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Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.
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OBJECTIVES: The present study aimed to investigate the relationship between male hormones and metabolic dysfunction-associated fatty liver disease (MAFLD) in males. METHODS: Data from the Fangchenggang Area Male Health and Examination Survey (FAMHES) were used to analyze the male hormone levels between MAFLD patients and controls. Univariate and multivariate logistic regression analyses were performed to identify risk factors for MAFLD. Receiver operating characteristic curve analysis was used to assess the diagnostic performance of male hormones for MAFLD. RESULT: A total of 1578 individuals were included, with 482 individuals (30.54%) of MAFLD, including 293 (18.57%) with mild disease and 189 (11.98%) with moderate-to-severe disease. The MAFLD patients were significantly older than those without MAFLD. The LH, FSH, and SHBG levels in the MAFLD patients were significantly greater than those in the control group. Age, FSH, LH, SHBG, and estradiol were all risk factors for MAFLD. Age, FSH, and LH were risk factors for moderate-to-severe MAFLD. FSH was an independent risk factor for MAFLD and moderate-to-severe MAFLD. FSH showed an excellent diagnostic value, with an AUC of 0.992 alone and 0.996 after adjusting age. CONCLUSIONS: Our findings indicate that FSH may be a potential diagnostic and predictive biomarker for MAFLD.
Subject(s)
Follicle Stimulating Hormone , Luteinizing Hormone , Sex Hormone-Binding Globulin , Humans , Male , Follicle Stimulating Hormone/blood , Middle Aged , Adult , Luteinizing Hormone/blood , Risk Factors , Sex Hormone-Binding Globulin/metabolism , Sex Hormone-Binding Globulin/analysis , Estradiol/blood , Non-alcoholic Fatty Liver Disease/blood , China/epidemiology , Case-Control Studies , ROC Curve , Biomarkers/blood , Fatty Liver/blood , AgedABSTRACT
The Chinese tree shrew ( Tupaia belangeri chinensis) has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, macaques, and mice. Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. Biochemical analysis confirmed the production of aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands. Furthermore, genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Overall, this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland. Our comprehensive results (publicly available at http://gxmujyzmolab.cn:16245/scAGMap/) should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.
Subject(s)
Adrenal Glands , Steroids , Animals , Adrenal Glands/metabolism , Humans , Steroids/biosynthesis , Steroids/metabolism , Transcriptome , Mice , Tupaiidae , Female , MultiomicsABSTRACT
OBJECTIVE: Although the current European Association of Urology(EAU) guideline recommends that patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) should accept intravesical chemotherapy or Calmette-Guerin (BCG) for no more than one year after transurethral resection of bladder tumor(TURBT), there is no consensus on the optimal duration of chemotherapy. Hence, we explored the optimal duration of maintenance intravesical chemotherapy in patients with intermediate-risk NMIBC. SUBJECTS AND METHODS: This was a real-world single-center retrospective cohort study. In total 158 patients with pathologically confirmed intermediate-risk NMIBC were included, who were divided into 4 subgroups based on the number of instillations given. We used Cox regression analysis and survival analysis chart to explore the 3-yr recurrence outcomes of tumor.The optimal duration was determined by receive operating characteristic curve (ROC). RESULTS: The median follow-up was 5.2 years. Compared with instillation for 1-2 months, the Hazard Ratios(HR) values of instillation for less than 1 month, maintenance instillation for 3-6 months and > 6 months were 3.57ã1.57 and 0.22(95% CI 1.27-12.41;0.26-9.28;0.07-0.80, P = 0.03;0.62;0.02, respectively). We found a significant improvement in 3-yr relapse-free survival in intermediate-risk NMIBC patients who maintained intravesical instillation chemotherapy for longer than 6 months, and the best benefit was achieved with 10.5 months of maintenance chemotherapy by ROC. CONCLUSIONS: In our scheme, the optimal duration of intravesical instillation with pirrubicin is 10.5 months. This new understanding provides valuable experience for the precise medical treatment model of intermediate-risk NMIBC.
