Neutrophil-to-lymphocyte ratio predicts acute kidney injury occurrence after gastrointestinal and hepatobiliary surgery.

BACKGROUND: Postoperative acute kidney injury (AKI) is a complex pathological process involved intrarenal and systemic inflammation caused by renal hypoperfusion, nephrotoxic drugs and urinary obstruction. Neutrophil-to-lymphocyte ratio (NLR) is a marker of inflammation reflecting the progress of many diseases. However, whether NLR at admission can predict the occurrence of AKI after surgery in the intensive care unit (ICU) remains unknown. AIM: To clarify the relationship between NLR and the occurrence of AKI in patients with gastrointestinal and hepatobiliary surgery in the ICU. METHODS: A retrospective analysis of 282 patients receiving surgical ICU care after gastrointestinal and hepatobiliary surgery in our hospital from December 2014 to December 2018 was performed. RESULTS: Postoperative AKI occurred in 84 patients (29.79%) in this cohort. NLR by the multivariate analysis was an independent risk factor for occurrence of postoperative AKI in patients with gastrointestinal and hepatobiliary surgery in the ICU. In this cohort, receiver operating characteristic curves of AKI occurrence showed that the optimal cut-off value of NLR was 8.380. NLR was found to be significantly correlated with the white blood cell count, neutrophil count, lymphocyte count, arterial lactate and dialysis (P < 0.05). Additionally, NLR value at admission was higher in AKI patients compared with the non-AKI patients and increased with the severity of AKI. Patients with NLR ≥ 8.380 exhibited significantly higher incidences of postoperative AKI and severe AKI than patients with NLR < 8.380 (AKI: 38.12% vs 14.85%, P < 0.001; severe AKI: 14.36% vs 1.98%, P = 0.001). CONCLUSION: NLR at admission is a predictor of AKI occurrence in patients with gastrointestinal and hepatobiliary surgery in ICU. NLR should be included in the routine assessment of AKI occurrence.

Overexpression of Platelet-Derived Growth Factor Receptor Α D842V Mutants Prevents Liver Regeneration and Chemically Induced Hepatocarcinogenesis via Inhibition of MET and EGFR.

Platelet-derived growth receptor α (PDGFRα) is a key factor in many pathophysiological processes. The expression level of PDGFRα is significantly elevated in the early stage of liver development and maintained at a lower level in adult normal livers. In this study, we constructed a liver-specific PDGFRαD842 mutant transgenic (TG) mice model to explore the effect of continuous activation of PDGFRα on liver regeneration and hepatocarcinogenesis. 14-day-old TG and wild-type (WT) mice were intraperitoneally injected with diethylnitrosamine (DEN) at a dose of 25 µg/g body weight. Two-month-old male TG and WT mice were subjected to partial hepatectomy (PH). The liver tissues were collected for further analysis at different time points. Overexpression of PDGFRα D842V and its target genes, Akt, c-myc and cyclin D1 in hepatocytes with no overt phenotype versus WT mice were compared. Unexpectedly, a dramatic decrease in hepatocyte proliferation was noted after PH in TG versus WT mice, possibly due to the downregulation of hepatocyte growth factor receptor (MET) and epidermal growth factor receptor (EGFR). No TG mice developed HCC spontaneously after 14 months follow-up. However, TG mice were more resistant to DEN-induced hapatocarcinogenesis at 6, 10, and 12 months of age, showing delayed hepatocyte proliferation and apoptosis, lower tumor incidence, smaller size and fewer number, compared with age-matched WTs, partially through downregulation of MET and EGFR. In conclusion, continuous activation of PDGFRα signaling by expression of PDGFRα D842V does not promote, but inhibit hepatic regeneration and hepatocarcinogenesis, possibly through compensatory downregulation of MET and EGFR.

