.

2.
Nanoscale ; 11(38): 17860-17868, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31553002

RESUMO

In this work, the impact of oxygen vacancies and nitrogen-doped carbon coating on the sodium-ion storage properties of anatase TiO2 has been demonstrated. Oxygen vacancies and nitrogen-doped carbon coating were introduced simultaneously by the calcination of core-shell structured TiO2 spheres in a reducing atmosphere. Compared to the anatase TiO2 with and without oxygen vacancies, TiO2-x@NC exhibits much better electrochemical performance in the storage of sodium ions. A high reversible capacity of 245.6 mA h g-1 is maintained at 0.1 A g-1 after 200 cycles, and a high specific capacity of 155.6 mA h g-1 is achieved at a high rate of 5.0 A g-1. The significantly improved electrochemical performance of the core-shell structured anatase TiO2 spheres is attributed to the synergistic effect of the oxygen vacancies in the anatase lattice and surface nitrogen-doped carbon coating. This work provides an efficient strategy for improving the electrochemical performance of metal-oxide-based electrode materials for sodium-ion batteries.

3.
Atherosclerosis ; 289: 8-13, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31437611

RESUMO

BACKGROUND AND AIMS: Epidemiological evidence on the association between elevated lipoprotein (a) (Lp (a)) with risk of stroke remains inconsistent. We aimed to investigate the association between serum Lp (a) level and the risk of stroke among middle-aged and elderly Chinese. METHODS: A community-based prospective cohort study of 8500 participants aged 40 years or older was conducted in Jiading district, Shanghai, China, in 2010. The incident strokes were documented at follow-up visit during 2014-2015. RESULTS: During a mean follow-up of 5.1 years, 444 incident cases of stroke occurred. The incidences of stroke were 4.44%, 5.14% and 6.14% from the lowest to the highest serum Lp (a) tertile, respectively. A significant association between serum Lp (a) tertile and the risk of incident stroke was observed (p for trend<0.05). Compared with individuals in the lowest tertile of serum Lp (a), the multivariable adjusted hazards ratio (HR) and 95% confidence interval (CI) for incident stroke in Lp (a) tertile 3 were 1.34 (1.06-1.70). CONCLUSIONS: Serum Lp (a) concentration was associated with increased risk of incident stroke in Chinese adults.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31438503

RESUMO

Climate change has made countries around the world realize the importance of reducing carbon emissions. Reductions in carbon emissions needs the support of policy, technology, and financial capital. The single/double/three-threshold model is used here with data from China to study the different impact of financial development in carbon emissions in high-energy industries when the threshold variables are in different intervals. The results show that when loan size is the core explanatory variable, and research and development (R and D) expenditure and energy structure are the threshold variables, the loan size variable has a significant effect on emission reductions in high-energy industries, and this effect is strengthened with increases in R and D expenditure and decreases in the proportion of energy from coal. Taking energy intensity as the threshold variable, the relationship between loan size and carbon dioxide emissions is V-shaped. With economic structure as the threshold variable, loan size has a significant effect on emissions reduction when the proportion of industrial added value in high-energy industries is low. When using foreign investment as the core explanatory variable, R and D expenditure, energy consumption intensity, and industrial structure are threshold variables. The impact of foreign investment on carbon dioxide emissions is negative, but when the threshold variable is within different intervals, this negative impact differs. With stock market value as the core explanatory variable, and R and D expenditure and energy structure as the threshold variables, the stock market value can promote reductions in carbon emissions, but when R and D expenditure and the proportion of coal consumption is high, stock market value has no significant effect on emissions reduction. When energy consumption intensity is the threshold variable, the relationship between stock market value and carbon dioxide emissions is V-shaped.

