[Study on protective effects and mechanisms of total glucosides of Paeony on Graves disease in BALB/c mice].

Objective: To investigate the protective effect and its immunoregulatory mechanism of Total Glucosides of Paeony (TGP) against Graves' Disease (GD) model on BALB/c mice. Methods: Fifty female (6 weeks old, weighing 16-18 g) BALB/c mice of specific pathogen free were divided into control group according to random number table method, model group, early low-dose TGP intervention group (250 mg·kg-1·d-1), early high-dose TGP intervention group (500 mg·kg-1·d-1), and late TGP intervention group, with 10 mice in each group. Except the control group, the other 4 groups were immunized 3 times (0, 3rd, and 6th week) with recombinant adenovirus expressing the thyroid stimulating hormone receptor (TSHR) A subunit to establish the GD model. The early low-dose and high-dose intervention group were given diets containing different doses of TGP throughout the whole process, and the late intervention group was given diets containing low doses of TGP from the 1st week after the 2nd immunization (week 4). The levels of thyrotropin receptor antibody (TRAb) and total thyroxine (TT4) were detected in the tail venous blood of mice at the 4th week. At the 10th week, the serum TRAb and TT4 levels and the ratio of regulatory T cells (Treg) in each group were detected, and the pathological changes of thyroid tissue were observed. Serum helper T cell 1(Th1) and Th2 cell-related factors interleukin-2 (IL-2), IL-4, IL-5, IL-10, IL-12p70, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ) and tumor necrosis factors-α (TNF-α) were detected to investigate the protective effect of TGP on GD model in BALB/c mice and its mechanism. Results: At the 4th week, The level of TT4 [(55.07±12.89) µg/L] in early high-dose intervention group was lower than that in model group [(74.33±8.63) µg/L] (all P<0.05). The level of TT4 in early low-dose intervention group and late intervention group and model group had no statistical significance (all P>0.05). TRAb level of mice between early low-dose, early high-dose, late intervention groups and model group was no significant difference (all P>0.05). At the 10th week, TRAb [(90.00±26.89) U/L] and TT4[(32.66±8.11) µg/L] levels in the early high-dose intervention group were lower than those in the model group [(396.97±95.35) U/L, (73.70±16.33) µg/L] (all P<0.05). The TRAb and TT4 levels in the early low-dose intervention group and late intervention group were not significantly different from those in the model group (all P>0.05). The thyroid tissue of hyperthyroidism mice in the early high dose intervention group showed focal hypertrophic changes, while the thyroid tissue of other hyperthyroidism mice showed diffuse hypertrophic changes. The CD4+CD25+/CD4+Treg ratio in early high-dose intervention group was higher than that in model group at the 10th week (4 weeks after three recombinant adenovirus immunization) (P<0.05). Compared with the model group at the 10th week, the levels of IL-2, IL-12p70 and IFN-γ in the early high-dose intervention group were all decreased (all P<0.05), and the levels of IL-10 were increased (P<0.05). Conclusion: Early high-dose (500 mg·kg-1·d-1) TGP intervention group displays a protective effect against GD mice, the mechanism of which may be related to regulatory T cell function changes and Th1/Th2 cytokine balance restoration.

[The assistant effects of porcine fibrin sealant in improving stone clearance rate in flexible ureteroscopy lithotripsy in ex vivo porcine kidney model].

