Evaluation of CD47 in the Suppressive Tumor Microenvironment and Immunotherapy in Prostate Cancer.

Background: CD47 has high levels of expression in malignant cancer cells, which binds to SIRP-α to release the "don't eat me" signal and prevents mononuclear macrophages from phagocytosing the cells. Resistance to drugs and metastases are potential barriers for prostate cancer endocrine therapy. Although immunotherapy for tumors has developed rapidly in the last few decades, its effectiveness in treating prostate cancer is unsatisfactory. Prostate cancer has a high-expression level of CD47. Therefore, a novel approach for potential immunotherapy may be provided by investigating the relationship among CD47 and the infiltration of immune cells in the prostate carcinoma. Methods: The GEPIA database was utilized to compare the abundance of CD47 in malignant tissues with tissues that were normal. Furthermore, the function of CD47 in prostate carcinoma was assessed by CancerSEA. The association among CD47 and the tumor microenvironment was assessed utilizing the TISCH single cell data database. By using TIMER, the connection among CD47 and immunological invasion of prostate cancer was explored. Moreover, macrophages were cocultured with mouse prostate cancer cell RM-1 blocked by CD47 antibody to observe the changes in phagocytosis efficiency in vitro. Results: Expression level of CD47 is upregulated in prostate carcinoma, and it is closely connected with prostate cancer's inadequate immune invasion. CD47 antibody blocking promotes macrophage phagocytosis of RM-1. Conclusion: Our research demonstrates a closely relationship among CD47 and the immunological microenvironment of prostate cancer, and blocking CD47 can promote macrophages to phagocytosis of prostate cancer cells. Therefore, CD47 may provide novel strategies for potential immunotherapy of prostate cancer.

An animal model induced by bilateral cavernous nerve crushing mimics post-radical prostatectomy erectile dysfunction in old rats.

AIM: Over the years, the cavernous nerve (CN) crushing injury rat model has been frequently used for studying post-radical prostatectomy erectile dysfunction (pRP-ED). However, models based on young and healthy rats reportedly exhibit spontaneous recovery of erectile function. Our investigation purpose was to evaluate bilateral CN crushing (BCNC) effects on erectile function besides penile corpus cavernosum pathology in young and old rats and verify whether the BCNC modeling in old rats is more suitable to mimic pRP-ED. MATERIALS AND METHODS: Thirty young and old male Sprague-Dawley (SD) rats had been divided into three groups in a random manner: sham-operated group (Sham), CN-injured 2-week group (BCNC-2W), and CN-injured 8-week group (BCNC-8W). At 2 and 8 weeks postoperatively, mean arterial pressure (MAP) along with intracavernosal pressure (ICP) had been determined, respectively. Then, the penis was harvested for histopathological studies. KEY FINDING: We found that young rats exhibited erectile function spontaneous recovery 8 weeks following BCNC, while old ones failed to recover erectile function. After BCNC, the abundance of nNOS-positive nerve and smooth muscle were reduced, whereas apoptotic levels and collagen I content increased. These pathological modifications gradually resumed over time in young rats, unlike in old rats. SIGNIFICANCE: Our findings demonstrate that 18-month-old rats do not spontaneously regain erectile function at 8 weeks after BCNC. Therefore, CN-injury ED modeling in 18-month-old rats may be more suitable for studying pRP-ED.

Alkaline phosphatase combines with CT factors for differentiating small (≤ 4 cm) fat-poor angiomyolipoma from renal cell carcinoma: a multiple quantitative tool.

PURPOSE: This study aimed to evaluate the diagnostic value of serum and CT factors to establish a convenient diagnostic method for differentiating small (≤ 4 cm) fat-poor angiomyolipoma (AML) from renal cell carcinoma (RCC). MATERIALS AND METHODS: This study analyzed the preoperative serum laboratory data and CT data of 32 fat-poor AML patients and 133 RCC patients. The CT attenuation value of tumor (AVT), relative enhancement ratio (RER), and heterogeneous degree of tumor were detected using region of interest on precontrast phase (PCP) and the corticomedullary phase. Multivariate regression was performed to filter the main factors. The main factors were selected to establish the prediction models. The area under the curve (AUC) was measured to evaluate the diagnostic efficacy. RESULTS: Fat-poor AML was more common found in younger (47.91 ± 2.09 years vs 53.63 ± 1.17 years, P = 0.02) and female (70.68 vs 28.13%, P < 0.001) patients. Alkaline phosphatase (ALP) was higher in RCC patients (81.80 ± 1.75 vs 63.25 ± 2.95 U/L, P < 0.01). For CT factors, fat-poor AML was higher in PCP_AVT (40.30 ± 1.49 vs 32.98 ± 0.69Hu, P < 0.01) but lower in RER (67.17 ± 3.17 vs 84.64 ± 2.73, P < 0.01). Gender, ALP, PCP_AVT and RER was found valuable for the differentiation. When compared with laboratory-based or CT-based diagnostic models, the combination model integrating gender, ALP, PCP_AVT and RER shows the best diagnostic performance (AUC = 0.922). CONCLUSION: ALP was found higher in RCC patients. Female patients with ALP < 70.50U/L, PCP_AVT > 35.97Hu and RER < 82.66 are more likely to be diagnose as fat-poor AML.