5.
Asian J Androl ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31464203

RESUMO

Partial congenital hypogonadotropic hypogonadism (PCHH) is caused by an insufficiency in, but not a complete lack of, gonadotropin secretion. This leads to reduced testosterone production, mild testicular enlargement, and partial pubertal development. No studies have shown the productivity of spermatogenesis in patients with PCHH. We compared the outcomes of gonadotropin-induced spermatogenesis between patients with PCHH and those with complete congenital hypogonadotropic hypogonadism (CCHH). This retrospective study included 587 patients with CHH who were treated in Peking Union Medical College Hospital (Beijing, China) from January 2008 to September 2016. A total of 465 cases were excluded from data analysis for testosterone or gonadotropin-releasing hormone treatment, cryptorchidism, poor compliance, or incomplete medical data. We defined male patients with PCHH as those with a testicular volume of ≥4 ml and patients with a testicular volume of <4 ml as CCHH. A total of 122 compliant, noncryptorchid patients with PCHH or CCHH received combined human chorionic gonadotropin and human menopausal gonadotropin and were monitored for 24 months. Testicular size, serum luteinizing hormone levels, follicle-stimulating hormone levels, serum total testosterone levels, and sperm count were recorded at each visit. After gonadotropin therapy, patients with PCHH had a higher spermatogenesis rate (92.3%) than did patients with CCHH (74.7%). During 24-month combined gonadotropin treatment, the PCHH group took significantly less time to begin producing sperm compared with the CCHH group (median time: 11.7 vs 17.8 months, P < 0.05). In conclusion, after combined gonadotropin treatment, patients with PCHH have a higher spermatogenesis success rate and sperm concentrations and require shorter treatment periods for sperm production.

6.
Diabetes Care ; 42(11): 2117-2126, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31455687

RESUMO

OBJECTIVE: Comprehensive assessment of serum lipidomic aberrations before type 2 diabetes mellitus (T2DM) onset has remained lacking in Han Chinese. We evaluated changes in lipid coregulation antecedent to T2DM and identified novel lipid predictors for T2DM in individuals with normal glucose regulation (NGR). RESEARCH DESIGN AND METHODS: In the discovery study, we tested 667 baseline serum lipids in subjects with incident diabetes and propensity score-matched control subjects (n = 200) from a prospective cohort comprising 3,821 Chinese adults with NGR. In the validation study, we tested 250 lipids in subjects with incident diabetes and matched control subjects (n = 724) from a pooled validation cohort of 14,651 individuals with NGR covering five geographical regions across China. Differential correlation network analyses revealed perturbed lipid coregulation antecedent to diabetes. The predictive value of a serum lipid panel independent of serum triglycerides and 2-h postload glucose was also evaluated. RESULTS: At the level of false-discovery rate <0.05, 38 lipids, including triacylglycerols (TAGs), lyso-phosphatidylinositols, phosphatidylcholines, polyunsaturated fatty acid (PUFA)-plasmalogen phosphatidylethanolamines (PUFA-PEps), and cholesteryl esters, were significantly associated with T2DM risk in the discovery and validation cohorts. A preliminary study found most of the lipid predictors were also significantly associated with the risk of prediabetes. Differential correlation network analysis revealed that perturbations in intraclass (i.e., non-PUFA-TAG and PUFA-TAGs) and interclass (i.e., TAGs and PUFA-PEps) lipid coregulation preexisted before diabetes onset. Our lipid panel further improved prediction of incident diabetes over conventional clinical indices. CONCLUSIONS: These findings revealed novel changes in lipid coregulation existing before diabetes onset and expanded the current panel of serum lipid predictors for T2DM in normoglycemic Chinese individuals.

7.
Medicine (Baltimore) ; 98(31): e16616, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374027

RESUMO

BACKGROUND: To compare the efficacies of gonadotropin-releasing hormone (GnRH) pulse subcutaneous infusion with combined human chorionic gonadotropin and human menopausal gonadotropin (HCG/HMG) intramuscular injection have been performed to treat male hypogonadotropic hypogonadism (HH) spermatogenesis. METHODS: In total, 220 idiopathic/isolated HH patients were divided into the GnRH pulse therapy and HCG/HMG combined treatment groups (n = 103 and n = 117, respectively). The luteinizing hormone and follicle-stimulating hormone levels were monitored in the groups for the 1st week and monthly, as were the serum total testosterone level, testicular volume and spermatogenesis rate in monthly follow-up sessions. RESULTS: In the GnRH group and HCG/HMG group, the testosterone level and testicular volume at the 6-month follow-up session were significantly higher than were those before treatment. There were 62 patients (62/117, 52.99%) in the GnRH group and 26 patients in the HCG/HMG (26/103, 25.24%) group who produced sperm following treatment. The GnRH group (6.2 ±â€Š3.8 months) had a shorter sperm initial time than did the HCG/HMG group (10.9 ±â€Š3.5 months). The testosterone levels in the GnRH and HCG/HMG groups were 9.8 ±â€Š3.3 nmol/L and 14.8 ±â€Š8.8 nmol/L, respectively. CONCLUSION: The GnRH pulse subcutaneous infusion successfully treated male patients with HH, leading to earlier sperm production than that in the HCG/HMG-treated patients. GnRH pulse subcutaneous infusion is a preferred method.


