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Yuan-Yuan Ju,1,2 Ming Jiang,2 Feifei Xu,1,3 Dongqin Wang,1,3 Bixiao Ding,1,3 Ling-Jie Ma,2 Hao Wu1 1Department of Otolaryngology, Head, and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China; 2Institute of Pain Medicine, Institute of Nautical Medicine, Nantong University, Nantong, Jiangsu, People’s Republic of China; 3Medical School of Nantong University, Nantong, Jiangsu, People’s Republic of ChinaCorrespondence: Hao WuDepartment of Otolaryngology, Head, and Neck Surgery, Affiliated Hospital of Nantong University, Xisi Road 20#, Nantong, Jiangsu Province 226001, People’s Republic of ChinaEmail entwuhao@163.comLing-Jie MaInstitute of Pain Medicine, Institute of Nautical Medicine, Nantong University, Seyuan Road 9#, Nantong, Jiangsu Province 226019, People’s Republic of ChinaEmail malingjie@ntu.edu.cnPurpose: Trigeminal neuropathic pain is very common clinically, but effective treatments are lacking. Chemokines and their receptors have been implicated in the pathogenesis of chronic pain. This study explored the role of the chemokine CXCL10 and its receptor, CXCR3, in trigeminal neuropathic pain in mice.Materials and Methods: Trigeminal neuropathic pain was established by partial infraorbital nerve ligation (pIONL) in wild-type and Cxcr3−/− mice. Facial mechanical allodynia was evaluated by behavioral testing. A lentivirus containing Cxcr3 shRNA (LV-Cxcr3 shRNA) was microinjected into the trigeminal ganglion (TG) to knock down Cxcr3 expression. Quantitative polymerase chain reaction assays and immunofluorescence staining were used to examine Cxcl10/Cxcr3 mRNA expression and protein distribution. Western blotting was performed to examine activation of extracellular signal-regulated kinase (ERK) and AKT in the TG. Intra-TG injection of an AKT inhibitor was performed to examine the role of AKT in trigeminal neuropathic pain.Results: pIONL induced persistent trigeminal neuropathic pain, which was alleviated in Cxcr3−/− mice. Intra-TG injection of LV-Cxcr3 shRNA attenuated pIONL-induced mechanical allodynia. Furthermore, pIONL increased the expression of CXCR3 and its major ligand, CXCL10, in TG neurons. Intra-TG injection of CXCL10 induced pain hypersensitivity in wild-type mice but not in Cxcr3−/− mice. CXCL10 also induced activation of ERK and AKT in the TG of wild-type mice. Finally, pIONL-induced activation of ERK and AKT was reduced in Cxcr3−/− mice. Intra-TG injection of the AKT inhibitor alleviated pIONL-induced mechanical allodynia in WT mice but not in Cxcr3−/− mice.Conclusion: CXCL10 acts on CXCR3 to induce ERK and AKT activation in TG neurons and contributes to the maintenance of trigeminal neuropathic pain.Keywords: CXCR3, CXCL10, trigeminal ganglion, neuropathic pain, mice

Background/Purpose Pentosan polysulfate sodium (PPS), a semi-synthetic polysaccharide that adheres to bladder mucosa, is effective in treating interstitial cystitis. We evaluated the clinical benefit of PPS for the prevention of recurrent urinary tract infection (UTI) in women. Methods We conducted a multicenter, open-label, prospective, phase II, randomized controlled trial enrolling women with recurrent UTI ≥ 2 times in the past 6 months or ≥ 3 times in the past 12 months. Patients received oral PPS monotherapy for 16 weeks in treatment group. All patients were followed every 28 days until UTI recurrence or up to 112 days. The primary endpoint was the UTI recurrence-free survival. Adverse events were recorded as secondary endpoint. Results A total of 26 women were eligible for analysis. In the PPS group, none (0%) of the 12 patients had UTI recurrence during the study period. However, 9 (64%) of 14 patients had UTI recurrence in the control group. The UTI recurrence-free survival was significantly higher in the PPS group than in the control group (log-rank test p = 0.0004). One adverse event which led to discontinuation of the trial regimen was regarded as irrelevance of PPS treatment. The limitation was the small number of cases. Conclusion Among women with recurrent UTI, 16-week PPS monotherapy significantly reduced UTI recurrence when compared with the control group.