Subject(s)
Non-Muscle Invasive Bladder Neoplasms , Urinary Bladder Neoplasms , Humans , Administration, Intravesical , Maintenance Chemotherapy , Retrospective Studies , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Urinary Bladder Neoplasms/pathology , BCG Vaccine/therapeutic use , Neoplasm InvasivenessABSTRACT
Purpose It is well-established that the lack of accurate diagnostic modalities for prostate cancer (PCa) leads to overdiagnosis and overtreatments. Accordingly, this study aimed to assess the value of urine-derived exosomal prostate-specific membrane antigen (PSMA) as a biomarker for the diagnosis of PCa and clinically significant prostate cancer (csPCa). Methods A total of 284 urine samples were collected from patients after the digital rectal examination (DRE). Urinary exosomes were extracted using commercial kits, and urine-derived exosomal PSMA was determined via enzyme-linked immunosorbent assay (ELISA). Evaluation of diagnostic accuracy of PSMA was performed via receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and waterfall plots. Results We found that urine-derived exosomal PSMA was significantly higher in PCa and csPCa than in benign prostatic hyperplasia (BPH) and BPH + non-aggressive prostate cancer (naPCa) groups (P < 0.001). Furthermore, the urine-derived exosome PSMA yielded area under the ROC curve (AUC) values of 0.876 and 0.826 for detecting PCa and csPCa, respectively, suggesting better performance than traditional clinical biomarkers. Besides, when the cutoff value used corresponded to a sensitivity of 95%, urine-derived exosomal PSMA could avoid unnecessary biopsies in 41.2% of cases and missed only 0.7% of csPCa cases. Conclusions Urine-derived exosomal PSMA exhibits a good diagnostic yield for detecting PCa and csPCa. Findings of the present study provide the foothold for future studies on cancer management and research in this patient population (AU)
Subject(s)
Humans , Male , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/urine , Exosomes/pathology , Prostatic Hyperplasia/pathology , Biomarkers, Tumor/urine , Prostate-Specific Antigen , BiopsyABSTRACT
PURPOSE: It is well-established that the lack of accurate diagnostic modalities for prostate cancer (PCa) leads to overdiagnosis and overtreatments. Accordingly, this study aimed to assess the value of urine-derived exosomal prostate-specific membrane antigen (PSMA) as a biomarker for the diagnosis of PCa and clinically significant prostate cancer (csPCa). METHODS: A total of 284 urine samples were collected from patients after the digital rectal examination (DRE). Urinary exosomes were extracted using commercial kits, and urine-derived exosomal PSMA was determined via enzyme-linked immunosorbent assay (ELISA). Evaluation of diagnostic accuracy of PSMA was performed via receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and waterfall plots. RESULTS: We found that urine-derived exosomal PSMA was significantly higher in PCa and csPCa than in benign prostatic hyperplasia (BPH) and BPH + non-aggressive prostate cancer (naPCa) groups (P < 0.001). Furthermore, the urine-derived exosome PSMA yielded area under the ROC curve (AUC) values of 0.876 and 0.826 for detecting PCa and csPCa, respectively, suggesting better performance than traditional clinical biomarkers. Besides, when the cutoff value used corresponded to a sensitivity of 95%, urine-derived exosomal PSMA could avoid unnecessary biopsies in 41.2% of cases and missed only 0.7% of csPCa cases. CONCLUSIONS: Urine-derived exosomal PSMA exhibits a good diagnostic yield for detecting PCa and csPCa. Findings of the present study provide the foothold for future studies on cancer management and research in this patient population.
Subject(s)
Exosomes , Prostatic Hyperplasia , Prostatic Neoplasms , Male , Humans , Prostatic Hyperplasia/pathology , Prostatic Neoplasms/pathology , Biopsy , Biomarkers , Exosomes/pathology , Prostate-Specific AntigenABSTRACT
Pancreatic cancer refers to the development of malignant tumors in the pancreas: it is associated with high mortality rates and mostly goes undetected in its early stages for lack of symptoms. Currently, surgical treatment is the only effective way to improve the survival of pancreatic cancer patients. Therefore, it is crucial to diagnose the disease as early as possible in order to improve the survival rate of patients with pancreatic cancer. Liquid biopsy is a unique in vitro diagnostic technique offering the advantage of earlier detection of tumors. Although liquid biopsies have shown promise for screening for certain cancers, whether they are effective for early diagnosis of pancreatic cancer is unclear. Therefore, we reviewed relevant literature indexed in PubMed and collated updates and information on advances in the field of liquid biopsy with respect to the early diagnosis of pancreatic cancer.