Objectives: To investigate the feasibility of using a porcine fibrin sealant to wrap and remove kidney calculi fragments through an isolated porcine kidney model. Methods: In the isolated porcine kidney stone model (implanted with 100 mg, air dried, ≤1 mm human stone fragments, n=6;implanted with 100 mg, air dried, ≤3 mm human stone fragments, n=6), the ureteral soft mirror combined with the 12/14Fr UAS was used to test the effect of stone extraction using only two stone extraction methods: basket extraction (control group, ≤1 mm stone fragments, n=3; ≤3 mm stone fragments, n=3) and basket-sealant extraction (test group, ≤1 mm stone fragments, n=3; ≤3 mm stone fragments, n=3). Compare the stone removal rate and operation time of the two stone retrieval methods. The sealant was put into urine of normal human and observed. Results: Porcine Fibrin Sealant can form a gel in saline and urine and adhere and wrap stone fragments. The time of procedures of test (basket-sealant) and control (basket) group in kidneys implanted with ≤ 1 mm stone fragments were (14.0±4.2) and (29.0±0.7)min (P<0.05) stone clearance rates were (90.9±1.4)% and (48.4±15.7)% (P<0.05), respectively. In kidneys implanted with ≤ 3 mm fragments, time of procedures were (12.8±4.0) and (30.0±0)min (P<0.05) Stone clearance rates were (91.1±5.0)% and (20.7±8.0)% (P<0.05). The Sealant dissolves by itself in normal human urine and normal saline at 37 ℃ for 24 hours. Conclusion: The appropriate concentration of Porcine Fibrin Sealant assisted stone retrieval may become a new method for removing small stone fragments in retrograde intrarenal surgery.

[Updates in the pathological diagnosis of Pleural Malignant Mesothelioma in the WHO classification of thoracic tumors (5(th) edition)].

The WHO Classification of Thoracic Tumors (5(th) edition) mainly has the following changes in the chapter of pleural malignant mesothelioma. (1) The concept of mesothelioma in situ and its diagnostic method have been established for the first time; (2) The tumour grading of pleural malignant mesothelioma was added, it was divided into low grade and high grade according to the cellular atypia, mitotic activity and presence of necrosis. (3) The morphological features of pleural malignant mesothelioma was classified into architectural pattern, cellular and stromal features, the correlation between histological features and prognosis was refined, and some of the controversial cellular types have been reclassified. In this review, we introduced the changes of related pathologic diagnosis, in the WHO Classification of Thoracic Tumors (5(th) edition) and discussed its clinical significance.

LncRNA CASC15 promotes migration and invasion in prostate cancer via targeting miR-200a-3p.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "LncRNA CASC15 promotes migration and invasion in prostate cancer via targeting miR-200a-3p, by C. Zhang, G.-X. Wang, B. Fu, X.-C. Zhou, Y. Li, Y.-Y. Li, published in Eur Rev Med Pharmacol Sci 2019; 23 (19): 8303-8309-DOI: 10.26355/eurrev_201910_19141-PMID: 31646560" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19141.

[Analysis of the pregnancy outcomes in pregnant women with COVID-19 in Hubei Province].

Objective: To study the effect of COVID-19 on pregnancy outcomes and neonatal prognosis in Hubei Province. Method: s A retrospective comparison of the pregnancy outcomes was done between 16 women with COVID-19 and 45 women without COVID-19. Also, the results of laboratory tests, imaging examinations, and the 2019 novel coronavirus (2019-nCoV) nucleic acid test were performed in 10 cases of neonatal delivered from women with COVID-19. Result: s (1) Of the 16 pregnant women with COVID-19, 15 cases were ordinary type and 1 case was severe type. No one has progressed to critical pneumonia.The delivery method of the two groups was cesarean section, and the gestational age were (38.7±1.4) and (37.9±1.6) weeks,there was no significant difference between the two groups (P>0.05). Also, there wee no significant differences in the intraoperative blood loss and birth weight of the newborn between the two groups (all P>0.05). (2) Ten cases of neonates delivered from pregnant women with COVID-19 were collected. The 2019-nCoV nucleic acid test were all negative.There were no significant differences in fetal distress, meconium-stained amniotic fluid, preterm birth, and neonatal asphyxia between the two groups (all P>0.05).(3) In the treatment of uterine contraction fatigue, carbetocin or carboprost tromethamine was used more in cesarean section for pregnant women with COVID-19 (1.3±0.6), compared with Non-COVID-19 group (0.5±0.7),the difference was statistically significant (P=0.001). Conclusions: If there is an indication for obstetric surgery or critical illness of COVID-19 in pregnant women, timely termination of pregnancy will not increase the risk of premature birth and asphyxia of the newborn, but it is beneficial to the treatment and rehabilitation of maternal pneumonia. Preventive use of long-acting uterotonic agents could reduce the incidence of postpartum hemorrhage during surgery. 2019-nCoV infection has not been found in neonates delivered from pregnant women with COVID-19.