To evaluate the predictive accuracy of the %p2PSA and prostate health index (PHI) in predicting aggressive pathological outcomes in patients with prostate cancer (PCa) undergoing radical prostatectomy (RP), we enrolled 91 patients with organ-confined PCa who were treated with robot-assisted RP. p2PSA levels and the PHI were investigated for their ability to predict pathological results. The %p2PSA and PHI were both significantly higher in patients with ≥pT3 disease, high-risk disease, positive surgical margin, or seminal vesical invasion (SVI). In univariable analysis, p2PSA derivatives were significant predictors of the presence of ≥pT3 disease, high-risk disease, positive surgical margin, and SVI. To predict adverse pathological outcomes at a sensitivity of 90%, p2PSA derivatives had higher specificity than standard PSA derivatives. In multivariable analysis, additional increases in the area under the receiver operating characteristic curve (AUC) were observed with the %p2PSA and PHI for ≥pT3 disease, high-risk disease, and positive surgical margin (8.2% and 2.7%, 6.2% and 4.1%, and 8.6% and 5.4%, respectively). A PHI ≥61.26 enhanced the predictive accuracy of the model for SVI by increasing the AUC from 0.624 to 0.819 (p = 0.009). The preoperative %p2PSA and PHI accurately predict adverse pathological results and are useful for decision-making.

International audience; Tunneling nanotubes (TNTs) are actin-based transient tubular connections that allow direct communication between distant cells. TNTs play an important role in several physiological (development, immunity, and tissue regeneration) and pathological (cancer, neurodegeneration, and pathogens transmission) processes. Here, we report that the Wnt/Ca2+ pathway, an intracellular cascade that is involved in actin cytoskeleton remodeling, has a role in TNT formation and TNT-mediated transfer of cargoes. Specifically, we found that Ca2+ /calmodulin-dependent protein kinase II (CaMKII), a transducer of the Wnt/Ca2+ pathway, regulates TNTs in a neuronal cell line and in primary neurons. We identified the β isoform of CaMKII as a key molecule in modulating TNT formation and transfer, showing that this depends on the actin-binding activity of the protein. Finally, we found that the transfer of vesicles and aggregated α-synuclein between primary neurons can be regulated by the activation of the Wnt/Ca2+ pathway. Our findings suggest that Wnt/Ca2+ pathway could be a novel promising target for therapies designed to impair TNT-mediated propagation of pathogens.

INTRODUCTION AND OBJECTIVES:Prostate health index (PHI) is a promising biomarker in the prediction of aggressive prostate cancer. Since prostate volume has been regarded as an important factor cont...

Human caseinolytic protease proteolytic subunit (HsClpP) is a highly conserved serine protease that plays an essential role in cell homeostasis through removal of the damaged and/or misfolded proteins. Recently, due to its critical role in cancer proliferation and metastasis, HsClpP has been considered as a promising target for the cancer treatment. In this paper, through a random screening toward a library of 2086 bioactive chemicals, a novel compound I, 3-(3,5-dibromo-4-hydroxybenzylidene) -5-iodoindolin-2-one, was identified as a potent suppressor of HsClpP. Herein, a series of compound I derivatives were synthesized, and evaluated for their anti-cancer activities on a variety of cancers cells. Through the preliminary biological assay in vitro, including MTT assay and proteolytic activity assay, compound I was identified as the most potent inhibitor. Treatment with compound I impaired the migration of Hela cells. In addition, compound I disrupted the mitochondrial function, and reduced the level of the SDHB and induced the production of the ATF4. In general, compound I is a promising probe of HsClpP for cancer treatment, and is a good lead compound for the development of novel anti-cancer agent.

Uterine sarcoma is a very aggressive and highly lethal disease. Even after a comprehensive staging surgery or en block cytoreduction surgery followed by multimodality therapy (often chemotherapy and/or radiation therapy), many patients relapse or present with distant metastases, and finally die of diseases. The worst outcome of uterine sarcomas is partly because of their rarity, unknown etiology, and highly divergent genetic aberration. Uterine sarcomas are often classified into four distinct subtypes, including uterine leiomyosarcoma, low-grade uterine endometrial stromal sarcoma, high-grade uterine endometrial stromal sarcoma, and undifferentiated uterine sarcoma. Currently, evidence from tumor biology found that these tumors showed alternation and/or mutation of genomes and the intracellular signal pathway. In addition, some preclinical studies showed promising results for targeting receptor tyrosine kinase signaling, phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway, various kinds of growth factor pathways, Wnt/beta-catenin signaling pathway, transforming growth factor β/bone morphogenetic protein signal pathway, aurora kinase A, MDM2 proto-oncogene, histone deacetylases, sex hormone receptors, certain types of oncoproteins, and/or loss of tumor suppressor genes. The current review is attempted to summarize the recurrent advance of targeted therapy for uterine sarcomas.

