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Background: Management of non-neurogenic, non-obstructive dysuria represents one of the most challenging dilemmas in urological practice. The main clinical symptom is the increase in residual urine. Voiding dysfunction is the main cause of dysuria or urinary retention, mainly due to the decrease in bladder contraction (the decrease in contraction amplitude or duration) or the increase in outflow tract resistance. Sacral neuromodulation (SNM) has been used for > 10 years to treat many kinds of lower urinary tract dysfunction. It has become increasingly popular in China in recent years. Consequently, studies focusing on non-neurogenic, non-obstructive dysuria patients treated by SNM are highly desirable., Aim: To assess the outcome of two-stage SNM in non-neurogenic, non-obstructive dysuria., Methods: Clinical data of 54 patients (26 men, 28 women) with non-neurogenic, non-obstructive dysuria treated by SNM from January 2012 to December 2016 in ten medical centers in China were retrospectively analyzed. All patients received two or more conservative treatments. The voiding diary, urgency score, and quality of life score before operation, after implantation of tined lead in stage I (test period), and during short-term follow-up (latest follow-up) after implantation of the implanted pulse generator in stage II were compared to observe symptom improvements., Results: Among the 54 study patients, eight refused to implant an implanted pulse generator because of the unsatisfactory effect, and 46 chose to embed the implanted pulse generator at the end of stage I. The conversion rate of stage I to stage II was 85.2%. The average follow-up time was 18.6 mo. There were significant differences between baseline (before stage I) and the test period (after stage I) in residual urine, voiding frequency, average voiding amount, maximum voiding amount, nocturia, urgency score, and quality of life score. The residual urine and urgency score between the test period and the latest follow-up time (after stage II) were also significantly different. No significant differences were observed for other parameters. No wound infection, electrode breakage, or other irreversible adverse events occurred., Conclusion: SNM is effective for patients with non-neurogenic, non-obstructive dysuria showing a poor response to traditional treatment. The duration of continuous stimulation may be positively correlated with the improvement of residual urine., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: The present study aimed to identify differentially expressed circRNAs in thyroid cancer and verify their potential functions., Methods: Next-generation sequencing was used to identify differentially expressed circRNAs between papillary thyroid carcinoma (PTC) tissues and paired pericarcinomatous tissues. Polymerase chain reaction and Sanger sequencing methods successfully identified hsa_circ_0007694. A hsa_circ_0007694 over-expression vector was prepared to determine the effect of this circRNA on proliferation, migration, invasion, apoptosis, and the cell cycle in PTC cells. An in vivo animal assay was conducted by injecting PTC cells into the chests of mice. Further, RNA-seq was performed, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, to verify the regulatory mechanism of hsa_circ_0007694. Western blotting was used to verify the genes thought to be involved in the hsa_circ_0007694 regulatory pathways based on KEGG analysis., Results: We identified a circRNA, hsa_circ_0007694 that was down-regulated in PTC tissues compared to pericarcinomatous tissues. Over-expression of hsa_circ_0007694 promoted apoptosis and inhibited proliferation, migration, and invasion in PTC cells in vitro , and decreased tumor growth in vivo . Transcriptome sequence analysis suggested 129 differentially expressed genes between PTC tissue and paired pericarcinomatous tissue. KEGG analysis and western blotting indicated that the PI3K/AKT/mTOR and Wnt signaling networks are most likely to be related to hsa_circ_0007694 in thyroid cancer., Conclusion: The circRNA hsa_circ_0007694 is down-regulated in PTC and is therefore a potential therapeutic target., Competing Interests: None., (AJTR Copyright © 2020.)

Premise: Outcomes of species interactions, especially mutualisms, are notoriously dependent on environmental context, and environments are changing rapidly. Studies have investigated how mutualisms respond to or ameliorate anthropogenic environmental changes, but most have focused on nutrient pollution or climate change and tested stressors one at a time. Relatively little is known about how mutualisms may be altered by or buffer the effects of multiple chemical contaminants, which differ fundamentally from nutrient or climate stressors and are especially widespread in aquatic habitats., Methods: We investigated the impacts of two contaminants on interactions between the duckweed Lemna minor and its microbiome. Sodium chloride (salt) and benzotriazole (a corrosion inhibitor) often co-occur in runoff to water bodies where duckweeds reside. We tested three L. minor genotypes with and without the culturable portion of their microbiome across field-realistic gradients of salt (3 levels) and benzotriazole (4 levels) in a fully factorial experiment (24 treatments, tested on each genotype) and measured plant and microbial growth., Results: Stressors had conditional effects. Salt decreased both plant and microbial growth and decreased plant survival more as benzotriazole concentrations increased. In contrast, benzotriazole did not affect microbial abundance and even benefited plants when salt and microbes were absent, perhaps due to biotransformation into growth-promoting compounds. Microbes did not ameliorate duckweed stressors; microbial inoculation increased plant growth, but not at high salt concentrations., Conclusions: Our results suggest that multiple stressors matter when predicting responses of mutualisms to global change and that beneficial microbes may not always buffer hosts against stress., (© 2019 Botanical Society of America.)

Enterovirus and Coxsackievirus are the major viruses that cause hand, foot, and mouth disease (HFMD) outbreaks worldwide. Several studies have shown the potential of viral envelope protein 1 (VP1) on providing protective effects from viral strains of different genotypes. However, whether VP1 has the cross-protection in Enteroviruses or Coxsackievirus has not been studied in-depth. In this study, the vp1 gene of Enterovirus 71 (EV71) and Coxsackievirus B3 (CB3) was inserted into the vector pET22b (+) to form the respective expression plasmids pEVP1 or pCVP1, and then transformed into Escherichia coli strain BL21 (DE3). The recombinant EVP1 or CVP1 protein was overexpressed successfully and effectively purified to homogeneity. Then, we identified that EVP1 and CVP1 protein could generate effectively specific humoral immunity and cellular immunity in mice, what's more, we determined the cross-protection of VP1 between EV71 and CB3 in a murine model. The results showed that immunization with EVP1 could effectively induce specific IgG and secretory IgA against CVP1 and the sera from EVP1-immunized mice could neutralize CB3 with mean titers 1:440. In contrast, no measurable neutralizing antibodies to EV71 were detected in CVP1-immunized mice. Then, newborn BALB/C mice, whose mother was immunized with EVP1 or CVP1, were administered with different lethal doses of EV71 or CB3. The EVP1 immunized group showed a 90% protective efficacy for a CB3 dosage of 120 LD 50 , but the CVP1 immunized group showed no significantly different protective efficacy against 15 LD 50 of EV71 compared with the BSA immunized group. Hence, EVP1 is a promising subunit vaccine candidate against Enterovirus 71 and Coxsackievirus B3 caused HFMD., (Copyright © 2019 Chen, Liu, Fang, Nan, Li, Ning, Luo, Li and Wang.)

