ABSTRACT
A systematic review and meta-analysis were performed to investigate the efficacy of the AirSeal Valveless Trocar Needle Insufflation System in robot-assisted partial nephrectomy (RAPN). The study compared the differences in perioperative outcomes between the AirSeal insufflation group (AIS) and the conventional insufflation group (CIS). A systematic search of databases such as PubMed, Embase, Cochrane library, and Web of science was performed to identify studies reporting perioperative outcomes between the AirSeal insufflation group (AIS) and the conventional insufflation group (CIS) in RAPN. The study protocol is registered with PROSPERO (CRD42024524335). The primary outcome was to compare the incidence of subcutaneous emphysema (SCE) and postoperative pain scores between the two approaches. The review included four studies with 379 patients, 194 in the AIS group and 185 in the CIS group. Baseline characteristics of the two groups were similar in all outcomes. SCE was significantly lower in the AIS group than in the CIS group [(OR) 0.30 (0.16, 0.54), p < 0.001]. Postoperative 12-h pain scores were also significantly lower in the AIS group compared to the CIS group [(WMD) - 0.93 (- 1.67, - 1.09), p = 0.014]. Both groups showed a significant reduction in length of hospitalization [(WMD) - 0.12 (- 0.84, 0.60), p = 0.746], thermal ischemia time [(WMD) 4.72 (- 5.71, 15.15), p = 0.375], amount of lost hemoglobin [(WMD) - 0.19 (- 0.53, 0.15), p = 0.284], pneumothorax [(OR) 0.13 (0.02,1.10), p = 0.062], mediastinal emphysema [(OR) 0.55 (0.20, 1.46), p = 0.230], and 4-h pain score [(WMD) - 0.25 (- 1.16, 0.65), p = 0.584]; no significant differences were observed. The incidence of subcutaneous emphysema SCE and 12-h pain scores were significantly lower in the AIS group compared to the CIS group. The AirSeal system demonstrated similar efficacy and a higher safety profile than the conventional insufflation system in robotic-assisted partial nephrectomy; however, due to the lack of a randomized study on the topic, further data are needed.
Subject(s)
Insufflation , Nephrectomy , Robotic Surgical Procedures , Robotic Surgical Procedures/methods , Robotic Surgical Procedures/adverse effects , Robotic Surgical Procedures/instrumentation , Humans , Nephrectomy/methods , Nephrectomy/adverse effects , Insufflation/methods , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Subcutaneous Emphysema/etiology , Subcutaneous Emphysema/prevention & control , Treatment Outcome , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Kidney Neoplasms/surgeryABSTRACT
Exploring targets for inhibiting androgen receptor (AR) activity is an effective strategy for suppressing the development of castration-resistant prostate cancer (CRPC). Upregulation of histone demethylase JMJD2A activity is an important factor in increasing AR expression in CRPC. Based on our research, we found that the binding affinity between JMJD2A and AR increases in CRPC, while the level of AR histone methylation decreases and the H3K27ac level increases in the AR enhancer region. Further investigations revealed that overexpression of the histone demethylase JMJD2A increased the binding affinity between JMJD2A and AR, decreased AR histone methylation levels, upregulated H3K27ac in the AR enhancer region, and increased AR activity. Conversely, knocking down JMJD2A effectively reversed these effects. Additionally, in CRPC, JMJD2A expression was upregulated, the tumor-intrinsic immune cGAS-STING signaling pathway was suppressed, the tumor microenvironment was altered, and AR expression was upregulated. However, both knocking down JMJD2A and inhibiting the cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS-STING) signaling pathway reversed these effects. In summary, our study indicates that in CRPC, JMJD2A can directly bind to AR and activate residual AR enhancers through its demethylation activity, thereby promoting AR expression. Furthermore, upregulation of JMJD2A expression inhibits the innate immune cGAS-STING signaling pathway of the tumor, leading to a decrease in antitumor immune function, and further promoting AR expression.