Endometrial stromal tumors are rare uterine tumors (

Purpose: The objective of this study was to evaluate the efficacy of antibiotic prophylaxis in patients with a tentative diagnosis of ureteral stones undergoing ureterorenoscopic surgery. Materials and Methods: This is a single-surgeon, open-label randomized controlled trial, which enrolled 109 patients from May 2014 to September 2018. The patients were equally randomized into three groups: a group with a single dose of intravenous cefazolin (1g), a group with oral cefuroxime (500 mg), and a control group with no prophylactic antibiotics. The primary end points were the rate of febrile urinary tract infections (UTIs) and postoperative pyuria. Results: The rate of postoperative fever was 9.4% in the cefazolin group (3 in 32), 0% in the cefuroxime group (0 in 29), and 6.9% in the control group (2 in 36). There was no statistically significant difference between the cefazolin and control groups (P = 0.1). The rate of postoperative pyuria was 64.3% in the cefazolin group, 58.3% in the cefuroxime group, and 33.3% in the control group, without statistically significant differences between the groups. Conclusion: Antibiotic prophylaxis could not reduce the incidence of postoperative febrile UTI and pyuria in ureterorenoscopic lithotripsy.

Congenital microcephaly is highly associated with intellectual disability. Features of autosomal recessive primary microcephaly subtype 3 (MCPH3) also include hyperactivity and seizures. The disease is caused by biallelic mutations in the Cyclin-dependent kinase 5 regulatory subunit-associated protein 2 gene CDK5RAP2. In the mouse, Cdk5rap2 mutations similar to the human condition result in reduced brain size and a strikingly thin neocortex already at early stages of neurogenesis that persists through adulthood. The microcephaly phenotype in MCPH arises from a neural stem cell proliferation defect. Here, we report a novel role for Cdk5rap2 in the regulation of dendritic development and synaptogenesis of neocortical layer 2/3 pyramidal neurons. Cdk5rap2-deficient murine neurons show poorly branched dendritic arbors and an increased density of immature thin spines and glutamatergic synapses in vivo. Moreover, the excitatory drive is enhanced in ex vivo brain slice preparations of Cdk5rap2 mutant mice. Concurrently, we show that pyramidal neurons receive fewer inhibitory inputs. Together, these findings point towards a shift in the excitation - inhibition balance towards excitation in Cdk5rap2 mutant mice. Thus, MCPH3 is associated not only with a neural progenitor proliferation defect but also with altered function of postmitotic neurons and hence with altered connectivity.

The aim of this study was to compare single and tandem ureteral stenting in the management of malignant ureteral obstruction (MUO). Our hospital’s institutional review board approved this prospective study. Between November 2014 and June 2017, single ureteral stenting was performed in 56 patients (94 renal units) and tandem ureteral stenting in 48 patients (63 renal units) for MUO. A comparative analysis of the technical success rate, patient survival, stent patency, and complications was performed. Similar demographic data were observed in patients receiving either single or tandem ureteral stenting. The technical success rate was 93.6% (88/94) for single ureteral stenting and 95.2% (60/63) for tandem ureteral stenting. There was no difference in overall survival between patients receiving single or tandem ureteral stenting (p = 0.41), but the duration of stent patency in tandem ureteral stenting was significantly longer (p = 0.022). The mean patency time was 176.7 ± 21.3 days for single ureteral stenting, and 214.7 ± 21.0 days for tandem ureteral stenting. The complications of ureteral stenting were urinary tract infection (n = 18), lower urinary tract symptoms (n = 5), haematuria (n = 3), and stent migration (n = 1). Tandem ureteral stenting is a safe and feasible treatment for MUO, and had better efficacy compared to single ureteral stenting. • Ureteral stenting is an established treatment for the management of malignant ureteral obstruction (MUO) • Prospective single-centre study showed that tandem ureteral stenting is a safe and feasible treatment for MUO • Tandem ureteral stenting provides longer stent patency compared to single ureteral stenting in patient with MUO