MiR-378a-5p inhibits angiogenesis of oral squamous cell carcinoma by targeting KLK4.

Oral squamous cell carcinoma (OSCC) is still a leading cause of cancer death owing to distant metastasis, which is largely facilitated by tumor angiogenesis. MicroRNA (miR)-378a-5p and Kallikrein-related peptidase 4 (KLK4) participate in tumorigenesis and tumor metastasis according to previous studies, yet the exact role they play in tumor angiogenesis remains poorly understood. The aim of the present study is to investigate the effect of miR-378a-5p and KLK4 on angiogenesis of OSCC. MTT assay showed that the expression level of miR-378a-5p was negatively correlated with the proliferation of OSCC cells. ELISA and Western blot assay showed that down-regulation of miR-378a-5p promotes VEGF expression. Tube formation and in vivo chicken chorioallantoic membrane (CAM) assay showed that inhibition of miR-378a-5p reduced tube formation of human umbilical vein endothelial cells (HUVECs) and newly formed microvessel. On the contrary, over-expression of KLK4 enhanced angiogenesis of OSCC cells with increased VEGF expression, tube formation activity of HUVECs and newly formed microvessel. Moreover, the dual-luciferase assay validated that KLK4 was a target gene of miR-378a-5p. MiR-378a-5p silencing induced tube formation was suppressed by the downregulation of KLK4. Besides, the activation of Wnt/ß-catenin signaling pathway in miR-378a-5p antagomir transfected cells was also blocked by the KLK4 shRNA. To sum up, our study suggests that miR-378a-5p suppressed angiogenesis of OSCC at least partly by the regulation of KLK4.

LncRNA CASC15 promotes migration and invasion in prostate cancer via targeting miR-200a-3p.

OBJECTIVE: Prostate cancer (PC) is one of the most ordinary malignant cancers. Recent researches have proved that long noncoding RNAs (lncRNAs) act as an important role in cancers. Our study aims to explore the function of lncRNA CASC15 in the tumor metastasis of PC. PATIENTS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was utilized to detect CASC15 expression in 50 PC patients. Besides, the wound healing assay and transwell assay were performed to identify the biological behavior changes of PC cells after CASC15 was silenced in PC cells. In addition, the potential mechanism was also explored using the luciferase assay. RESULTS: CASC15 expression level was significantly higher in PC tissues and cell lines. Results of wound healing assay and transwell assay revealed that cell migrated ability and invaded ability were suppressed via silence of CASC15 in PC cells. Furthermore, the expression of miR-200a-3p was upregulated via silence of CASC15 in PC cells. Luciferase assay showed that miR-200a-3p was a direct target of CASC15 in PC. In addition, miR-200a-3p expression was negatively correlated with CASC15 expression in PC tissues. Rescue experiments also revealed that the inhibition of PC migration and invasion by silence of CASC15 could be reversed through knockdown of miR-200a-3p. CONCLUSIONS: Our study uncovers that CASC15 could enhance cell migration and invasion of PC cells by sponging miR-200a-3p, which might be applied as a novel therapeutic target for PC patients.

An effective indicator in predicting cardiovascular events: urine albumin to creatinine ratio.