Introduction and Objective: Several studies have focused on the treatment and recurrence of urethral diverticulum (UD). However, few investigations have addressed sexual function in pati-ents with UD. Therefore, we sought to examine sexual function in women affected by UD., Materials and Methods: There were 108 accepted cases involving transvaginal diverticulectomy at our institution. Ultimately, 83 women were included for further analysis, only 61 of these wo-men had sexual partners. We collected data for the Female Sexual Function Index (FSFI) from the female patients and the Male Sexual Health Questionnaire (MSHQ) from their male partners before and after surgery., Results: Preoperatively, the UD size affected the female patient's arousal and lubrication (p=0.04), and the UD location affected their satisfaction. However, no significant between-group differences were found in the total FSFI score. For all women, sexual activity improved after surgery (p=0.0087). In addition to improvements in arousal for women with a large UD, improvements in lubrication were affected by the UD size, number and shape, increases in sa-tisfaction scores were impacted by the UD location and shape, and pain relief was linked to the UD number and shape. Analysis of the MSHQ results revealed no between-group differences among the male partners., Conclusion: Only the UD size and location affected sexual function in women with a small UD. Surgery could improve female sexual function but did not affect the sexual function of the patient's partners., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Purpose: This five-year, retrospective, multicenter study evaluated the long-term safety and efficiency of sacral neuromodulation (SNM) in Chinese patients with urinary voiding dysfunction., Patients and Methods: This is a Chinese national, multicenter, retrospective study that included 247 patients (51.2% female) who received an implantable pulse generator (IPG) (InterStim, Medtronic, Minneapolis, MN, USA) between 2012 and 2016. Success was considered if the initial ≥50% improvement in any of primary voiding diary variables persisted compared with baseline. The results were further stratified by identifying patients who showed >50% improvement and those although showed <50% improvement but still wanted to receive IPG; these data were collected and analyzed for general improvement., Results: Following test stimulation, 187 patients (43%) declined implantation and 247 (57%) underwent implantation using InterStim®. Among 247 patients, 34 (13.7%) had overactive bladder (OAB), 59 (23.8%) had interstitial cystitis/bladder pain syndrome (IC/BPS), 47 (19%) had idiopathic urinary retention (IUR), and 107 (44.1%) had neurogenic bladder (NB). IPG efficiency rate for OAB, interstitial cystitis/bladder pain syndrome, idiopathic urinary retention, and neurogenic bladder were 42.5, 72.4, 51.6, and 58.8%, respectively. The mean duration of follow-up was 20.1 ± 12.8 months., Conclusions: SNM appears effective in the long term, with a total IPG implantation rate of approximately 57% (ranging between 42.5 and 72.4% depending on indication). Interstitial cystitis/bladder pain syndrome appear to be the best indication for stage I testing. Chinese neurogenic bladder patients are most inclined to choose SNM. SNM is relatively safe, with low postoperation adverse events of 16.1% and reoperation rate of 3.2% during the follow-up period., (© 2019 International Neuromodulation Society.)

Background: Vesicovaginal fistula (VVF) is a distressing disorder in women. The transvaginal method of VVF repair is generally preferred, as its minimally invasive nature appears to offer several advantages compared with the abdominal approach, including decreased pain and blood loss and reduced hospital stay. A common technique used in VVF repair surgery is the Latzko technique, which may be difficult for the fistula located at the vaginal apex, due to the firm transverse scar left after the inciting gynecological surgery., Objective: To show the efficacy and safety of an alternative modified transvaginal repair technique for apical vesciovaginal fistula., Design, Setting, and Participants: A retrospective cohort study was conducted at a high-volume hospital. A total of 108 female patients, previously diagnosed with apical VVF, underwent fistula repair between 2009 and 2016. Those patients were contacted, and they underwent a follow-up examination., Surgical Procedure: The modified Latzko technique for apical VVF repair was performed., Measurements: A chart review was performed., Results and Limitations: The mean age of the patients was 47 (22-77)yr. The average follow-up time was 40.7 (12-84)mo. The VVF was closed in all procedures. There was no immediate or delayed complication. All patients scored higher in the Patient Global Impression of Improvement questionnaire after the surgery., Conclusions: Our study indicates that the transvaginal repair of apical VVF with a modified Latzko technique is feasible and effective, and offers durable results without apparent complications., Patient Summary: We studied an alternative surgical technique for the treatment of apical vesicovaginal fistula. We conclude that this technique is simple, safe, and effective, with no apparent complications., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Buckwheat constitutes a good source of bioactive components. A dry fractionation of surface abrasion for polyphenol-enriched protein combined with hydrothermal treatment was evaluated as an alternative to conventional wet extraction from tartary buckwheat (Fagopyrum esculentum Moench). The protein contents and the total polyphenol contents of both free and bound polyphenol gradually decreased in the order from the outer to the inner fractions. Polyphenol-enriched buckwheat protein flour was successfully enrichment with a maximum polyphenol content of 55 mg/g. Moreover, starch digestibility and polyphenols bioaccessibility of the buckwheat protein were increased with hydrothermal treatment time, while protein digestibility decreased slightly. Besides, most of the aroma compounds increased during the hydrothermal treatment. The assessment results demonstrate that the sustainability dry surface abrasion process in combination with hydrothermal treatment should be encouraged in processing functional protein fractions and improving both qualities of end use products and health benefits., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Lessons Learned: The upregulation of dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) are important mechanisms of resistance to 5-fluorouracil (5-FU) in metastatic colorectal cancer (mCRC) after long exposure to 5-FU.S-1 (containing a DPD inhibitor) combined with raltitrexed (a TS inhibitor) showed a moderate effect, which needs further study as a third- or later-line therapy in mCRC., Background: 5-fluorouracil (5-FU) is a fundamental drug in the treatment of metastatic colorectal cancer (mCRC). Patients with mCRC are often exposed to 5-FU and/or its analogues for a long time because of its central role in treatment regimens. The upregulation of dihydropyrimidine dehydrogenase (DPD) and/or thymidylate synthase (TS) are important mechanisms of resistance of 5-FU. To evaluate the efficacy and safety of S-1 (containing a DPD inhibitor) and raltitrexed (a TS inhibitor) for refractory mCRC, a one-center, single-arm, prospective phase II trial was conducted., Methods: Patients who had mCRC that had progressed after treatment with fluoropyrimidine, irinotecan, and oxaliplatin and who had at least one measurable lesion were eligible for this trial. Patients received oral S-1 (80-120 mg for 14 days every 3 weeks) plus an intravenous infusion of raltitrexed (3 mg/m 2 on day 1 every 3 weeks). The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity., Results: In total, 46 patients were enrolled. Three patients did not complete the first assessment because of adverse events and unwillingness, leaving tumor response evaluation available in 43 patients. Of 43 evaluable patients, the ORR was 13.9% and disease control rate was 58.1%. In the intention-to-treat population ( n = 46), the ORR was 13.0% and disease control rate was 54.3%. Median PFS and median OS were 107 days (95% confidence interval [CI], 96.3-117.7) and 373 days (95% CI, 226.2-519.8), respectively. Most of the adverse effects were mild to moderate., Conclusion: S-1 combined with raltitrexed for refractory mCRC showed moderate effect, and it is worthy of further study as third- or later-line therapy in mCRC., (© AlphaMed Press; the data published online to support this summary are the property of the authors.)

Background: To determine the efficacy of magnetic stimulation (MS) in female patients with stress urinary incontinence (SUI) by performing a meta-analysis on peer-reviewed randomized controlled trails (RCTs)., Methods: PubMed, Embase, and Cochrane library were retrieved for any peer-reviewed original articles in English. Databases were searched up to July 2018. Included studies investigated effects of MS on SUI. The data were analyzed by review manager 5.3 software (Cochrane Collaboration, Oxford, UK)., Results: A total of 4 studies involving 232 patients were identified and included in present meta-analysis. Compared with the sham stimulation, the MS group had statistically significantly fewer leaks/3 days (MD = -1.42; 95%CI: -2.42 to -0.59; P = .007), less urine loss on pad test (g.)/24 h (MD = -4.99; 95%CI: -8.46 to -1.53; P = .005), higher QoL scores (MD = 0.42; 95%CI: 0.02-0.82; P = .009), and lower ICIQ scores (MD = -4.60; 95%CI: -5.02 to -4.19; P < .001). MS presented higher cure or improvement rate, with a statistically significant improvement in UDI and IIQ-SF scores compared to sham stimulation. No MS-related adverse effects were reported in study., Conclusion: MS leads to an improvement in SUI without any reported safety concerns and an improvement in patient quality of life. The long-term outcome of this technique remains unclear and is the subject of ongoing research.