Background/Purpose: Prostate specific antigen (PSA) with low specificity that causes unnecessary prostate biopsies increases clinical morbidities, psychological stress, and medical expenses. We aimed to test the accuracy and cutoff value of Prostate Health Index (PHI) in men for prostate cancer detection. Methods: We prospectively enrolled 213 men who underwent prostate biopsy with PSA≦10 ng/ml or abnormal findings on digital rectal examination. Total PSA (tPSA), free PSA (fPSA) and p2PSA levels were measured by serum samples before prostate biopsy. PHI was calculated as (p2PSA/fPSA) × √tPSA. Multivariable logistic regression analyses were used to predict the risk of cancer and detect clinically significant prostate cancer. Results: 33 (27.0%) patients were confirmed with the diagnoses of prostate cancer by prostate biopsy. The levels of p2PSA, %p2PSA, and PHI showed statistically significant differences between prostate cancer patients and non-cancer patients. %p2PSA and PHI had the highest area under the receiver operating characteristic curve (AUC) of 0.723 and 0.772 (both p

Objective Extra-adrenal pheochromocytomas are known as paragangliomas. The majority of extra-adrenal tumors occur intra-abdominally along the sympathetic chain. However, they may also occur in the urinary tract, including the urinary bladder. Materials and methods In this study, we report a clinical series of six patients diagnosed with bladder paragangliomas in our hospital over the past two decades, and review the literature regarding this unusual disease. Results Among the six cases, two were male and four were female. The most common presentation was painless gross hematuria, with five of the six patients (83.3%) having this chief complaint. Two patients presented with hypertension and one with palpitations. Two had malignant bladder paragangliomas, and one died within one year after the diagnosis. Four patients received transurethral resection of the bladder tumors, and one patient developed tumor recurrence within one year of follow-up. Conclusion Bladder paraganglioma is an extremely rare tumor with a high recurrence rate, and the most common presenting symptom in our series was painless gross hematuria. Large, polypoid, and multiple tumors indicate malignancy.

To provide clinical outcomes of the Resonance metallic ureteral stent in patients with malignant ureteral obstruction, as well as clinical factors predicting stent failure.Cancer patients who have received Resonance stents from July 2009 to March 2012 for ureteral obstruction were included for chart review. Stent failure was detected by clinical symptoms, image studies, and renal function tests. Survival analysis for stent duration was used to estimate patency rate and factors predicting stent failure.A total of 117 stents were inserted successfully into 94 ureteral units in 79 patients. There were no major complications. These stents underwent survival analysis and proportional hazard regression. The median duration for the stents was 5.77 months. In multivariate analysis, age (P=0.043), preoperative serum creatinine level (P=0.0174), and cancer type (P=0.0494) were significant factors associated with stent failure. Cancer treatment before and after stent insertion had no effect on stent duration.Resonance stents are effective and safe in relieving malignant ureteral obstructions. Old age and high serum creatinine level are predictors for stent failure. Stents in patients with lower gastrointestinal cancers have longer functional duration.

The objective of this study is to evaluate the effects of solifenacin on double-J stent-related symptoms following uncomplicated ureterosocpic lithotripsy (URSL). A total of 70 patients who underwent double-J ureteral stent insertion following URSL were consecutively recruited and received solifenacin postoperatively. Another 70 age- and sex-matched subjects without solifenacin therapy were enrolled as a control group. The clinical data including stone and stent characteristics were collected. All subjects completed the brief-form Ureteral Symptom Score Questionnaire (Chinese-version) to assess the lower urinary tract symptoms, stent-related body pain and hematuria 2 weeks after operation. The severity of stent-related symptoms was compared between two groups. The mean age was 53.8 in solifenacin group and 53.4 years in the control group (p = 0.87). The stone characteristics, stent size, position and curl completeness were similar in both groups. Compared to the control group, solifenacin group had significantly lower total symptom score, urgency and urge incontinence scores. As for stent-related body pain, solifenacin group had significantly less flank, abdominal, urethral pain and hematuria scores (all p