Irisin attenuates intestinal injury, oxidative and endoplasmic reticulum stress in mice with L-arginine-induced acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is often associated with intestinal injury, which in turn exaggerates the progression of AP. Our recent study has shown that a low level of serum irisin, a novel exercise-induced hormone, is associated with poor outcomes in patients with AP and irisin administration protects against experimental AP. However, the role of irisin in intestinal injury in AP has not been evaluated. AIM: To investigate the effect of irisin administration on intestinal injury in experimental AP. METHODS: AP was induced in male adult mice by two hourly intraperitoneal injections of L-arginine. At 2 h after the last injection of L-arginine, irisin (50 or 250 µg/kg body weight) or 1 mL normal saline (vehicle) was administered through intraperitoneal injection. The animals were sacrificed at 72 h after the induction of AP. Intestinal injury, apoptosis, oxidative and endoplasmic reticulum (ER) stress were evaluated. RESULTS: Administration of irisin significantly mitigated intestinal damage, reduced apoptosis, and attenuated oxidative and ER stress in AP mice. In addition, irisin treatment also effectively downregulated serum tumor necrosis factor-alpha and interleukin-6 levels and alleviated injury in the pancreas, liver and lung of AP mice. CONCLUSION: Irisin-mediated multiple physiological events attenuate intestinal injury following an episode of AP. Irisin has a great potential to be further developed as an effective treatment for patients with AP.

Ureteral Ewing's sarcoma in an elderly woman: A case report.

BACKGROUND: Ewing's sarcoma (ES) is regarded as a skeletal tumor, with few instances of extra-skeletal ES. A primary ES in the ureter is extremely rare. CASE SUMMARY: We report the case of a 69-year-old woman who presented with intermittent flank pain and hematuria and was found to have a mass in the left ureter. Pathology of the excised mass indicated ES. The clinical treatment and pathologic characteristics in this case, and a review of the literature describing ES in the urinary system, are presented. CONCLUSION: Due to the rarity and malignancy of ES in ureter, early diagnosis and prompt surgical treatment are critical.

Effect of low-dose aspirin administration on long-term survival of cirrhotic patients after splenectomy: A retrospective single-center study.

BACKGROUND: Cirrhosis is a major risk factor for the development of hepatocellular carcinoma (HCC). Portal vein thrombosis is not uncommon after splenectomy in cirrhotic patients, and many such patients take oral anticoagulants including aspirin. However, the long-term impact of postoperative aspirin on cirrhotic patients after splenectomy remains unknown. AIM: The main purpose of this study was to investigate the effect of postoperative long-term low-dose aspirin administration on the development of HCC and long-term survival of cirrhotic patients after splenectomy. METHODS: The clinical data of 264 adult patients with viral hepatitis-related cirrhosis who underwent splenectomy at the First Affiliated Hospital of Xi'an Jiaotong University from January 2000 to December 2014 were analyzed retrospectively. Among these patients, 59 who started taking 100 mg/d aspirin within seven days were enrolled in the aspirin group. The incidence of HCC and overall survival were analyzed. RESULTS: During follow-up, 41 (15.53%) patients developed HCC and 37 (14.02%) died due to end-stage liver diseases or other serious complications. Postoperative long-term low-dose aspirin therapy reduced the incidence of HCC from 19.02% to 3.40% after splenectomy (log-rank test, P = 0.028). Univariate and multivariate analyses showed that not undertaking postoperative long-term low-dose aspirin therapy [odds ratio (OR) = 6.211, 95% confidence interval (CI): 1.142-27.324, P = 0.016] was the only independent risk factor for the development of HCC. Similarly, patients in the aspirin group survived longer than those in the control group (log-rank test, P = 0.041). Univariate and multivariate analyses showed that the only factor that independently associated with improved overall survival was postoperative long-term low-dose aspirin therapy [OR = 0.218, 95%CI: 0.049-0.960, P = 0.044]. CONCLUSION: In patients with viral hepatitis-related cirrhosis, long-term post-splenectomy administration of low-dose aspirin reduces the incidence of HCC and improves the long-term overall survival.

Inhibition of miR-34a-5p can rescue disruption of the p53-DAPK axis to suppress progression of clear cell renal cell carcinoma.