Assuntos
Hormônio Liberador de Gonadotropina/uso terapêutico , Hipogonadismo/tratamento farmacológico , Substâncias para o Controle da Reprodução/uso terapêutico , Espermatogênese/efeitos dos fármacos , Adolescente , Adulto , Gonadotropina Coriônica/uso terapêutico , Vias de Administração de Medicamentos , Esquema de Medicação , Combinação de Medicamentos , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/administração & dosagem , Humanos , Bombas de Infusão , Hormônio Luteinizante/sangue , Masculino , Menotropinas/uso terapêutico , Substâncias para o Controle da Reprodução/administração & dosagem , Testosterona/sangue , Adulto Jovem
8.
J Diabetes ; 11(11): 884-894, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30941862

RESUMO

BACKGROUND: This study examined whether resting heart rate (RHR) was associated with metabolic syndrome (MetS) and the 10-year predicted risk of cardiovascular disease in a Chinese population. METHODS: The associations of RHR with MetS and 10-year risk of atherosclerotic cardiovascular diseases (ASCVD) was examined in a cross-sectional study conducted in Shanghai, China (n = 9486). RESULTS: Compared with individuals in the lowest RHR quintile (≤71 b.p.m.), those in the highest quintile (≥91 b.p.m.) had a higher prevalence of MetS (21.2% vs 32.6%, respectively; P < 0.001). Logistic regression analyses showed that the multivariate-adjusted odds ratio (OR) and 95% confidence interval (CI) for MetS was 1.13 (1.08-1.18) for each 10-b.p.m. increment of RHR (P < 0.0001). Furthermore, RHR was strongly associated with the prevalence of hypertension, high blood glucose, and dyslipidemia, but not with central obesity. A stronger association of RHR with MetS was observed among individuals aged <65 years, male, with a body mass index <24 kg/m2 , without diabetes, hypertension, abnormal lipids, and insulin resistance than among their counterparts (P < 0.05 for all). A significantly higher 10-year risk for ASCVD was observed with each 10-b.p.m. increment in RHR in both men and women (ORs [95% CIs] 1.20 [1.07-1.33] and 1.28 [1.17-1.39], respectively; Ptrend = 0.002 and < 0.0001, respectively). CONCLUSIONS: In this study, RHR was associated with a higher prevalence of MetS and elevated 10-year predicted risk of ASCVD in both Chinese men and women. Whether RHR may serve as an indicator for MetS among relatively healthy individuals requires further investigation.

9.
Endocr Res ; 44(4): 153-158, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30966827

RESUMO

Objective: Pituitary hormones are critical for bone development and maturation. It is currently unknown whether congenital multiple pituitary hormone deficiency (CMPHD) is associated with osteonecrosis of femoral head (ONFH). Methods: Clinical presentations and hormonal profiles of three patients with CMPHD and ONFH were retrospectively described. The incidence of ONFH in this population was studied. Results: (1) Congenital hypopituitarism was diagnosed in three patients. Femoral epiphyseal fusion in these patients was markedly delayed, and they had very low bone mineral density. (2) Hip pain, which is the main presentation of ONFH, occurred at the age of 20-30 years. ONFH induced by excessive glucocorticoids was excluded. (3) The estimated incidence of ONFH was approximately 694:100,000. Conclusions: CMPHD, especially a lack of growth and sex hormones, may contribute to ONFH.

