Risk factor analysis and nomogram construction in patients with distant metastatic prostate cancer at different PSA levels: a study based on the SEER database.

OBJECTIVE: Prostate cancer (PCa) is the most common malignant tumor in the male genitourinary system. Once PCa has metastasized, it is very difficult to cure. The purpose of this study was to investigate the prognostic risk factor analysis of patients with different prostate-specific antigen (PSA) levels in distant metastatic PCa. At the same time, we construct effective models for predicting the survival rate of prostate cancer patients. PATIENTS AND METHODS: Data on prostate cancer patients with the presence of distant metastases were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. PCa patients with distant metastases were categorized into two groups based on PSA levels, one with PSA <20 ng/mL and the other with PSA ≥20 ng/mL. Univariate and multivariate COX regression analyses were used to identify independent factors affecting the prognosis of the patients. A nomogram was constructed using the independent prognostic factors, and the results were evaluated using calibration curves, timeROC curves, and Kaplan-Meier curves. RESULTS: In the PSA <20 ng/mL group, there were a total of 1,832 patients. COX regression analysis showed that age, marital status, N stage, grade, Gleason score, and medical household income inflation were independent prognostic factors for overall survival (OS) in patients. In addition, we found that age, marital status, N stage, bone metastasis, grade, and Gleason score were independent prognostic factors for cancer-specific survival (CSS) in patients. In the PSA ≥20 ng/mL group, there were a total of 5,314 patients. It was found that age, ethnicity, marital status, bone metastasis, first malignant primary indicator, grade, Gleason score, and medical household income inflation were patients' independent prognostic factors for OS. For CSS, we found that age, ethnicity, marital status, T stage, radiotherapy, bone metastasis, Gleason score, and Median household income inflation were independent prognostic factors. Constructing a nomogram can accurately predict the prognosis of this group of patients. CONCLUSIONS: We found different independent prognostic factors for different PSA levels in patients with distant metastatic PCa. A new nomogram was constructed to predict OS and CSS in patients, which helps in clinical-assisted decision-making.

A comprehensive analysis of essential meiotic endonuclease 1 to prognosis and immune infiltration in kidney renal clear cell carcinoma.

OBJECTIVE: Clear cell renal cell carcinoma (ccRCC) is the most common type of cancer, and its molecular pathogenesis is unclear. In this study, we investigated the prognostic value of essential meiotic endonuclease 1 (EME1) in kidney renal clear cell carcinoma (KIRC). MATERIALS AND METHODS: We downloaded the RNA-Seq expression of 526 KIRC tissues and 72 normal tissues from the TCGA database and the corresponding clinical data. The gene expression profiles associated with four clear cell renal cell carcinomas were downloaded from the GEO database for analysis. The expression of EME1 in clear renal cell carcinoma and its correlation with the clinical baseline data were analyzed. Kaplan-Meier survival curve analysis was performed to assess the relationship between EME1 and patient survival. Enrichment analysis was performed to elucidate the possible functions of EME1. We also analyzed the relationship between the EME1 expression and immune infiltration through TIMER2.0 and TISIDB online databases as well as the relationship between EME1 and common immune checkpoints. RESULTS: EME1 was identified as a risk factor for overall survival in clear cell renal cell carcinoma with a hazard ratio of 3.201 (95% confidence interval: 2.430-4.215; p < 0.001). EME1 was highly expressed in KIRC compared to that in normal tissues (p < 0.001) and in the worse TNM stages and late stages (stage 3/4) (p < 0.001). High EME1 expression was strongly associated with the advanced T stage (p = 0.003), advanced N stage (p = 0.002), and advanced M stage (p = 0.006). Research data on KIRC were simultaneously collected and analyzed from the GEO database, including GSE40435, GSE53000, GSE68417, and GSE53757. EME1 predicted the survival status in KIRC patients (AUC = 0.62). We further established a nomogram including the correlation between the high and low EME1 expression, and EME1 was found to contribute to the prediction of the probability of patient survival with a c-index = 0.796. Kaplan-Meier analysis revealed a lower likelihood of survival with a high EME1 expression (p < 0.001). In addition, further bioinformatics analysis suggested that EME1 may be associated with the extent of immune infiltration in KIRC. CONCLUSIONS: An increased expression of EME1 in KIRC is thus associated with advanced clinicopathological features, possibly acting as a potential biomarker of poor prognosis in KIRC.