OBJECTIVE: To study elderly hypertensive patients with trace albuminuria (urine albumin to creatinine ratio (UACR)) and the relationship between the occurrence of new cardiovascular events, to provide a basis for early prevention in elderly patients with high blood pressure. PATIENTS AND METHODS: A total of 3564 elderly patients with high blood pressure were enrolled in the study. Based on UACR, patients were divided into four groups (group A: 0.05-3.20 mg/g; group B:3.21-10.04 mg/g; group C: 10.05-19.33 and group D: 19.34-30.00 mg/g). All patients underwent follow-up for an average period of 3.8 years. Four groups were compared for new cardiovascular events and they were correlated with UACR. RESULTS: Through multivariate Cox proportional hazards regression analysis, the relative risk of cardiocerebrovascular events, cerebral infarction, and acute myocardial infarction (mi), in group D was 1.74 times (p < 0.05), 1.66 times (p < 0.05), and 2.48 times (p < 0.05), respectively. UACR level in females and those with higher age, body mass index, systolic blood pressure, fasting blood glucose, TG, TC, LDL-C levels and lower HDL-C were higher. During follow-up, patients from group D with sudden cardiac death, acute myocardial infarction, cerebral hemorrhage, cerebral infarction occurrence was significantly higher than group A (χ2 = 79.3, p = 79.3) CONCLUSIONS: According to UACR level, we can perform early prevention for elderly patients with high blood pressure, thus reducing the occurrence of cerebral infarction and myocardial infarction.

In vivo osseointegration of dental implants with an antimicrobial peptide coating.

This study aimed to evaluate the in vivo osseointegration of implants with hydrophobic antimicrobial GL13K-peptide coating in rabbit femoral condyles by micro-CT and histological analysis. Six male Japanese Rabbits (4 months old and weighing 2.5 kg each) were included in this study. Twelve implants (3.75 mm wide, 7 mm long) were randomly distributed in two groups, with six implants in the experimental group coated with GL13K peptide and six implants in the control group without surface coating. Each implant in the test and the control group was randomly implanted in the left or right side of femoral condyles. On one side randomly-selected of the femur, each rabbit received a drill that was left without implant as control for the natural healing of bone. After 3 weeks of healing radiographic evaluation of the implant sites was taken. After 6 weeks of healing, rabbits were sacrificed for evaluation of the short-term osseointegration of the dental implants using digital radiography, micro-CT and histology analysis. To perform evaluation of osseointegration, implant location and group was double blinded for surgeon and histology/radiology researcher. Two rabbits died of wound infection in sites with non-coated implants 2 weeks after surgery. Thus, at least four rabbits per group survived after 6 weeks of healing. The wounds healed without suppuration and inflammation. No implant was loose after 6 weeks of healing. Radiography observations showed good osseointegration after 3 and 6 weeks postoperatively, which proved that the tissues followed a natural healing process. Micro-CT reconstruction and analysis showed that there was no statistically significant difference (P > 0.05) in volume of bone around the implant between implants coated with GL13K peptide and implants without coating. Histomorphometric analysis also showed that the mineralized bone area was no statistically different (P > 0.05) between implants coated with GL13K peptide and implants without coating. This study demonstrates that titanium dental implants with an antimicrobial GL13K coating enables in vivo implant osseointegration at similar bone growth rates than gold-standard non-coated dental implants up to 6 weeks of implantation in rabbit femurs.

[Application study of droplet digital PCR to detect maternal cell contamination in prenatal diagnosis].

Objective: To develop a new method based on droplet digital PCR (DD-PCR) for detection and quantification of maternal cell contamination in prenatal diagnosis. Methods: Invasive prenatal samples from 40 couples of ß(IVS-Ⅱ-654)/ß(N) thalassemia gene carriers who accepted prenatal diagnosis in Affiliated Women and Children's Hospital of Guangzhou Medical University from October 2015 to December 2016 were analyzed retrospectively. Specific primers and probes were designed. The concentration gradient were 50%, 25%, 12.5%, 6.25%, 3.125%, 1.562 5%. There were 40 groups of prenatal diagnostic samples. Comparing DD-PCR with quantitative fluorescent-PCR (QF-PCR) based on the short tandem repeats for assement of the sensitivity and accuracy of maternal cell contamination, respectively. Results: DD-PCR could quantify the maternal cell contamination as low as 1.562 5%. The result was proportional to the dilution titers. In the 40 prenatal samples, 6 cases (15%, 6/40) of maternal cell contamination were detected by DD-PCR, while the QF-PCR based on short tandem repeat showed 3 cases (7.5%, 3/40) with maternal cell contamination, DD-PCR was more accurate (P=0.002) . Conclusion: DD-PCR is a precise and sensitive method in the detection of maternal cell contamintation. It could be useful in clinical application.