10.
J Diabetes ; 11(9): 752-760, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30652427

RESUMO

BACKGROUND: Serum apolipoprotein (apo) B has been associated with an increased risk of atherosclerotic cardiovascular diseases. However, findings on the association between apoB and the risk of metabolic syndrome (MetS) are inconsistent. The purpose of this study was to investigate the association between serum apoB and MetS risk in Chinese population. METHODS: A baseline survey was conducted in a population-based cohort of 10 340 adults aged ≥40 years in Shanghai, China, in 2010. A follow-up visit was conducted to assess incident diabetes in 2015. RESULTS: At baseline, 2794 of 10 340 participants (27.02%) had MetS. Serum apoB was significantly associated with an increased risk of prevalent MetS. Multivariable-adjusted odds ratios and 95% confidence intervals (CIs) for quintiles 2-5 compared with quintile 1 (reference) were 1.29 (1.02-1.63), 1.47 (1.18-1.84), 1.32 (1.06-1.65), and 2.02 (1.61-2.51), respectively (Ptrend < 0.05). During an average of 5.1 years follow-up, 4627 individuals without MetS at baseline showed a significant association between apoB and the risk of incident MetS. Multivariable-adjusted risk ratios (95% CIs) for subjects in apoB quintiles 2-5 compared with the reference were 1.43 (1.13-1.82), 1.57 (1.25-1.98), 1.74 (1.38-2.18), and 2.07 (1.66-2.58), respectively (Ptrend < 0.05). Stratified analysis suggested that the above association was much stronger among normal weight individuals than in those who were overweight or obese. CONCLUSION: These cross-sectional and prospective studies provide evidence that serum apoB is associated with existing MetS and is a possible predictor of the risk of MetS, especially among normal weight individuals.

11.
Biomed Pharmacother ; 109: 744-750, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30551527

RESUMO

Saponins as small organic molecules and polysaccharides as biomacromolecules are the main bioactive substances of Momordica charantia L. (M. charantia) with anti-hyperglycemic activities. This study was aimed to fully compare the antidiabetic effects and the potential mechanism of saponins (SMC) and polysaccharides (PMC) from M. charantia in STZ-induced type 2 diabetic mice with high-fat diet. Three dosages of SMC (L-SMC: 20 mg/kg, M-SMC: 40 mg/kg, H-SMC: 80 mg/kg) have a certain of therapeutic effect on type 2 diabetic mice, and M-SMC (40 mg/kg) is the optimal dosage for the prevention and treatment of diabetes. The results showed that oral administration of SMC, especially M-SMC (40 mg/kg) compared to PMC (500 mg/kg), could significantly restore the body weight, reduce fasting blood glucose levels, ameliorate insulin resistance and increase the proportion of hepatic phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK)/total protein. The above results proved that hypoglycemic mechanism of SMC might involve in the AMPK/NF-κB signal pathway by activating AMPK phosphorylation and regulating the energy metabolism of the body. However, oral administration of PMC could significant improve the antioxidant capacity by increasing the level of SOD and decreasing the level of MDA, and alleviate the STZ-induced organ tissues (kidney and pancreas), which proved that the hypoglycemic mechanism of PMC might by repairing the pancreatic ß cells damaged by STZ.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Momordica charantia , Extratos Vegetais/uso terapêutico , Polissacarídeos/uso terapêutico , Saponinas/uso terapêutico , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Hipoglicemiantes/isolamento & purificação , Masculino , Camundongos , Extratos Vegetais/isolamento & purificação , Polissacarídeos/isolamento & purificação , Saponinas/isolamento & purificação , Estreptozocina/toxicidade , Resultado do Tratamento
12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 49(4): 665-669, 2018 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-30378326

RESUMO

OBJECTIVE: To determine the relationship between serum levels of 25(OH)D and 1, 25(OH)2 D and the hand-grip strength and balance ability of women in Sichuan, China. METHODS: A cross-sectional study on a representative sample of 1 095 women aged 29-95 yr. in Sichuan Province was undertaken. Their hand-grip strength and balance ability were assessed using a hand-held dynamometer and the short physical performance battery (SPPB), respectively. The participants were divided into four groups according to the level of serum 25(OH)D: sufficient (>75 nmol/L), insufficient (51-75 nmol/L), deficiency (25-50 nmol/L), and serious deficiency (<25 nmol/L). General liner models were established to compare the differences of the four groups in balance ability. Logistic regression models were established to examine the associations of serum 25(OH)D and 1, 25(OH)2 D withhand-grip strength and physical performance. RESULTS: About 70.9% of the participants had vitamin D deficiency. Those with vitamin D insufficiency or deficiency were more likely to reside in a higher latitudinal area (P<0.001), spend less time in outdoor activities (P=0.013), and take less vitamin D supplements (P<0.001). Older women (≥65 years) had lower serum 25(OH)D (P=0.001) and were more likely to have ≤50 nmol/L 25(OH)D than their younger counterparts (74.6% vs. 68.9%, P=0.046). However, no significant age differences were found in serum 1, 25(OH)2 D. Serum levels of 25(OH)D and 1, 25(OH)2 D were not found to be associated with hand-grip strength and balance ability after adjusting for confounding factors. Hand-grip strength and balance ability decreased with age (OR=1.066, P<0.001; OR=1.111, P<0.001). Higher body mas was associated with higher hand-grip strength (OR=0.958, P<0.001). Higher serum albumin (OR=0.896, P=0.001) and longer walking time (OR=0.799, P=0.001) were associated with higher balance ability. CONCLUSION: Serum levels of 25(OH)D and 1, 25(OH)2D are not associated with hand-grip strength and balance ability.