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Prostate adenocarcinoma (PRAD) is one of the most common types of malignancy in males and at present, effective prognostic indicators are limited. The development of PRAD has been associated with abnormalities in alternative splicing (AS), a requisite biological process of gene expression in eukaryotic cells; however, the prognostic value of AS products and splicing events remains to be elucidated. In the present study, the data of splicing events and the clinical information of PRAD patients were obtained from The Cancer Genome Atlas (TCGA)SpliceSeq and TCGA databases, respectively. A prognostic index (PI) was generated from disease-free survival-associated splicing events (DFS-SEs), which were identified by univariate/multivariate Cox regression analysis. A total of 6,909 DFS-SEs were identified in PRAD. The corresponding genes for the DFS-SEs were significantly enriched in mitochondria and their associated pathways according to Gene Ontology annotation and in the pathways of fatty acid metabolism, oxidative phosphorylation and Huntington's disease according to a Kyoto Encyclopedia of Genes and Genomes pathway analysis. The PI for mutually exclusive exons had the greatest ability to predict the probability of five-year disease-free survival of patients with PRAD, with an area under the time-dependent receiver-operating characteristic curve of 0.7606. Patients with PRAD, when divided into a 'low' and a 'high' group based on their median PI for exon skip values, exhibited a marked difference in disease-free survival (low vs. high, 3,588.45±250.51 vs. 1,531.08±136.50 days; P=7.43x10-9). A correlation network between DFS-SEs of splicing factors and non-splicing factors was constructed to determine the potential mechanisms in PRAD, which included the potential regulatory interaction between the splicing event of splicing factor RNA binding motif protein 5-alternate terminator (AT)-64957 and the splicing event of non-splicing factor heterochromatin protein 1 binding protein 3-AT-939. In conclusion, the PIs derived from DFS-SEs are valuable prognostic factors for patients with PRAD, and the function of splicing events in PRAD deserves further exploration.
Subject(s)
Adenocarcinoma/genetics , Alternative Splicing , Gene Regulatory Networks , Prostatic Neoplasms/genetics , Disease-Free Survival , Humans , Male , Prognosis , Regression Analysis , Sequence Analysis, RNAABSTRACT
INTRODUCTION: Colorectal cancer (CRC) is the fourth most common cause of cancer-related mortality worldwide. The tumor, node, metastasis (TNM) stage remains the standard for CRC prognostication. Identification of meaningful microRNA (miRNA) and gene modules or representative biomarkers related to the pathological stage of colon cancer helps to predict prognosis and reveal the mechanisms behind cancer progression. MATERIALS AND METHODS: We applied a systems biology approach by combining differential expression analysis and weighted gene co-expression network analysis (WGCNA) to detect the pathological stage-related miRNA and gene modules and construct a miRNA-gene network. The Cancer Genome Atlas (TCGA) colon adenocarcinoma (CAC) RNA-sequencing data and miRNA-sequencing data were subjected to WGCNA analysis, and the GSE29623, GSE35602 and GSE39396 were utilized to validate and characterize the results of WGCNA. RESULTS: Two gene modules (Gmagenta and Ggreen) and one miRNA module were associated with the pathological stage. Six hub genes (COL1A2, THBS2, BGN, COL1A1, TAGLN and DACT3) were related to prognosis and validated to be associated with the pathological stage. Five hub miRNAs were identified to be related to prognosis (hsa-miR-125b-5p, hsa-miR-145-5p, hsa-let-7c-5p, hsa-miR-218-5p and hsa-miR-125b-2-3p). A total of 18 hub genes and seven hub miRNAs were predominantly expressed in tumor stroma. Proteoglycans in cancer, focal adhesion, extracellular matrix (ECM)-receptor interaction and so on were common pathways of the three modules. Hsa-let-7c-5p was located at the core of miRNA-gene network. CONCLUSION: These findings help to advance the understanding of tumor stroma in the progression of CAC and provide prognostic biomarkers as well as therapeutic targets.