Subject(s)
Gene Expression Regulation, Neoplastic , Jumonji Domain-Containing Histone Demethylases , Membrane Proteins , Nucleotidyltransferases , Prostatic Neoplasms, Castration-Resistant , Receptors, Androgen , Signal Transduction , Male , Humans , Prostatic Neoplasms, Castration-Resistant/genetics , Prostatic Neoplasms, Castration-Resistant/metabolism , Prostatic Neoplasms, Castration-Resistant/pathology , Receptors, Androgen/metabolism , Receptors, Androgen/genetics , Jumonji Domain-Containing Histone Demethylases/metabolism , Jumonji Domain-Containing Histone Demethylases/genetics , Nucleotidyltransferases/metabolism , Nucleotidyltransferases/genetics , Membrane Proteins/metabolism , Membrane Proteins/genetics , Animals , Cell Line, Tumor , Mice , Enhancer Elements, Genetic , Tumor Microenvironment , Cell ProliferationABSTRACT
The study aims to synthesize all available prospective comparative studies and reports the latest systematic analysis and updated evidence comparing robot-assisted radical prostatectomy (RARP) with open radical prostatectomy (ORP) for perioperative, functional, and oncological outcomes in patients with clinically localized prostate cancer (PCa). PubMed, Embase, Web of Science, and the Cochrane Library were retrieved up to March 2023. Only randomized controlled trials (RCTs) and prospective comparative studies were included, and weighted mean differences (WMD) and odds ratios (OR) were used to evaluate the pooled results. Twenty-one articles were included in the present meta-analysis. The results indicated that compared to ORP, RARP had longer operative time (OT) (WMD: 51.41 min; 95%CI: 28.33, 74.48; p < 0.0001), reduced blood loss (WMD: -516.59 mL; 95%CI: -578.31, -454.88; p < 0.00001), decreased transfusion rate (OR: 0.23; 95%CI: 0.18, 0.30; p < 0.00001), shorter hospital stay (WMD: -1.59 days; 95%CI: -2.69, -0.49; p = 0.005), fewer overall complications (OR: 0.61; 95%CI: 0.45, 0.83; p = 0.001), and higher nerve sparing rate (OR: 1.64; 95%CI: 1.26, 2.13; p = 0.0003), as well as was more beneficial to postoperative erectile function recovery and biochemical recurrence (BCR). However, no significant disparities were noted in major complications, postoperative urinary continence recovery, or positive surgical margin (PSM) rates. RARP was superior to ORP in terms of hospital stay, blood loss, transfusion rate, complications, nerve sparing, postoperative erectile function recovery, and BCR. It is a safe and effective surgical approach to the treatment of clinically localized PCa.
Subject(s)
Erectile Dysfunction , Prostatic Neoplasms , Robotic Surgical Procedures , Robotics , Male , Humans , Erectile Dysfunction/etiology , Prospective Studies , Treatment Outcome , Robotic Surgical Procedures/methods , Prostatectomy/adverse effects , Prostatectomy/methods , Prostatic Neoplasms/surgeryABSTRACT
Purpose: Added sugar is associated with a variety of adverse health outcomes, but its association with kidney stones is unclear. This study was to determine whether added sugar is associated with kidney stones. Materials and methods: This nationally representative study used National Health and Nutrition Examination Survey (NHANES) datasets from 2007 to 2018 for analysis. People aged ≥20 years who reported a history of kidney stones and provided dietary recall data on added sugars were included. Weighted proportions, multivariable logistic regression analysis and stratified logistic regression were used to evaluate the associations between added sugars and kidney stones by adjusting potential confounders. Results: Totally 28,303 adults were included, with weighted mean age [95% confidence interval (CI)] of 48.03 (47.56, 48.51) years, 47.74% (47.09, 48.40%) males and 52.26% (51.60, 52.91%) females. The overall mean (95% CI) energy intake from added sugars was 272.10 (266.59, 277.60) kilocalories. In the fully-adjusted multivariable model, the percentage of energy intake from added sugars was positively correlated with kidney stones. Compared to the first quartile of added sugar energy intake percentage, the population in the fourth quartile had a higher prevalence of kidney stones (OR = 1.39; 95% CI 1.17 to 1.65). Compared with the less than 5% calories from added sugar population, the more than or equal to 25% calories from added sugar had a higher kidney stone prevalence (OR = 1.88; 95% CI 1.52 to 2.32). Conclusion: A higher percentage of energy intake from added sugars is significantly associated with a higher prevalence of kidney stones. This study provides cross-sectional evidence for the relationship between added sugars and health outcomes.
ABSTRACT
BACKGROUND: To investigate underlying mechanism of JMJD2A in regulating cytoskeleton remodeling in castration-resistant prostate cancer (CRPC) resistant to docetaxel. METHODS: Tissue samples from CRPC patients were collected, and the expression of JMJD2A, miR-34a and cytoskeleton remodeling-related proteins were evaluated by qPCR, western blot and immunohistochemistry, and pathological changes were observed by H&E staining. Further, JMJD2A, STMN1 and TUBB3 were knocked down using shRNA in CRPC cell lines, and cell viability, apoptosis and western blot assays were performed. The interaction between miR-34a/STMN1/ß3-Tubulin was analyzed with dual-luciferase reporter and co-immunoprecipitation assays. RESULTS: In clinical experiment, the CRPC-resistant group showed higher expression of JMJD2A, STMN1, α-Tubulin, ß-Tubulin and F-actin, and lower expression of miR-34a and ß3-Tubulin compared to the sensitive group. In vitro experiments showed that JMJD2A could regulate cytoskeletal remodeling through the miR-34a/STMN1/ß3-Tubulin axis. The expression of miR-34a was elevated after knocking down JMJD2A, and miR-34a targeted STMN1. The overexpression of miR-34a was associated with a decreased expression of STMN1 and elevated expression of ß3-Tubulin, which led to the disruption of the microtubule network, decreased cancer cell proliferation, cell cycle arrest in the G0/G1 phase, and increased apoptosis. CONCLUSION: JMJD2A promoted docetaxel resistance in prostate cancer cells by regulating cytoskeleton remodeling through the miR-34a/STMN1/ß3-Tubulin axis.