13.
Dalton Trans ; 47(45): 16155-16163, 2018 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-30378603

RESUMO

A top-down method was developed to synthesize hierarchical composites consisting of NiCo2O4 nanocubes and graphene nanosheets through the electrostatic interaction of negatively charged graphene oxide nanosheets and positively charged NiCo2O4 spheres. Employed as anode materials for lithium-ion batteries, the hierarchical composites exhibit remarkably high electrochemical performance, including large reversible capacity, superior rate capability, and excellent cycling performance. Large reversible capacities of 1024 and 648 mA h g-1 are maintained at a current density of 500 and 3000 mA g-1, respectively, for over 200 cycles. The excellent electrochemical performance of the composite is attributed to the synergistic effect of the hierarchical structure, the well dispersed NiCo2O4 nanocubes and the uniform graphene coating. This work provides an effective and promising strategy for the rational structural design of the metal oxide electrode material.

14.
BMC Endocr Disord ; 18(1): 85, 2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30453944

RESUMO

BACKGROUND: After hormonal replacement therapy (HRT) including androgen replacement or sequential therapy of estrogen and progesterone, The combination of human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) and pulsatile GnRH, is not sufficient to produce sufficient gametes in some patients with Congenital hypogonadotropic hypogonadism (CHH). A Systematic review and meta-analysis was performed to determine that assisted reproductive techniques (ART) can effectively treat different causes of infertility. METHODS: To determine the effect of ART on fertility of CHH patients and investigate whether outcomes are similar to infertility due to other causes, we conducted a systematic review and meta-analysis of retrospective trials. Clinical trials were systematically searched in Medline, Embase, and the Cochrane central register of controlled trials databases. The keywords and major terms covered "hypogonadotropic hypogonadism", "kallmann syndrome", "assisted reproductive techniques", "intrauterine insemination", "intracytoplasmic sperm injection", "testicular sperm extraction", "in vitro fertilization", "embryo transplantation" and "intra-Fallopian transfer". RESULTS: A total of 388 pregnancies occurred among 709 CHH patients who received ART (effectiveness 46, 95% confidence interval 0.39 to 0.53) in the 20 studies we included. The I2 in trials assessing overall pregnancy rate (PR) per embryo transfer (ET) cycle was 73.06%. Similar results were observed in subgroup analysis by different gender. Regression indicates pregnancy rate decreases with increasing age. Fertilization, implantation and live birth rates (72, 36 and 40%) showed no significant differences as compared to infertility due to other causes. CONCLUSIONS: Despite CHH patients usually being difficult to generate gametes, their actual chances of fertility are similar to subjects with other non-obstructive infertility. ART is a suitable option for CHH patients who do not conceive after long-term gonadotropin treatment.

