ABSTRACT
Objectives: To investigate the effect of the expression of low-density lipoprotein receptor associated protein (LDLR) on the vascular abnormalities in hepatocellular carcinoma (HCC) and its mechanisms. Methods: Based on the information of Oncomine Cancer GeneChip database, we analyzed the correlation between the expression level of LDLR and the expression level of carcinoembryonic antigen (CEA) and CD31 in hepatocellular carcinoma tissues. Lentiviral transfection of short hairpin RNA target genes was used to construct LDLR-knockdown MHCC-97H and HLE hepatocellular carcinoma cells. The differential genes and their expression level changes in LDLR-knockdown hepatocellular carcinoma cells were detected by transcriptome sequencing, real-time fluorescence quantitative polymerase chain reaction, and protein immunoblotting. The gene-related signaling pathways that involve LDLR were clarified by enrichment analysis. The effect of LDLR on CEA was assessed by the detection of CEA content in conditioned medium of hepatocellular carcinoma cells. Angiogenesis assay was used to detect the effect of LDLR on the angiogenic capacity of human umbilical vein endothelial cells, as well as the role of CEA in the regulation of angiogenesis by LDLR. Immunohistochemical staining was used to detect the expression levels of LDLR in 176 hepatocellular carcinoma tissues, and CEA and CD31 in 146 hepatocellular carcinoma tissues, and analyze the correlations between the expression levels of LDLR, CEA, and CD31 in the tissues, serum CEA, and alanine transaminase (ALT). Results: Oncomine database analysis showed that the expressions of LDLR and CEA in the tissues of hepatocellular carcinoma patients with portal vein metastasis were negatively correlated (r=-0.64, P=0.001), whereas the expressions of CEA and CD31 in these tissues were positively correlated ( r=0.46, P=0.010). The transcriptome sequencing results showed that there were a total of 1 032 differentially expressed genes in the LDLR-knockdown group and the control group of MHCC-97H cells, of which 517 genes were up-regulated and 515 genes were down-regulated. The transcript expression level of CEACAM5 was significantly up-regulated in the cells of the LDLR-knockdown group. The Gene Ontology (GO) function enrichment analysis showed that the differential genes were most obviously enriched in the angiogenesis function. The Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis showed that the relevant pathways involved mainly included the cellular adhesion patch, the extracellular matrix receptor interactions, and the interactions with the extracellular matrix receptors. The CEA content in the conditioned medium of the LDLR-knockdown group was 43.75±8.43, which was higher than that of the control group (1.15±0.14, Pï¼0.001). The results of angiogenesis experiments showed that at 5 h, the number of main junctions, the number of main segments, and the total area of the lattice formed by HUVEC cells cultured with the conditioned medium of MHCC-97H cells in the LDLR-knockdown group were 295.3±26.4, 552.5±63.8, and 2 239 781.0±13 8211.9 square pixels, which were higher than those of the control group (113.3±23.5, 194.8±36.5, and 660 621.0±280 328.3 square pixels, respectively, all Pï¼0.01).The number of vascular major junctions, the number of major segments, and the total area of the lattice formed by HUVEC cells cultured in conditioned medium with HLE cells in the LDLR-knockdown group were 245.3±42.4, 257.5±20.4, and 2 535 754.5±249 094.2 square pixels, respectively, which were all higher than those of the control group (113.3±23.5, 114.3±12.2, and 1 565 456.5±219 259.7 square pixels, respectively, all Pï¼0.01). In the conditioned medium for the control group of MHCC-97H cells,the number of main junctions, the number of main segments, and the total area of the lattice formed by the addition of CEA to cultured HUVEC cells were 178.9±12.0, 286.9±12.3, and 1 966 990.0±126 249.5 spixels, which were higher than those in the control group (119.7±22.1, 202.7±33.7, and 1 421 191.0±189 837.8 square pixels, respectively). The expression of LDLR in hepatocellular carcinoma tissues was not correlated with the expression of CEA, but was negatively correlated with the expression of CD31 (r=-0.167, P=0.044), the level of serum CEA (r=-0.061, P=0.032), and the level of serum ALT(r=-0.147,P=0.05). The expression of CEA in hepatocellular carcinoma tissues was positively correlated with the expression of CD31 (r=0.192, P=0.020). The level of serum CEA was positively correlated with the level of serum ALT (r=0.164, P=0.029). Conclusion: Knocking down LDLR can promote vascular abnormalities in HCC by releasing CEA.