Hepatitis E Virus Seroprevalence Indicated a Significantly Increased Risk Selectively in Patients with Gastric Cancer among 17 Common Malignancies.

Background: The impact of hepatitis E virus (HEV) infection on cancer development has been poorly investigated. This study aimed to explore the relationship between HEV seroprevalence and cancer risks and to identify high cancer risk subgroups in HEV-exposed populations. Methods: HEV seroprevalence status was determined in cancer and non-cancer subjects. Logistic regression and sensitivity analyses were used to assess the relationship between HEV antibody seropositivity and cancer risk for 17 cancer types. Additionally, interaction analyses were applied to interpret the association of HEV seroprevalence and other cancer risk factors. Results: Of the enrolled 4948 cancer and 4948 non-cancer subjects, cancer subjects had a higher anti-HEV seropositivity than non-cancer subjects (46.36% vs. 32.50%, p < 0.01). However, this divergency varied in degrees across different cancer types. Additionally, HEV seroprevalence was associated with cancer risk in young males (OR: 1.64, 95% CI: 1.19−2.27, p < 0.01). Remarkably, a significant association between HEV seroprevalence and cancer risk was observed only in gastric cancer patients (OR: 1.82, 95% CI: 1.07−3.09, p = 0.03). Conclusions: HEV seroprevalence was associated with cancer risk selectively in gastric cancer patients and young males, suggesting that cancer screening, particularly gastric cancer, should be regularly performed in young males with a history of HEV exposure.

Integrated bioinformatical analysis, machine learning and in vitro experiment-identified m6A subtype, and predictive drug target signatures for diagnosing renal fibrosis.

Renal biopsy is the gold standard for defining renal fibrosis which causes calcium deposits in the kidneys. Persistent calcium deposition leads to kidney inflammation, cell necrosis, and is related to serious kidney diseases. However, it is invasive and involves the risk of complications such as bleeding, especially in patients with end-stage renal diseases. Therefore, it is necessary to identify specific diagnostic biomarkers for renal fibrosis. This study aimed to develop a predictive drug target signature to diagnose renal fibrosis based on m6A subtypes. We then performed an unsupervised consensus clustering analysis to identify three different m6A subtypes of renal fibrosis based on the expressions of 21 m6A regulators. We evaluated the immune infiltration characteristics and expression of canonical immune checkpoints and immune-related genes with distinct m6A modification patterns. Subsequently, we performed the WGCNA analysis using the expression data of 1,611 drug targets to identify 474 genes associated with the m6A modification. 92 overlapping drug targets between WGCNA and DEGs (renal fibrosis vs. normal samples) were defined as key drug targets. A five target gene predictive model was developed through the combination of LASSO regression and stepwise logistic regression (LASSO-SLR) to diagnose renal fibrosis. We further performed drug sensitivity analysis and extracellular matrix analysis on model genes. The ROC curve showed that the risk score (AUC = 0.863) performed well in diagnosing renal fibrosis in the training dataset. In addition, the external validation dataset further confirmed the outstanding predictive performance of the risk score (AUC = 0.755). These results indicate that the risk model has an excellent predictive performance for diagnosing the disease. Furthermore, our results show that this 5-target gene model is significantly associated with many drugs and extracellular matrix activities. Finally, the expression levels of both predictive signature genes EGR1 and PLA2G4A were validated in renal fibrosis and adjacent normal tissues by using qRT-PCR and Western blot method.

Muscle-derived Stem Cells Combined With Nerve Growth Factor Transplantation in the Treatment of Stress Urinary Incontinence.