[The impact of the number of previous miscarriages on embryo euploid rate and pregnancy outcomes in patients with unexplained recurrent pregnancy loss].

Objective: To investigate the impact of the number of previous miscarriages on embryo euploid rate and pregnancy outcomes after preimplantation genetic testing for aneuploidies (PGT-A) in patients with unexplained recurrent pregnancy loss (uRPL). Methods: A retrospective cohort study was conducted. 799 women with uRPL who underwent PGT-A for the first time between January 2015 and December 2021 at the Reproductive center of Shandong University were enrolled. These patients were divided into three groups according to the number of previous miscarriages (2, 3, and≥4). Stratified analysis was conducted according to female age (≤37 years and>37 years). The embryo euploidy rate, good-quality blastocyst formation rate, cumulative live birth rate, and cumulative clinical pregnancy loss rate of three groups were compared in younger and older patients, respectively. Meanwhile, the cumulative live birth rate, clinical pregnancy loss rate, and embryo euploidy rate were analyzed by multivariate logistic regression analysis. Results: Patients' age was (34.7±5.1) years old. In the three groups with 2, 3 and ≥4 previous miscarriages, there was no significant difference in the embryo euploidy rate between groups in the younger [48.9% (539/1 103), 50.6% (354/700) and 52.1% (152/292), P=0.567] and older [26.2% (103/393), 28.8% (55/191) and 20.5% (16/78), P=0.377] age population. Compared with 2 and 3 previous miscarriages, the cumulative live birth rate was significantly decreased [52.6% (153/291), 52.8% (93/176) and 34.3% (25/73), P=0.014] and the cumulative clinical pregnancy loss rate was significantly increased [15.8% (31/196), 15.3% (18/118) and 46.9% (23/49), P<0.001] in younger women with ≥4 miscarriages. After adjusting for maternal age, BMI, AMH, endometrial thickness on hCG trigger day and antral follicle count, the number of previous miscarriages ≥4 was a relevant factor for cumulative live birth rate (OR=0.461, 95%CI: 0.263-0.807, P=0.007) and the cumulative clinical pregnancy loss rate (OR=4.382, 95%CI: 2.165-8.873, P<0.001) in younger patients, but it was not significantly correlated with the cumulative live birth rate, cumulative clinical pregnancy loss rate and embryo euploidy rate in patients with advanced age. Conclusion: In uRPL patients,≥4 previous miscarriages decreased cumulative live birth rate and increased cumulative clinical pregnancy loss rate in women aged≤37 years old.

[Structural characteristics of lower respiratory tract microflora in patients with pneumoconiosis].

Objective: To explore the composition of bacteria in lower respiratory tract of patients with pneumoconiosis and dust exposure, and to compare and analyze the difference and correlation between them. Methods: From May 2020 to January 2021, a prospective multicenter cross-sectional study was conducted to select patients with pneumoconiosis who underwent bronchoalveolar lavage treatment at the Respiratory and Critical Care Medical Department of the 920th Hospital of the Joint Support Force and the Respiratory Department of Tongren Hospital in Kunming, as well as the population of dust recipients. A total of 24 patients with pneumoconiosis (pneumoconiosis group) were included, and 16 dust exposed individuals (dust exposed group) were used as controls. Two groups of patients' alveolar lavage fluid were collected. The 16SrRNA gene V3-V4 sequencing technology and bioinformatics analysis platform were used to measure and analyze the differences in microbial structure composition and associations between bacterial communities. Results: Compared with the dust exposed group, the top 5 bacterial phyla in the alveolar lavage fluid level of patients with pneumoconiosis were the same, followed by Proteobacteria, Firmicutes, Bacteroidetes, Fusobacteria, and Actinobacteria. Compared with the dust exposure group, the pneumoconiosis group patients belong to the top 5 genera of horizontal flora abundance, which are different. The dust exposure group is respectively: Pseudomonas, Proctor, Streptococcus, Achromobacter, and Neisseria. The pneumoconiosis group is respectively: Pseudomonas, Achromobacter, Streptococcus, Ralstonia, and Proctor. The Alpha diversity analysis results showed that compared with the dust exposed group, the level of bacterial diversity in the pneumoconiosis group was difference (P<0.05), and there was no statistically significant difference in bacterial evenness (P>0.05) ; Beta diversity showed differences in microbial community structure between the two groups (P<0.05 ). Single factor microbial association network analysis showed that there was a high correlation between Firmicutes and Bacteroidetes in the pneumoconiosis and dust exposed groups and other species, showing a positive correlation; The correlation between Proteobacteria and other species is high, showing a negative correlation. Conclusion: The structure and relative abundance of bacteria in lower respiratory tract were different between patients with pneumoconiosis and dust exposure, and the diversity of bacteria in lower respiratory tract increased in patients with pneumoconiosis, which may be related to disease status.