Aristolochic acid (AA), a component of all Aristolochia-based herbal medicines, is a potent nephrotoxin and human carcinogen associated with upper urinary tract urothelial carcinoma (UUC). To investigate the clinical and pathological characteristics of AA-induced UUC, this study included 152 UUC patients, 93 of whom had been exposed to AA based on the presence of aristolactam-DNA adducts in the renal cortex. Gene sequencing was used to identify tumors with A:T-to-T:A transversions in TP53, a mutational signature associated with AA. Cases with both aristolactam-DNA adducts and A:T-to-T:A transversions in TP53 were defined as AA-UUC, whereas patients lacking both of these biomarkers were classified as non-AA-UUC. Cases with either biomarker were classified as possible-AA-UUC. Forty (26%), 60 (40%), and 52 (34%) patients were classified as AA-UUC, possible-AA-UUC and non-AA-UUC, respectively. AA-UUC patients were younger (median ages: 64, 68, 68 years, respectively; p=0.189), predominately female (65%, 42%, 35%, respectively; p=0.011), had more end-stage renal disease (28%, 10%, 12%, respectively; p=0.055), and were infrequent smokers (5%, 22%, 33%, respectively; p=0.07) compared to possible-AA-UUC and non-AA-UUC patients. All 14 patients who developed contralateral UUC had aristolactam-DNA adducts; ten of these also had signature mutations. The contralateral UUC-free survival period was shorter in AA-UUC compared to possible- or non-AA-UUC (p=0.019 and 0.002, respectively), whereas no differences among groups were observed for bladder cancer recurrence. In conclusion, AA-UUC patients tend to be younger and female, and have more advanced renal disease. Notably, AA exposure was associated with an increased risk for developing synchronous bilateral and metachronous contralateral UUC.

Uterine sarcomas account for 3–7% of all uterine cancers. Because of their rarity, unknown etiology, and highly divergent genetic aberration, there is a lack of consensus on risk factors for occurrence and predictive poor outcomes as well as optimal therapeutic choices. Tumor types according to the World Health Organization classification include leiomyosarcoma, endometrial stroma sarcoma, and undifferentiated sarcoma. Staging is done using the 2014 Federation International Gynecology and Obstetrics and 2010 American Joint Committee on Cancer tumor, lymph node, and metastases systems. Tumor grade can be classified based on the French Federation of Cancer Centers Sarcoma Group system or the Broder’s system that incorporates tumor differentiation, mitotic count, and tumor necrosis. This review is a series of articles discussing uterine sarcoma, and this is Part I, which focuses on one of the subtypes of uterine sarcomas—uterine leiomyosarcoma. The clinical characteristics, diagnosis, outcome, and recent advances are summarized in this article.

Objective: The objective of this study is to evaluate the impact of body mass index (BMI) on clinical outcomes and safety profiles of percutaneous nephrolithotomy (PCNL). Materials and Methods: We retrospectively reviewed the patients who received PCNL between January 2015 and December 2016. A total of 182 consecutive patients were enrolled. The patients were categorized into three groups according to BMI (normal: BMI ≤24, overweight: 24 < BMI ≤27, obesity: BMI >27). The stone clearance rate, operation time, duration of hospital stay, postoperative analgesic use, and postoperation complications were compared among groups. The categorical variable was analyzed by Chi-square test, and the continuous variable was analyzed by Kruskal–Wallis test. The possible prognosticators for stone clearance were also analyzed using logistic regression method. Results: There were no significant differences among groups in terms of age, gender, stone character, stone size, and laterality. A higher proportion of hypertension was observed in the larger BMI groups and lower hemoglobin level in the smaller BMI group. No significant differences of stone clearance rate (66%, 76%, 70% in normal size, overweight, and obesity groups, respectively), duration of hospital stay, postoperative analgesic use, and complication rate were identified among groups. The most common complication was postoperative fever in overweight and obesity groups. Multivariable analysis showed the stone character was a significant prognosticator for stone clearance. Conclusion: BMI did not reveal the impact on the stone clearance, operative time, duration of hospital stay, postoperative analgesic requirement, and postoperative complication in patients undergoing PCNL.

Granule cells are major targets of entorhinal afferents terminating in a laminar fashion in the outer molecular layer of the dentate gyrus. Since Borna disease virus (BDV) infection of newborn rats causes a progressive loss of granule cells in the dentate gyrus, entorhinal fibres become disjoined from their main targets. We have investigated the extent to which entorhinal axons react to this loss of granule cells. Unexpectedly, anterograde DiI tracing has shown a prominent layered termination of the entorhinal projection, despite an almost complete loss of granule cells at 9 weeks after infection. Combined light- and electron-microscopic analysis of dendrites at the outer molecular layer of the dentate gyrus at 6 and 9 weeks post-infection has revealed a transient increase in the synaptic density of calbindin-positive granule cells and parvalbuminergic neurons after 6 weeks. In contrast, synaptic density reaches values similar to those of uninfected controls 9 weeks post-infection. These findings indicate that, after BDV infection, synaptic reorganization processes occur at peripheral dendrites of the remaining granule cells and parvalbuminergic neurons, including the unexpected persistence of entorhinal axons in the absence of their main targets.

Endometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities.