DAPK, a transcriptional target of the p53 protein, has long been characterized as a tumor suppressor that acts as a negative regulator in multiple cellular processes. However, increasing studies have suggested that the role of DAPK may vary depending on cell type and cellular context. Thus far, the expression and function of DAPK in clear cell renal cell carcinoma (ccRCC) remain ambiguous. Since ccRCC behaves in an atypical way with respect to p53, whether the p53-DAPK axis functions normally in ccRCC is also an intriguing question. Here, tissue specimens from 61 ccRCC patients were examined for DAPK expression. Functional studies regarding apoptosis, growth, and migration were used to determine the role of DAPK in renal cancer cells. The validity of the p53-DAPK axis in ccRCC was also determined. Our study identified DAPK as a negative regulator of ccRCC, and its expression was reduced in certain subgroups. However, the p53-DAPK axis was disrupted due to upregulation of miR-34a-5p under stressed conditions. miR-34a-5p was identified as a novel repressor of DAPK acting downstream of p53. Inhibition of miR-34a-5p can correct the p53-DAPK axis disruption by upregulating DAPK protein and may have potential to be used as a therapeutic target to improve outcomes for ccRCC patients.

Overexpression of SNHG12 regulates the viability and invasion of renal cell carcinoma cells through modulation of HIF1α.

BACKGROUND: Cumulative evidences demonstrated the aberrant overexpression of Small Nucleolar RNA Host Gene 12 (SNHG12) in diverse human cancer. However, the expression status and involvement of SNHG12 in renal cell carcinoma is still elusive. METHODS: The expression of SNHG12 was determined by q-PCR. The transcriptional regulation was interrogated by luciferase reporter assay. Cell viability was measured with CCK-8 kit. The anchorage-independent was evaluated by soft agar assay. Cell apoptosis was analyzed by Annexin V/7-AAD double staining. The migration and invasion were determined by trans-well assay and wound scratch closure. The in vivo tumor growth was monitored in xenograft mice model. Protein expression was quantified by immunoblotting. RESULTS: SNHG12 was aberrantly up-regulated in renal carcinoma both in vivo and in vitro. High expression of SNHG12 associated with poor prognosis. Deficiency of SNHG12 significantly suppressed cell viability, anchorage-independent growth and induced apoptosis. In addition, SNHG12 silencing inhibited migrative and invasive in vitro and xenograft tumor growth in vivo. Mechanistically, SNHG12 modulated HIF1α expression via competing with miR-199a-5p, which consequently contributed to its oncogenic potential. MiR-199a-5p inhibition severely compromised SNHG12 silencing-elicited tumor repressive effects. CONCLUSION: Our data uncovered a crucial role of SNHG12-miR-199a-5p-HIF1α axis in human renal cancer.

miR-19 promotes the proliferation of clear cell renal cell carcinoma by targeting the FRK-PTEN axis.

BACKGROUND: The non-receptor tyrosine kinase Fyn-related kinase (FRK) has been reported to affect cell proliferation in several cancer types. However, its effect on the proliferation of clear cell renal cell carcinoma (ccRCC) remains largely unknown. PURPOSE: The objective of this study was to investigate the expression pattern and function of FRK in ccRCC. We further determined how FRK interacted with other molecules to regulate ccRCC proliferation. PATIENTS AND METHODS: The expression of FRK in ccRCC samples and paired normal renal tissues from 30 patients were analyzed by immunoblotting, immunohistochemistry and quantitative PCR. Then the role of FRK in ccRCC proliferation was analyzed by Cell Counting Kit-8, colony formation assay and EdU incorporation assay. In addition, the miRNA targeting FRK was predicted through a bioinformatic approach and validated by quantitative PCR, immunoblotting and luciferase reporter assay. Finally, the underlying mechanism of FRK regulation of ccRCC proliferation was also determined. RESULTS: Low expression of FRK was detected in ccRCC samples and predicted poor survival for ccRCC patients. FRK inhibited the proliferation of ccRCC cells via phosphorylating downstream PTEN. miR-19 was identified as a novel suppressor of FRK in renal cancer cells and it promoted the proliferation of ccRCC by inhibiting the FRK-PTEN axis. CONCLUSION: Our results unravel a new regulatory mechanism involved in ccRCC proliferation and may be useful in the identification of therapeutic targets for ccRCC.