MiRNA-616 aggravates the progression of bladder cancer by regulating cell proliferation, migration and apoptosis through downregulating SOX7.

The article "MiRNA-616 aggravates the progression of bladder cancer by regulating cell proliferation, migration and apoptosis through downregulating SOX7, by X. Zhao, D. Li, S.-T. Zhao, Y. Zhang, A. Xu, Y.-Y. Hu, Z. Fang, published in Eur Rev Med Pharmacol Sci 2019; 23 (21): 9304-9312-DOI: 10.26355/eurrev_201911_19423-PMID: 31773697" has been retracted by the authors due to controversial issues in some inconsistencies in the data provided. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19423.

MiRNA-616 aggravates the progression of bladder cancer by regulating cell proliferation, migration and apoptosis through downregulating SOX7.

OBJECTIVE: To investigate the regulatory effect of microRNA-616 (miRNA-616) on cellular behaviors of bladder cancer and the potential mechanism. PATIENTS AND METHODS: The expressions of miRNA-616 and SOX7 in bladder cancer tissues and cell lines were examined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between miRNA-616 and SOX7 was assessed through Dual-Luciferase Reporter Gene Assay. The regulatory effects of miRNA-616 and SOX7 on cellular behaviors of bladder cancer were evaluated through cell counting kit-8 (CCK-8), colony formation, transwell migration assay, and flow cytometry. RESULTS: MiRNA-616 was upregulated, whereas SOX7 was downregulated in bladder cancer tissues and cell lines. The silence of miRNA-616 attenuated the proliferative and migratory abilities, arrested cell cycle progression in the G2 phase, and stimulated apoptosis in UMUC3 and T24 cells. SOX7 was the target gene of miRNA-616, and its level was negatively regulated by miRNA-616. The knockdown of SOX7 enhanced the proliferative and migratory abilities, and attenuated apoptosis of bladder cancer cells. CONCLUSIONS: MiRNA-616 accelerates bladder cancer cells to proliferate and migrate and inhibits apoptosis by downregulating SOX7. MiRNA-616/SOX7 may be potential therapeutic targets for bladder cancer.

[Clinical and genetic analysis of eleven pediatric patients with Alagille syndrome].