Subject(s)
Jumonji Domain-Containing Histone Demethylases , Prostatic Neoplasms, Castration-Resistant , Humans , Male , Apoptosis/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Docetaxel/pharmacology , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , MicroRNAs/metabolism , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/genetics , Tubulin/genetics , Tubulin/metabolism , Jumonji Domain-Containing Histone Demethylases/metabolismABSTRACT
OBJECTIVE: The long-term effect of extracorporeal shock wave lithotripsy (SWL) is still controversial. A previous meta-analysis showed no association between new-onset hypertension and entire upper urinary urolithiasis after SWL. Recently, there have been some reports on this topic. Therefore, we aimed to examine the association between new-onset hypertension and nephrolithiasis after SWL therapy. METHODS: Embase, the Cochrane Central Search Library, and PubMed were used to search for reports on new-onset hypertension and patients with nephrolithiasis after SWL. A meta-analysis of the association between new-onset hypertension and nephrolithiasis after SWL was carried out. The data of relevant research were synthesized and the relative risk was computed. RESULTS: Seven eligible studies were included in our meta-analysis. There was a significant association between nephrolithiasis after SWL and new-onset hypertension. The overall relative risk with a 95% confidence interval was 1.21 (1.11-1.31) in a fixed-effects model. CONCLUSION: Our meta-analysis suggests an association between new-onset hypertension and patients with nephrolithiasis after SWL, which is in contrast with the finding of a previous meta-analysis.
Subject(s)
Hypertension , Kidney Calculi , Lithotripsy , Urolithiasis , Humans , Hypertension/etiology , Kidney Calculi/etiology , Kidney Calculi/therapy , Lithotripsy/adverse effects , Urolithiasis/etiologyABSTRACT
This study aims to investigate the possible association between Interleukin-31 (IL-31) gene polymorphisms and cryptorchidism risk.Two single nucleotide polymorphisms of IL-31, rs7977932 (C/G) and rs4758680 (C/A), were selected to be investigated in this study. Polymerase chain reaction-restriction fragment length polymorphism methods were used to discriminate the selected single nucleotide polymorphisms of IL-31 gene. A hospital-based case-control study of 112 cryptorchidism patients and 425 healthy controls was conducted.The frequencies of the C allele of rs4758680 in the patients with cryptorchidism were significantly higher compared with those in controls (89% vs 83%, Pâ=â.02, ORâ=â0.58, 95% CIâ=â0. 37-0.92). Compared with CC genotype in dominant model, notable decreased frequencies of A carriers (CA/AA genotypes) were observed in cryptorchidism patients (Pâ=â. 03, ORâ=â0.58, 95% CIâ=â0.35-0.96).Results demonstrated that IL-31 gene polymorphisms were associated with the genetic susceptibility to cryptorchidism in a Chinese population. Compared with CC genotype, the A carriers (CA/AA genotypes) of rs4758680 were protect factors in cryptorchidism susceptibility.