TRPM7 is overexpressed in bladder cancer and promotes proliferation, migration, invasion and tumor growth.

Recent findings suggest that the melastatin transient receptor potential channel 7 (TRPM7) is overexpressed in many types of cancers and is involved in tumorigenesis. However, its expression pattern and the potential role in bladder cancer remain unclear. The aim of the present study was to investigate the expression status of TRPM7 and its relationship with the development of bladder cancer. In the present study, we observed that the expression of TRPM7 was significantly elevated in bladder cancer tissues compared with that noted in the adjacent non-tumor tissues. Furthermore, increased TRPM7 expression was significantly associated with recurrence, metastasis and prognosis. In addition, after knockdown of the expression of TRPM7 by siRNA, the proliferation and the motility of T24 and 5637 cells were obviously inhibited, and downregulation of TRPM7 was found to play an important role in bladder cancer cell apoptosis. In conclusion, our findings suggest that TRPM7 plays an important role in bladder cancer, and TRPM7 may serve as a potentially unfavorable factor and novel target for human bladder cancer.

Hydrogen-rich water protects against inflammatory bowel disease in mice by inhibiting endoplasmic reticulum stress and promoting heme oxygenase-1 expression.

AIM: To investigate the therapeutic effect of hydrogen-rich water (HRW) on inflammatory bowel disease (IBD) and to explore the potential mechanisms involved. METHODS: Male mice were randomly divided into the following four groups: control group, in which the mice received equivalent volumes of normal saline (NS) intraperitoneally (ip); dextran sulfate sodium (DSS) group, in which the mice received NS ip (5 mL/kg body weight, twice per day at 8 am and 5 pm) for 7 consecutive days after IBD modeling; DSS + HRW group, in which the mice received HRW (in the same volume as the NS treatment) for 7 consecutive days after IBD modeling; and DSS + HRW + ZnPP group, in which the mice received HRW (in the same volume as the NS treatment) and ZnPP [a heme oxygenase-1 (HO-1) inhibitor, 25 mg/kg] for 7 consecutive days after IBD modeling. IBD was induced by feeding DSS to the mice, and blood and colon tissues were collected on the 7th d after IBD modeling to determine clinical symptoms, colonic inflammation and the potential mechanisms involved. RESULTS: The DSS + HRW group exhibited significantly attenuated weight loss and a lower extent of disease activity index compared with the DSS group on the 7th d (P < 0.05). HRW exerted protective effects against colon shortening and colonic wall thickening in contrast to the DSS group (P < 0.05). The histological study demonstrated milder inflammation in the DSS + HRW group, which was similar to normal inflammatory levels, and the macroscopic and microcosmic damage scores were lower in this group than in the DSS group (P < 0.05). The oxidative stress parameters, including MDA and MPO in the colon, were significantly decreased in the DSS + HRW group compared with the DSS group (P < 0.05). Simultaneously, the protective indicators, superoxide dismutase and glutathione, were markedly increased with the use of HRW. Inflammatory factors were assessed, and the results showed that the DSS + HRW group exhibited significantly reduced levels of TNF-α, IL-6 and IL-1ß compared with the DSS group (P < 0.05). In addition, the pivotal proteins involved in endoplasmic reticulum (ER) stress, including p-eIF2α, ATF4, XBP1s and CHOP, were dramatically reduced after HRW treatment in contrast to the control group (P < 0.05). Furthermore, HRW treatment markedly up-regulated HO-1 expression, and the use of ZnPP obviously reversed the protective role of HRW. In the DSS + HRW + ZnPP group, colon shortening and colonic wall thickening were significantly aggravated, and the macroscopic damage scores were similar to those of the DSS + HRW group (P < 0.05). The histological study also showed more serious colonic damage that was similar to the DSS group. CONCLUSION: HRW has a significant therapeutic potential in IBD by inhibiting inflammatory factors, oxidative stress and ER stress and by up-regulating HO-1 expression.