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INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) has been reported to have effects on kidney diseases; however, a link between NAFLD and urinary calculi remains to be confirmed. This study was conducted on a male population based on our previous Fangchenggang Area Male Health and Examination Survey in Guangxi, China in order to estimate the frequency of urinary calculi and assess the association between NAFLD and urinary calculi while controlling for possible confounders. MATERIALS AND METHODS: This was a population-based cross-sectional study conducted in the Fangchenggang region in Guangxi, China. The diagnoses of NAFLD and urinary calculi were made by ultrasonography. Clinical and laboratory findings were analyzed to investigate whether NAFLD was a risk factor for urinary calculi. RESULTS: A total of 3719 men were enrolled (age range, 17 to 88 years). Slightly more than a quarter (26.5%) of the participants were diagnosed with NAFLD. The percentage of urinary calculi in all participants was 6.9%, and the percentage of NAFLD patients with urinary calculi (8.4%) was significantly higher than that among patients without NAFLD (6.4%, P < .05). Advanced age; high body mass index; elevated levels of blood glucose, cholesterol, triglycerides, and low-density lipoprotein cholesterol; low education; lower or higher physical activity; and NAFLD were independent risk factors for urinary calculi (P < .05). CONCLUSIONS: Our results showed that NAFLD was associated with a higher incidence of urinary calculi in this cohort and NAFLD might represent a risk factor for urinary calculi.
Subject(s)
Non-alcoholic Fatty Liver Disease/epidemiology , Urinary Calculi/epidemiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , China/epidemiology , Comorbidity , Cross-Sectional Studies , Educational Status , Exercise , Health Surveys , Humans , Incidence , Life Style , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Risk Factors , Ultrasonography , Urinary Calculi/diagnostic imaging , Young AdultABSTRACT
BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a common malignant tumor with a high rate of recurrence. Immunohistochemical analysis of the marker of proliferation Ki-67 (MKI67) is used to assess proliferation activity of HCC The regulation of MKI67 expression remains unclear in HCC This study aims to explore the association between MKI67 expression and gene variants. METHODS: A total of 195 hepatitis B virus (HBV)-related HCC patients were genotyped using Illumina HumanExome BeadChip-12-1_A (242,901 markers). An independent cohort (97 subjects) validated the association of polymorphism determinants and candidate genes with MKI67 expression. The relationships between MKI67 with p53 and variants of candidate genes in the clinical outcomes of HCC patients were analyzed. RESULTS: We found that MKI67 combined with p53 was associated with a 3-year recurrence-free survival and five variants near TTN and CCDC8 were associated with MKI67 expression. TTN harboring rs2288563-TT and rs2562832-AA+CA indicated a favorable outcome for HCC patients. CONCLUSION: Variants near TTN and CCDC8 were associated with MKI67 expression, and rs2288563 and rs2562832 in TTN are potential biomarkers for the prediction of clinical outcomes in HBV-related HCC patients.
Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/genetics , Gene Expression Regulation, Neoplastic , Hepatitis B, Chronic/genetics , Ki-67 Antigen/genetics , Liver Neoplasms/genetics , Aged , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/mortality , Carrier Proteins/genetics , Carrier Proteins/metabolism , China , Cohort Studies , Connectin/genetics , Connectin/metabolism , Female , Genome-Wide Association Study , Hepatitis B virus/growth & development , Hepatitis B virus/pathogenicity , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/mortality , Humans , Ki-67 Antigen/metabolism , Liver Neoplasms/diagnosis , Liver Neoplasms/etiology , Liver Neoplasms/mortality , Male , Middle Aged , Polymorphism, Single Nucleotide , Prognosis , Survival Analysis , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolismABSTRACT
OBJECTIVE: Upper urinary calculi (UUC) is considered to be a comprehensive disease associated with many risk factors, but the role of physical activity (PA) is undefined. Here, we conducted a cross-sectional study to investigate this relationship in Asian populations. MATERIALS AND METHODS: Patients diagnosed with UUC were the subjects of study and those who participated in a health examination in local medical center were included as controls. Information was collected through the same standard questionnaire. A metabolic equivalent score (METs) was measured for each kind of activity. OR of UUC in categories of PA were determined by logistic regression. RESULTS: A total of 1,782 controls and 1,517 cases were enrolled. People who took higher PA (5-9.9, 10-19.9, 20-29.9 and >30 METs/wk) weekly were associated with lower risks of UUC than those took lower PA (<4.9 METs/wk) after adjusting for age, ethnicity, body mass index, systolic blood pressure, water intake, history of gout, history of diabetes mellitus, history of supplemental calcium use and history of hypertension (adjusted OR 0.11, 0.32, 0.24, 0.34; 95% CI 0.08-0.15, 0.23-0.43, 0.15-0.40, 0.22-0.53, respectively; p value <0.001). CONCLUSIONS: In our cross-sectional study, PA was associated with UUC.
Subject(s)
Exercise , Urinary Calculi/epidemiology , Urinary Calculi/therapy , Adolescent , Adult , Asian People , Body Mass Index , Calcium/therapeutic use , Case-Control Studies , China , Cross-Sectional Studies , Diabetes Complications , Ethnicity , Female , Gout/complications , Humans , Hypertension/complications , Male , Odds Ratio , Regression Analysis , Risk Factors , Surveys and Questionnaires , Systole , Urinary Calculi/prevention & control , Young AdultABSTRACT
OBJECTIVE: To determine the zinc levels in the expressed prostatic secretion (EPS) of the patients with different types of chronic nonbacterial prostatitis, and explore the reference value of zinc concentration in EPS in the diagnosis and treatment of prostatitis. METHODS: We collected EPS samples from 35 healthy men and 173 patients with chronic nonbacterial prostatitis, including 65 cases of type â ¢A, 69 cases of type â ¢B, and 39 cases of type â £, according to the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). We compared the zinc levels in the EPS samples among different groups and analyzed the correlations of zinc concentration with the NIH-CPSI scores, WBC count, pH value, and age of the subjects. RESULTS: The participants were aged 17ï¼65 (32.5±8.5) years. The zinc concentrations in the EPS were significantly lower in the â ¢A (ï¼»162.2±10.8ï¼½ µg/ml) and â ¢B (ï¼»171.2±12.0ï¼½ µg/ml) than in the â £ (ï¼»234.6±17.9ï¼½ µg/ml) (P<0.05 ) and the control group (ï¼»259.5±14.6ï¼½ µg/ml) (P<0.05 ). The zinc level was correlated negatively with the NIH-CPSI pain score (r=ï¼0.248, P<0.01), quality of life score (r=ï¼0.232, P<0.01), severity score (r=ï¼0.270, P<0.01), total NIH-CPSI score (r=ï¼0.281, P<0.01), and the pH value in EPS (r=ï¼0.208, P<0.01), but showed no correlation with the WBC count and age of the subjects. CONCLUSIONS: The reduced zinc concentration in the EPS of the patients with chronic nonbacterial prostatitis may be associated with the pain symptoms of the disease, which suggests the potential reference value of measuring the zinc concentration in EPS in the diagnosis and treatment of prostatitis.