Phospholipid complex (PLC) based self-nanoemulsifying drug delivery system (PLC-SNEDDS) has been developed for efficient delivery of drugs with poor solubility and low permeability. In the present study, a BCS class IV drug and a P-glycoprotein (P-gp) substrate, morin, was selected as the model drug to elucidate the oral absorption mechanism of PLC-SNEDDS. PLC-SNEDDS was superior to PLC in protecting morin from degradation by intestinal enzymes in vitro. In situ perfusion study showed increased intestinal permeability by PLC was duodenum-specific. In contrast, PLC-SNEDDS increased morin permeability in all intestinal segments and induced a change in the main absorption site of morin from colon to ileum. Moreover, ileum conducted the lymphatic transport of PLC-SNEDDS, which was proven by microscopic intestinal visualization of Nile red labeled PLC-SNEDDS and lymph fluids in vivo. Low cytotoxicity and increased Caco-2 cell uptake suggested a safe and efficient delivery of PLC-SNEDDS. The increased membrane fluidity and disrupted actin filaments were closely associated with the increased cell uptake of PLC-SNEDDS. PLC-SNEDDS could be internalized into enterocytes as an intact form in a cholesterol-dependent manner via clathrin-mediated endocytosis and macropinocytosis. The enhanced oral absorption of morin was attributed to the P-gp inhibition by Cremophor RH and the intact internalization of M-PLC-SNEDDS into Caco-2 cells bypassing P-gp recognition. Our findings thus provide new insights into the development of novel nanoemulsions for poorly absorbed drugs.

Pharmacological therapy for urolithiasis using medicinal plants has been increasingly adopted for the prevention of its recurrence. A Drosophila melanogaster model developed for translational research of urolithiasis was applied to evaluate agents with potential antilithic effects and calcium oxalate (CaOx) formation. Potential antilithic herbs were prepared in a mixture of food in a diluted concentration of 5,000 from the original extract with 0.5% ethylene glycol (EG) as the lithogenic agent. The control group was fed with food only. After 3 weeks, flies ( for each group) were killed using CO2 narcotization, and the Malpighian tubules were dissected, removed, and processed for polarized light microscopy examination of the crystals. The crystal formation rate in the EG group was 100.0%. In the study, 16 tested herbal drugs reached the crystal formation rate of 0.0%, including Salviae miltiorrhizae, Paeonia lactiflora, and Carthami flos. Scutellaria baicalensis enhanced CaOx crystal formation. Two herbal drugs Commiphora molmol and Natrii sulfas caused the death of all flies. Our rapid screening methods provided evidence that some medicinal plants have potential antilithic effects. These useful medicinal plants can be further studied using other animal or human models to verify their effects.

Background Chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1 (MCP-1), belongs to the CC chemokine family which is associated with the disease status and outcomes of cancers. Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to the bone. However, the effect of CCL2 on human prostate cancer cells is largely unknown. The aim of this study was to examine the role of CCL2 in integrin expression and migratory activity in prostate cancers. Methods Prostate cancer migration was examined using Transwell, wound healing, and invasion assay. The PKCδ and c-Src phosphorylations were examined by using western blotting. The qPCR was used to examine the mRNA expression of integrins. A transient transfection protocol was used to examine AP-1 activity. Results Stimulation of prostate cancer cell lines (PC3, DU145, and LNCaP) induced migration and expression of integrin αvβ3. Treatment of cells with αvβ3 antibody or siRNA abolished CCL2-increased cell migration. CCL2-increased migration and integrin expression were diminished by CCR2 but not by CCR4 inhibitors, suggesting that the CCR2 receptor is involved in CCL2-promoted prostate cancer migration. CCL2 activated a signal transduction pathway that includes PKCδ, c-Src, and AP-1. Reagents that inhibit specific components of this pathway each diminished the ability of CCL2 to effect cell migration and integrin expression. Conclusions Interaction between CCL2 and CCR2 enhances migration of prostate cancer cells through an increase in αvβ3 integrin production. General significance CCL2 is a critical factor of prostate cancer metastasis.