A promising prediction model for survival in gallbladder carcinoma patients: pretreatment prognostic nutrient index.

The pretreatment nutritional and immunological status play indispensable roles in predicting the outcome of patients with various types of malignancies. The aim of the study was to investigate whether preoperative prognostic nutritional index (PNI), which simply accounts for nutritional and immunological status, was associated with overall survival (OS) in patients with gallbladder carcinoma (GBC). The retrospective study included a total of 315 GBC patients after surgery between 2002 and 2012. PNI was calculated according to the following formula: 10× serum albumin (g/dl) +0.005× total lymphocyte count (per mm3). A receiver operating characteristic (ROC) curve for survival prediction was plotted to verify the optimal cutoff value for LMR, which was set at 46.14. According the value, patients were categorized into two different groups, namely high-PNI group (n = 133) and low-PNI group (n = 182). The univariate and multivariate Cox regression models were used to identify the independent prognostic factors. The results showed that low pretreatment PNI value was significantly associated with elderly age, partial surgery procedure, and advanced tumor status such as tumor stage, node stage, and tumor-node-metastasis stage (P < 0.05). The low-PNI group had a worse OS compare with the high-PNI group (P < 0.05). Via univariate and multivariate analyses, pretreatment PNI was identified as an independent prognostic factor for OS [HR: 0.613; 95%CI: 0.448-0.838; P < 0.001]. Subgroup analyses further revealed that PNI was significantly associated with postoperative OS independent of tumor node metastasis stage and surgical procedure. In conclusion, pretreatment PNI might serve as an effective predictor to evaluate prognosis of GBC patients after surgery. Based on the findings, PNI, characterized with accessibility, objectivity and noninvasiveness, should be included in the routine assessment of GBC.

Prognostic significance of pretreatment albumin/globulin ratio in patients with hepatocellular carcinoma.

BACKGROUND: Pretreatment nutritional and immunological statuses play an indispensable role in predicting the outcome of patients with various types of malignancies. The purpose of this study is to evaluate the predictive value of albumin/globulin ratio (AGR) in overall survival (OS) and recurrence in patients with hepatocellular carcinoma (HCC) following radical hepatic carcinectomy. PATIENTS AND METHODS: This retrospective study included a total of 172 patients with HCC with complete medical and follow-up information between 2002 and 2012. AGR was calculated according to the following formula: AGR = albumin/globulin. Receiver operating characteristic curve analysis was performed to determine the optimal cutoff value. The associations of AGR with clinicopathological characteristics and prognosis were assessed. Further multivariate analysis using Cox regression model and subgroup analysis was performed to evaluate the predictive value. RESULTS: Receiver operating characteristic curve determined 37.65, 31.99, and 1.48 as the optimal cutoff values of albumin, globulin, and AGR in terms of 5-year OS or death, respectively. On the basis of the cutoff value of AGR, all the patients were divided, respectively, into low-AGR (n=105) and high-AGR (n=67) groups. AGR was found to be significantly correlated with age, cancer embolus, international normalized ratio, and postoperative outcome (P<0.05). Hepatitis B virus infection (hazard ratio [HR]: 2.125; 95% confidence interval [CI]: 1.285-3.153), tumor node metastasis stage (HR: 1.656; 95% CI: 1.234-2.223), serum albumin (HR: 0.546; 95% CI: 0.347-0.857), and AGR (HR: 0.402; 95% CI: 0.233-0.691) were independent predictors of OS via univariate and multivariate survival analyses. However, alpha-fetoprotein (HR: 1.708; 95% CI: 1.027-2.838), tumor node metastasis stage (HR: 1.464; 95% CI: 1.078-1.989), and AGR (HR: 0.493; 95% CI: 0.293-0.828) functioned as independent risk variables for predicting recurrence. Moreover, AGR showed superior prognostic value for OS and recurrence in the subgroups with normal level of albumin or survival time beyond 6 months. CONCLUSION: Pretreatment AGR might serve as an effective biomarker to evaluate the prognosis of patients with a diagnosis of HCC. Based on the results, AGR, characterized with easy accessibility, objectivity, and noninvasiveness, should be included in the routine assessment of HCC.