OBJECTIVE: To investigate the efficacy of muscle-derived stem cells (MDSCs) combined with nerve growth factor (NGF) in the treatment of stress urinary incontinence (SUI) METHODS: MDSCs were isolated and extracted from 90 SD rats, and the stem cell characteristics of the cells were identified using flow cytometry. NGF overexpression (oe-NGF) plasmid was coated with adenovirus and qRT-PCR was applied to verify adenovirus transfection efficiency. The rat models of SUI were constructed and randomly divided into 5 groups: control group, phosphate buffer (PBS) group, MDSCs + oe-NGF group, MDSCs + vector group, and MDSCs group. After 8 weeks of feeding, the leakage point pressure (LPP) rats, and Masson staining of rat urethral sections were detected. The expression of NGF and vascular endothelial growth factor (VEGF) was detected by western blot and IHC staining. RESULTS: Compared with the control group, the LPP and the ratio of muscle fibers/collagen fibers were significantly increased in the MDSCs treated groups, with the highest increase in the MDSCs + oe-NGF group. Western blot and IHC results showed that the expression of NGF and VEGF in the urethral tissues in the MDSCs treated groups were significantly up-regulated comparing with the control group, with the highest increase in the MDSCs + oe-NGF group. CONCLUSION: MDSCs alone can relieve SUI, while MDSCs combined with NGF is more effective, which may be related to the up-regulating of VEGF.

Association between hepatitis B and E virus infection and hepatocellular carcinoma risk.

The role of hepatitis E virus (HEV) in developing hepatocellular carcinoma (HCC) is unclear. Our study aimed to investigate the role of HE infection in HCC development and the effect of hepatitis B virus (HBV) and HEV coinfection on HCC risk. A hospital-based case-control study was conducted. A total of 474 eligible HCC cases and 586 control patients were successfully recruited. The fasting venous blood was collected from the patients at the first visited to hospital and HBV infection and HEV infection were examined within 5 days. Crude and adjusted odd ratios (ORs) with 95% confidence interval (95% CI) were estimated by using logistic regression model. HBV infection (OR: 63.10, 95% CI: 42.02-97.26) rather than HEV infection (OR: 1.08, 95% CI: 0.721-1.65) was associated with an increased risk of HCC after adjustment for confounders. The association between HBV infection and HCC risk was more remarkable in male (OR: 72.61, 95% CI: 45.10-121.38) than in female (OR: 61.89, 95% CI: 25.74-169.26). In comparison with patients who infected with neither HEV nor HBV, those who infected with only HBV (OR: 69.62, 95% CI: 40.90-123.52) and who coinfected with HEV and HBV (OR: 67.48, 95% CI:37.23-128.19) were significantly associated with an increased risk after adjustment for potential confounders. The results showed that HBV infection rather than HEV infection was associated with an increased risk of HCC, and the HEV infection may alleviate the promoting impact of HBV on HCC development.

Androgen Receptor Splice Variant 7 Predicts Shorter Response in Patients with Metastatic Hormone-sensitive Prostate Cancer Receiving Androgen Deprivation Therapy.

BACKGROUND: Whether AR-V7 expression can predict the response in patients with metastatic hormone-sensitive prostate cancer (mHSPC) who receive androgen deprivation therapy (ADT) remains to be explored. OBJECTIVE: To evaluate the predictive value of AR-V7 expression in the prognosis of mHSPC patients receiving ADT. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter prospective cohort study, 310 mHSPC patients commencing ADT were enrolled. Standard immunohistochemical staining was used to assess AR-V7 protein expression in biopsy tissues collected before initiation of ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier survival estimates and Cox regression analyses were used to evaluate associations of AR-V7 status (positive vs negative) with progression-free survival (PFS) and overall survival (OS). RESULTS AND LIMITATIONS: Sixty-four (21%) patients were AR-V7-positive and 246 (79%) patients were AR-V7-negative. The median follow-up for patients not confirmed dead was 25 mo (interquartile range 10-30). Compared to AR-V7-negative patients, AR-V7-positive patients had significantly shorter PFS (hazard ratio [HR] 47.39, 95% confidence interval [CI] 25.83-86.94) and OS (HR 3.57, 95% CI 1.46-8.72). In multivariable analysis, AR-V7 was an independent predictive factor (HR 7.61, 95% CI 5.24-11.06) for shorter PFS. Limitations include the sample size and follow-up period. CONCLUSIONS: AR-V7 expression in primary cancer tissue is correlated with poor prognosis for mHSPC patients receiving ADT. PATIENT SUMMARY: In this study of men with metastatic hormone-sensitive prostate cancer, AR-V7 protein expression in primary cancer tissue was associated with poor outcomes on androgen deprivation therapy.