Objective: To explore the clinical and molecular genetic features of patients with Alagille syndrome (AS). Methods: The clinical data of eleven pediatric patients, who were suspected to have AS at the Department of Pediatrics in the First Affiliated Hospital of Jinan University from August 2010 to March 2017, were collected and analyzed. Genomic DNA was extracted from peripheral blood leukocytes of the patients and their parents. For 5 patients collected before March 2006, all JAG1 exons and their flanking sequences were directly sequenced. For the remaining 6 patients, high-throughput gene capture technology, chromosomal microarray analysis (CMA) and whole-genome copy-number variant(CNV) analysis were utilized, when necessary, to explore the genetic causes. Results: All patients had cholestasis. However, the γ-glutamyl transpeptidase (GGT) levels in one patient were normal. Nine patients had posterior embryotoxon and facial malformations. Eight patients displayed heart defects. Seven patients presented with vertebral anomalies and among them, 1 patient had sacralization of the cubitus and radius. The condition of nine patients tended to be stabilized on follow-up, but 1 patient died of liver failure in late infancy and 1 got worse. Seven JAG1 variants were detected in 9 out of the 11 AS patients, with c.1977G>A (p.Trp659*) and c.1106_1107delCC (p.Pro369fs) being two novel variants. Two heterozygous interstitial deletions of 3.0 Mb and 9.24 Mb in size, respectively, in chromosome 20 were discovered in the remaining 2 patients. Both deletions involved the entire JAG1 gene. De novo origin was unveiled for the detected variants in 7 patients and interstitial deletions in two. Although the mother of 2 patients carried the relevant variant, she did not demonstrate any clinical features of AS. Conclusions: With cholestasis, posterior embryotoxon, facial malformations, heart defects and vertebral anomalies being the major manifestations, AS demonstrated variable clinical expressivities and incomplete penetrance. This study identified a total of 7 JAG1 variants as well as 2 interstitial deletions involving this gene, and among them, the variants c.1977G>A (p.Trp659* ) and c.1106_1107delCC (p.Pro369fs) as well as the 9.24 Mb chromosomal interstitial deletion had not been reported previously.

Effect of dietary supplementation of Ligustrum lucidum on performance, egg quality and blood biochemical parameters of Hy-Line Brown hens during the late laying period.

The fruit of Ligustrum lucidum (FLL, Nuzhenzi in Chinese) is an important traditional medicine, and have attracted significant research attention because of their various biological activities. However, there are few research reports available on the use of FLL as a feed additive in livestock nutrition, particularly in layers. This study was conducted to determine the effects of supplementation of the diet of laying hens with FLL on laying performance, egg quality and blood metabolites. A total of 360 72-week-old hens were allocated to three dietary treatments (eight replications of 15 hens/treatment group) and were fed either a control diet or a diet supplemented with an inclusion level of 0.25% or 0.50% of FLL powder in the final feed, until 78 weeks of age. Hens were housed in a three-tier cage system. Feed and water were provided ad libitum. Blood samples and eggs were collected at the end of the experiment. The results showed that dietary supplementation with FLL did not affect egg weight, feed conversion ratio, eggshell thickness, albumen height, egg yolk color, eggshell breaking strength or egg shape index. However, FLL supplementation significantly decreased (P<0.001) mortality, cracked-egg rate and blood serum levels of cholesterol, low-density lipoprotein cholesterol, triglycerides and alanine aminotransferase, and increased (P<0.001) blood serum levels of high-density lipoprotein cholesterol. No differences in serum levels of total protein, albumin, glucose, calcium, aspartate aminotransferase or alkaline phosphatase were observed in hens fed FLL compared with the control group. It can be concluded that FLL, at a supplementation level of 0.25% final feed, can be used as an effective feed additive to improve the performance of laying hens during the late laying period.

Significance of platelet distribution width as a severity marker of erectile dysfunction.

Mean platelet volume (MPV) and Platelet distribution width (PDW) are potential markers in platelet activation. In present study, we aimed to evaluate MPV and PDW as potential severity markers for those patients who are complaining erectile dysfunction (ED). A total of 358 participants were enrolled in this study. The whole cohort was asked to complete the International Index of Erectile Function-5 (IIEF-5) questionnaire. The participants were classified into 3 groups: control group (n = 120), mild ED (n = 118) and severe ED (n = 120). We found in our cohort MPV and PDW were significantly higher in both mild ED group and severe ED group than control group (9.24 ± 0.70 and 9.71 ± 0.80 versus 8.56 ± 0.62 for MPV; 14.48 ± 1.29 and 14.98 ± 1.60 versus 12.86 ± 1.13 for PDW respectively). The MPV and PDW increased as the disease progressed. In the mild and severe ED groups, a significant inverse correlation was detected between the mean values of IIEF-5 score and PDW. Furthermore, in the receiver operating characteristic curve analysis, the area under the curve of the MPV and PDW to predict severe ED was 0.818 and 0.848 respectively. Our study establishes a dose-dependent association between the PDW and ED. Therefore, the PDW can serve as a potential marker for predicting the severity of ED.