Simple models based on gamma-glutamyl transpeptidase and platelets for predicting survival in hepatitis B-associated hepatocellular carcinoma.

BACKGROUND: Several hepatic cirrhosis-derived noninvasive models have been developed to predict the incidence and outcomes of hepatocellular carcinoma (HCC). We aimed to investigate the prognostic significance of the two novel established cirrhosis-associated models based on gamma-glutamyl transpeptidase (GGT) and platelets in hepatitis B-associated HCC. METHODS: We retrospectively evaluated 182 HCC patients with positive hepatitis B surface antigen who received radical therapy at a single institution between 2002 and 2012. Laboratory data prior to operation were collected to calculate the GGT to platelets ratio (GPR) and the S-index. Predictive factors associated with overall survival and recurrence-free survival were assessed using log-rank test and multivariate Cox analysis. Additional analyses were performed after patients were stratified based on cirrhosis status, tumor size, therapy methods, and so forth, to investigate the prognostic significance in different subgroups. RESULTS: During a median follow-up time of 45.0 months, a total of 88 (48.4%) patients died and 79 (43.4%) patients recurred. The cut-off points for GPR and S-index in predicting death were determined to be 0.76 and 0.56, respectively. Compared with patients with a lower GPR, those with GPR ≥0.76 had a higher probability of cirrhosis and a larger tumor (both P<0.05). GPR and S-index were both found to be significantly associated with survival by univariate log-rank test. Multivariate analysis identified tumor size ≥5 and high level of GPR, but not high Barcelona Clinic Liver Cancer stage or S-index, as independent factors for predicting poor overall survival and recurrence-free survival. CONCLUSION: The GPR is an effective preoperative predictor for outcomes in hepatitis B-associated HCC.

King's score as a novel prognostic model for patients with hepatitis B-associated hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: King's score (KS) has been developed to predict the presence of cirrhosis and hepatocellular carcinoma (HCC) in patients with chronic liver diseases. We aimed to investigate the prognostic significance of the KS in hepatitis B-associated HCC. PATIENTS AND METHODS: We retrospectively analyzed 319 hepatitis B-associated HCC patients. Preoperative data were collected to calculate the KS (age × aspartate aminotransferase × international normalized ratio/platelet count). The primary outcomes were overall survival (OS) and disease-free survival (DFS), which was estimated using the Kaplan-Meier method. Then, we carried out a multivariate Cox analysis to assess the independent significance of the KS. Additional analyses were carried out after patients were stratified on the basis of cirrhosis status and therapy methods to investigate the significance of KS in different subgroups. RESULTS: During a median follow-up period of 44 months, 199 (62.4%) patients died and 144 (45.1%) experienced recurrence. The cut-off value for the KS was determined to be 33.31 with 56.8% sensitivity and 66.7% specificity. Compared with patients with low KS, the high group showed a higher probability of cirrhosis and worse Child-Pugh class (both P<0.05). Multivariate analysis identified older age, tumor size 5 or more, palliative therapy, high Barcelona Clinic Liver Cancer stage, and high KS as significant factors for predicting poor OS and DFS. A combination of the KS and tumor size showed better discrimination ability for survival than Barcelona Clinic Liver Cancer stage. CONCLUSION: The KS is an effective index for predicting OS and DFS in hepatitis B-associated HCC. Larger cohorts are needed to validate our finding.

Thrombocytopenia for prediction of hepatocellular carcinoma recurrence: Systematic review and meta-analysis.