In this paper, the correlations between the continuously monitored gamma dose rate (GDR) and meteorological parameters, including precipitation, air temperature, relative humidity, air pressure, wind direction, and wind speed, were analyzed by using one year of the hourly dataset from a monitoring system with ten stations. The correlation coefficients are varied by the range of each meteorological parameter. Precipitation would enhance the GDR up to 84%, which is highly related to precipitation intensity and ground type. Strong and positive correlation between the GDR and light precipitation was identified, while the correlation was reduced with increasing of precipitation. Air temperature could cause a fluctuation of the average GDR within the range 1.8-5.3 nGy h -1 , and different correlation characteristics were indicated for low and high air temperature. The GDR was positively correlated with relative humidity, though relative humidity is inversely correlated with air temperature. Correlations between the GDR and air pressure were mainly negative. Diurnal variations between the GDR and the air temperature, relative humidity, and air pressure were also analyzed. The wind played an important role also in the fluctuation of the GDR with the GDR difference up to 2.00 nGy h -1 averaged from the sixteen wind-directions. Lower GDR can be found in the direction of prevailing wind because of the dilution effect of the radon progenies in the surface air. In this paper, some exploratory interpretation of physical influence mechanisms of meteorological parameters on the GDR was also presented, which suggests further work should be carried out to explore the variation and correlation principle., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Transvaginal mesh (TVM) is a minimally invasive but effective treatment for pelvic organ prolapse (POP). However, mesh exposure is a common and problematic complication after TVM. This study assessed the safety and long-term outcomes of TVM. A retrospective review was performed on the medical records of 175 consecutive patients who underwent TVM with the anatomical implant technique for pelvic organ prolapse at our center from April 2007 to December 2012. All operations were performed using TVM with the anatomical implant technique. Intraoperative variables, postoperative complications, and TVM outcomes were assessed. In average of 8 years (ranging from 4 to 10 years), the objective cure ratio reached 99.4%; and the subjective success rate of the TVM operation was 91.4%. Only 2 cases (1.1%) were identified as having mesh exposure. The reoperation rate was 4.0% (95% CI, 1.1-6.9%). No patients abstained from sex due to the operation or postoperative discomfort. Our anatomical implant technique for correcting POP is feasible in TVM procedures, which lead to favourable subjective and objective outcomes with the lowest rates of mesh exposure (1.1%) in published data. Therefore, performing TVM operations with the appropriate technique could consider to be permitted.

Purpose: To identify keys genes and elucidate miRNA-mRNA regulatory networks in Bladder smooth muscle cell (BSMC) response to mechanical stimuli., Methods: Human BSMCs, seeded on a silicone membrane, were subjected to mechanical stretch or without stretch. Microarray was used to analyze the differential expression of mRNAs and miRNAs between human BSMCs under mechanical stretch and control static control group. Differentially expressed genes(DEGs) and miRNAs (DEMs) in these two groups were identified. Subsequently, differentially expressed DEGs were conducted with functional analysis, and then PPI network was constructed. Finally, miRNA-mRNA regulatory network was visualized using Cytoscape., Results: 1639 significant DEGs and three DEMs were identified between the stretch group and control static group. The PPI network of DEGs was constructed by STRING, which was composed of 1459 nodes and 1481 edges, including 188 upregulated genes and 255 downregulated genes. Moreover, 36 genes in the PPI network were identified as hub genes in BSMCs response to mechanical stretch, e.g. CCNH, CPSF2, TSNAX, ARPC5 and PSMD3 genes. Subsequently, 39 clusters were selected from PPI network using MCODE, and it was shown that the most significant cluster consisted of 14 nodes and 91 edges. Besides, miR-503HG was the most significantly downregulated miRNA and was predicted to target five upregulated genes, including SMAD7, CCND3, WIPI2, NYNRIN and PVRL1., Conclusions: Our data mining and integration help reveal the mechanotransduction mechanism of BSMCs' response to mechanical stimulation and contribute to the early diagnosis of bladder outlet obstruction (BOO) as well as the improvement of pathogenesis of BOO treatment.

A general and concise method was developed for the synthesis of highly functionalized morphans 3-4 by the Michael and hetero-Michael addition reaction of different types of quinone monoketals 1 and 1,1-enediamines 2 in ethanol or 1,4-dioxane at reflux. This method is suitable for the efficient parallel syntheses of N-containing heterocycles. A library of highly functional morphan derivatives was easily constructed using the Michael/hetero-Michael reaction., Competing Interests: The authors declare no competing financial interest.

Background/aims: Antimuscarinic agents can delay the progression of bladder dysfunction caused by bladder outlet obstruction (BOO). To date, the relationship between muscarinic receptor activity and the bladder extracellular matrix (ECM) remains unclear. Thus, an animal model of partial BOO (PBOO) in female rats was established to explore the variation in bladder wall ECM proteins under PBOO conditions with antimuscarinic agent administration., Methods: Rats were randomly divided into three groups: sham, PBOO, and PBOO plus tolterodine. Picrosirius red staining was used to examine the smooth muscle and collagen content of bladder samples. Gene microarray and RT-PCR were performed to survey the expression of ECM proteins, receptors, and metabolism regulators in the rat bladder. Positive results were further evaluated by immunohistochemistry., Results: Picrosirius red staining showed that smooth muscle volume significantly increased in the PBOO and PBOO plus tolterodine groups (p < 0.05), while collagen significantly increased in the PBOO group (p < 0.05) but not in the PBOO plus tolterodine group. Gene microarray and RT-PCR revealed that none of the collagen subtypes exhibited significant changes after PBOO establishment and tolterodine administration. However, matrix metalloproteinases (MMPs) increased significantly in the PBOO plus tolterodine group (p < 0.05). Additionally, PBOO inhibited the expression of non-collagen ECM proteins in the rat bladder wall, while tolterodine induced the expression of non-collagen ECM proteins and ECM receptors., Conclusions: Tolterodine decreased the volume of collagen in PBOO rat bladder wall, possibly via MMPs, and regulated the expression of ECM proteins and receptors., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Purpose: Miniaturized percutaneous nephrolithotomy (MPCNL), including minipercutaneous nephrolithotomy (PCNL), ultramini-PCNL, and micro-PCNL, have been developed recently. The aim of this meta-analysis was to compare the safety and efficacy of different tract sizes of MPCNL with retrograde intrarenal surgery (RIRS) in the management of kidney stones., Materials and Methods: We searched PubMed, Embase, and Web of Science to identify case-control trials and randomized controlled trials, which evaluated MPCNL vs RIRS before February 2017. Two reviewers independently evaluated the methodologic quality of the included studies, and the disagreements were solved by discussion. Meta-analysis was performed with Review Manager version 5.3 software., Results: Fourteen publications involving 1279 patients were included. Mini-PCNL provided a significantly higher stone-free rate (SFR; odds ratio [OR] OR 1.66; p = 0.005), especially for lower pole renal stones (OR 2.65; p = 0.003), but brought longer hospital stay (weighted mean difference [WMD] 1.23; p = 0.0001) and larger hemoglobin drop (WMD 0.77; p < 0.00001). There were no statistically significant differences between mini-PCNL and RIRS in the complications (OR 0.77; p = 0.23) and operative time (WMD: -6.52; p = 0.42). For ultramini-PCNL and micro-PCNL, the safety and efficacy were similar to RIRS., Conclusions: Mini-PCNL offers a significantly higher SFR than RIRS, for lower pole renal stones, the advantage of mini-PCNL is more obvious. However, RIRS is associated with shorter hospital stay and less hemoglobin drop. For ultramini-PCNL and micro-PCNL, tract size is smaller than mini-PCNL, and the SFR is similar to RIRS. In terms of the evidence at present, we recommend mini-PCNL for patients focusing more on the high SFR.