The objective of the study was to evaluate the effect of auricular acupressure in controlling intraocular pressure (IOP) in patients with glaucoma.Thirty-three (33) patients were recruited through advertisement at the clinic for glaucoma. These patients were divided into the auricular acupressure group (16 patients, 28 glaucoma eyes) and the sham group (17 patients, 32 glaucoma eyes). Patients in the acupressure group received auricular acupoint (kidney, liver, and eye) stimulator tapping and regular massage twice a day for 4 weeks. Patients in the sham group received tapping at sham auricular acupoints (wrist, shoulder, and jaw) without massage stimulation. The IOP and visual acuity (VA) were assessed before and after the treatment in the first 4 weeks and followed up, up to 8 weeks.After the treatment and at the 8-week follow-up, IOP and VA improved significantly in the acupressure group when compared with pretreatment (p 0.05). The most significant IOP-lowering effect was seen at about 3-4 weeks after auricular acupressure. IOP returned to the initial level after acupressure had been discontinued for 4 weeks. Significant improvement of the uncorrected VA (UCVA) was noted at about 2-4 weeks in the acupressure group. UCVA improvement was also noted in the sham group. The difference was only significant in week 3. Improvement of the best-corrected VA was noted in both groups, but was only significant in week 2.Our data suggest that auricular acupressure can be used as a complementary treatment to ameliorate IOP and VA for patients with glaucoma.

Background and objective Hyperglycaemia is a common result of stress signals caused by pain and surgical procedure. Volatile anaesthetics also directly manipulate glucose homeostasis by affecting pancreatic insulin release and induce hyperglycaemia without surgical stress. We determined the preoperative application of transcutaneous electrical nerve stimulation (TENS) to the Chinese acupoints ST36 (Zusanli) and SP6 (Sanyinjiao) as a complementary therapy for controlling plasma glucose and improving insulin resistance during anaesthesia. Methods We designed a single-blind, randomised controlled clinical study of female patients, scheduled for elective hysterectomy. The 52 patients consented to enrolment and were assigned to receive either TENS (n = 26) on bilateral ST36 and SP6 acupoints with continuous mode at a frequency of 15 Hz and the intensity of 10 mA synchronously for 30 min or non-stimulation (placebo group, n = 26) preoperatively. Haemodynamics, blood glucose and plasma insulin were measured during general anaesthesia. Results At baseline, there was no significant difference between the TENS group and the placebo group in plasma glucose and insulin levels as well as homeostasis model assessment (HOMA) index. In the placebo group, plasma glucose, insulin and HOMA index increased during induction of general anaesthesia, surgical incision, and throughout the operation. Plasma glucose and insulin levels as well as HOMA index were significantly lower in the TENS group as compared to the placebo group at different time points after discontinuation of TENS application. These results indicate the positive effect of prevention of hyperglycaemia and the increased sensitivity of plasma insulin in the TENS group. Conclusion We found TENS at bilateral ST36 and SP6 acupoints to be an alternative means of managing the plasma glucose level and improving insulin resistance perioperatively.

Xanthogranulomatous pyelonephritis (XGP) is a chronic inflammatory condition of the kidneys. Nevertheless, disparities between the pre-operative and pathological diagnoses are frequently encountered. We reviewed all patients with XGP over a 17-year period to identify and characterize the pre-operative and pathological characteristics of the disease in our patients. A comprehensive review of all nephrectomy patients with a pre-operative diagnosis of pyelonephritis at National Taiwan University Hospital from 1991 to 2008 with the pathological diagnosis of XGP was conducted to demonstrate the clinical and radiological characteristics of XGP. XGP was diagnosed in 30 (18.6%) of the 160 nephrectomies performed for pyelonephritis. Of the 30 patients with XGP, 25 were women (83.3%) and 20 (66.7%) were overweight (body mass index >23). Their mean age was 55.17 years. The average serum creatinine level was 1.68 mg/dL. The image findings included renal calculi (56.7%), staghorn stones (26.7%), and spread of the disease to the retroperitoneum and psoas muscle (33.3%). Escherichia coli (36.7%) was the most prevalent pathogen. The mortality of the two-stage surgical treatment was zero, and morbidity developed in only 1 patient (4.8%). The key to accurate pre-operative diagnosis is to keep risk factors in mind such as age, sex, and renal calculi. Clinicians should maintain a high suspicion of XGP for early recognition and be aware of the care of chronic kidney disease. Finally, the association between XGP and central obesity warrants further research.