[The relationship between myocardial bridge in mural coronary artery segment and coronary atherosclerosis].

Objective: The myocardial bridging (MB) prevalence, anatomic characteristics of MB, and the relationship between characteristics of MB in mural coronary artery segment and coronary atherosclerosis were analyzed. Methods: In this perspective nonrandomized controlled study, a total of 1 132 patients who admitted to our hospital for suspected or known coronary artery disease from January 2012 to June 2013 were enrolled. All patients underwent dual-source 64-slice spiral CT coronary angiography. The general patient characteristics including gender, age, history of hypertension, diabetes, hyperlipidemia and smoking, serum level of total cholesterol (TC) and LDL-C were recorded. The length, depth and the degree of compression of myocardial bridge in systolic or diastolic phase were also analyzed in patients with MB. The relationship between MB and coronary atherosclerosis, the characteristics of MB and coronary atherosclerosis were analyzed by Spearman correlation analysis, univariate logistic regression analysis, variate logistic regression analysis and linear regression analysis. Results: Myocardial bridging was detected in 330 out of 1 132 patients, and MB was mostly located in the mural coronary artery (329/330) and at the mid-distal segment of the left anterior descending artery (LAD). Average MB length was 20.1 mm (3.3-95.5 mm) and the average depth was 2.13 mm (0.24-12.40 mm). There were 140 patients with intramyocardial MB (42.6%) and 189 patients with superficial MB (57.4%). Myocardial bridging was an independent protective factor of coronary atherosclerosis (OR=0.361, P=0.000) and the proximal segment of MB was more susceptible to atherosclerosis compared to the distal segment of MB (P=0.000). Multivariate analysis revealed that age, hypertension and the degree of compression of myocardial bridge in diastolic phase were independent factors related to the atherosclerosis (odds ratio: 1.064, 2.186 and 1.049 respectively, P value: 0.000, 0.002 and 0.000). The depth of MB was significantly correlated with systolic or diastolic narrowing(OR: 4.227, 3.398 and P value: 0.000, 0.001). Conclusions: The prevalence of myocardial bridging is 29% in this patient cohort. The proximal segment of myocardial bridging in mural coronary artery is more susceptible to atherosclerosis. In addition, the depth of myocardial bridging and the degree of compression of myocardial bridge in diastolic phase are the independent factors related to atherosclerosis.

[Study on Indole-3-carbinol inhibits nasopharyngeal carcinoma cells growth in vitra and in vivo].

Objective:The aim of this study is to investigate the inhibition of nasopharyngeal carcinoma cells by indole-3-carbinol in vitro and in vivo.Method:The human nasopharyngeal carcinoma cell line CNE2 was treated in different concentrations 0,100,200,300 µmol/L of indole-3-carbinol. Then we detected cell proliferation after 0,24,48 and 72 h, apoptosis after 48 h and the levels of PI3K/Akt pathway-related proteins in vitro. The BALB/c nude mice were divided into three groups: prevention group, treatment group and control group. In vivo, the nude mice in every group were inoculated with nasopharyngeal carcinoma cells CNE2, and mice in prevention and treatment groups were given feed containing 0.5% indole-3-carbinol. We investigated the tumoricidal effect of I3C in nude mice , and eight weeks later, the PI3K/Akt pathway-related proteins expressions in tumors from nude mice of each group were detected.Result:With the indole-3-carbinol concentration increased, cell proliferation decreased and apoptosis increased significantly.The levels of PI3K/Akt pathway-related proteins were decreased.In animal experiments, the prevention and treatment group developed smaller tumors, and the expression of PI3K/Akt pathway-related proteins in prevention and treatment groups PI3K/Akt pathway also reduced, compared to control group. Meanwhile, nearly no changes of heart, liver and kidney tissues in all groups were seen in HE staining.Conclusion:Indole-3-carbinol inhibited the growth of nasopharyngeal carcinoma cells and induced apoptosis effectively in vivo and in vitro. The mechanism might be that indole-3-carbinol could suppress PI3K/Akt pathway.