Tryptophan-2,3-dioxygenase (TDO) is a homotetrameric heme-containing protein catalyzing the initial step in the kynurenine pathway, which oxidates the 2,3-double bond of the indole ring in L-tryptophan and catalyzes it into kynurenine (KYN). The upregulation of TDO results in a decrease in tryptophan and the accumulation of KYN and its metabolites. These metabolites can affect the proliferation of T cells. Increasing evidence demonstrates that TDO is a promising therapeutic target in the anti-tumor process. Despite its growing popularity, there are only a few reviews focusing on TDO in tumors. Hence, we herein review the biological features and regulatory mechanisms of TDO. Additionally, we focus on the role of TDO in the anti-tumor immune response in different tumors. Finally, we also provide our viewpoint regarding the future developmental directions of TDO in cancer research, especially in relation to the development and application of TDO inhibitors as novel cancer treatments.

AKT1, also known as v-akt murine thymoma viral oncogene homolog 1, is involved in the regulation of cell-survival and anti-apoptotic activities, which may affect the pathogenesis of various cancers. However, the association between genetic variants of AKT1 and the risk of developing prostate cancer has not been investigated before. This study investigated the associations between three polymorphisms (rs1130214, rs3730358, and rs2494732) in AKT1 and the risk of development of prostate cancer in the Chinese Han population. Sequenom MassARRAY & iPLEX technology were used to genotype these polymorphisms in 493 Chinese Han patients with prostate cancer and 309 age-matched healthy individuals. Compared to the CC genotype of the rs3730358 polymorphism, the CT genotype of the same polymorphism was strongly associated with a decreased risk of prostate cancer (OR = 0.617, 95%CI = 0.390-0.976, P = 0.037). However, there was no significant difference between the allele frequency of the rs3730358 polymorphism and those of the other two polymorphisms (P > 0.05). Moreover, no significant difference was found in the haplotype analysis (P > 0.05). Our study found that the variant genotype CT of rs3730358 of AKT1 was associated with a decreased risk of prostate cancer, which suggested that this polymorphism could play an important role in the development of the disease.

This study was performed to investigate the incidence of and risk factors for postoperative cleft relapse and oronasal fistula after Furlow palatoplasty in infants. Sixty-two infants with cleft palate, aged 6-12 months (mean 8.25 months), who underwent cleft repair by Furlow double opposing Z-plasty between March 2012 and August 2014, were enrolled in the study. Risk factors for postoperative cleft relapse and oronasal fistula after Furlow palatoplasty were identified by logistic regression analysis. The incidence rates of cleft relapse at 1 week and oronasal fistula at 3 months after surgery were 24.2% (15/62) and 9.7% (6/62), respectively. Among all of the variables screened, only the width of the cleft was significantly associated with the incidence of postoperative cleft relapse (P=0.001) and oronasal fistula (P=0.011); the incidence rates were positively correlated with the width of the cleft when it exceeded 6.8mm and 7.5mm, respectively. Based on these findings, in order to reduce the incidence of postoperative cleft relapse and oronasal fistula, Furlow repair is not recommended for patients with wide clefts. An appropriate angle between the Z-flap incision and the central axis, use of a bilateral relaxation incision, and postoperative nursing care can help reduce the incidence of postoperative cleft relapse., (Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Purpose: We aimed to report surgical outcomes in female urethral diverticula and to investigate the risk factors for diverticula recurrence., Methods: A total of 66 patients underwent urethral diverticulectomies from January 2009 to October 2015 at out institution. Patient and diverticula characteristics were collected. Mean follow-up was 28.8 months (range 4-85 months). Recurrence was defined as requiring a repeat diverticulectomy., Results: Mean age was 44.9 years. Mean duration of symptoms was 28.1 months. Seven cases had previous urethral surgeries. Mean diverticula size was 2.8 cm. Main clinical symptoms included dribbling (n = 41), vaginal mass (n = 41), dysuria (n = 33), frequency/urgency (n = 29), infection (n = 24), stress urinary incontinence (SUI) (n = 20) and dyspareunia (n = 8). 10 cases had proximal diverticula, 10 cases had multiple diverticula, and 35 cases had horseshoe/circumferential diverticula. Postoperatively, the recurrence rate was 19.7 %. Preoperative SUI disappeared in 14 cases, and de novo SUI was developed in six cases. One case developed urethral stricture, and no cases reported urinary fistula. Among 60 cases with pathological results, neoplastic change was seen in one case (1.7 %). Besides, atypical hyperplasia (n = 2) and metaplasia (n = 3) were observed. Univariate analysis suggested that age, duration, follow-up, diverticula size and diverticula shape were not associated with surgical outcomes. Patients with multiple diverticula (p = 0.032), proximal diverticula (p = 0.042) and those with previous urethral procedures (p = 0.004) were at risk of recurrent diverticula confirmed by multivariate logistic regression analysis., Conclusions: The surgical outcomes of urethral diverticulectomies were acceptable. Multiple diverticula, proximal diverticula and previous urethral surgery were three independent risk factors for recurrent diverticula.

Introduction: We aimed to report the outcomes of patients undergoing vesicovaginal fistula (VVF) repair to identify prognostic factors., Materials and Methods: Patients who underwent VVF repair between January 2009 and October 2015 were reviewed. Primary outcome was fistula closure at 3 months., Results: A total of 123 patients and 139 procedures of VVF repair were reviewed. The overall success rate was 85.6%. There were no significant differences in age (p = 0.476), etiology (p = 0.900), fistula duration (p = 0.491) and number of repairs (p = 0.509) between success and fail group. Moderate or severe perifistula fibrosis and multiple fistula were associated with failure in repair of fistula (70.8 vs. 93.4%, p < 0.001; 62.5 vs. 88.6%, p = 0.005). No difference was seen in success rate of vaginal and abdominal approaches (86.0 vs. 85.0%, p = 0.800). Logistic regression analysis identified fistula number (p = 0.003) and perifistula fibrosis (p = 0.002) as 2 independent prognostic factors. Medium/large fistulas were 3.2 times more likely to fail in repair than small fistulas (OR 3.2, 95% CI 0.95-10.6, p = 0.061)., Conclusions: Fistula number and perifistula fibrosis were 2 independent prognostic factors for fistula repair. Unsuccessful closure was more likely in medium/large VVF., (© 2016 S. Karger AG, Basel.)

Objective: To assess the outcome of cystectomy and cystourethrectomy in patients with intractable interstitial cystitis or bladder pain syndrome, and to identify whether urethrectomy is necessary., Methods and Materials: During 2007-2014, 18 women were eligible and elected for surgical treatment after conservative treatment failed. Seven cystectomies with ileal conduit urinary diversions, 8 cystourethrectomies with ileal conduit urinary diversions, and 3 supratrigonal cystectomy with orthotopic ileocystoplasty were performed. Patient histories, perioperative medical records, and follow-up outcomes were evaluated and summarized., Results: Patients reported subjectively improved social function and mental condition secondary to decreased urination frequency postoperatively. Pain also significantly decreased compared with baseline. To date, additional surgery to alleviate persistent symptoms or postoperative complications has not been necessary. Furthermore, there was no association between reported urethral pain and the initial transvaginal urethrectomy incidence (P = .326). More operation time and longer postoperative hospitalization duration were recorded without better surgical outcomes in the urethrectomy group (P values <.05)., Conclusion: Cystectomy and cystourethrectomy is effective and adequate treatment for interstitial cystitis or bladder pain syndrome, and our experience indicates that urethrectomy is not routinely needed. However, further long-term, prospective studies involving a larger study group are needed., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Human bladder smooth muscle cells (HBSMCs) were subjected to pressure cycles of up to 200 cm H2O to a pressure of 0 cm H2O for 24 hours. The total RNA extracted from each group was subjected to microarray analysis. miR-3180-5p emerged as the most overexpressed of all the differentially expressed microRNAs, and this finding was validated by PCR. We then used CCK-8 to quantify cell proliferation after liposome-mediated transfection. Subsequently, we investigated the change in PODN and its downstream signaling proteins, including cyclin-dependent kinase 2 (cdk2) and p21. In addition, flow cytometry was performed to quantify cell-cycle distribution. The results show that miR-3180-5p, the microRNA that was most overexpressed in response to HP, reduced the expression of PODN and podocan (p = 0.004 and p = 0.041, respectively). Silencing of PODN via miR-3180-5p overexpression revealed a significant promotion of cell proliferation increased in the CCK-8 experiment, p = 0.00077). This cell proliferation was accompanied by an increase in cdk2 expression (p = 0.00193) and a decrease in p21 expression (p = 0.0095). The percentage of cells in (S + G2/M) improved after transfection (p = 0.002). It was apparent that HP upregulates miR-3180-5p, which inhibits the expression of PODN and promotes HBSMC proliferation via the cdk2 signaling pathway.