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Neovascularization, Pathologic , Receptors, LDL , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/genetics , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/blood supply , Receptors, LDL/metabolism , Receptors, LDL/genetics , Cell Line, Tumor , Neovascularization, Pathologic/metabolism , Carcinoembryonic Antigen/metabolism , Carcinoembryonic Antigen/genetics , Human Umbilical Vein Endothelial Cells/metabolism , Signal Transduction , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Transcriptome , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Platelet Endothelial Cell Adhesion Molecule-1/geneticsABSTRACT
Objective: To assess the safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use on different immunization procedures in healthy people aged 9-65 years. Methods: A randomized, blind, positive-controlled clinical study was conducted in March 2015. The eligible residents aged 9-65 were recruited in Dengfeng city and Biyang County, Henan Province. A total of 1 956 subjects were enrolled. The subjects were randomly (1â¶1â¶1) assigned to 5-dose control group, 4-dose trial group and 5-dose trial group, with 652 subjects in each group. The subjects of 5-dose control group were immunized with control vaccine on days 0, 3, 7, 14 and 28. The subjects of 4-dose trial group were immunized with trial vaccine on days 0, 7 and 21 (2-1-1 phases) and the subjects of 5-dose trial group were immunized with trial vaccine on days 0, 3, 7, 14 and 28. A combination of regular follow-up and active reporting was used to observe local and systemic adverse reactions till 30 days after the first and full immunization, and the incidence rate of adverse reactions in three groups was analyzed and compared. The venous blood was collected before the first immunization, 7 days after the first immunization, 14 days after the first immunization and 14 days after the full immunization. The neutralizing antibody of rabies virus was detected by rapid fluorescent focus inhibition test (RFFIT), and the seropositive conversion rate and geometric mean concentration (GMC) of antibody were calculated. Results: The adverse reaction rates in 5-dose control group, 4-dose trial group and 5-dose trial group were 41.87% (273/652), 35.43% (231/652) and 34.97% (228/652), respectively. The adverse reaction rates of 4-dose trial group and 5-dose trial group were lower than those of the 5-dose control group (P<0.05). The local reactions were mainly pain, itching, swelling and redness in injection site, while the systemic reactions were mainly fever, fatigue, headache and muscle pain. The severity of adverse reactions was mainly mild (level 1), accounting for 85.33% (518/607), 89.02% (373/419) and 88.96% (427/480) of the total number of adverse reactions in each group. At 14 days after the first immunization and 14 days after the full immunization, the antibody positive conversion rates of three groups were all 100%. At 7 days, 14 days after the first immunization and 14 days after the full immunization, the GMCs of three groups were 0.60, 0.72, 0.59 IU/ml, 20.42, 23.99, 24.38 IU/ml and 22.95, 23.52, 24.72 IU/ml, respectively, with no significant difference (P>0.05). Conclusion: The freeze-dried rabies vaccine (Vero-cells) for human use has good safety and immunogenicity when inoculated according to 5-dose and 4-dose immunization procedures.
Subject(s)
Rabies Vaccines , Rabies virus , Rabies , Humans , Antibodies, Viral , Antibodies, Neutralizing , Vaccination , Rabies/prevention & controlABSTRACT
Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogenic bacterium with complex pathogenesis and drug resistance mechanisms. It has high morbidity and mortality and can cause acute and chronic infections in immunocompromised individuals, with lung infections, wound infections, and bloodstream infections being the most common. The animal infection model of P. aeruginosa is of great value for in-depth research on the pathogenicity, drug resistance, and therapeutic measures of P. aeruginosa by simulating the pathways of human bacterial infections. This article firstly summarizes the selection, anesthesia, and disposal of experimental animals in the construction of animal models of P. aeruginosa infection, and then reviews the methods of construction, model evaluation, and applications of animal models of P. aeruginosa pulmonary infection, wound infection, and bloodstream infection, in order to provide a reference for scientific research related to P. aeruginosa infectious diseases.