Subject(s)
Pain/metabolism , Prostatitis/physiopathology , Zinc/metabolism , Adolescent , Adult , Aged , Chronic Disease , Humans , Male , Middle Aged , Prostatitis/metabolism , Quality of Life , Young AdultABSTRACT
OBJECTIVE: To investigate whether γH2AX levels were different in the spermatozoa of healthy men compared with infertility patients, and to assess the possible correlations between γH2AX and conventional semen parameters and double-stranded breaks (DSBs) identified with the use of comet assay. DESIGN: Prospective study. SETTING: Clinical laboratory. PATIENT(S): Semen from 100 male infertile patients and 100 healthy sperm donors. INTERVENTION(S): Human sperm samples were analyzed in terms of World Health Organization parameters. The γH2AX levels were detected by means of flow cytometry. DSBs of sperm were detected by means of comet assay. Morphology slides were made and the sperm morphology assessed according to strict criteria. MAIN OUTCOME MEASURE(S): Conventional semen analyses, γH2AX levels in sperm, DNA DSBs in sperm, and correlations among γH2AX, conventional semen analyses, and DSBs. RESULT(S): Concentration, viability, motility, and normal sperm morphology were significantly lower in male infertility patients compared with healthy men. Also, γH2AX levels and the number of DSBs were significantly higher in the sperm of infertile subjects compared with healthy men. γH2AX levels correlated negatively with conventional semen parameters and positively with DSBs. A threshold γH2AX level of 18.55% was identified as a cutoff value to discriminate infertile subjects from fertile control subjects with a specificity of 86.0% and a sensitivity of 83.0%. The positive and negative predictive values of the 18.55% γH2AX threshold were high: 87.7% and 85.5%, respectively. CONCLUSION(S): γH2AX levels were higher in the sperm of male infertility patients than in healthy men. γH2AX levels in sperm, as evaluated with the use of flow cytometry, might be a useful biomarker for evaluating DSBs in human spermatozoa.
Subject(s)
Fertility , Histones/analysis , Infertility, Male/metabolism , Spermatozoa/chemistry , Adult , Area Under Curve , Biomarkers/analysis , Case-Control Studies , Cell Shape , Cell Survival , Comet Assay , DNA Breaks, Double-Stranded , Flow Cytometry , Humans , Infertility, Male/diagnosis , Infertility, Male/genetics , Infertility, Male/physiopathology , Male , Phosphorylation , Predictive Value of Tests , Prospective Studies , ROC Curve , Sperm Count , Sperm Motility , Spermatozoa/pathology , Up-Regulation , Young AdultABSTRACT
OBJECTIVES: Increasing number of studies suggested that biallelic CEBPA (bi CEBPA) mutations were associated with favorable prognosis in patients with acute myeloid leukemia (AML), but the results remain inconclusive. We therefore present a meta-analysis to evaluate the prognostic value of bi CEBPA mutations in patients with AML. METHODS: A comprehensive literature search was undertaken through August 2014 looking for eligible studies. Pooled hazard ratios (HRs) estimates and 95% confidence intervals (95% CIs) in overall survival (OS) and event-free survival (EFS) were used to calculate estimated effect. RESULTS: Ten studies covering a total of 6219 subjects were included in this analysis. Overall, bi CEBPA mutations were associated with favorable clinical outcome in patients with AML (HR for EFS: 0.41, 95% CI: 0.32-0.52; for OS: 0.37, 95% CI: 0.27-0.50), in cytogenetically normal (CN)-AML (HR for EFS: 0.38, 95% CI: 0.29-0.49; for OS: 0.32, 95% CI: 0.23-0.43). When took the cohort of monoallelic CEBPA (mo CEBPA) mutated and wild-type CEBPA (wt CEBPA) AML as a reference group, bi CEBPA mutated AML also shown beneficial outcomes (HR for OS: 0.52, 95% CI: 0.37-0.72). No significant difference was found between mo CEBPA mutation and wt CEBPA in patients with AML or CN-AML (P > 0.05). CONCLUSION: Bi CEBPA mutations in patients with AML are strongly associated with a favorable prognosis, which suggested that bi CEBPA mutations would potentially serve as a novel prognostic marker in AML.