Tryptophan-2, 3-dioxygenase (TDO) is a heme-containing protein catalyzing the first reaction in the kynurenine pathway, which incorporates oxygen into the indole moiety of tryptophan and catalyzes it into kynurenine (KYN). The activation of TDO results in the depletion of tryptophan and the accumulation of kynurenine and its metabolites. These metabolites can affect the function of neurons and inhibit the proliferation of T cells. Increasing evidence demonstrates that TDO is a potential therapeutic target in the treatment of brain diseases as well as in the antitumor and transplant fields. Despite its growing popularity, there are few reviews only focusing on TDO. Hence, we herein review TDO by providing a comprehensive overview of TDO, including its biological functions as well as the evolution, structure and catalytic process of TDO. Additionally, this review will focus on the role of TDO in the pathology of three groups of brain diseases: Schizophrenia, Alzheimer's disease (AD) and Glioma. Finally, we will also provide an opinion regarding the future developmental directions of TDO in brain diseases, especially whether TDO has a potential role in other brain diseases as well as the development and applications of TDO inhibitors as treatments.

An efficient and convenient method to synthesize highly functionalized 3,7'-bisindole derivatives has been developed via a Michael addition and cyclic condensation reaction of heterocyclic ketene aminals (HKAs) with 2-(1H-indol-3-yl)cyclohexa-2,5-diene-1,4-dione derivatives in ethanol-based solvents at room temperature. This strategy provides an efficient, environmentally friendly approach for easy access to various novel 3,7'-bisindole derivatives in moderate to good yields.

Peritoneal carcinomatosis (PC) of gastric origin is currently recognized as a terminal disease with a poor prognosis. Advancements in novel therapeutic approaches, including intraperitoneal chemotherapy (IPC), have recently been made and it is believed that this may have contributed to the improved survival observed in patients with PC. The present study aimed to investigate overall survival (OS) and the associated prognostic factors in patients with PC of gastric origin who underwent IPC. A total of 57 patients were studied, with a median age of 51 years. The median follow-up time was 12.4 months. PC was diagnosed in all patients with gastric cancer. The median survival time of all patients was 10.1 months, whilst the OS rate at 1, 2 and 3 years was observed to be 46, 19 and 12%, respectively. Symptomatic ascites and a signet ring cell (SRC) histopathological type were demonstrated to signify a poor prognosis. Complete resection of all gross disease (CCR-0) and an increased number of cycles of systemic chemotherapy were independent factors that were observed to correlate with increased OS. The most common morbidities of grade 3/4 adverse effects were bone marrow suppression, nausea or vomiting, and diarrhea. In conclusion, IPC is an important treatment option for patients with PC that has originated from gastric cancer. Symptomatic ascites and SRC adenocarcinoma serve as negative clinicopathological prognostic factors, whilst CCR-0 and increased systemic chemotherapy cycles (≥4 cycles) may prove to be an important therapeutic option for PC patients.

Background: Malignant mesothelioma (MM) is a rare and fatal neoplasm. For diffuse malignant mesothelioma (DMM) patients that were not suitable for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, systemic chemotherapy is the main treatment. There are no convenient tumor markers to predict the efficacy of treatment and disease progression. This study aimed to evaluate serum CA125 level as a biochemical marker of response to therapy and prognosis in patients with DMM., Methods: A retrospective study was performed in a single medical institution from April 2008 to April 2014. Overall survival (OS) and prognostic factors were assessed., Results: Forty-one patients were included with a median age of 53 years. The median OS of all patients was 10 months. Patients with baseline CA125 > 280 U/ml had worse OS compared with the patients that baseline CA125 ≤ 280 U/ml. Baseline level of CA125, stage of disease, primary tumor location and systemic chemotherapy were independent prognostic factors associated with OS. In patients who received systemic chemotherapy, the decline in serum CA125 was associated with favorable OS and objective response according to modified Response Evaluation Criteria in Solid Tumors criteria., Conclusions: The baseline level of serum CA125, accompanied with stage of disease, primary tumor location and systemic chemotherapy, could be regarded as independent prognostic factors for DMM patients. Otherwise, the change in serum CA125 can predict OS and response to systemic chemotherapy.

Background: Fluoropyrimidine and oxaliplatin are widely used for patients with colorectal cancer. This phase II study was conducted to evaluate the efficacy and safety of the combination of S-1, oxaliplatin, and leucovorin (SOL) in the treatment of Chinese patients with metastatic colorectal cancer (mCRC)., Methods: Eligible patients with untreated mCRC from four hospitals in China received intravenous oxaliplatin (85 mg/m(2)) on day 1, oral S-1 twice daily (80-120 mg per day) on day 1-7, and leucovorin twice daily (50 mg per day) simultaneously with S-1, every 2 weeks., Results and Discussion: Forty patients were enrolled in our study. In total, 296 cycles of SOL were administered. The overall response rate was 50.0%. At a median follow-up of 27 months, progression-free survival and overall survival were 7.0 months (95% confidence interval [CI] 6.0-10.6 months) and 22.2 months (95% CI 15.1-29.3 months), respectively. The most common grade 3/4 non-hematological adverse events were diarrhea (n = 8, 20.0%), nausea (n = 3, 7.5%), and vomiting (n = 3, 7.5%). The most common grade 3/4 hematological toxicities were thrombocytopenia (n = 3, 7.5%), neutropenia (n = 1, 2.5%), and abnormal alanine transaminase/aspartate transaminase levels (n = 1, 2.5%). There was one treatment-related death., Conclusions: The data indicate that the SOL regimen is effective and moderately tolerated in Chinese patients with mCRC., Clinical Trial Information: ChiCTR-TNRC-100000838.

Purpose: The purpose of this study was to describe and test a kind of stretch pattern which is based on modified BOSE BioDynamic system to produce optimum physiological stretch during bladder cycle. Moreover, we aimed to emphasize the effects of physiological stretch's amplitude upon proliferation and contractility of human bladder smooth muscle cells (HBSMCs)., Methods: HBSMCs were seeded onto silicone membrane and subjected to stretch simulating bladder cycle at the range of stretches and time according to customized software on modified BOSE BioDynamic bioreactor. Morphological changes were assessed using immunofluorescence and confocal laser scanning microscope. Cell proliferation and cell viability were determined by BrdU incorporation assay and Cell Counting Kit-8, respectively. Contractility of the cells was determined using collagen gel contraction assay. RT-PCR was used to assess phenotypic and contractility markers., Results: HBSMCs were found to show morphologically spindle-shaped and orientation at various elongations in the modified bioreactor. Stretch-induced proliferation and viability depended on the magnitude of stretch, and stretches also regulate contractility and contraction markers in a magnitude-dependent manner., Conclusion: We described and tested a kind of stretch pattern which delivers physiological stretch implemented during bladder cycle. The findings also showed that mechanical stretch can promote magnitude-dependent morphological, proliferative and contractile modulation of HBSMCs in vitro.