Subject(s)
Pseudomonas Infections , Humans , Animals , Pseudomonas Infections/drug therapy , Pseudomonas Infections/microbiology , Models, Animal , Virulence , Pseudomonas aeruginosa , Disease Models, AnimalABSTRACT
Objective: The study investigated the clinical distribution, antimicrobial resistance and epidemiologic characteristics of hypervirulent Carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) in a hospital in Henan Province to provide a scientific basis for antibiotic use and nosocomial infection prevention and control. Methods: A retrospective analysis of the clinical data from the cases was carried out in this study. Clinical data of patients infected with the CRKP strain isolated from the clinical microbiology laboratory of Henan Provincial Hospital of Traditional Chinese Medicine from January 2020 to December 2022 were retrospectively analyzed. A string test, virulence gene screening, serum killing, and a G. mellonella infection model were used to screen hv-CRKP isolates. The clinical characteristics of hv-CRKP and the drug resistance rate of hv-CRKP to twenty-five antibiotics were analyzed using WHONET 5.6. Carbapenemase phenotypic characterization of the hv-CRKP was performed by colloidal gold immunochromatographic assay, and Carbapenemase genotyping, multi-locus sequence typing (MLST) and capsular serotyping of hv-CRKP isolates were performed by PCR and Sanger sequencing. Results: A total of non-duplicate 264 CRKP clinical isolates were detected in the hospital from 2020 to 2022, and 23 hv-CRKP isolates were detected, so the corresponding detection rate of hv-CRKP was 8.71% (23/264). The hv-CRKP isolates in this study were mainly from the intensive care unit (10/23) and neurosurgery department (8/23), and the main sources of hv-CRKP isolates were sputum (10/23) and bronchoalveolar lavage fluid (6/23). The hv-CRKP isolates in this study were highly resistant to ß-lactam antibiotics, fluoroquinolones and aminoglycosides, and were only susceptible to colistin, tigecycline and ceftazidime/avibactam. The detection rate of the blaKPC-2 among 23 hv-CRKP isolates was 91.30% (21/23) and none of the class B and class D carbapenemases were detected. Results of MLST and capsular serotypes showed that ST11 type hv-CRKP was the dominant strain in the hospital, accounting for 56.52% (13/23), and K64 (9/13) and KL47 (4/13) were the major capsular serotypes. Conclusion: The hv-CRKP isolates from the hospital are mainly from lower respiratory tract specimens from patients admitted to the intensive care department and the drug resistance is relatively severe. The predominant strains with certain polymorphisms are mainly composed of the KPC-2-producing ST11-K64 and ST11-KL47 hv-CRKP isolates in the hospital.
Subject(s)
Carbapenem-Resistant Enterobacteriaceae , Klebsiella Infections , Humans , Klebsiella pneumoniae/genetics , Multilocus Sequence Typing , Retrospective Studies , Klebsiella Infections/epidemiology , Klebsiella Infections/drug therapy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Hospitals , Carbapenem-Resistant Enterobacteriaceae/genetics , Microbial Sensitivity Tests , Carbapenems/pharmacologyABSTRACT
The gallbladder is the most common site of tumor occurrence among biliary tract cancer. Gallbladder cancer accounts for approximately 0.6% of new cancers and 0.9% of cancer-related deaths. The risk factors identified for the development of gallbladder cancer include being female,>65 years of age, asymptomatic gallstone disease,and obesity. Surgical resection is the only curative treatment for early-stage gallbladder cancer, and some intermediate or advanced gallbladder cancers can be radically cured by extended resection. However, the extent of liver resection or lymph node dissection and whether to combine it with bile duct removal, revascularisation,and multiple organ resection remain somewhat controversial. After neoadjuvant treatment, up to a third of patients with locally advanced gallbladder cancer benefit from secondary surgical treatment. Only a small proportion of patients with gallbladder cancer at high risk for recurrence will benefit from postoperative adjuvant therapy. With the advent of different target-targeted drugs and the use of genetic tests in biliary tract cancer, targeted therapy and PD-1/PD-L1 inhibitors may become the new standard of care for gallbladder cancer and need to be further explored.