s / Urological Science 26 (2015) 294e300 299 the stone negative group. This prevalence rate in the ED population is higher but not statistically different from previous study of the general population of southern Taiwan. The average age, IIEF score, prevalence of HTN, DM, dyslipidemia, smoking and obesity were compatible between the two groups without difference. By contrast, 8 (38.1%) patients in the stone positive group have low serum testosterone level, which is significant higher compared to 20 (12.1%) from the stone negative group (P1⁄4 0.005). Conclusions: In patients with ED, we found a higher incidence of stone prevalence. For ED patients with urolithiasis, higher prevalence of low serum testosterone level was found compared to those without urolithiasis. MP4-2: COMPARISON OF THE POST-OPERATIVE INFECTION BY USING DIFFERENT TYPE OF PROPHYLACTIC ANTIBIOTICS AND PLACEBO IN HEALTHY ADULT PATIENTS WHO UNDERWENT URETERORENOSCOPIC SURGERY Tsai-Feng Chen , Yuan-Ju Lee . Division of Urology, Department of Surgery, Cardinal Tien Hospital and Fu-Jen Catholic University, Taipei, Taiwan; Department of Urology, National Taiwan University Hospital, Taipei, Taiwan Purpose: To compare the efficacy of prophylactic antibiotics in reduction of post-operative infections in patients undergoing ureterorenoscopy (URS) as the intervention. Materials and Methods: The study is a open-labeled, prospective, randomized controlled trial. Between 2013 to 2014, 63 patients with preoperative sterile urine undergoing URS were randomly and equally allocated by the randomization to three groups, and each group received prophylactic antibiotics with single-dose intravenous cefazolin (1gm), oral cefuroxime (500mg) or placebo (control group), respectively. The Urine analysis and urine cultures were obtained around postoperative day 5 to 7. We defined pyuria as WBCS 10/HPF at urine sediment study, and significant bacteriuria was defined as S105 CFU pathogens/ml in the urine.. Febrile urinary tract infection (fUTI) was defined as body temperature more than 38 Celsius degree with pyuria or significant bacteriuria within 7 days post-operatively. Results: Total 61 patients were recruited for the analysis. The postoperative pyuriawere significantly lower in patients with prophylaxis than the placebo group. Patients receiving prophylactic antibiotics with cefazolin and oral cefuroxime were subjected to significantly lower risks of pyuria compared with the control group (23.8% and 30% vs. 60.%, p

Background Ureteral obstruction caused by extrinsic compression is often associated with intra-abdominal cancers. Internal drainage with ureteral stents is typically the first-line therapy to relieve such obstructions. Novel designs of ureteral stents made of different materials have been invented to achieve better drainage. In this study, we described the functional outcomes of a Resonance metallic ureteral stent (Cook Medical, Bloomington, Indiana, USA) in patients with malignant ureteral obstruction and compare the functional duration of Resonance stents with regular polymeric stents in the same cohort. Methods Cancer patients who received polymeric stents and subsequent Resonance stents for ureteral obstruction between July 2009 and November 2012 were included in a chart review. Stent failure was detected by clinical symptoms, imaging studies, and renal function tests. The functional durations of each stent were calculated, and possible factors affecting stent patency were investigated. Results A total of 50 stents were successfully inserted into 50 ureteral units in 42 patients with malignant ureteral obstruction. There were 7 antegrade stents and 43 retrograde stents. There were no major complications. Stent-related symptoms were similar in both kinds of stents. After polymeric stents were replaced with Resonance metallic stents, hydronephrosis subsided or remained stable in 90% (45/50) of the ureteral units. Serum creatinine decreased or remained stable in 90% (38/42) of these patients. The Resonance stent exhibited a mean increase in functional duration of 4 months compared with the polymeric stents (p

(−)-Epigallocatechin-3-gallate (EGCG), a constituent of green tea, has been extensively studied and shown to be a powerful antioxidant protecting skin cells against photodamage. In this study, however, we demonstrated that another gallated catechin, (−)-epicatechin-3-gallate (ECG), was also able to protect human keratinocytes against damage induced by ultraviolet A (UVA) light. We found that ECG dose-dependently inhibited UVA-induced keratinocyte death as determined by cell viability assay. Moreover, ECG had similar potency to EGCG in inhibiting UVA-induced cell death. Therefore, the mechanism of action of ECG was further investigated. As assayed by flow cytometry, UVA-induced hydrogen peroxide (H2O2) production in keratinocytes was inhibited by ECG in a concentration-dependent manner, suggesting that ECG can act as a free radical scavenger while keratinocytes were photodamaged. The scavenging effect of ECG was confirmed by the fact that ECG treatment attenuated cell damage induced by H2O2 and hypoxanthine-xanthine oxidase. In a parallel experiment, UVA-induced activation of extracellular signal-regulated kinase in keratinocytes was blocked by ECG. We provided here the first evidence that ECG is a potent protectant that protects keratinocytes from photodamage. Because ECG is abundant in green tea, we believe that this compound is beneficial for skin care.