The incidence rate of erectile dysfunction (ED) is reportedly as high as 30-90% after radical prostatectomy for prostate cancer, which seriously affects the patients' quality of life. Penile rehabilitation is defined as the use of any drug or device at or after radical prostatectomy to maximize erectile function recovery. A variety of treatment options are available for post-prostatectomy ED patients, including oral phosphodiesterase 5 inhibitors (PDE5I) , intracorporal injections, vacuum erection device, and penile prosthesis. This article presents an overview of the currently used methods for the drug treatment and penile rehabilitation of the ED patients after radical prostatectomy. It seems proper to recommend daily use of a vacuum erection device plus oral PDE5I in the early postoperative period. For those who fail to respond to this therapy, intraurethral alprostadil, intracorporal injections, or a penile prosthesis could be considered.

Objective: To study the influence factors for encrustation of double J stent in patients with urolithiasis., Methods: In this study, there were 84 urolithiasis patients with double J stent included from February to July 2014 in our hospital. The encrustation on double J stent was evaluated by a PC stereo microscope. The nterrelated clinical data were obtained, then the factors which may affect the encrustation were studied by logistic regression analysis., Results: The mean indwelling time was (17. 0±6. 0) d, and a thin encrustation formed on the stents for most cases [67/84(79. 8%)]. Compared with the cases who did not form a thin encrustation, those having a thin encrustation formation on the stent were younger [(44. 9±11. 5) vs. (54. 4±12. 6), P=0. 004]; The patients with proteinuria got a higher rate of encrustation [62/73(84. 9%) vs. 5/11 (45. 5%), P=0. 002]. The patients with urinary tract infection had a higher rate of encrustation [26/28(92. 9%) vs. 41/56(73. 2%), P 3. 035]. The patients with hematuriaalso got a higher rate of encrustation [67/80(83. 8%) vs. 0/4, P=0. 001]. Different sex, retention time,serum calcium,inorganic phosphorus, uric acid, urine pH,lithiasis component had no effects on encrustation (P>0. 05). Logistic regression analysis showed that age and proteinuria was retained as idependent correlated factors with encrustation (P<0. 05), while hematuria and urinary tract infections had a low ntensity correlation with encrustation (P>0. 05)., Conclusion: For encrustation of double J stentin patients with urolithiasis, younger age, increased urinary protein, hematuria and infections are important risk-factors.

The present study aimed to investigate whether the cyclic stretch‑induced proliferation of human bladder smooth muscle cells (HBSMCs) is mediated by muscarinic (M) receptors, together with the signal transduction mechanisms involved in this process. HBSMCs seeded onto silicone membranes were subjected to different cyclic stretches (5, 10, 15 and 20%) for 6 and 12 h. As the effect of cyclic stretch on M2 and M3 mRNA expression levels was maximal at 6 h 10% stretch, all subsequent experiments were performed at this stretch. Western blot analysis was used to quantify M2, M3, protein kinase C (PKC) and phosphorylated (p)‑PKC protein expression levels, flow cytometry was employed to examine cell cycle distribution and a 5-bromo‑2-deoxyuridine (BrdU) incorporation assay was used to assess cell proliferation at this stretch. Subsequently, HBSMCs were exposed to different acetylcholine concentrations and/or cyclic stretch, M receptor antagonists [AF-DX16, an M2 receptor antagonist; 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP), an M3 receptor antagonist and atropine, a non‑selective antagonist] and GF 109203X, a PKC antagonist, to assess the possible underlying signaling mechanisms. Cyclic stretch was found to increase the proliferation of HBSMCs and the expression levels of M2, M3, PKC and p‑PKC proteins. M receptor and PKC antagonists exerted no apparent effect on nonstretched cells, but reduced the incorporation of BrdU into stretched cells; the most pronounced effects were observed when non‑selective M receptor and PKC antagonists were applied. Notably, 4‑DAMP did not inhibit stretch‑induced PKC activation. These results indicate that the activation of the M3 receptor signaling pathway in stretch‑induced HBSMC proliferation occurs via PKC-independent mechanisms.

Purpose: To investigate the influence of exogenous p53 upregulated modulator of apoptosis (PUMA) expression on cell proliferation and apoptosis in human non-small cell lung cancer A549 cells and transplanted tumor cell growth in nude mice., Materials and Methods: A549 cells were divided into the following groups: control, non- carrier (NC), PUMA (transfected with pCEP4- (HA) 2-PUMA plasmid), DDP (10 μg/mL cisplatin treatment) and PUMA+DDP (transfected with pCEP4-(HA)2-PUMA plasmid and 10 μg/mL cisplatin treatment). The MTT method was used to detect the cell survival rate. Cell apoptosis rates were measured by flow cytometry, and PUMA, Bax and Bcl-2 protein expression levels were measured by Western blotting., Results: Compared to the control group, the PUMA, DDP and PUMA+DDP groups all had significantly decreased A549 cell proliferation (p<0.01), with the largest reduction in the PUMA+DDP group. Conversely, the apoptosis rates of the three groups were significantly increased (P<0.01), and the PUMA and DDP treatments were synergistic. Moreover, Bax protein levels significantly increased (p<0.01), while Bcl-2 protein levels significantly decreased (p<0.01). Finally, both the volume and the weights of transplanted tumors were significantly reduced (p<0.01), and the inhibition ratio of the PUMA+DDP group was significantly higher than in the single DDP or PUMA groups., Conclusions: Exogenous PUMA effectively inhibited lung cancer A549 cell proliferation and transplanted tumor growth by increasing Bax protein levels and reducing Bcl-2 protein levels.

Microvessel density (MVD), an indicator of angiogenesis, has been proposed to predict prognosis of patients with renal cell carcinoma (RCC), but its ability to predict survival of patients with RCC remains controversial. The present study sought to address this question rigorously by systematically reviewing the literature on MVD and RCC prognosis. We identified relevant studies in PubMed, EMBASE and the Cochrane Library, and two reviewers independently assessed study quality and extracted relevant data to compare survival based on MVD stratification in patients with RCC. We identified 15 studies that satisfied the inclusion criteria; eight studies assessed MVD in surgical samples by immunohistochemistry to label factor VIII; four studies, by immunohistochemistry to label CD34; two studies, CD31; and one study, CD105. Survival meta-analysis was performed using data pooled from 10 studies: five based on factor VIII, two based on CD34, two based on CD31 and one based on CD105. The overall survival hazard ratio describing the relationship between MVD and survival in all 10 pooled studies was 0.964 (95% CI: 0.873-1.065), while the individual hazard ratios for pooled studies based on factor VIII were 1.673 (95% CI: 0.860-3.252); CD34, 0.903 (95% CI: 0.853-0.956); and CD31, 0.926 (95% CI: 0.868-0.989). The corresponding result for the sole trial based on CD105 was 0.1759 (95% CI: 0.036-0.856). These findings suggest that MVD is not reliably associated with survival time of patients with RCC, which may reflect the need to take into account whether the microvasculature is differentiated or not. MVD as currently calculated may not be an ideal prognostic factor for patients with RCC.