Comparison of survival in elderly patients treated with uretero-cutaneostomy or ileal conduit after radical cystectomy.

BACKGROUND: In bladder cancer patients with age ≥ 80 years old, there have been controversies in performing uretero-cutaneostomy or ileal conduit as urinary diversion after radical cystectomy. Limited study evaluated overall survival (OS) and cancer-specific survival (CSS) between the two urinary diversions in elderly patients. This study is to compare OS and CSS between uretero-cutaneostomy and ileal conduit after radical cystectomy in bladder cancer patients with age ≥ 80 years old. PATIENTS AND METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Bladder cancer patients diagnosed between 2004 and 2016 with age ≥ 80 years old who underwent radical cystectomy with either UC or IC were selected. After propensity score matching, Cox regression and Kaplan-Meier analysis were used to analyze the survival. We calculated statistical power for survival. RESULTS: Of 1394 patients who met the inclusion criteria, 1093 underwent ileal conduit and 301 underwent uretero-cutaneostomy. After propensity score matching, 285 patients were included in each group. Multivariable Cox analysis showed urinary diversion was not a risk factor of OS and CSS (HR 1.044, [95% CI 0.867-1.257] and 1.012 [0.748-1.368], respectively). Both OS and CSS were not significantly different, with median survival of ileal conduit and uretero-cutaneostomy were 19 [16-24] months and 19 [15-26] months respectively. Additionally, We found OS had the following risk factors: tumor stage (distant vs regional vs localized, 5.332 [3.610-7.875] vs 1.730 [1.375-2.176] vs 1), node density (>0.2 vs ≤0.2 vs none, 1.410 [1.047-1.898] vs 0.941 [0.658-1.344] vs 1) and age (1.067 [1.032-1.103] for each year). While CSS had the following risk factors: tumor stage (distant vs regional vs localized, 4.035 [2.046-7.959] vs 2.476 [1.651-3.713] vs 1), node density (>0.2 vs ≤0.2 vs none, 2.501 [1.645-3.804] vs 1.062 [0.590-1.914] vs 1) and tumor size (greater than 3 cm vs less than 3 cm, 1.596 [1.057-2.412] vs 1). Our analysis obtained 0.707 power for overall survival. CONCLUSION: Urinary diversion by uretero-cutaneostomy or by ileal conduit was not associated with overall and cancer-specific survival. It is reasonable to consider uretero-cutaneostomy as a regular procedure of urinary diversion in elderly bladder cancer patients after radical cystectomy to avoid associate complications.

Observation on the changes of clinical symptoms, blood and brain copper deposition in Wilson disease patients treated with dimercaptosuccinic acid for 2 years.

OBJECTIVE: To compare the clinical symptoms, brain copper deposition changes of Meso-2,3-dimercaptosuccinic acid (DMSA) and penicillamine therapy in patients with Wilson disease (WD) within 2 years. METHODS: 68 drug-naive patients with WD were enrolled. 10 WD patients treated with zinc gluconate alone were used as the control group. Neurological symptoms were scored using the modified Young Scale. Liver function tests, copper indices and sensitive weighted imaging (SWI) examination were collected. The values of corrected phase (CP) were collected. WD patients were treated with DPA (group 1) or DMSA (group 2) for two years, and followed up every 2 months. RESULTS: The ratio of neurological improvement in group 2 was higher than that in group 1 (P = 0.029). Higher rate of neurologic worsening was noticed in patients treated with DPA vs DMSA (P = 0.039). The post-treatment neurological score of DMSA group was lower than that of Zn group (P = 0.037). Hepatic function in 63.3% of patients was stable, while 16.7% was improved, and 20% was deteriorated, after DMSA therapy. Urinary copper levels were lower 1 month (p = 0.032), 4 months (p = 0.041), 12 months (p = 0.037) after initiation of treatment in group 2 than in group 1. At the first year of treatment, the CP values in globus pallidus and substantia nigra in group 2 were higher than those in group 1 (P = 0.034,0.039). At the second year of treatment, the CP values of substantia nigra in group 2 were higher (P = 0.041). Discontinuation was more common in patients on DPA therapy (P = 0 0.032). CONCLUSIONS: DMSA could remove metal from brain tissue faster than DPA. DMSA is effective for neurologic symptoms, while the outcome for hepatic symptoms is not entirely satisfactory. DMSA therapy is better tolerated than DPA.