Subject(s)
Alleles , CCAAT-Enhancer-Binding Proteins/genetics , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/genetics , Mutation , Female , Gene Expression , Humans , Leukemia, Myeloid, Acute/pathology , Male , Prognosis , Survival AnalysisABSTRACT
BACKGROUND: Despite evidence suggesting roles for caspase-8 (CASP8) -652 6N del and D302H polymorphisms in prostate cancer (PCa), the association of these polymorphisms with PCa risk remains inconclusive. Therefore, a meta-analysis was performed to more precisely estimate the association of CASP8 -652 6N del and D302H polymorphisms with PCa susceptibility. MATERIALS AND METHODS: A comprehensive literature search was conducted to identify all case-control studies of CASP8 D302H and -652 6N del polymorphisms and PCa risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association and the precision of the estimate, respectively. RESULTS: Nine -625 6N del studies and 4 D302H studies were included. CASP8 -652 6N del and D302H polymorphisms were not significantly associated with PCa risk in the overall analyses. However, in the subgroup analysis stratified by ethnicity, -625 6N del was significantly associated with PCa risk in the East Asian and Indian populations under the recessive model. Furthermore, the subgroup analysis strongly suggested that D302H was associated with lower PCa risk in the Non-Indian population under the dominant model. CONCLUSIONS: In our meta-analysis, ethnic-specific differences were evident in the association of CASP8 -625 6N del and D302H polymorphisms with PCa risk.
Subject(s)
Caspase 8/genetics , Ethnicity/genetics , Genetic Predisposition to Disease , Polymorphism, Genetic/genetics , Prostatic Neoplasms/ethnology , Prostatic Neoplasms/genetics , Case-Control Studies , Humans , Male , Prognosis , Risk FactorsABSTRACT
OBJECTIVE: To investigate the influence of body mass index (BMI) on the serum prostate-specific antigen (PSA) level in males in the Fangcheng area of Guangxi. METHODS: We reviewed the health examination data of males collected from September 2009 to December 2011, including their height, weight, BMI, and serum PSA level. The subjects were categorized as underweight (BMI <18.5 kg/m2), normal (BMI 18.5-22.9 kg/m2), overweight (BMI 23.0-27.4 kg/m2), and obese (BMI > or = 27.5 kg/m2), and divided into four age groups: 20-29, 30-39, 40-49, and > or = 50 years old. The PSA levels were stratified by the BMI category for statistical analysis. RESULTS: A total of 2,397 men were included in this study, with a mean age of (37.4 +/- 11.0) yr, BMI of (23.3 +/- 3.4) kg/m2, and PSA level of (0.98 +/- 0.93) microg/L. There were significant differences in the age-associated PSA levels in the groups with BMI < 23 (0.81 microg/L) and > or = 23 kg/m2 (0.78 microg/L) (P < 0.05), as well as in those with BMI < 27.5 (0.81 microg/L) and > or = 27. 5 kg/m2 (0.70 microg/L) (P < 0.05). In the 30-39 and 40-49 age groups, the PSA levels were significantly decreased with the increase of BMI (P < 0.05). CONCLUSION: Increased BMI is associated with decreased PSA in men <50 years old in the Fangcheng area of Guangxi, which should be taken into consideration while determining whether to carry out prostate biopsy as part of early prostate cancer detection in young men with marginal PSA levels.
Subject(s)
Body Mass Index , Body Weight , Prostate-Specific Antigen/blood , Adult , China , Humans , Male , Middle Aged , Obesity/blood , Young AdultABSTRACT
AIM: To determine serum osteocalcin levels in South Chinese males with non-alcoholic fatty liver disease (NAFLD) and to examine the relation between serum osteocalcin and NAFLD. METHODS: Data were collected from 1683 men attending the Fangchenggang Area Male Healthy and Examination Survey (FAMHES) from September 2009 to December 2009. Serum osteocalcin was measured with electrochemiluminescence immunoassay. An abdominal ultrasonographic examination for all individuals was performed by two experienced ultrasonographers. The associations of serum osteocalcin with NAFLD were evaluated. RESULTS: The levels of serum osteocalcin were lower in 364 NAFLD participants than in 1319 non-NAFLD participants (24.51 ± 1.38 ng/mL vs. 20.81 ± 1.33 ng/mL, p < 0.001). Serum osteocalin level was associated with the scale of NAFLD (r = -0.150, p < 0.01). Serum osteocalin level tended to decrease with the scale of NAFLD. Binary logistic regression analysis showed that decreased ORs for NAFLD were observed from the first to the fourth osteocalcin quartiles. CONCLUSIONS: Our findings suggest that a lower serum osteocalcin level is associated with the presence of NAFLD.