AIM: To investigate the association between thrombocytopenia and relapse after treatment for hepatocellular carcinoma (HCC). METHODS: We searched the PubMed, EMBASE, and Web of Science databases to obtain eligible studies. The hazard ratios (HRs) values and 95% confidence intervals (CIs) were pooled by random effects model. Subsequently, we estimated the heterogeneity, performed a sensitivity analysis, determined the publication bias, and performed subgroup and meta-regression analyses. Study quality was assessed by using the Oxford Center for Evidence Based Medicine tool. RESULTS: We identified 18 eligible studies by retrieval (published during 2000-2014). Out of the 4163 patients with HCC who were recruited, 2746 (66.0%) experienced recurrence. In general, our meta-analysis suggested that low platelet count (PLT) before therapy significantly increased the probability of postoperative recurrence (HR = 1.53, 95%CI: 1.29-1.81). PLT was also valuable in the prediction of intrahepatic distant recurrence (HR = 1.49, 95%CI: 1.25-1.77). Subgroup and meta-regression analyses identified various therapeutic modalities as the source of a high degree of heterogeneity. The pooled HR values showed no obvious change when a single study was removed, but otherwise, an opposite-effects model was used. In addition, no significant publication bias was detected. CONCLUSION: Thrombocytopenia before treatment might be an inexpensive and useful predictor of postoperative recurrence in patients with HCC.

Platelet to lymphocyte ratio as a novel prognostic tool for gallbladder carcinoma.

AIM: To preliminarily investigate the prognostic significance of the platelet to lymphocyte ratio (PLR) in patients with gallbladder carcinoma (GBC). METHODS: Clinical data of 316 surgical GBC patients were analyzed retrospectively, and preoperative serum platelet and lymphocyte counts were used to calculate the PLR. The optimal cut-off value of the PLR for detecting death was determined by the receiver operating characteristic (ROC) curve. The primary outcome was overall survival, which was estimated by the Kaplan-Meier method. The log-rank test was used to compare the differences in survival. Then, we conducted multivariate Cox analysis to assess the independent effect of the PLR on the survival of GBC patients. RESULTS: For the PLR, the area under the ROC curve was 0.620 (95%CI: 0.542-0.698, P = 0.040) in detecting death. The cut-off value for the PLR was determined to be 117.7, with 73.6% sensitivity and 53.2% specificity. The PLR was found to be significantly positively correlated with CA125 serum level, tumor-node-metastasis (TNM) stage, and tumor differentiation. Univariate analysis identified carcinoembryonic antigen (CEA), CA125 and CA199 levels, PLR, TNM stage, and the degree of differentiation as significant prognostic factors for GBC when they were expressed as binary data. Multivariate analysis showed that CA125 > 35 U/mL, CA199 > 39 U/mL, PLR ≥ 117.7, and TNM stage IV were independently associated with poor survival in GBC. When expressed as a continuous variable, the PLR was still an independent predictor for survival, with a hazard ratio of 1.018 (95%CI: 1.001-1.037 per 10-unit increase, P = 0.043). CONCLUSION: The PLR could be used as a simple, inexpensive, and valuable tool for predicting the prognosis of GBC patients.

[Clinical efficacy of daily low-dose tadalafil on erectile dysfunction-no sexual life].

OBJECTIVE: Erectile dysfunction-no sexual life (ED-NS) is defined as the inability to have enough penile erection hardness and duration so as to have enough confidence in attempting sexual intercourse for more than six months. This study was to investigate the effect of daily low-dose tadalafil on ED-NS. METHODS: We treated 35 ED-NS patients aged 17-35 (25.9 +/- 3.9) years with oral tadalafil at 5 mg qd for 3 months and followed them up for another 3 months after drug withdrawal. We obtained the scores of the patients on Self-estimation Index of Erectile Function-No Sexual Life (SIEF-NS) and compared them before and after medication and at 3 months after drug withdrawal. RESULTS: The patients' SIEF-NS scores were 43.2 +/- 7.1 after medication and 42.1 +/- 7.4 at 3 months after drug withdrawal, both significantly higher than 21.2 +/- 5.9 before treatment (P < 0.05), though there was no significant difference between the former two scores (P > 0.05). CONCLUSION: Daily medication of low-dose tadalafil can significantly improve the erectile function of the patients with ED-NS.

The role of fascin in migration and invasion of urothelial carcinoma of the bladder.