Three branches of phospholipase C signaling pathway promote hepatocyte growth in rat liver regeneration.

In general, the phospholipase C (PLC) signaling pathway is involved in many physiological activities, including cell growth. However, little is known regarding how the PLC signaling pathway participates in regulating hepatocyte (HC) growth during liver regeneration (LR). To further explore the influence of the PLC signaling pathway on HCs at the cellular level, HCs of high purity and vitality were isolated using Percoll density-gradient centrifugation after partial hepatectomy. The genes of the PLC signaling pathway and target genes of transcription factors in the pathway were obtained by searching the pathways and transcription factor databases, and changes in gene expression of isolated HCs were examined using the Rat Genome 230 2.0 Microarray. The results suggested that various genes involved in the pathway (including 151 known genes and 39 homologous genes) and cell growth (including 262 known genes and 37 homologous genes) were associated with LR. Subsequently, the synergetic effect of these genes in LR was analyzed using a mathematical model (Et) according to their expression profiles. The results showed that the Et values of G protein-coupled receptor/PLC, integrin/PLC, and growth factor receptor/PLC branches of the PLC pathway were all significantly strengthened during the progression and termination phases of LR. The synergetic effect of target genes, in parallel with target gene-related cell growth, was also enhanced during whole rat LR, suggesting the potential positive effect of PLC on HC growth. The present data indicate that the PLC signaling pathway may promote HC growth through 3 mechanisms during rat LR after partial hepatectomy.

Factors affecting the repeatability of gamma camera calibration for quantitative imaging applications using a sealed source.

Several applications in nuclear medicine require absolute activity quantification of single photon emission computed tomography images. Obtaining a repeatable calibration factor that converts voxel values to activity units is essential for these applications. Because source preparation and measurement of the source activity using a radionuclide activity meter are potential sources of variability, this work investigated instrumentation and acquisition factors affecting repeatability using planar acquisition of sealed sources. The calibration factor was calculated for different acquisition and geometry conditions to evaluate the effect of the source size, lateral position of the source in the camera field-of-view (FOV), source-to-camera distance (SCD), and variability over time using sealed Ba-133 sources. A small region of interest (ROI) based on the source dimensions and collimator resolution was investigated to decrease the background effect. A statistical analysis with a mixed-effects model was used to evaluate quantitatively the effect of each variable on the global calibration factor variability. A variation of 1 cm in the measurement of the SCD from the assumed distance of 17 cm led to a variation of 1-2% in the calibration factor measurement using a small disc source (0.4 cm diameter) and less than 1% with a larger rod source (2.9 cm diameter). The lateral position of the source in the FOV and the variability over time had small impacts on calibration factor variability. The residual error component was well estimated by Poisson noise. Repeatability of better than 1% in a calibration factor measurement using a planar acquisition of a sealed source can be reasonably achieved. The best reproducibility was obtained with the largest source with a count rate much higher than the average background in the ROI, and when the SCD was positioned within 5 mm of the desired position. In this case, calibration source variability was limited by the quantum noise.

Change in PSA velocity is a predictor of overall survival in men with biochemically-recurrent prostate cancer treated with nonhormonal agents: combined analysis of four phase-2 trials.