[A three years longitudinal follow-up study of pulmonary function changes in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the characteristics and the risk factors of pulmonary function in patients with chronic obstructive pulmonary disease (COPD) for a 3 year follow-up. METHODS: Subjects diagnosed as COPD were followed up for 3 years in the Management Center of Chronic Respiratory Disease at XINQIAO Hospital from September 2009 to June 2012.This was a retrospective study. Parameters related to respiratory function mainly first second forced expiratory volume (FEV1), COPD assessment test (CAT), 6 minutes walking distance (6MWD) and acute exacerbation were recorded during follow-up. RESULTS: Although the majority of patients were treated with drugs such as inhaled corticosteroid combined with long-term bronchial dilatation during the three years, FEV1 decreased progressively. The average annual decline of FEV1 was(31.80±61.99)ml, translating into a mean annual decline of(3.74±6.18)%. However, there were significant differences in changes of FEV1. Approximately, FEV1 in 78.3% (47/60) patients decreased, only 21.7%(13/60) patients kept stable FEV1. There was a correlation between decrease of FEV1, FEV1%predicted and the exacerbation (r=0.298, 0.361, 0.273; P<0.05). Logistic regression showed that the positive bronchodilator reversibility and the initial FEV1 were the independent factors associated with significant changes in FEV1 (respectively, OR=5.54, 95%CI 1.55-19.73; OR=8.28, 95%CI 1.42-48.32). CONCLUSION: The changes of pulmonary function in patients with COPD are heterogeneous, although most patients are treated in a standard way. Nearly 80% patients still represent deterioration of pulmonary function. Decline of FEV1 is closely related to the initial pulmonary function and bronchodilator reversibility.

Src controls neuronal migration by regulating the activity of FAK and cofilin.

Migration of postmitotic neurons in the developing cortex along radial glial fiber is essential for the formation of cortical layers. Several neurological diseases are caused by defects in neuronal migration, underlining the importance of this process for brain function. Multiple molecules are involved in this process. However, the precise mechanisms are largely unknown. In the present study, we examined the expression of Src in the developing cortex and investigated the role of Src in neuronal migration and its cellular and molecular mechanisms. Our results showed that Src was strongly expressed in the cerebral cortex during corticogenesis and mainly targeted to the leading processes of migrating neurons. Overexpression of wildtype Src (Src-WT) and its mutants, constitutively active Src (Src-CA) and dominant negative Src (Src-DN) in the mouse brain by in utero electroporation perturbed neuronal migration through affecting the adhesion properties and cytoskeletal dynamics of migrating neurons. Overexpression of Src-WT and Src-CA induced aggregation and branching of migrating neurons, whereas overexpression of Src-DN led to abnormal elongation of the leading processes of migrating neurons. Furthermore, we showed that Src activates the focal adhesion kinase (FAK) and cofilin by regulating their phosphorylation levels. We conclude that Src controls neuronal migration by regulating adhesion properties and F-actin dynamics of migrating neurons.

Evaluation of three different promoters driving gene expression in developing chicken embryo by using in vivo electroporation.

To investigate the variance of exogenous gene expression driven by different promoters by in vivo electroporation, 3 plasmid vectors carrying different promoters were selected, and their driving strength was compared in developing chicken embryos. The 3 promoters included: 1) the CAG promoter (containing the cytomegalovirus (CMV) immediate early enhancer and the chicken ß-actin promoter), 2) the CMV promoter (the human CMV immediate early region enhancer), and 3) the SV40 promoter (Simian virus 40). The intensity of GFP expression driven by the 3 promoters was detected by fluorescence microscopy. The results clearly showed that the expression intensity of the reporter gene differed significantly among the 3 promoters. Chicken ß-actin promoter induced the highest intensity of GFP expression, while SV40 promoter induced the lowest intensity. Our results indicate that plasmids with appropriate promoters should be carefully selected to obtain strong exogenous gene expression by in vivo electroporation.

Expression profile analysis reveals putative prostate cancer-related microRNAs.