The ceRNA Network Has Potential Prognostic Value in Clear Cell Renal Cell Carcinoma: A Study Based on TCGA Database.

Clear cell renal cell carcinoma (ccRCC) is a very common cancer in urology. Many evidences suggest that complex changed pathways take a nonnegligible part in the occurrence and development of ccRCC. Nevertheless, the underlying mechanism is not clear. In this study, the expression data between ccRCC and normal tissue samples in TCGA database were compared to distinguish differentially expressed genes (DEGs: mRNAs, miRNAs, and lncRNAs). Afterwards, we used GO enrichment and KEGG pathway enrichment analyses to explore the functions of these DEGs. We also found the correlation between three RNAs and created a competing endogenous RNA (ceRNA) network. Moreover, we used univariate Cox regression analysis to select DEGs that are connected with overall survival (OS) of ccRCC patients. We found 1652 mRNAs, 1534 lncRNAs, and 173 miRNAs that were distinguished in ccRCC compared with normal tissues. According to GO analysis, the maladjusted mRNAs are mainly concentrated in immune cell activation and kidney development, while according to KEGG, they are mainly concentrated in pathways related to cancer. A total of 5 mRNAs, 1 miRNA, and 4 lncRNAs were connected with patients' OS. In this article, a network of lncRNA-miRNA-mRNA was established; it is expected to be able to indicate possible molecular mechanisms for initial of ccRCC and provide a new viewpoint for diagnosis of ccRCC.

A study of susceptibility-weighted imaging in patients with Wilson disease during the treatment of metal chelator.

OBJECTIVE: A randomized-controlled trial comparing study of the changes in brain sensitive-weighted imaging (SWI) of Wilson disease (WD) patients during the treatment with metal chelator was done. METHODS: 100 untreated WD patients (80 cases of cerebral type, 20 cases of hepatic type, age 20.13 ± 9.12 years old) and 20 normal controls were selected. Neurological symptoms were scored using the modified Young scale. Liver function tests and copper indices were collected. All study objects received SWI test of the brain. The values of corrected phase (CP) were calculated on SWI. Cerebral-type WD patients were treated with D-penicillamine (DPA) (group 1) or Dimercaptopropane Sulfonate (DMPS) + Dimercaptosuccinic Acid (DMSA) (group 2). Hepatic-type WD patients were treated with DPA (group 3). All patients received annual neurological symptom score, liver function, copper indices, and SWI examination. RESULTS: At the first year of treatment, score of the modified Young scale in group 2 was lower than that in group 1 (P = 0.023) and lower than that before treatment (P = 0.040). After 2 years of treatment, the score of the modified Young scale in group 1 was lower than that before treatment (P = 0.012). At the second year after treatment, the urinary copper in group 2 was higher than that in group 1 (P = 0.014). Urinary copper was maintained at 200 µg/day in group 1 and 300 µg/day in group 2 after 3 years of treatment. At the first year of treatment, serum copper in group 1 was lower than that in group 2 (P = 0.032). At the first year of treatment, CP values of the pallidum and substantia nigra in group 2 were higher than those in group 1 (P = 0.026, 0.040). At the second year of treatment, CP value of substantia nigra in group 2 was higher than that in group 1 (P = 0.037). After 3 years of treatment, there was no difference in CP values between WD patients and normal controls. CONCLUSIONS: Therapy with DMPS and DMSA improves neurological symptoms of WD patients more quickly and leads to less aggravation, compared with therapy with DPA. The metal content in the brain of WD patients was at a low level after 3 years of treatment. DMPS and DMSA can remove metal from brain tissue faster than DPA.

Injury factors and pathological features of toxic milk mice during different disease stages.