BACKGROUND: Multiple phase-2 trials in men with biochemically-recurrent prostate cancer (BRPC) have assessed the impact of nonhormonal agents on PSA kinetics. We have previously demonstrated that changes in PSA kinetics correlate with metastasis-free survival; however, it is unknown whether these changes also correlate with overall survival (OS). METHODS: We performed a combined retrospective analysis of 146 men with BRPC treated on phase-2 trials using one of four investigational drugs: lenalidomide (n=60), marimastat (n=39), ATN-224 (n=22) and imatinib (n=25). We examined factors influencing OS, including within-subject changes in PSA kinetics (PSA slope, PSA doubling time and PSA velocity), before and 6 months after treatment initiation. RESULTS: After a median follow-up of 83.1 months, 49 of 146 men had died. In univariate Cox regression analysis, two factors were associated with OS: baseline PSA velocity and change in PSA velocity on therapy. In a landmark multivariable model, stratified by study (which controlled for age, Gleason score, type of local therapy and use of androgen-deprivation therapy prior to metastases), baseline PSA velocity and increase in PSA velocity on therapy remained independent predictors of OS. Median OS for men with an increase in PSA velocity on treatment was 115.4 months and was not reached for men with a decrease in PSA velocity (hazard ratio=0.47, 95% confidence interval 0.25-0.88; P=0.02). CONCLUSIONS: This hypothesis-generating study suggests that within-subject changes in PSA velocity after initiation of nonhormonal therapy may correlate with OS in men with BRPC. If validated in prospective trials, change in PSA velocity may represent a reasonable intermediate end point for screening new agents in these patients.

Metastasis-free survival is associated with overall survival in men with PSA-recurrent prostate cancer treated with deferred androgen deprivation therapy.

BACKGROUND: Clinical trials in men with biochemically recurrent prostate cancer (BRPC) have been hampered by long survival times, making overall survival (OS) a difficult end point to reach. Intermediate end points are needed in order to conduct such trials within a more feasible time frame. PATIENTS AND METHODS: This is a retrospective analysis of 450 men with BRPC following prostatectomy treated at a single institution between 1981 and 2010, of which 140 developed subsequent metastases. Androgen deprivation therapy (ADT) was deferred until after the development of metastases. Cox regression models were developed to investigate factors influencing OS. RESULTS: Median metastasis-free survival (MFS) was 10.2 years [95% confidence interval (CI) 7.6-14.0 years]; median OS after metastasis was 6.6 years (95%CI 5.8-8.4 years). Multivariable Cox regressions identified four independently prognostic variables for OS: MFS (HR 0.77; 95% CI 0.63-0.94), number of metastases (≤3 versus ≥4; HR 0.50; 95% CI 0.29-0.85), pain (absent versus present; HR 0.43; 95% CI 0.25-0.72), and bisphosphonate use (yes versus no; HR 0.60; 95% CI 0.37-0.98). CONCLUSIONS: MFS emerged as an independent predictor of OS in men with BRPC treated with deferred ADT after the development of metastases. MFS may be a reasonable intermediate end point in future clinical trials. This observation requires prospective validation.

Meta-analysis of epidemiological studies of association of two polymorphisms in the interleukin-10 gene promoter and colorectal cancer risk.

In order to make a comprehensive assessment of the potential association between two genetic variants in the IL-10 gene promoter, -1082 A>G (rs1800896) and -592 C>A (rs1800872), and colorectal cancer (CRC) risk, we conduced a meta-analysis of seven epidemiological studies, which included 1469 colorectal cancer cases and 2566 controls. Neither of the two polymorphisms had any association with increased CRC risk in overall population [for rs1800896: odds ratio (OR) = 0.90, 95% confidence interval (95%CI) = 0.76-1.06 in the dominant model and for rs1800872: OR = 1.06, 95%CI = 0.91-1.23 in the dominant model]. In subgroup analysis of the rs1800896 polymorphism, the results did not change when the analyses were restricted to individual studies, or those fulfilling Hardy-Weinberg equilibrium, or according to the source of controls. For rs1800872, however, when stratifying by the source of controls, the A allele had a significant increased risk of CRC among studies with population-based controls in the codominant model (AC vs CC: OR = 1.30, 95%CI = 1.04-1.63) and dominant model (AA/AC vs CC: OR = 1.25, 95% CI = 1.01-1.55). Based on this meta-analysis, we conclude that the IL-10 rs1800872 polymorphism could be a risk factor for CRC development among European populations. However, we found no association between the IL-10 rs1800896 polymorphism and CRC risk. Further studies, either with larger sample size or involving other SNPs and haplotypes of the IL-10 gene, are necessary to clarify the contribution of IL-10 genetic variations in colorectal carcinogenesis.