This study investigated the expression and role of chemokine receptor-4 (CXCR4) in bone marrow mesenchymal stem cells (BMSCs) from experimental rats with abdominal aortic aneurysms (AAA) for migration of BMSCs. Sprague-Dawley rats were divided into an experimental group and control group (n = 18 each). AAA was induced with 0.75 M solution infiltrate for 30 minutes, after which the abdomen was rinsed and closed. Saline was used in place of CaCl2 in the control group. CD34 and CD29 were detected by flow cytometry, the gene and protein expression of CXCR4 were detected by real-time polymerase chain reaction and western blot, respectively. The migration of BMSCs with stromal-derived factor-1 was detected by Transwell chamber. CD34 expression was negative and CD29 expression was positive. The gene and protein expression of CXCR4 were significantly higher in experimental group than them in control group (p < 0.05), the migration ability of BMSCs from the experimental group was significantly higher than that from the control group (p < 0.05). Stromal-derived factor -1/CXCR4 can enhance the migration of BMSCs in vitro in a rat AAA model., (Copyright © 2014. Published by Elsevier B.V.)

Several midurethral sling (MUS) procedures, such as tension-free vaginal tape (TVT), TVT obturator (TVT-O), tension-free vaginal tape SECUR (TVT-S), and pubovaginal sling (PVS), have been used for the treatment of female stress urinary incontinence (SUI); however, which method is best for a particular patient group is not known. This study aimed to identify the best rationale for choosing the optimal MUS procedure for each patient. In total, 453 consecutive female patients with SUI who were treated with MUSs in West China Hospital of Sichuan University from September 2003 to September 2011 were enrolled in this study. All the patients underwent comprehensive pre-, intra-, and postoperative evaluations, including collection of demographic information, pelvic examination, and urodynamic testing, and operation-related complications were recorded. The Incontinence Quality of Life questionnaire was also completed. Under local or general anesthesia, 105 cases were treated with TVT, 243 with TVT-O, 90 with TVT-S, and 15 with PVS. Patients with different profiles in terms of age, symptom duration, concomitant procedures, urodynamic parameters, and pelvic organ prolapse (POP) quantification score were treated successfully; the body mass index did not differ significantly among the various treatment options. The cure and improvement rates were similar among the treatment groups: 97.14% (102/105) in TVT, 100% (243/243) in TVT-O, 98.89% (89/90) in TVT-S, and 100% (15/15) in PVS. Only minor complications were experienced by the patients. In conclusion, each MUS procedure was observed to be safe and effective in different subpopulations of patients, and the results suggest that appropriate patient selection is crucial for the success of each MUS procedure., (Copyright © 2013. Published by Elsevier B.V.)

Background: High expression of aldehyde dehydrogenase 1 (ALDH1) has been confirmed in many tumors. This enzyme plays an important role in tumor proliferation, metastasis, and drug resistance. However, in the case of papillary thyroid carcinoma (PTC), the relationship between ALDH1 expression and prognosis remains unknown., Method: We used tissue microarrays to evaluate ALDH1A1 expression in 247 surgically resected PTC specimens by immunochemistry, and correlated the findings with the clinicopathological parameters., Result: ALDH1A1 levels were significantly higher than in normal thyroid tissues. Moreover, ALDH1A1 overexpression was significantly associated with extrathyroid extension (P = 0.001), pT status (P < 0.001), pN status (P = 0.016) and TNM stage (P < 0.001). The Kaplan-Meier survival analysis suggested that high ALDH1A1 expression reflects a poorer lymph node recurrence-free survival (LN-RFS) and distant recurrence-free survival (DRFS) in PTC patients, as compared with patients having low ALDH1A1 expression. Multivariate analysis confirmed the ALDH1A1 expression was an independent prognostic factor for LN-RFS and DRFS in PTC patients., Conclusion: In conclusion, high ALDH1A1 expression correlates with poor survival in PTC patients.

The constant outbreaks of influenza in a global scale have aroused great concern all over the world. Vaccine has been the most effective and economic means against influenza. However, the broad tropism and high mutation of influenza viruses have limited the effectiveness of influenza vaccines. Current influenza virus vaccines provide effective protection against virus strains that are identical or highly similar to the vaccine strain. Once a highly mutated or new strain of influenza virus appears, the current vaccine would lose its effectiveness. Therefore, the development of a universal vaccine against highly mutated or new influenza virus subtypes has become a hot spot in the field of influenza vaccine research. The major methods of developing the universal influenza vaccine are to select a conserved protein of influenza virus as an antigen. At least three universal influenza vaccines have been tested in clinical trials. Moreover, changing the routes of vaccine immunization and immunization schemes could also improve the effect of heterosubtypic immunity. This review summarized the research progresses of universal influenza vaccines and provided our prospective on universal influenza vaccine research.

Purpose: The requirement of integrins for mechanotransduction has been recognized for some time. We investigated the role of integrin subunits and their pathway in the physiological stretch induced contractility and proliferation of human bladder smooth muscle cells., Materials and Methods: Human bladder smooth muscle cells were seeded on silicone membrane and subjected to stretch, simulating bladder cycles of various stretches and times, as controlled by customized software on a modified BioDynamic bioreactor. Cell proliferation, viability and cycle were determined by BrdU incorporation assay, the Cell Counting Kit-8 (Beyotime Institute of Biotechnology, Haimen, People's Republic of China) and flow cytometry, respectively. Cell contractility was determined using a collagen gel contraction assay., Results: Physiological stretch increased cell contractility, proliferation and viability. Knockdown of integrin αv but not α4 in the cells disrupted the enhanced contractility induced by stretch. Under physiological stretch conditions, the integrin αv level and phospho-FAK/FAK ratio correlated positively with cell stretch induced enhanced contractility. Further examination revealed that contractile marker expression was associated with integrin αv activation through the FAK pathway. At the same time integrin α4 but not integrin αv mediated stretch induced cell proliferation and viability., Conclusions: These data revealed that different integrins have different roles in the contractility and proliferation of human bladder smooth muscle cells under physiological stretch. This suggests that different integrins may become specific therapeutic targets in patients with voiding dysfunction. They may also be used to design a specific microenvironment for optimal bladder tissue regeneration., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To determine protein kinase C (PKC), c-Jun NH2-Terminal Kinase (JNK) and P38 mitogen-activated protein kinases (p38MAPK) expression levels and effects of their respective inhibitors on proliferation of human bladder smooth muscle cells (HBSMCs) when physiologically stretched in vitro., Materials and Methods: HBSMCs were grown on silicone membrane and stretch was applied under varying conditions; (equibiaxial elongation: 2.5%, 5%, 10%, 15%, 20%, 25%), (frequency: 0.05, 0.1, 0.2, 0.5, 1Hz). Optimal physiological stretch was established by assessing proliferation with 5-Bromo-2-deoxyuridine (BrdU) assay and flow cytometry. PKC, JNK and p38 expression levels were analyzed by Western blot. Specificity was maintained by employing specific inhibitors; (GF109203X for PKC, SP600125 for JNK and SB203580 for p38MAPK), in some experiments., Results: Optimum proliferation was observed at 5% equibiaxial stretch (BrdU: 0.837±0.026 (control) to 1.462±0.023)%, (P<0.05) and apoptotic cell death rate decreased from 16.4±0.21% (control) to 4.5±0.13% (P<0.05) applied at 0.1Hz. Expression of PKC was upregulated with slight increase in JNK and no change in p38MAPK after application of stretch. Inhibition had effects on proliferation (1.075±0.024, P<0.05 GF109203X); (1.418±0.021, P>0.05 SP600125) and (1.461±0.01, P>0.05 SB203580). These findings show that mechanical stretch can promote magnitude-dependent proliferative modulation through PKC and possibly JNK but not via p38MAPK in hBSMCs., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To investigate whether cyclic stretch induces proliferation and contraction of human smooth muscle cells (HBSMCs), mediated by P2X purinoceptor 1 and 2 and the signal transduction mechanisms of this process., Methods: HBSMCs were seeded on silicone membrane and stretched under varying parameters; (equibiaxial elongation: 2.5%, 5%, 10%, 15%, 20%, 25%), (Frequency: 0.05Hz, 0.1Hz, 0.2Hz, 0.5Hz, 1Hz). 5-Bromo-2-deoxyuridine assay was employed for proliferative studies. Contractility of the cells was determined using collagen gel contraction assay. After optimal physiological stretch was established; P2X1 and P2X2 were analyzed by real time polymerase chain reaction and Western Blot. Specificity of purinoceptors was maintained by employing specific inhibitors; (NF023 for P2X1, and A317491for P2X2), in some experiments., Results: Optimum proliferation and contractility were observed at 5% and 10% equibiaxial stretching respectively, applied at a frequency of 0.1Hz; At 5% stretch, proliferation increased from 0.837±0.026 (control) to 1.462±0.023%, p<0.05. Mean contraction at 10% stretching increased from 31.7±2.3%, (control) to 78.28 ±1.45%, p< 0.05. Expression of P2X1 and P2X2 was upregulated after application of stretch. Inhibition had effects on proliferation (1.232±0.051, p<0.05 NF023) and (1.302±0.021, p<0.05 A314791) while contractility was markedly reduced (68.24±2.31, p<0.05 NF023) and (73.2±2.87, p<0.05 A314791). These findings shows that mechanical stretch can promote magnitude-dependent proliferative and contractile modulation of HBSMCs in vitro, and P2X1 and 2 are at least partially responsible in this process., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The purpose of this study was to compare the efficacy and safety of a single subcutaneous injection of pegylated filgrastim with daily filgrastim as a prophylaxis for neutropenia induced by commonly used chemotherapy regimens. Fifteen centers enrolled 337 chemotherapy-naive cancer patients with normal bone marrow function. All patients randomized into AOB and BOA arms received two cycles of chemotherapy. Patients received a single dose of pegylated filgrastim 100 µg/kg in cycle 1 (AOB) or cycle 2 (BOA) and daily doses of filgrastim 5 µg/kg/day in cycle 1 (BOA) or cycle 2 (AOB). Efficacy and safety parameters were recorded. The primary end point was the rate of protection against grade 4 neutropenia after chemotherapy [defined as the rate at which the absolute neutrophil count (ANC) remained >0.5×10(9)/l throughout the entire cycle]. Ninety-four percent of patients receiving pegylated filgrastim or filgrastim did not develop grade 4 neutropenia. The incidence of ANC<1.0×10(9)/l was 16.0% (50/313) after support with either pegylated filgrastim or filgrastim. The incidences of febrile neutropenia and antibiotic administration were similar in both groups. Notably, faster ANC recovery was observed with pegylated filgrastim support. The ANC nadir was also earlier with pegylated filgrastim (day 7) support than with filgrastim support (day 9), although the depth of nadir was not significantly different. A single subcutaneous injection of pegylated filgrastim 100 μg/kg provided adequate and safe neutrophil support comparable with daily subcutaneous injections of unmodified filgrastim 5 μg/kg/day in patients receiving commonly used standard-dose mild-to-moderate myelosuppressive chemotherapy regimens.