ABSTRACT
An age-related cataract patient who underwent femtosecond laser intrastromal keratotomy in the right eye for presbyopia correction 8 years ago was subjected to femtosecond laser-assisted phacoemulsification, with implantation of a monofocal intraocular lens (IOL) and a trifocal IOL in the right and left eyes, respectively. The corneal stromal ring was complementary to the monofocal IOL, which recovered the distance and near visual acuity, in the right eye postoperatively. The trifocal IOL provided good intermediate visual acuity for the left eye. The vision of the patient reached an ideal level for all visual distances. The binocular fusion was within the normal range, and the stereoscopic vision was restored. We hope that this case report can act as a reference for the treatment of cataract after presbyopia corrective surgery.
Subject(s)
Keratotomy, Radial , Lens Implantation, Intraocular , Phacoemulsification , Presbyopia , Cataract Extraction/methods , Humans , Keratotomy, Radial/methods , Laser Therapy/methods , Lens Implantation, Intraocular/methods , Lenses, Intraocular , Phacoemulsification/methods , Presbyopia/surgery , Reoperation , Treatment OutcomeABSTRACT
Pseudomonas aeruginosa is one of the common multidrug-resistant bacteria in the clinic. Because it can produce a "protective" biofilm, it can affect the penetration and killing efficacy of antibacterial drugs, leading to the formation of a persistent and persistent chronic infection in the host. Biofilms make Pseudomonas aeruginosa resistant to antibacterials and evasive to the host's immune system. Therefore, traditional conventional antibacterials are difficult to achieve effective bactericidal treatment. Understanding the process of P. aeruginosa biofilm formation and the regulatory mechanisms that affect biofilms can provide ideas and methods for our future research on new antibacterial drugs.
Subject(s)
Biofilms , Pseudomonas aeruginosa , Anti-Bacterial Agents/pharmacologyABSTRACT
ABSTRACT: Objective To explore a kind of visual evoked potential test equipment and method that is more suitable for the application of forensic clinical visual acuity evaluation. Methods Thirty-four volunteers ï¼68 eyesï¼ were selected, including 15 males and 19 females, aged between 20 and 40 years. Test lenses were placed before the tested eyes of volunteers to induce refractive myopia with insert method, and the diopter lenses were adjusted so that the visual acuity level of one eye of volunteers was above 0.8, and the visual acuity of the other eye was at moderate damage level ï¼<0.3 and ≥0.1ï¼. The tests were carried out under the binocular simultaneous asynchronous stimulation mode ï¼hereinafter referred to as "binocular mode"ï¼ and monocular separate stimulation mode ï¼hereinafter referred to as "monocular mode"ï¼ of virtual reality-pattern visual evoked potential ï¼VR-PVEPï¼, and the amplitude of PVEP of volunteers under the two modes was compared at four spatial frequencies of 8×8, 16×16, 24×24 and 32×32. Results The differences in the amplitude of P100 wave between monocular and binocular modes at 8×8 spatial frequency had no statistical significance and the differences in amplitude of P100 wave between monocular and binocular modes at 16×16, 24×24, and 32×32 spatial frequencies had statistical significance ï¼P<0.05ï¼. The amplitude of the same eye in monocular mode was higher than that in binocular mode. Through correlation analysis, it was found that the amplitude of P100 wave in monocular mode was moderately correlated with amplitude of P100 wave in binocular mode. Conclusion In forensic identification practice, VR-PVEP is helpful for overcoming the disturbance of poor fixation, and to increase the reliability of PVEP evaluation results. It can greatly shorten the detection time of PVEP and improve work efficiency.