Subject(s)
Cryptorchidism/genetics , Genetic Predisposition to Disease/genetics , Interleukins/genetics , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide , Asian People/genetics , Case-Control Studies , Child , Child, Preschool , China , Gene Frequency , Genotype , Humans , Male , Polymerase Chain Reaction , Risk FactorsABSTRACT
Heat shock protein 70 (HSP70) was a highly conserved protein which was significantly induced in response to cellular stresses. HSP70 played an important role in the pathogenesis of cancer which stabilized the production of large amount of oncogenic proteins and finally supported growth and survival of tumor. However, there was no report about the diagnosis of circulating HSP70 in lung cancer patients. In this study, a total of 297 participants (lung cancer: 197, healthy control: 100) were enrolled in the detection of circulating HSP70 level in plasma by ELISA assay. The results indicated that circulating HSP70 significantly decreased in lung cancer patients compared to healthy controls (P < 0.0001). Receiver operating characteristic (ROC) analysis showed that HSP70 (AUC: 82.2%, SN: 74.1%, SP: 80.0%) had higher diagnosis value than clinical existing biomarkers CEA (AUC: 80.1%, SN: 76.8%, SP: 67.3%) and CA 19-9 (AUC: 63.7%, SN: 64.2%, SP: 54.0%). In the analysis of early lung cancer patients, ROC results also revealed that HSP70 (AUC: 83.8%, SN: 71.2%, SP: 84.0%) have higher sensitivity, specificity, and AUC than CEA (AUC: 73.7%, SN: 73.2%, SP: 69.1%) and CA 19-9 (AUC: 61.5%, SN: 69.4%, SP: 53.4%). In analysis of specific histological classifications, HSP70 showed more valuable in the diagnosis of SCC (AUC: 85.9%, SN: 86.1.9%, SP: 81.0%) than ADC (AUC: 81.0%, SN: 69.1%, SP: 81.0%). Combined analysis of HSP70 and existing biomarker: CEA and CA 19-9 exhibited that HSP70 combined CEA and CA 19-9 showed the highest AUC (0.945, 95% CI, 0.855-1.000). The importance of our results was that we found decreased circulating HSP70, in combination with elevated CEA and CA 19-9, could be utilized in the diagnosis of early (stage I and II) lung cancer.
Subject(s)
Biomarkers, Tumor/blood , HSP70 Heat-Shock Proteins/blood , Lung Neoplasms/blood , Lung Neoplasms/pathology , Adenocarcinoma of Lung/blood , Adenocarcinoma of Lung/diagnosis , Adenocarcinoma of Lung/pathology , Adult , Aged , Area Under Curve , Case-Control Studies , Early Detection of Cancer , Enzyme-Linked Immunosorbent Assay , Female , Humans , Lung Neoplasms/diagnosis , Male , Middle Aged , Neoplasms, Squamous Cell/blood , Neoplasms, Squamous Cell/diagnosis , Neoplasms, Squamous Cell/pathology , ROC Curve , Sensitivity and SpecificityABSTRACT
Interleukin-31 is a crucial cytokine triggering inflammation which could be one of the risk factors of tumors. However, data for correlation between IL-31 and tumors are limited. The purpose of our study was to discuss whether genetic polymorphisms of IL-31 were associated with the susceptibility and clinical outcomes of bladder cancer. Our study enrolled 478 controls, 156 non-muscle-invasive bladder cancer (NMIBC) and 138 muscle-invasive bladder cancer (MIBC) patients. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping two single nucleotide polymorphisms (SNPs) of IL-31 gene including rs7977932 and rs4758680. Our results showed that A allele and CA/AA genotypes of rs4758680 were associated with susceptibility to bladder cancer (P = 0.04, OR 1.32, 95% CI 1.01-1.72, and P = 0.02, OR 1.43, 95% CI 1.05-1.96, respectively), and G allele of rs7977932 might be a protect factor for tobacco smoking patients compared with non-smoking patients (P = 0.005, OR 0.42, 95% CI 0.23-0.76). Furthermore, CA/AA genotypes of rs4758680 might be the independent risk factors for the decreased recurrence-free survival of the patients with MIBC (P = 0.03, OR 2.02, 95% CI 1.06-3.85. Our data indicated that polymorphisms of IL-31 are associated with bladder cancer, and rs4758680 could be an independent prediction for MIBC patients with a high risk of recurrence.
Subject(s)
Interleukins/genetics , Polymorphism, Single Nucleotide , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/mortality , Aged , Case-Control Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Prognosis , Urinary Bladder Neoplasms/pathologyABSTRACT
OBJECTIVES: To provide a systematic review and meta-analysis of studies comparing ureterolithotripsy (URS) with percutaneous nephrolithotripsy (PCNL) or laparoscopic ureterolithotomy (LU) techniques for the management of large proximal ureteral stones (diameter greater than 10 mm). METHODS: A literature search was performed using PubMed, EMBASE, EBSCO, Web of Science, and Cochrane Library to identify suitable studies until November 2016. We used weighted mean difference to measure operative time and hospital stay, OR to measure stone free rate (SFR), and complication rate. Subgroup analyses were assessed for heterogeneity. RESULTS: Fourteen publications strictly met our eligibility criteria of which 7 were randomized control studies (RCTs) and 7 non-RCTs. Meta-analysis of extractable data showed that LU and PCNL had higher SFR than URS. URS led to a similar hospital stay like that of LU. However, it had a shorter operative time and lower complication rate than LU. When we compared URS with PCNL, we found a shorter hospital stay in the URS group. However, there was no significant difference in terms of the operative time and complication rate between URS and PCNL. CONCLUSION: URS should be considered standard therapy for treating large proximal ureteral stones.