15.
Am J Med ; 131(12): 1515.e1-1515.e10, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30075104

RESUMO

BACKGROUND: Cardiovascular health has been proven to be associated with major cardiometabolic diseases. However, little is known of associations between cardiovascular health and nonalcoholic fatty liver disease. METHODS: This study included 3424 adults aged ≥40 years who were free of nonalcoholic fatty liver disease at baseline from a community cohort followed for up to 5 years. Liver ultrasonography was conducted at baseline and at follow-up to diagnose incident nonalcoholic fatty liver disease. Six metrics including smoking, physical activity, body mass index, total cholesterol, blood pressure, and fasting glucose were used to define cardiovascular health status. Associations of individual cardiovascular health metrics, number of cardiovascular health metrics, and overall cardiovascular health status at baseline, as well as changes in cardiovascular health during follow-up with risks of developing nonalcoholic fatty liver disease, were examined. RESULTS: A total of 649 participants developed nonalcoholic fatty liver disease during follow-up. Risks of nonalcoholic fatty liver disease reduced in a dose-response manner in participants with 3-4 ideal cardiovascular health metrics (odds ratio 0.50; 95% confidence interval, 0.41-0.61) and in participants with 5-6 ideal metrics (odds ratio 0.34; 95% confidence interval 0.22-0.51) compared with participants with 0-2 ideal metrics. An overall ideal or intermediate cardiovascular health was associated with 37% reduction in developing nonalcoholic fatty liver disease compared with poor cardiovascular health. In addition, improving cardiovascular health during follow-up reduced the risk by 71% compared with deteriorating cardiovascular health. Furthermore, an overall ideal or intermediate cardiovascular health was significantly associated with a lower fibrosis score in nonalcoholic fatty liver disease patients compared with an overall poor cardiovascular health. CONCLUSIONS: Ideal cardiovascular health was inversely associated with risks of nonalcoholic fatty liver disease. Although treatment of nonalcoholic fatty liver disease and subsequent inflammation and fibrosis remains a challenge, cardiovascular health goals should be advocated for nonalcoholic fatty liver disease prevention.

16.
Clin Endocrinol (Oxf) ; 89(5): 613-620, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30103258

RESUMO

OBJECTIVE: To analyze nuclear receptor subfamily 5 group A member 1 (NR5A1) gene mutations in a cohort of Chinese patients with 46, XY Disorders of Sex Development (DSD). METHODS: Sixty 46, XY DSD patients were recruited at Peking Union Medical College Hospital. Targeted next-generation and Sanger sequencing were performed to investigate pathogenic gene variants and validate NR5A1 gene variants, respectively. In silico tools and in vitro function studies were used to analyze the pathogenicity of rare variants. The clinical and endocrinological characteristics of patients with NR5A1 variants were retrospectively analyzed. RESULTS: A total of four novel and three recurrent NR5A1 variants were identified in seven 46, XY DSD patients. These variants widely spread almost all the functional domains. Functional studies showed that novel mutations including p.S32N, p.N44del and p.G91D reduced transactivation of CYP11A1, while the other missense variant p.A168E did not impact protein function. All patients with NR5A1 rare variants had normal adrenal function and showed genital defects. Results of the genitalia examination showed female external genitalia (three patients), ambiguous external genitalia (two patients), female external genitalia with clitoromegaly (one patient), and hypospadias (one patient). All seven patients had bilateral testis and five of seven patients lacked Müllerian structures. CONCLUSIONS: Four novel mutations in the NR5A1 gene were identified in our cohort with 46, XY DSD, expanding the spectrum of NR5A1 gene mutations. All patients with NR5A1 rare variants had normal adrenal function and showed genital defects.

17.
Chem Sci ; 9(23): 5270-5277, 2018 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-29997882

RESUMO

A novel single organic molecule-carborane conjugate, CAN, was synthesized in a high yield via a modified nickel-catalyzed cross-coupling reaction incorporating an anthracene unit and an o-carborane moiety. CAN exhibits multiple functions of tricolored mechanochromism and mechanically triggered thermochromism. The fluorescence could be switched from blue to bright yellow then to pink by grinding. The robust and reversible thermochromic process was triggered by the mechanical force. The locally excited (LE) state emission, intermolecular excimer formation and twisted intermolecular charge transfer (TICT) are the primary origins of this tricolor switching property. High temperature sensitivity of the heavily ground CAN powders contribute to the mechanical force induced TICT emission enhancement and color switching.

18.
Psychoneuroendocrinology ; 95: 34-42, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29793095

RESUMO

BACKGROUND: Alterations in peripheral sex hormones may play an important role in sex differences in terms of stress responses and mood disorders. It is not yet known whether and how stress-related brain systems and brain sex steroid levels fluctuate in relation to changes in peripheral sex hormone levels, or whether the different sexes show different patterns. We aimed to investigate systematically, in male and female rats, the effect of decreased circulating sex hormone levels following gonadectomy on acute and chronic stress responses, manifested as changes in plasma and hypothalamic sex steroids and hypothalamic stress-related molecules. METHOD: Experiment (Exp)-1: Rats (14 males, 14 females) were gonadectomized or sham-operated (intact); Exp-2: gonadectomized and intact rats (28 males, 28 females) were exposed to acute foot shock or no stressor; and Exp-3: gonadectomized and intact rats (32 males, 32 females) were exposed to chronic unpredictable mild stress (CUMS) or no stressor. For all rats, plasma and hypothalamic testosterone (T), estradiol (E2), and the expression of stress-related molecules were determined, including corticotropin-releasing hormone, vasopressin, oxytocin, aromatase, and the receptors for estrogens, androgens, glucocorticoids, and mineralocorticoids. RESULTS: Surprisingly, no significant correlation was observed in terms of plasma sex hormones, brain sex steroids, and hypothalamic stress-related molecule mRNAs (p > 0.113) in intact or gonadectomized, male or female, rats. Male and female rats, either intact or gonadectomized and exposed to acute or chronic stress, showed different patterns of stress-related molecule changes. CONCLUSION: Diminished peripheral sex hormone levels lead to different peripheral and central patterns of change in the stress response systems in male and female rats. This has implications for the choice of models for the study of the different types of mood disorders which also show sex differences.