Annotation of prostate cancer (PC) genomes provides a foundation for discoveries that can improve the understanding and treatment of the disease. Therefore, in the present study, we used the Student t-test to identify differentially expressed PC-related mRNAs and microRNAs (miRNAs). Then, we performed interrelated mapping of miRNA target genes between abnormally expressed mRNAs and miRNAs, and explored mRNA-target miRNA interrelated pairs to explain the biological functions of miRNA during the progression of PC, thus revealing the occurrence of miRNA-mediated PC. After Gene Set Functional Similarity analysis, we obtained 20 abnormal PC-related candidate miRNAs, including hsa-miR-26a, hsa-miR-152, hsa-miR-19a, hsa-miR-30c, hsa-miR-19b, and hsa-miR-146b-5p, among others. These results suggest that it may be possible to predict the clinical behavior of prostate cancer based on gene expression analysis.

Optimal combination of radiotherapy and endocrine drugs in breast cancer treatment.

PURPOSE: Breast cancer is the most common cancer in women. Radiotherapy is considered a standard treatment option after surgery and adjuvant endocrine therapy is also universally used. Tamoxifen and letrozole are the current first-line endocrine therapy drugs. However, information has been scarce about how best to sequence these therapies to maximize their effectiveness and keep toxic effects to a minimum. In this study, we observed the effect of different sequence combination of radiotherapy and endocrine drugs, tamoxifen or letrozole, to get the best treatment sequence. MATERIALS AND METHODS: The combination effect of radiotherapy and tamoxifen was observed on breast tumour cell line MCF-7, radiotherapy and letrozole on aromatase-expressing breast tumour cell line MCF-7CA. Irradiation was performed with 6Gy, except for doses ranging from 0 to 8Gy for clone formation assay. Tamoxifen or letrozole was added before or after irradiation, respectively. Radiosensitivity was evaluated by clonogenic assay, cell viability by 3-(4,-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. To explore the potential mechanism, cell apoptosis was determined by DNA-binding dye 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) assay, the change of Bcl-2 and Bax expression was by western blot. RESULTS: Although no significant statistical difference was observed between different sequence, tamoxifen and letrozole both increased radiosensitivity. Furthermore, the above inhibitory effect was related with apoptosis signaling pathway, especially Bcl-2 and Bax. CONCLUSION: Taken together, these results suggested that endocrine drugs, such as tamoxifen and letrozole, have potential application with radiotherapy.

Correlation of tumor relapse and elevated expression of survivin and vascular endothelial growth factor in superficial bladder transitional cell carcinoma.

Survivin and vascular endothelial growth factor (VEGF) are newly discovered tumor markers closely correlated with bladder cancer. We analyzed the expression of survivin and VEGF in paraffin-embedded tumor tissues from 78 patients with bladder transitional cell carcinoma (BTCC) using an immunohistochemistry method. Normal bladder mucosae from 10 non-BTCC cases were also included as a control group. All patients were closely followed up for tumor recurrence after undergoing transurethral resection of bladder tumor procedures. The positive expression rates of survivin and VEGF in superficial BTCC were 66.7% (52/78) and 69.2% (54/78), respectively, which were significantly higher than those in the control group, 0% (0/10). A positive correlation was found between survivin and VEGF expression (r = 0.283, P < 0.01). Thirty-two of 78 patients (41.0%) displayed recurrence during follow-up (median: 47; range: 7-62 months). The tumor recurrence rate in survivin(+) patients was 53.8% (28/52), which was significantly higher than that in survivin(-) patients [15.4% (4/26); P < 0.05]. The recurrence rate in VEGF(+)/ VEGF(-) patients was 50.0% (27/54) and 20.8% (5/24), respectively (P < 0.05). The sensitivity for predicting the relapse of superficial BTCC was 87.5% in the survivin(+) group, 84.4% in the VEGF(+) group, and 78.1% in the survivin(+)/VEGF(+) group, and the specificity was 47.8, 41.3, and 65.2%, respectively. Survivin and VEGF interact and jointly regulate the biological behavior of bladder cancer. Our results suggest that overexpression of survivin and VEGF accompany a higher risk of BTCC recurrence, making survivin and VEGF biomarkers for predicting the relapse of bladder cancer.