Subject(s)
Fatty Liver/blood , Osteocalcin/blood , Adolescent , Adult , Aged , Aged, 80 and over , China , Humans , Male , Middle Aged , Non-alcoholic Fatty Liver Disease , Young AdultABSTRACT
OBJECTIVE: To explore the safety and efficiency of transurethral plasmakinetic enucleation of prostate (TUPKEP) and suprapubic small cut in the treatment of high-risk and senior patients with benign prostatic hyperplasia and bladder stones. METHODS: A retrospective review was conducted for 68 high-risk and senior patients with benign prostatic hyperplasia and bladder stones. All of them were treated by TUPKEP and suprapubic small cut. RESULTS: Operation was successfully performed in all 68 cases. And there was no instance of transurethral resection syndrome, shock, myocardial infarct, cerebral infarction, cerebral hemorrhage, permanent urinary incontinence or surgical site infection. Seven patients with temporal urinary incontinence recovered at a mean time of (9.48 ± 1.52) days post-operation. The mean operative duration was (48.63 ± 4.14) min and the mean volume of blood loss (50.97 ± 5.33) ml. The changes of maximum flow rate (Qmax), international prostatic symptom score (I-PSS) and quality-of-life (QOL) were statistically significant before and after operation. Qmax increased from (4.56 ± 0.35) to (18.82 ± 1.65) ml/s (P < 0.001), I-PSS decreased form (21.96 ± 1.89) to (11.23 ± 0.86) (P = 0.018) and QOL decreased from (4.94 ± 0.35) to (1.95 ± 0.32) (P = 0.011). CONCLUSION: The approach of TUPKEP and suprapubic small cut is both safe and effective in the treatment of high-risk and senior patient with benign prostatic hyperplasia and bladder stones and should be widely applied.
Subject(s)
Prostatic Hyperplasia/surgery , Transurethral Resection of Prostate/methods , Urinary Bladder Calculi/surgery , Aged, 80 and over , Humans , Male , Prostatic Hyperplasia/complications , Retrospective Studies , Treatment Outcome , Urinary Bladder Calculi/complicationsABSTRACT
Both hepatitis B virus (HBV) and aflatoxin B1 (AFB1) exposure can cause liver damage as well as increase the probability of hepatocellular carcinoma (HCC). To investigate the underlying genetic changes that may influence development of HCC associated with HBV infection and AFB1 exposure, HCC patients were subdivided into 4 groups depending upon HBV and AFB1 exposure status: (HBV(+)/AFB1(+), HBV(+)/AFB1(-), HBV(-)/AFB1(+), HBV(-)/AFB1(-)). Genetic abnormalities and protein expression profiles were analyzed by array-based comparative genomic hybridization and isobaric tagging for quantitation. A total of 573 chromosomal aberrations (CNAs) including 184 increased and 389 decreased were detected in our study population. Twenty-five recurrently altered regions (RARs; chromosomal alterations observed in ≥10 patients) in chromosomes were identified. Loss of 4q13.3-q35.2, 13q12.1-q21.2 and gain of 7q11.2-q35 were observed with a higher frequency in the HBV(+)/AFB1(+), HBV(+)/AFB1(-) and HBV(-)/AFB1(+) groups compared to the HBV(-)/AFB(-) group. Loss of 8p12-p23.2 was associated with high TNM stage tumors (P = 0.038) and was an unfavorable prognostic factor for tumor-free survival (P =0.045). A total of 133 differentially expressed proteins were identified in iTRAQ proteomics analysis, 69 (51.8%) of which mapped within identified RARs. The most common biological processes affected by HBV and AFB1 status in HCC tumorigenesis were detoxification and drug metabolism pathways, antigen processing and anti-apoptosis pathways. Expression of AKR1B10 was increased significantly in the HBV(+)/AFB1(+) and HBV(-)/AFB1(+) groups. A significant correlation between the expression of AKR1B10 mRNA and protein levels as well as AKR1B10 copy number was observered, which suggest that AKR1B10 may play a role in AFB1-related hepatocarcinogenesis. In summary, a number of genetic and gene expression alterations were found to be associated with HBV and AFB1- related HCC. The possible synergistic effects of HBV and AFB1 in hepatocarcinogenesis warrant further investigations.