19.
Chem Biol Interact ; 288: 24-31, 2018 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-29604266

RESUMO

Patulin (PAT) is a secondary metabolite produced by certain species of Penicillium, Byssochlamys and Aspergillus. It has been shown to induce liver toxicity, but the possible molecular mechanisms are not completely elucidated. In our study, we treated Human Hepatoma G2 (HepG2) cells by 3-methyladenine (3-MA), an autophagosome formation inhibitor, and rapamycin, an autophagosome formation stimulator. The results showed that 3-MA protected the HepG2 cells against PAT cytotoxicity, while rapamycin decreased the cell viability. Thus, autophagy may play an important role in PAT-induced toxicity. To uncover the mechanism by which cells decrease proliferation and activation of autophagy, we found that collapses of mitochondrial membrane potential (ΔΨm) and reactive oxygen species (ROS) level were increased under treatment with PAT. Further, we elucidated that the expression of p-Akt1 and p-MTOR was inhibited during this process. N-acetyl-l-cysteine (NAC), a ROS inhibitor, protected against PAT-induced cytotoxicity, decreased the protein expression of LC3-II, and up-regulated the level of p-Akt1 and p-MTOR. These findings suggested that PAT-induced autophagic cell death was ROS-dependent in HepG2 cells. In conclusion, it is possible that PAT elicited autophagy through ROS-Akt1-MTOR pathway in the HepG2 cells.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Patulina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Acetilcisteína/farmacologia , Antineoplásicos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Patulina/química , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Regulação para Cima/efeitos dos fármacos
20.
Asian J Androl ; 20(4): 319-323, 2018 Jul-Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29516878

RESUMO

Pulsatile gonadotropin-releasing hormone (GnRH) may induce spermatogenesis in most patients with congenital hypogonadotropic hypogonadism (CHH) by stimulating gonadotropin production, while the predictors for a pituitary response to pulsatile GnRH therapy were rarely investigated. Therefore, the aim of our study is to investigate predictors of the pituitary response to pulsatile GnRH therapy. This retrospective cohort study included 82 CHH patients who received subcutaneous pulsatile GnRH therapy for at least 1 month. Patients were categorized into poor or normal luteinizing hormone (LH) response subgroups according to their LH level (LH <2 IU l-1 or LH ≥2 IU l-1) 1 month into pulsatile GnRH therapy. Gonadotropin and testosterone levels, testicular size, and sperm count were compared between the two subgroups before and after GnRH therapy. Among all patients, LH increased from 0.4 ± 0.5 IU l-1 to 7.5 ± 4.4 IU l-1 and follicle-stimulating hormone (FSH) increased from 1.1 ± 0.9 IU l-1 to 8.8 ± 5.3 IU l-1. A Cox regression analysis showed that basal testosterone level (ß = 0.252, P = 0.029) and triptorelin-stimulated FSH60min(ß = 0.518, P = 0.01) were two favorable predictors for pituitary response to GnRH therapy. Nine patients (9/82, 11.0%) with low LH response to GnRH therapy were classified into the poor LH response subgroup. After pulsatile GnRH therapy, total serum testosterone level was 39 ± 28 ng dl-1 versus 248 ± 158 ng dl-1 (P = 0.001), and testicular size was 4.0 ± 3.1 ml versus 7.9 ± 4.5 ml (P = 0.005) in the poor and normal LH response subgroups, respectively. It is concluded that higher levels of triptorelin-stimulated FSH60minand basal total serum testosterone are favorable predictors of pituitary LH response to GnRH therapy.

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