Subject(s)
Evoked Potentials, Visual , Virtual Reality , Adult , Eye , Female , Humans , Male , Reproducibility of Results , Visual Acuity , Young AdultABSTRACT
In this work, we investigate the Fourier characteristics of wavelength-scanned optical spectrum of low-finesse Fabry-Pérot (FP) acoustic sensor both theoretically and experimentally. The wavelength scanning will transform the time-domain acoustic signal into phase modulation loaded on the FP sensor spectrum distributed along wavelength. Therefore the interference spectrum can be regarded as carrier signal in the wavelength domain. From this perspective, it is intelligible that the phase modulation loaded on the spectrum (carrier signal) will introduce sidebands in Fourier domain. The spatial frequency and phase of sideband components contain unique information of both acoustic signal and the corresponding sensor. These conclusions are experimentally proved by single sensor head as well as two parallel sensors. The Fourier characteristics of sideband components can be utilized to recognize and distinguish acoustic signals received by different sensors, indicating that it has potential applications in multiplexed FP sensor array and source localization, and so forth.
ABSTRACT
MicroRNAs (miRNAs) have recently been shown to play a role in normal wound healing process. miRNAs may be linked to pathologic wound healing and closely related to the formation of hypertrophic scars. This study aimed to explore the effects of tetrandrine on the miRNA expression profile in human hypertrophic scar fibroblasts (HSFs) in vitro. HSFs were randomly divided into two groups: the tetrandrine treatment group and the control group. The experimental and control groups were collected and analyzed by miRNA array after a 48-h culture. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to confirm the array results. The targets of differentially expressed miRNA were functionally annotated using bioinformatic approaches. miRNA microarray analysis identified 193 differentially expressed miRNAs and the expression of 186 miRNAs in the experimental group decreased while that of 7 miRNAs increased compared to the control group. The most significantly downregulated miRNA was hsa-miR-1246, and hsa-miR-27b had the highest expression level. Significant differentially expressed miRNAs were predicted to be related to several important signaling pathways related to scar wound healing. The differential miRNA expression identified in this study provides the experimental basis for further understanding the anti-fibrosis effect of tetrandrine.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Benzylisoquinolines/pharmacology , Cicatrix, Hypertrophic/genetics , Fibroblasts/drug effects , MicroRNAs/genetics , Cicatrix, Hypertrophic/metabolism , Cicatrix, Hypertrophic/pathology , Drugs, Chinese Herbal , Fibroblasts/metabolism , Fibroblasts/pathology , Gene Expression Profiling , Gene Expression Regulation , Humans , MicroRNAs/agonists , MicroRNAs/antagonists & inhibitors , MicroRNAs/metabolism , Molecular Sequence Annotation , Primary Cell Culture , Real-Time Polymerase Chain ReactionABSTRACT
UNLABELLED: This meta-analysis aimed to investigate the associations between osteocalcin (Ocn) and fasting plasma glucose (FPG) and glycated hemoglobin A1c (HbA1c). It was revealed that both total Ocn and undercarboxylated Ocn (unOcn) were negatively related with FPG and HbA1c, and the association of unOcn with FPG was more pronounced in men. INTRODUCTION: The aim of this study was to investigate the strength of associations between Ocn and FPG and HbA1c using a meta-analysis approach. METHODS: A search was carried out using the databases of PubMed, ISI Web of Science, and the Cochrane library from 2007 to 2014 to identify related studies. A pooled effect size with 95 % confidence intervals (CI) was derived. RESULTS: The meta-analysis included 39 studies involving 23,381 participants. The overall correlation was -0.16 (95 % CI, -0.19 to -0.14) between total Ocn (tOcn) and FPG and -0.15 (95 % CI, -0.20 to -0.11) between undercarboxylated Ocn (unOcn) and FPG. In the analysis of the association between Ocn and HbA1c, the pooled correlation was -0.16 (95 % CI, -0.18 to -0.14) for tOcn and -0.16 (95 % CI, -0.23 to -0.08) for unOcn. The magnitude of the correlation between unOcn and FPG is significantly higher in men than in women (r = -0.18, 95 % CI, -0.21 to -0.14; r = -0.09, 95 % CI, -0. 13 to -0.05, respectively; P for interaction < 0.05). Similar trend was also found between unOcn and HbA1c but without significance (for men, r = -0.19, 95 % CI, -0.24 to -0.14; for women, r = -0.09, 95 % CI, -0.22 to 0.04, respectively; P for interaction > 0.05). No indication of significant publication bias was found in any method. CONCLUSIONS: This meta-analysis demonstrated that both unOcn and tOcn were similarly and negatively correlated with FPG and HbA1c in humans. The negative correlations between unOcn and glucose metabolism appear to be more pronounced in men than in women.