OBJECTIVE: To evaluate different injury factors and pathological characteristics of the brain at different disease stages in toxic milk (TX) mice, an animal model of Wilson's disease (WD). METHODS: Thirty TX mice (10 each at 3, 6 and 12 months old) and 30 age-matched C57 mice were used in this study. Corrected phase (CP) values were determined from susceptibility-weighted images. Myelin content was determined by measuring inhibition optical density values of Luxol fast blue-stained sections. Neurofilament protein 68 kDa (NF68), ß-amyloid precursor protein (ß-APP), and myelin basic protein (MBP) levels, as well as copper and iron content, in brain nuclei of the TX mouse were evaluated. Gene amplification ratios for catalase (CAT), GSH peroxidase (GSH-PX), nitric oxide synthase (NOS), and superoxide dismutase (SOD) in mouse brain were also determined. RESULTS: Compared with C57 mice, neuronal cell counts were decreased in 12-months-old TX mice (p = .011). Myelin content was decreased in the lenticular nucleus (p = .029), thalamus (p = .030), and brainstem (p = .034) of 6-months-old TX mice; decreases in the corresponding nuclei (p = .044, .037, and .032, respectively) were also found in 12-months-old TX mice. MBP values were lower in the lenticular nucleus and thalamus (p = .027 and .016, respectively) of 6-months-old TX mice and in the corresponding nuclei (p = .24 and .040) of 12-months-old TX mice. NF-68 values were lower in the lenticular nucleus and thalamus (p = .034 and .037, respectively) of 6-months-old TX mice and in the corresponding nuclei (p = .006 and .012) of 12-months-old TX mice. ß-APP values were higher in the thalamus of 6-months-old (p = .037) and 12-months-old (p = .012) TX mice. Iron content was higher in the lenticular nucleus, thalamus, and cerebellum (p = .044, .038, and .029, respectively) of 6-months-old TX mice and in the corresponding nuclei (p = .017, .024, and .029) of 12-months-old TX mice. The NOS gene amplification multiple was higher (p = .039), whereas the SOD1 gene amplification multiple was lower (p = .041) in 12-months-old TX mice. There was no correlation between metal content or oxidation index and pathological index. CONCLUSIONS: The pathological characteristics of the brains of TX mice may differ at different ages. Different pathogenic factors, including copper and iron deposition and abnormal oxidative stress, are present at different stages.

Carnitine/organic cation transporter 2 (OCTN2) contributes to rat epididymal epithelial cell growth and proliferation.

Carnitine/organic cation transporter 2 (OCTN2) is localized at the basolateral membrane of epididymal epithelial cells, and mainly serves to reabsorb carnitine as an essential factor for sperm maturation; however, its functional features in epididymal epithelial cells have remained unclear. We isolated primary epididymal epithelial cells from rat epididymides and verified their phenotype by detecting the presence of cytokeratin-19 (CK-19, an epithelial cell marker) and the absence vimentin (an interstitial cell marker). We found that cultured epididymal epithelial cells isolated from rat epididymides expressed high levels of CK-19 but barely expressed vimentin. Gain-of-function assays, which included the CCK-8 assay and EdU flow cytometry assay, indicated that overexpression of OCTN2 significantly promoted epididymal epithelial cell growth and proliferation. Moreover, forced expression of OCTN2 inhibited the cell apoptosis process, and at the same time increased expression of the pro-apoptosis factor BAX, and decreased expression of the anti-apoptosis factors BCL-2 and Survivin. Furthermore, we also found that OCTN2 overexpression dramatically increased the levels of biomarkers associated with spermatogenesis, including azoospermia-like (DAZL), phosphoglycerate kinase 2 (PGK2), and protamine 2 (PRM2). These results demonstrate that OCTN2 plays a positive role in epididymal epithelial cells, and might be useful in the clinical treatment of male infertility by serving as a key regulatory factor.

[Logistic regression analysis of risk factors of serious complications related with double-J ureteral stenting following percutaneous nephrolithotomy].

OBJECTIVE: To investigate the risk factors of the serious complications related with double-J ureteral stent placement following percutaneous nephrolithotomy (PCNL). METHODS: Clinical data were reviewed for 272 patients treated with PCNL and indwelling double-J stents between January, 2014 and April, 2016. The risk factors of serious complications were identified using univariate and multivariate logistic regression analysis. RESULTS: Serious complications of double-J ureteral stenting occurred in 63 patients (23.1%). Univariate and multivariate logistic regression analysis indicated that the ureter abnormalities (ß=1.735, P=0.000, OR=5.670), stent indwelling duration (ß=1.206, P=0.028, OR=3.340), gender (ß=0.895, P=0.016, OR=2.446), preoperative urinary tract infection (ß=0.849, P=0.020 , OR=2.338) and stent size (ß=0.847, P=0.011, OR=2.333) were all risk factors of serious complications related with the procedure. CONCLUSION: Male patients are exposed to a higher risk of serious complications following PCNL. Effective management of urinary tract infection and choice of appropriate stent size in cases of ureteral abnormalities help to reduce these complications. The double-J stent should be withdrawn as soon as possible in patients with good postoperative recovery.