Subject(s)
Hysteroscopy/methods , Laparoscopy/methods , Lithotripsy/methods , Nephrolithotomy, Percutaneous/methods , Ureteral Calculi/surgery , Chi-Square Distribution , Humans , Hysteroscopy/adverse effects , Laparoscopy/adverse effects , Length of Stay , Lithotripsy/adverse effects , Nephrolithotomy, Percutaneous/adverse effects , Odds Ratio , Operative Time , Postoperative Complications/etiology , Risk Factors , Treatment Outcome , Ureteral Calculi/diagnostic imagingABSTRACT
BACKGROUND: Interleukin-27 (IL-27) has been recognized as a pleiotropic cytokine with both pro- and anti-inflammatory properties. Few studies have investigated polymorphisms and serum/plasma levels of IL-27 in diseases including cancers. This study has analyzed the associations of IL-27 gene polymorphisms, as well as plasma levels of IL-27, with susceptibility to bladder cancer and clinical outcome. METHODS: Three hundred and thirty-two patients (nonmuscle-invasive bladder cancer (NMIBC)/muscle-invasive bladder cancer (MIBC): 176/156) included in a 60-month follow-up program and 499 controls were enrolled. Two single nucleotide polymorphisms (SNPs), rs153109 and rs17855750, were genotyped by polymerase chain reaction (PCR) -restriction fragment length polymorphism (RFLP) method. Plasma concentration of IL-27 was determined by ELISA in 124 patients (NMIBC/MIBC: 50/74) and 151 controls. RESULTS: Significantly increased risk for bladder cancer was associated with AG/GG genotypes of rs153109 (P = 0.029). No GG genotype of rs17855750 was observed in controls, while 4 patients were found to be GG homozygotes, suggesting GG genotype may be associated with bladder cancer risk (P = 0.006). For bladder cancer patients, SNP rs17855750 was also associated with increased risk for MIBC. For MIBC patients, but not NMIBC, TG/GG genotypes of rs17855750 turned out to be a protective factor for overall survival (P = 0.035). Significantly reduced plasma levels of IL-27 were observed in both NMIBC and MIBC patients compared with controls (P < 0.0001). CONCLUSION: Our data suggest that polymorphisms and reduced plasma levels of IL-27 may predict the susceptibility to bladder cancer, and rs17855750 may be a useful marker to distinguish patients with high risk of death.
Subject(s)
Genetic Predisposition to Disease , Interleukin-27/blood , Interleukin-27/genetics , Polymorphism, Single Nucleotide , Urinary Bladder Neoplasms/blood , Urinary Bladder Neoplasms/genetics , Aged , Alleles , Case-Control Studies , Female , Follow-Up Studies , Gene Frequency , Genotype , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Patient Outcome Assessment , Prognosis , Risk Factors , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathologyABSTRACT
BACKGROUND: Cryptorchidism is one of the most common congenital anomalies in newborn boys. Although the mechanism responsible for the pathophysiology of cryptorchidism has not yet been well addressed, the Wnt signaling pathway has been involved in the development of cryptorchidism. Axin1 is a central component of the Wnt signaling pathway and may play a critical role in the development of cryptorchidism. OBJECTIVE: We assumed that cryptorchidism risk and the AXIN1 gene may have an association. Thus we picked out three tag SNPs (single nucleotide polymorphisms) in the AXIN1 gene and aimed to investigate whether cryptorchidism risk is associated with polymorphisms in the AXIN1 gene. STUDY DESIGN: The variants were discriminated using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) methods. A total of 113 cases and 179 controls were recruited to participate in this study, including 92 unilateral cryptorchidism and 21 bilateral cases. In bilateral cases, the position of the testis was decided by the higher one. RESULTS: A significantly increased cryptorchidism risk was found to be associated with both the T allele (p = 2e(-4), OR 1.96, 95% CI 1.37-2.78) and T/T genotype (p = 6e(-4), OR 4.00, 95% CI 1.79-9.09) of rs370681 polymorphism, and, compared with the C/C genotype, a significantly increased cryptorchidism risk was associated with the C/T-T/T genotype (p = 4e(-4), OR 2.44, 95% CI 1.47-4.00) of rs370681 polymorphisms. DISCUSSION: Among the three tag SNPs we have chosen in AXIN1, two SNPs are located in the intron region, the other SNP is located in the synonymous codon region. Evidential research has indicated that introns and other non-protein-coding RNAs may have evolved to function as network control molecules in higher organisms. Therefore, we suspected that the tag SNPs may work as controls influencing the conduct of other genes rather than affecting the structure of the protein by influencing the coding of amino acid. There were limitations in our study. One is that we did not test the expression level of Axin1. Secondly, the number of the study subjects is limited. Finally, the molecular mechanisms by which AXIN1 is involved in susceptibility to cryptorchidism should be characterized. CONCLUSIONS: We assessed the impact of the genetic variability of the AXIN1 gene on cryptorchidism. We have offered primary evidence that the T allele and T/T genotype of rs370681 polymorphisms and C/T genotype of rs1805105 polymorphisms in AXIN1 gene are more frequent in patients with cryptorchidism.