Subject(s)
Blood Glucose/metabolism , Osteocalcin/blood , Glucose Tolerance Test , Glycated Hemoglobin/metabolism , Humans , Publication Bias , Sensitivity and SpecificityABSTRACT
The plant species Camellia oleifera is an important producer of edible oil in China. However, it suffers from a low fruit-setting rate. This study used high resolution scanning electron microscopy of semi-thin tissue sections to investigate anther development and pollen formation, and to determine whether problems in forming functional pollen cause low seed setting rates. During anther development, cell sizes within the epidermis and end othecium gradually increase, and at the beginning of the microsporocyte phase, the cells become highly vacuolated. The cell walls of the inner wall cells thicken in a ribbon pattern during the later part of the two-cell pollen stage. Middle layer cells become flattened during the later part of the secondary sporogenous cell stage. A tapetum also forms at this stage; the secondary sporogenous cells begin to degrade at the early microspore stage and completely disappear by the time the pollen is mature, thus forming a glandular tapetum. In microsporocyte, cytokinesis occurs simultaneously with microsporocyte meiosis, and a tetrahedral arrangement is present in tetrads. Reproductive cells begin to form at the later stage of microsporogenesis; the nuclei of the reproductive cells are enlarged as the reproductive cells begin to move away from the pollen wall. Two-cell pollen is first formed after reproductive cells have left the pollen wall, and the number of inclusions in the pollen subsequently increases. The pollen matures for 5-8 days before flowering occurs. No pollen abortion phenomena were observed, suggesting that anther development in C. oleifera is normal and that functional pollen are formed.
Subject(s)
Camellia/growth & development , Pollen/growth & development , Camellia/cytology , Cell Differentiation , Cell Wall/ultrastructure , Gametogenesis, Plant , Pollen/cytology , ReproductionABSTRACT
The aim of this study was to explore the effect of atorvastatin intervention on plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and inflammatory cytokine levels in patients with heart failure (HF). One hundred and twenty-three HF patients were selected from our hospital and randomly divided into control (N = 61) and observation (N = 62) groups; the former received conventional treatment, while the latter were given conventional treatment combined with atorvastatin. Plasma NT-proBNP, inflammatory cytokines [high-sensitive C-reactive protein (hs-CRP), interleukin (IL)-6, IL-10] and cardiac function [left ventricular end-diastolic dimension (LVEDD), left ventricular ejection fraction (LVEF), end-diastolic maximum flow rate ratio (E/A)] were compared among groups. The effective rate of treating HF significantly increased after atorvastatin treatment. The plasma NT-proBNP, IL-6, IL-10, hs-CRP, and LVEDD levels significantly decreased (P < 0.05), while the LVEF and E/A levels significantly increased (P < 0.05) in the observation group compared to the control group and before intervention. The NT-proBNP and cytokine levels significantly differed among patients with different classes of heart function (P < 0.05); the NT-proBNP and cytokine levels increased with the severity of heart function. Pearson's correlation analysis revealed a negative correlation between the NT-proBNP and inflammatory cytokine levels and LVEF and E/A values, and a positive correlation between these factors and LVEDD (P < 0.05). In conclusion, atorvastatin significantly improves cardiac function; the mechanism atorvastatin action was related to the decrease in plasma NT-proBNP and inflammatory cytokine levels.