Diffusion tensor imaging of the extracorticospinal network in the brains of patients with Wilson disease.

OBJECTIVE: To evaluate damage to the extracorticospinal tract in Wilson disease (WD) patients using diffusion tensor imaging (DTI). METHODS: 70 patients with WD, including 50 with cerebral type and 20 with hepatic type, and 20 age-matched healthy controls were enrolled. Neurological symptoms were scored using the modified Young Scale. Patients with cerebral type WD were divided into four subgroups: those with (1) hypokinesia, (2) parkinsonism, (3) mouth and throat dystonia, and (4) psychiatric symptoms. All study subjects underwent DTI of the brain. Five regions of interest (ROIs) were chosen. Fractional anisotropy (FA) and fiber volumes between ROIs were determined, and the relationships between DTI metrics and clinical status were evaluated. RESULTS: FA values and fiber volumes between subcortical nuclei were lower in WD patients. Fiber volumes between the putamen (PU) and the globus pallidus (GP), substantia nigra (SN), and thalamus (TH); between the head of the caudate nucleus (CA) and the GP and TH; and between the TH and cerebellum were lower in group 1 than in the other groups of WD patients. Fiber volumes between the GP and the SN and TH were lower in group 2, and fiber volumes between the SN and TH were lower in group 3. DTI metrics differed between patients with the cerebral and hepatic types of WD. CONCLUSIONS: DTI can reconstruct the network of the extracorticospinal tract. Fiber projection between subcortical nuclei was abnormal in WD patients. Damage to fiber connections may correlate with neurological symptoms in WD patients.

[Restriction landmark genomic scanning for screening aberrant CpG methylations in prostate cancer].

OBJECTIVE: To screen methylations of CpG islands in prostate cancer using restriction landmark genomic scanning (RLGS). METHODS: The DNA was extracted from homogeneous cells captured by laser capture microdissection in 20 prostate cancer and 18 benign prostatic hyperplasia (BPH) tissues for scanning the CpG islands using RLGS. The methylation status of each CpG island was compared between the cancer and BPH samples to screen the genes involved in prostate cancer development. The screened genes were uploaded to DAVID database for GO analysis, and the genes with the most significant methylation were analyzed by pyrosequencing. RESULTS AND CONCLUSION: Among all the tested CpG islands, 10245 (37.2%) in prostate cancer and 8658 (30.3%) in BPH samples were found to be abnormally methylated, and >60% of the methylated CpG islands were in the promoter region. Compared with BPH samples, the prostate cancer samples showed differential methyation in 735 CpG islands, including 458 hepermethyated and 256 hypomethelated ones. Seven genes (DPYS, P16, APC, GSTP1, TMEM122, RARB, and ARHGAP20) in prostate cancer were identified to have distinct methylations. Bioinformatics analysis suggested that these genes were associated with several biomolecular and biological processes, and among them DPYS gene was involved in 13 GO anotated biologic functions, development of 50 diseases and 47 protein interactions. Pyrosequencing of 7 sites of the CPG island in DPYS gene showed a methylation frequency of 32.7%, suggesting the importance of DPYS gene in the carcinogenesis and progression of prostate cancer.

[Comparison of laparoscopic pyelolithotomy and percutaneous nephrolithotomy for renal pelvic stones larger than 2.5 cm].

OBJECTIVE: To compare the safety, efficacy and complications of laparoscopic pyelolithotomy (LPL) and percutaneous nephrolithotomy (PCNL) for treatment of renal pelvic stones larger than 2.5 cm. METHODS: From 2011 to 2016, 32 patients underwent LPL and another 32 patients received PCNL for renal pelvic stones larger than 2.5 cm. The baseline characteristics of the patients, stone size, mean operative time, estimated blood loss, postoperative hospital stay, stone-free rate, postoperative analgesia, blood transfusion, and the intraoperative, early postoperative and long-term complications were compared between the two groups. RESULTS: The baseline characteristics and stone size were comparable between the two groups. The mean operative time of LPL and PCNL was 117∓23.12 and 118.16∓25.45 min, respectively (P>0.05). The two groups showed significant differences in the mean estimated blood loss (63∓11.25 vs 122∓27.78 mL, P<0.01) and blood transfusion rate (0 vs 6.2%, P<0.01) but not in postoperative hospital stay (4.5∓1.34 vs 4.8∓2.2 days, P>0.05), stone-free rate (93.1% vs 87.5%, P>0.05) or the postoperative analgesia time (1.7∓0.5 and 1.9∓0.6 days, P>0.05). The incidence of intraoperative complications were significant lower in LPL group than in PCNL group (6.2% vs 25.0%, P<0.01), but the incidences of early postoperative complications (25.0% vs 34.4%, P>0.05) and long-term postoperative complications (9.4% vs 12.5%, P>0.05) were similar between them. CONCLUSION: PCNL is the standard treatment for pelvic stones larger than 2.5 cm, but for urologists experienced with laparoscopic technique, LPL provides a feasible and safe option for management of such cases.