B- and T-lymphocyte attenuator/herpes virus entry mediator as early indicators for acute rejection following kidney transplantation.

OBJECTIVE: The objective of this study was to investigate the roles of B- and T-lymphocyte attenuator (BTLA) and herpes virus entry mediator (HVEM) in acute and chronic transplant rejection and immune tolerance. METHODS: The expression patterns of BTLA/HVEM, interleukin (IL)-2, IL-4, IL-10, and interferon (IFN)-γ were analyzed among patients presenting with acute rejection episodes versus those maintaining stable renal function during therapy with mycophenolate mofetil (MMF), cyclosporine, or tacrolimus (FK506) plus prednisolone. RESULTS: The expressions of BTLA/HVEM in the rejection group were obviously increased compared with the stable group (P < .05), followed by the elevation of serum levels of IL-2 and IFN-γ. CONCLUSION: The expression levels of BTLA/HVEM can be considered to be early indicators of an acute rejection episode following kidney transplantation.

Y-27632 improves the erectile dysfunction with ageing in SD rats through adjusting the imbalance between nNo and the Rho-kinase pathways.

We investigated whether the effect of Y-27632 to improve the erectile function in SD rats was associated with the degree of the imbalance between nNOS and the Rho-kinase pathways. Western blot analysis was used to evaluate nNOS and Rho-kinase protein expression in 10 young and 10 old SD rats. Imbalance value between nNOS and Rho-kinase protein levels was obtained by subtracting nNOS from Rho-kinase. A 5-V stimulus was given in SD rats before and after the administration of 200 nmol kg(-1) of Y-27632 intracavernosally and ICP/MAP was recorded. The improvement of erectile function induced by Y-27632 was expressed as the margin of ICP/MAP after and before the administration of Y-27632. In young rat group, the contents of nNOS and Rho-kinase protein were 1.7 +/- 0.15 and 1.8 +/- 0.14 respectively. In old rat group, the nNOS protein decreased to 1 +/- 0.15, and in contrast, the Rho-kinase protein increased to 2.6 +/- 0.2. The imbalance value between nNOS and Rho-kinase was 0.2986 +/- 0.1109 and 1.5961 +/- 0.1206 in young and old rat groups. The improvement of erectile function induced by Y-27632 was 0.0500 +/- 0.0294 and 0.3420 +/- 0.660 in young and old rat groups. In all rats, the correlation coefficient between the imbalance value of nNOS and Rho-kinase and the improvement of erectile function was 0.649, P < 0.01. In conclusion, this study suggested that impaired erectile function with ageing in SD rats be associated with the imbalance between nNO and Rho-kinase activity and Y-27632 could improve the erectile function in old SD rats through adjusting this imbalance.

Effect of diabetes and insulin treatment on nitric oxide synthase content in rat corpus cavernosum.

AIM: To study the effect of diabetes mellitus and insulin treatment on rat penile nitric oxide synthase content. METHODS: Male Wistar rats were divided at random into two groups: the Control (n = 8) and the Diabetic (n = 17). Diabetes mellitus was induced by intraperitoneal injection of streptozotocin. The diabetic animals were then randomly divided into two subgroups: diabetic rats without insulin treatment (n = 7) and diabetic rats with insulin treatment (n = 10). The neuronal nitric oxide synthase (nNOS) in the penile corpus cavernosum were assayed by immumohistochemical staining with specific antibody to nNOS and the nNOS-positive nerve fibers were counted semiquantitatively under a high power microscope. RESULTS: The nNOS- positive nerve fibres in diabetic rats with treatment was higher than that in diabetic rats without treatment (P < 0.05) and lower than that in the controls (P < 0. 01). The nNOS-positive nerve fibres in diabetic rat without treatment were also lower than that in the controls (P < 0. 01). CONCLUSION: In streptozotocin-induced diabetic rats, the nNOS content in the penile corpus cavernosum was significantly decreased. Insulin treatment at the dose level employed partially restores the penile nNOS content in these rats.