Seedling and Slow Rusting Resistance to Stripe Rust in Chinese Common Wheats.

Identification of seedling and slow stripe rust resistance genes is important for gene pyramiding, gene deployment, and developing slow-rusting wheat cultivars to control the disease. A total of 98 Chinese lines were inoculated with 26 pathotypes of Puccinia striiformis f. sp. tritici for postulation of stripe rust resistance genes effective at the seedling stage. A total of 135 wheat lines were planted at two locations to characterize their slow rusting responses to stripe rust in the 2003-2004 and 2004-2005 cropping seasons. Genes Yr2, Yr3a, Yr4a, Yr6, Yr7, Yr9, Yr26, Yr27, and YrSD, either singly or in combinations, were postulated in 72 lines, whereas known resistance genes were not identified in the other 26 accessions. The resistance genes Yr9 and Yr26 were found in 42 and 19 accessions, respectively. Yr3a and Yr4a were detected in two lines, and four lines may contain Yr6. Three lines were postulated to possess YrSD, one carried Yr27, and one may possess Yr7. Thirty-three lines showed slow stripe rusting resistance at two locations in both seasons.

Expression of Bcl-2 and Bax in rhesus monkey testis during germ cell apoptosis induced by testosterone undecanoate.

Apoptosis occurs spontaneously during spermatogenesis and can be induced by androgen withdrawal. However, the molecular events governing apoptosis have not been characterized. To study the molecular mechanism of apoptosis induced by a high dose of testosterone undecanoate (TU), the authors examined the temporal changes in proapoptotic Bax and antiapoptotic Bcl-2 in TU-treated monkey testes. Apoptotic cells were identified in tissue sections by in situ end labeling of fragmented DNA. The results showed that a great deal of the apoptotic cells occurred in the testes on day 30 after TU injection and that the dominant apoptotic germ cells are spermatocytes and spermatids. The expression of Bcl-2 and Bax was assessed by immunohistochemical method and Western blot. As compared with that of normal testes, the levels of Bcl-2 protein increased significantly from 7 to day 14 while that of Bax protein was almost unchanged in the testes from day 7 up to day 60 after TU treatment. Bcl-2 was localized to the spermatids in the normal testes and temporarily distributed in both the cytoplasm and nucleus of those cell types susceptible to TU-induced apoptosis on day 14 after TU injection. Therefore, it is suggested that Bax may not play a role in initiating germ cell apoptosis induced by TU injection and that the evaluation in Bcl-2 expression may represent a survival mechanism for the remaining germ cell.

Cloning and characterization of temperature-related gene TRS1.

To investigate the mechanism of spermatogenesis arrest derived from heat treatment and to screen temperature-related genes involved in spermatogenesis, the authors analyzed the differences in gene expression between cryptorchid and scrotal testes in rats, and cloned a full-length cDNA named TRS1. In situ hybridization showed that TRS1 mRNA was mainly expressed in spermatocyte and round spermatids in testis. The expression level decreased in cryptorchid testis, suggesting that the lower scrotal temperature is a key factor in keeping the normal expression of TRS1. At the N-terminal of TRS1, there was a plecstrin homology (PH) domain signature. This PH domain has high similarity to that in PEPP2, a homosapien protein, which has a characteristic of binding phosphatidylinositol 3-phosphate via its PH domain in vitro. These findings suggest that TRS1 may be important in spermatogenesis and give clues for further research on the function of TRS1.