Subject(s)
Asian People/genetics , Axin Protein/genetics , Cryptorchidism/genetics , Genetic Predisposition to Disease/genetics , Polymorphism, Single Nucleotide/genetics , Case-Control Studies , Child , Child, Preschool , China , Humans , Infant , Infant, Newborn , MaleABSTRACT
Programmed cell death 6 (PDCD6) has recently been found dysregulated in tumors of various origin. The aim of this study is to explore the association between PDCD6 genetic polymorphisms and susceptibility to bladder cancer and survival of patients with bladder cancer. Two tag SNPs of PDCD6, rs3756712 and rs4957014, were genotyped in 332 patients with bladder cancer and 509 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and correlated with patients' survival. The frequencies of G allele and GG genotype of rs3756712 in patients were significantly lower than that of controls (P = 0.001, odds ratio [OR] = 0.68 for G allele; P = 0.024, OR = 0.53 for GG genotype in the recessive genetic model, respectively). The GT genotype of rs4957014 was associated with decreased susceptibility to bladder cancer in the overdominant genetic model (P = 0.023, OR = 0.72). Kaplan-Meier curves revealed a significant higher risk for death in superficial bladder cancer patients harboring GG homozygous of rs3756712 (P < 0.001), and an increased risk for recurrence in invasive bladder cancer patients carrying GT heterozygous of rs4957014 (P = 0.04). Multiple Cox regression analysis identified rs3756712 GG genotype as an independent prognostic factor for death in superficial bladder cancer patients (hazard ratio [HR] = 5.11, P = 0.01), and rs4957014 GT genotype as an independent prognostic factor for recurrence in invasive bladder cancer patients (HR = 1.93, P = 0.03). PDCD6 may represent a biomarker candidate gene that could help to identify a group of patients at high risk for recurrence and death.
Subject(s)
Apoptosis Regulatory Proteins/genetics , Calcium-Binding Proteins/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Urinary Bladder Neoplasms/genetics , Adult , Aged , Case-Control Studies , Female , Gene Frequency , Genotype , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Prognosis , Proportional Hazards ModelsABSTRACT
To assess whether polymorphisms of the interleukin-23 receptor (IL23R) gene are associated with bladder transitional cell carcinoma because chronic inflammation contributes to bladder cancer and the IL23R is known to be critically involved in the carcinogenesis of various malignant tumors. 226 patients with bladder cancer and 270 age-matched controls were involved in the study. Polymerase chain reaction-restriction fragment length polymorphism was used for genotyping. Genotype distribution and allelic frequencies between patients and controls were compared. In all three single nucleotide polymorphisms of IL23R studied, the distribution of genotype and allele frequencies of rs10889677 differed significantly between patients and controls. The frequency of allele C of rs10889677 was significantly increased in cases compared with controls (0.2898 vs. 0.1833, odds ratio 1.818, 95 % confidence interval 1.349-2.449). The result indicates that IL23R may play an important role in the susceptibility of bladder cancer in Chinese population.
Subject(s)
Asian People/genetics , Carcinoma, Transitional Cell/genetics , Genetic Predisposition to Disease/genetics , Polymorphism, Single Nucleotide , Receptors, Interleukin/genetics , Urinary Bladder Neoplasms/genetics , Aged , Female , Genotype , Humans , Male , Middle Aged , Polymorphism, Restriction Fragment Length , Reverse Transcriptase Polymerase Chain Reaction , Risk FactorsABSTRACT
OBJECTIVE: To validate the therapeutic efficacy of paroxetine in the treatment of premature ejaculation (PE). METHODS: Eighty PE patients up to the inclusion criteria were equally randomized to an experimental and a control group. We observed all the patients for 4 weeks and recorded the baseline data on intravaginal ejaculatory latency time (IELT) and sexual satisfaction scores, followed by oral medication of paroxetine at 20 mg/d for the patients in the experimental group and placebo for the controls. Thirty days after the treatment, we again recorded IELT and sexual satisfaction scores of the patients. RESULTS: After the treatment, the experimental group showed significantly prolonged IELT ([5.75 +/- 1.24] min) and increased sexual satisfaction score (6.4 +/- 1.2) as compared with the baseline data ([0.89 +/- 0.21] min and [2.7 +/- 0.9]) (P < 0.01). The control group exhibited no significant differences before and after the medication either in the mean IELT or in sexual satisfaction scores ([1.06 +/- 0.28] min vs [0.97 +/- 0.18] min and 3.6 +/- 1.3 vs 3.1 +/- 1.1, P > 0.05). CONCLUSION: Oral medication of paroxetine at 20 mg/d for 30 days could improve IELT and sexual satisfaction in PE patients.