Subject(s)
Atorvastatin/therapeutic use , Cytokines/blood , Heart Failure/blood , Heart Failure/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Inflammation Mediators/blood , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Adult , Aged , Biomarkers , Case-Control Studies , Echocardiography , Female , Heart Failure/diagnosis , Heart Failure/physiopathology , Heart Function Tests , Humans , Male , Middle Aged , Treatment OutcomeABSTRACT
STUDY QUESTION: Are there abnormalities in gonadotrophin secretion, adrenal steroidogenesis and/or testicular steroidogenesis in brothers of women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Brothers of women with PCOS have increased gonadotrophin responses to gonadotrophin releasing hormone (GnRH) agonist stimulation and alterations in adrenal and gonadal steroidogenesis. WHAT IS KNOWN ALREADY: PCOS is a complex genetic disease. Male as well as female first-degree relatives have reproductive features of the syndrome. We previously reported that brothers of affected women have elevated circulating dehydroepiandrosterone sulfate levels. STUDY DESIGN, SIZE, DURATION: This was a case-control study performed in 29 non-Hispanic white brothers of 22 women with PCOS and 18 control men. PARTICIPANTS/MATERIALS, SETTING, METHODS: PCOS brothers and control men were of comparable age, weight and ethnicity. Adrenocorticotrophic hormone (ACTH) and GnRH agonist stimulation tests were performed. Gonadotrophin responses to GnRH agonist as well as changes in precursor-product steroid pairs (delta, Δ) across steroidogenic pathways in response to ACTH and GnRH agonist were examined. MAIN RESULTS AND THE ROLE OF CHANCE: Basal total (T) levels did not differ, but dehydroepiandrosterone (DHEA) levels (0.13 ± 0.08 brothers versus 0.22 ± 0.09 controls, nmol/l, P = 0.03) were lower in brothers compared with control men. ACTH-stimulated Δ17-hydroxypregnenolone (17Preg)/Δ17-hydroxyprogesterone (17Prog) (7.8 ± 24.2 brothers versus 18.9 ± 21.3 controls, P = 0.04) and ΔDHEA/Δandrostenedione (AD) (0.10 ± 0.05 brothers versus 0.14 ± 0.08 controls, P = 0.04) were lower in brothers than in the controls. GnRH agonist-stimulated Δ17Prog/ΔAD (0.28 ± 8.47 brothers versus 4.79 ± 10.28 controls, P = 0.003) was decreased and luteinizing hormone (38.6 ± 20.6 brothers versus 26.0 ± 9.8 controls, IU/l, P = 0.02), follicle-stimulating hormone (10.2 ± 7.5 brothers versus 4.8 ± 4.1 controls, IU/l P = 0.002), AD (1.7 ± 1.4 brothers versus 0.9 ± 1.5 controls, nmol/l, P = 0.02) and ΔAD/ΔT (0.16 ± 0.14 brothers versus 0.08 ± 0.12 controls, P = 0.005) responses were increased in brothers compared with controls. LIMITATIONS, REASONS FOR CAUTION: The modest sample size may have limited our ability to observe other possible differences in steroidogenesis between PCOS brothers and control men. WIDER IMPLICATIONS OF THE FINDINGS: Decreased ACTH-stimulated Δ17Preg/Δ17Prog and ΔDHEA/ΔAD responses suggested increased adrenal 3ß-hydroxysteroid dehydrogenase activity in the brothers. Decreased Δ17Prog/ΔAD and increased ΔAD/ΔT responses to GnRH agonist stimulation suggested increased gonadal 17,20-lyase and decreased gonadal 17ß-hydroxysteroid dehydrogenase activity in the brothers. Increased LH and FSH responses to GnRH agonist stimulation suggested neuroendocrine alterations in the regulation of gonadotrophin secretion similar to those in their proband sisters. These changes in PCOS brothers may reflect the impact of PCOS susceptibility genes and/or programming effects of the intrauterine environment. STUDY FUNDING/COMPETING INTERESTS: This research was supported by P50 HD044405 (A.D.), K12 HD055884 (L.C.T.), U54 HD034449 (A.D., R.S.L.) from the National Institute of Child Health and Development. Some hormone assays were performed at the University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core that is supported by U54 HD28934 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Partial support for some of the clinical studies was provided by UL1 RR025741 and UL1 TR000150 (Northwestern University Clinical and Translational Sciences Institute) from the National Center for Research Resources, National Institutes of Health, which is now the National Center for Advancing Translational Sciences. The authors have no conflict of interest to declare.