INTRODUCTION: To investigate the roles of fascin in migration and invasiveness in bladder urothelial carcinoma. MATERIALS AND METHODS: Immunohistochemical detection of fascin in urothelial carcinoma samples and inhibition the expression of fascin in the urothelial carcinoma cell line were performed, then the differences in cell behaviors before and after silencing of the fascin gene were tested. RESULTS: In our study, we found that overexpression of fascin was more frequent in urothelial carcinoma tissues (p < 0.001). Fascin expression was positively correlated with histological grade (p = 0.024) and pT stage (p < 0.001). After transfection of fascin shRNA, the expressions of fascin in 5637 cells and BIU87 cells were efficiently decreased according to real-time RT-PCR and Western blot analysis. When fascin was inhibited, a significant decrease in migration and invasion, and increase in adhesion were observed in 5637 cells and BIU87 cells. However, there was no significant change in the proliferation of 5637 cells or BIU87 cells with or without inhibition of the fascin gene. CONCLUSIONS: Fascin expression can be used as a predictor for transformation and progression of urothelial carcinoma, and reduction of fascin levels may represent a novel therapeutic strategy for urothelial carcinoma of the bladder.

Livin may serve as a marker for prognosis of bladder cancer relapse and a target of bladder cancer treatment.

OBJECTIVES: To evaluate the expression of Livin in bladder cancer, investigate its clinical and prognostic implications, and explore the effect of gene Livin transfection on the proliferation and apoptosis in bladder cancer cells. METHODS: The expression of Livinalpha and beta was detected in 48 bladder cancer samples (G(1) in 23 cases, G(2) in 17 cases, and G(3) in 8 cases. Of the 48 cases, 17 developed relapse) and 15 non-tumor bladder tissues by Western blot and reverse transcription PCR (RT-PCR). Livinalpha-pcDNA3.1(+) was constructed and transfected into T24, BIU-87 and EJ bladder cancer cells. The clone activity of the transfected cells was detected by colony formation analysis. MTT was used to determine the cell proliferation assay. Flow cytometry and acridine orange staining were used to examine apoptosis. Caspase 3 activity assay was also measured. RESULTS: Expression of Livinalpha, but not beta, was detected in 19 of the 48 bladder cancer samples; G(1) was 39.13%, G(2) and G(3) were 41.18% and 37.50%, respectively, which showed no significant (P > 0.05), but not in 15 non-tumor bladder tissues. The positive rate of Livinalpha was significant higher in relapse tumors (58.82%) than in primary tumors (29.03%) (P < 0.05). By the end of 2 years follow-up, the relapse rate in Livin positive patients was 68.42%, and 37.93% in Livin negative group. The difference between the two groups was significant (P < 0.05). Additionally, overexpression of Livinalpha clearly stimulated cell proliferation and inhibited chemical induced apoptosis in bladder cancer cells. CONCLUSIONS: Livin may serve as a promising marker to identify the relapse risk in bladder cancer, and targeting Livin could offer a therapeutic benefit in apoptosis-inducing treatment.

[Study on multiple aldosterone-producing adenomas].

OBJECTIVE: To investigate the experience on diagnosis and treatment of multiple adrenal aldosterone-producing adenomas (APA). METHODS: Eighteen cases of multiple adrenal APA were analyzed retrospectively, which were admitted from October 1992 to April 2006. RESULTS: Adrenalectomy was performed for 4 cases of unilateral synchronous multiple APA, which were discovered with three adenomas by 3D-CT; bilateral tumor resection was performed for 6 cases of bilateral synchronous multiple APA. There were 8 cases of bilateral metachronous multiple APA, including 2 cases of ipsilateral recurrent adrenal APA after adrenal tumor removal, which underwent tumor resection. Another 6 cases were contralateral APA following adrenalectomy due to adrenal APA, and underwent tumor resection. After operation, the adrenal function seemed to be normal, and no recurrence had been found on follow-up. CONCLUSIONS: Unilateral multiple synchronous APA require adrenalectomy. Tumor resection should be performed for bilateral or asynchronous APA, and it is very important to preserve healthy adrenal tissue as much as possible. 3D-CT has much value on diagnosis of small APA, unilateral multiple synchronous APA and ipsilateral recurrent adrenal APA.