Subject(s)
Paroxetine/therapeutic use , Selective Serotonin Reuptake Inhibitors/therapeutic use , Sexual Dysfunction, Physiological/drug therapy , Adult , Ejaculation , Humans , Male , Treatment Outcome , Young AdultABSTRACT
The evolutionarily conserved Six1-Eya1 transcription complex is central to mammalian organogenesis, and deletion of these genes in mice results in developmental anomalies of multiple organs that recapitulate human branchio-oto-renal (BOR) and DiGeorge syndromes. Here, we report that both Six1 and Eya1 are strongly expressed in the peri-cloacal mesenchyme (PCM) surrounding the cloaca, the terminal end of hindgut dilation. Six1 and Eya1 are absent from the intra-cloacal mesenchyme (ICM), a cell mass that divides the cloaca into dorsal hindgut and ventral urogenital sinus. Deletion of either or both Six1 and Eya1 genes results in a spectrum of genitourinary tract defects including persistent cloaca - hypoplastic perineum tissue between external urogenital and anorectal tracts; hypospadias - ectopic ventral positioning of the urethral orifice; and hypoplastic genitalia. Analyses of critical signaling molecules indicate normal expression of Shh in the cloaca and cloaca-derived endodermal epithelia. Using a Cre/loxP genetic fate mapping strategy, we demonstrate that Six1-positive PCM progenitors give rise to the most caudal structures of the body plan including the urogenital and anorectal complex, and the perineum region. Thus, Six1 and Eya1 are key regulators of both upper and lower urinary tract morphogenesis. Results from this study uncover essential roles of the PCM progenitors during genitourinary tract formation.
Subject(s)
Cloaca/embryology , Cloaca/metabolism , Homeodomain Proteins/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Nuclear Proteins/metabolism , Protein Tyrosine Phosphatases/metabolism , Urogenital System/embryology , Urogenital System/metabolism , Animals , Body Patterning , Bone Morphogenetic Proteins/genetics , Bone Morphogenetic Proteins/metabolism , Cell Proliferation , Cell Survival , Embryonic Stem Cells/cytology , Embryonic Stem Cells/metabolism , Female , Gene Expression Regulation, Developmental , Homeodomain Proteins/genetics , Humans , Intracellular Signaling Peptides and Proteins/deficiency , Intracellular Signaling Peptides and Proteins/genetics , Male , Mesoderm/cytology , Mesoderm/embryology , Mesoderm/metabolism , Mice , Mice, Knockout , Mice, Mutant Strains , Mice, Transgenic , Models, Biological , Nuclear Proteins/deficiency , Nuclear Proteins/genetics , Pregnancy , Protein Tyrosine Phosphatases/deficiency , Protein Tyrosine Phosphatases/genetics , Signal Transduction , Urogenital Abnormalities/embryology , Urogenital Abnormalities/genetics , Urogenital Abnormalities/metabolismABSTRACT
PURPOSE: There is increasing evidence that ischemic postconditioning may noticeably attenuate renal ischemic-reperfusion injury, although the specific mechanisms are not fully clear. We examined the role of the complement system, especially membrane bound complement regulatory proteins, in postconditioning after renal ischemic-reperfusion injury in a right nephrectomy rat model. MATERIALS AND METHODS: After right nephrectomy the left renal pedicles were occluded for 60 minutes, followed by 24-hour reperfusion. Postconditioning was induced by 6 cycles of 10-second ischemia and 10-second reperfusion before reperfusion. After 24-hour reperfusion without a control blood samples were obtained via the vena cava. Renal samples were also obtained. DAF, CD46, CD59, C3aR and C5aR mRNA and protein expression was examined by reverse transcriptase-polymerase chain reaction, Western blot and immunohistochemistry. C3/C9 deposition in tissue was detected by immunofluorescence. Renal function, histology and cellular apoptosis were also observed. RESULTS: In renal tissue postconditioning prevents DAF down-regulation, which is induced by ischemic-reperfusion injury. It results in the decreased renal necrosis caused by ischemic-reperfusion injury mediated complement activation. However, in all experimental groups renal CD46/CD59 expression was not altered. Increased DAF expression due to postconditioning may decrease C5aR expression in renal tissues compared with ischemic-reperfusion injury, which can decrease apoptosis. C3aR expression did not differ among the experimental groups. CONCLUSIONS: These findings provide new evidence that postconditioning protects kidneys from ischemic-reperfusion injury, at least in part, by preventing DAF down-regulation.