Subject(s)
Gonadotropins/blood , Polycystic Ovary Syndrome , Steroids/blood , 17-alpha-Hydroxypregnenolone/blood , 17-alpha-Hydroxyprogesterone/blood , Adolescent , Adult , Androstenedione/blood , Case-Control Studies , Cortodoxone/blood , Dehydroepiandrosterone Sulfate/blood , Female , Humans , Male , Middle Aged , SiblingsABSTRACT
Numerous studies have evaluated the association between the human interleukin-10 gene -592C>A polymorphism and gastric cancer risk. However, the results have been inconsistent. This meta-analysis was designed to resolve these controversies. Systematic searches of the electronic databases Embase, PubMed, and Google Scholar were performed to identify relevant studies. A meta-analysis was performed to examine the association between the interleukin-10 gene -592C>A polymorphism and gastric cancer risk. Odds ratios (OR) and its 95% confidence intervals (CI) were used for statistical analysis. Twelve studies were included in the meta-analysis, which included 2116 gastric cancer cases and 4077 controls. No significant association was found between the interleukin-10 gene -592C>A polymorphism and gastric cancer risk in total population analysis. In stratified analysis, a significant association was found in the Asian subgroup (AA vs AC: OR = 0.79, 95%CI = 0.64-0.98; dominant model: OR = 1.26, 95%CI = 1.04-1.57), and no significant association was observed among Caucasians. In addition, the corresponding pooled ORs were not substantially altered after excluding one study that deviated from Hardy-Weinberg equilibrium in the control group. This meta-analysis supports an association between the interleukin-10 gene -592C>A polymorphism and gastric cancer risk in Asians but not in Caucasians. Further large and well-designed studies are needed to confirm these conclusions.
Subject(s)
Genetic Predisposition to Disease/genetics , Interleukin-10/genetics , Polymorphism, Single Nucleotide , Stomach Neoplasms/genetics , Asian People/genetics , Gene Frequency , Genetic Predisposition to Disease/ethnology , Genotype , Humans , Linkage Disequilibrium , Odds Ratio , Risk Factors , Stomach Neoplasms/ethnology , White People/geneticsABSTRACT
Testicular seminoma has become the most common solid malignancy in young men, especially in the 20s group. We obtained the gene expression profile of human testicular seminoma cells from NCBI, identified the differentially expressed genes of testicular seminoma cells of different stages, and constructed the regulation networks of different stages of testicular seminoma using bioinformatics methodology. Forty differentially expressed genes of testicular seminoma cells of different stages were identified. These genes and pathways are apparently involved in the progression of testicular seminoma.
Subject(s)
Seminoma/metabolism , Testicular Neoplasms/metabolism , Transcriptome , Case-Control Studies , Disease Progression , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Humans , Male , Neoplasm Staging , Seminoma/pathology , Testicular Neoplasms/pathology , Testis/metabolism , Testis/pathology , Up-RegulationABSTRACT
The plasma current density profile plays a key role in the development of a high poloidal beta scenario, which is essential for long-pulse and high-performance plasma operation on a tokamak. Based on the polarimetry technique, a Motional Stark Effect (MSE) diagnostic has been built on the Experimental Advanced Superconducting Tokamak. To be prepared for real-time (RT) feedback control of the plasma current density profile in the future, a RT signal processing system has been developed. The RT signal processing system is composed of three functional modules: analog-to-digital conversion (ADC) module, polarization information extraction module, and digital-to-analog conversion (DAC) module. The final objective of this system is to acquire the polarization information of the MSE. Based on the field-programmable gate array unit, fast Fourier transformation is adopted to process the Photoelastic Modulator (PEM) digital signal, which was converted from a PEM signal via the ADC module. By means of frequency spectrum separation, the components around double modulating frequencies are restored through inverse fast Fourier transformation. Furthermore, the two amplitudes of their corresponding components can be obtained through a digital harmonic analyzer technique. Afterward, the ratio of the two amplitudes is calculated by arc tangent so that the polarization angle is obtained. Finally, the information of this polarization angle is converted into a voltage signal by the DAC module and then output in RT. The test results based on the RT signal processing system are in good agreement with those based on the phase lock-in amplifiers. The working cycle of this system is shorter than 10 ms, which meets the requirements of the MSE diagnostic as a RT controller. The algorithm of RT signal processing and the relevant technology applied for building this system are presented in the main body of this paper in detail.