Effects of insulin-like growth factor-1 on the relaxation responses of the cavernous smooth muscle from aged rats.

OBJECTIVE: The aim of this study was determine whether intracavernosal injection (ICI) of insulin-like growth factor-1 (IGF-1) protein can improve corpus cavernosal smooth muscle relaxation in aging rats. MATERIALS AND METHODS: Ten young (4-month-old) and 30 old (24-month-old) Sprague-Dawley male rats were enrolled in the study. The old rats were divided into three groups: vehicle-only (n = 10), IGF-1 1 µg/kg (n = 10) and IGF-1 10 µg/kg treatment groups (n = 10). After 4 weeks of single IGF-1 injection treatment, strips of corporal tissue were precontracted with phenylephrine, and dose-response curves were generated to evaluate endothelial-dependent [acetylcholine (ACh)], endothelial-independent [sodium nitroprusside (SNP)] and electrical field stimulation (EFS) vasoreactivity. The changes in percentage of cavernosal smooth muscle and the concentration of nitric oxide (NO) in penile tissue were also evaluated. RESULTS: After IGF-1 treatment, the vasoreactivity was significantly improved in both the 1 µg/kg and the 10 µg/kg treatment groups compared with the vehicle-only group at 4 weeks in response to ACh, SNP and EFS (all p < 0.05). The percentage of cavernosal smooth muscle was increased in the IGF-1 treatment groups. The NO concentrations were increased after IGF-1 treatment. CONCLUSIONS: These data demonstrate that ICI of IGF-1 can improve vasoreactivity via endothelium-dependent and endothelial-independent mechanisms in the corpus cavernosum of the aging rat.

[Clinical efficacy of transperitoneal verus retroperitoneal laparoscopic partial nephrectomy for renal tumors with R. E. N. A. L score over 7].

OBJECTIVE: To compare the safety, feasibility and efficacy of transperitoneal and retroperitoneal laparoscopic partial nephrectomy (LPN) in the treatment of renal tumors with R. E. N. A. L score more than 7. METHODS: The clinical data were collected from 62 patients undergoing transperitoneal LPN (32 cases) and retroperitoneal LPN (30 cases) for a complex renal mass (R.E.N.A.L. score≥7) between January 2012 and March 2014. The surgical and early postoperative outcomes and complications were analyzed to evaluate the efficacy of the treatments. The mean operative time, estimated blood loss, warm ischemia time, surgical complications, blood transfusion rate, tolerating regular diet time, postoperative hospital stay and surgical margin were compared between the two groups. RESULTS: The operations were completed successfully in all cases except for 1 case in transperitoneal group and 3 in retroperitoneal group that required conversion to open surgery. No significant differences were found in age, body mass index, ASA score, Charlson comorbidity index, tumor size or R.E.N.A.L. nephrometry score (P>0.05), nor in estimated blood loss, warm ischemia time, intraoperative complication, blood transfusion rate or surgical margin between the two groups (P>0.05, respectively). The transperitoneal LPN group had a shorter mean operative time than retroperitoneal LPN group (210.4∓59.2 vs 252∓58.3 min, P<0.05) but showed longer tolerating regular diet time (47∓10 h vs 23∓6 h, P<0.05) and postoperative hospital stay time (8.4∓1.9 days vs 6.5∓1.6 days, P<0.05). CONCLUSION: Both transperitoneal LPN and retroperitoneal LPN are safe, feasible and effective for surgical management of complex localized tumors, but the transperitoneal procedure offers larger operative space with better exposure; the retroperitoneal procedure better promotes postoperative recovery of the patients.