Subject(s)
CD55 Antigens/physiology , Down-Regulation , Kidney/blood supply , Reperfusion Injury/prevention & control , Animals , Male , Rats , Rats, WistarABSTRACT
Recently, a functional insertion/deletion polymorphism (-94 insertion/deletion ATTG) in the promoter of NFKB1 gene, which encodes the p50 subunit of nuclear factor-kappaB protein complex, was identified. The aim of this study was to explore the association between this polymorphism and bladder cancer in a Chinese population. The NFKB1 polymorphism was assessed in 207 patients with superficial transitional cell carcinomas in bladder and in 228 age-, sex-, and smoking-matched healthy volunteers. The polymerase chain reaction assay was used to determine the NFKB1 genotypes. Genomic DNA used for the assay was extracted from peripheral blood lymphocytes. This study found that the frequency of ATTG(2) allele in bladder cancer patients was significantly higher than that in control subjects (65.2% vs. 56.1%, p = 0.006, odds ratio = 1.465), suggesting that the functional NFKB1 promoter polymorphism is associated with increased risk for superficial transitional cell carcinoma of the bladder.
Subject(s)
Carcinoma/genetics , Genetic Predisposition to Disease , INDEL Mutation , NF-kappa B p50 Subunit/genetics , Urinary Bladder Neoplasms/genetics , Adult , Aged , Asian People/genetics , China , Female , Humans , Male , Middle Aged , Polymorphism, Genetic , Promoter Regions, Genetic/geneticsABSTRACT
OBJECTIVE: To investigate the effects of ischemic postconditioning(IPo) on cellular apoptosis in acute renal ischemic-reperfusion injury (IRI) in rats. METHODS: Model of acute renal ischemic-reperfusion injury (IRI) was constructed using Wistar rats. Forty healthy male rats were divided into 4 groups randomly,including group C,group IRI, group IPo and group Ado. Rats of group C received right nephronectomy and separation of left renal vessels. Before reperfusion, group IPo was perfused for 10 s, following ischemic reperfusion for another 10 s with 6 cycles. Group Ado was infused with adenosine intravenously 10 min before ischemia. Cellular apoptosis was determined with TUNEL (TdT-mediated dUTP Nick End Labelling), flowcytometry and histopathological staining. RESULTS: Compared with group C, the apoptotic index increased predominatly in group IRI (P<0.05), whereas, apoptosis index decreased obviousely in group IPo, Ado (P<0.05). In addition, the apoptosis index between group IPo and Ado was not statistically different. CONCLUSION: Ischemic postconditioning could decrease cellular apoptosis induced by IRI in rat kidney.
Subject(s)
Apoptosis/physiology , Ischemic Preconditioning , Kidney/blood supply , Kidney/pathology , Reperfusion Injury/prevention & control , Animals , Male , Random Allocation , Rats , Rats, WistarABSTRACT
OBJECTIVE: To investigate the transfection and expression of nm23-H1 gene in human bladder cancer cell line T-24, and to find out whether nm23-H1 could affect the metastases ability and the chemotherapeutic sensitivity of T-24 cell line. METHODS: By electroporation way, the pCMV-Bam-neo-nm23-H1 plasmid was transferred into bladder cancer line T-24, and the nm23-H1 vector-producer cell line T-24/nm23-H1 was isolated with G418 selection. The expression of nm23-H1 gene q,as detected by immunohistochemistry. The T-24 invasion, adherence and migration abilities between transfected and non-transfected cell lines were detected by transwell-room and wash techniques. The difference or change to the sensitivity of chemotherapeutic drug before and after cell transfected was evaluated by MTT. RESULTS: The stable expression of nm23-H1 was obtained by pCMV-Bam-Neo system with G418. The expression of nucleoside diphosphate kinase-A (NDPKA) was observed for significant difference between transfected and non-transfected T-24 cell lines; The invasive, adherence and migration abilities of transfected T-24 cells were decreased more than those of non-transfected T-24 (P < 0. 05); The chemo-sensitivity of transfected T-24 line cells to cis-diamminedichloroplatinum (CDDP) increased significantly. CONCLUSION: nm23-H1 gene can inhibit the metastasis of T-24 cell line and increase the chemo-sensitivity of T-24 cell line to CDDP significantly.