The present study aimed at evaluating the effects of Cdc6 downregulation on the proliferation of Tca8113 cells. Two lentiviral vectors (KD1 and KD2) expression cdc6 siRNA were constructed and then infected into Tca8113 cells. Real-time PCR and Western blot analysis were performed to detect the mRNA and protein expression of Cdc6. MTT assays were employed to delineate the growth curves, and flow cytometry was performed to assess cell-cycle progression and apoptosis in Tca8113 cells. Following infection with the lentiviral vectors, real-time PCR and Western blot analysis revealed that Cdc6 expression was markedly suppressed in Tca8113 cells. When compared with the negative control group, the mRNA expression of Cdc6 was reduced by 50% and 65% and the protein expression by 65.87% and 79.38% in cells harboring KD1 or KD2, respectively. Cell growth was slowed, and the growth inhibition rate was 25.84% and 30.34% in Tca8113 cells following infection with KD1 or KD2, respectively. In addition, cell-cycle progression was altered. In KD- infected Tca8113 cells, the proportion of cells in the S phase was markedly reduced, but the proportion in the G1 phase was significantly increased; this was accompanied by an increase in cell apoptosis. Downregulation of Cdc6 effectively inhibited the proliferation of Tca8113 cells.

Ameloblastomas have a high recurrence rate, and because of their biological tendency towards local invasion are considered borderline tumours. Despite this, reports of metastasis of these tumours are rare. This report presents a patient with mandibular ameloblastoma that recurred 29 years after surgery and metastasized to both lungs. Because of the large range of the area of metastasis, complete surgical resection of the tumours was impossible. After confirming the diagnosis by biopsy of the pulmonary lesions the pulmonary metastases were not treated actively. Observation over 4 years showed no obvious change in the lung metastasis. Recent cases are summarized and analyzed in this paper, with respect to its occurrence, pathological types, methods of treatment and other related aspects., (Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

This study's aim is provide an overview of the patients who suffered spinal cord injury (SCI) after the magnitude 8.0 Wenchuan earthquake, including each patient's demographic and epidemiological characteristics, bladder management status, and quality of life (QOL). We also assessed the relationships between bladder management methods, symptomatic urinary tract infection (SUTI), and QOL. Two years after the 2008 Wenchuan earthquake, a cross-sectional face-to-face survey was conducted on 180 patients with SCI. A self-administered questionnaire and the WHOQOL-BREF assessment were used to assess injury-related information, bladder management methods, and SUTI. Statistical analysis was performed using the Chi-square test and analysis of variance. A p value <0.05 was considered statistically significant. This study found that a male-to-female ratio of approximately 1.2:1, including 98 (54.4%) male patients and 82 (45.6%) female patients. Thoracic-level injuries were seen in 82 patients (45.56%), 60 (33.33%) patients had lumbar-level injuries, 18 (8.33%) patients had thoracolumbar-level injuries, and a small number of patients had cervical- or sacral-level injuries. Sixty-two patients (34.44%) demonstrated normal voiding, 65 (36.11%) required manually assisted voiding, 29 (16.11%) required catheterization, and 24 (13.33%) used aurine-collecting apparatus. The prevalence of SUTI was 43.89%. Patients who emptied their bladder via manually assisted voiding, catheterization, or with the use of a urine-collecting apparatus demonstrated higher rates of SUTI compared with patients who voided normally (p < 0.05); the patients who required catheterization had higher rates of SUTI compared with patients who required manually assisted voiding (p < 0.05). When manually assisted voiding and catheterization were compared with the use a urine-collecting apparatus, no statistically significant differences were observed in terms of the risk of developing SUTI. The patients in this study demonstrated low scores on the WHOQOL-BREF physical domain (11.61 ± 3.80), psychological domain (10.11 ± 3.63), social domain (11.46 ± 2.84), and environmental domain (11.86 ± 2.51). The patients who reported normal voiding also demonstrated the best QOL in terms of physical, psychological, and social component scores (p < 0.05). In conclusion, the percentage of women in this study is higher than that reported in other studies on traumatic causes of SCI. Patients who suffered SCI following the Wenchuan earthquake demonstrate poor bladder management status and are unable to take advantage of urodynamic testing that is used to monitor the functional state of the bladder. This study's findings indicate that bladder management methods influence the rate of SUTI and the QOL of patients with SCI. Caring for SCI patients following a disaster requires comprehensive long-term planning. Bladder management of patients with SCI is essential for improving the QOL of these patients., (Copyright © 2012. Published by Elsevier B.V.)

A fibrolipomatous hamartoma-also known as a fibrofatty overgrowth, perineural lipoma, intraneural lipoma, and lipomatous hamartoma-is a rare, benign, congenital lesion most commonly found in the median nerve, usually at the level of the wrist or hand. To our knowledge, no published cases report a hamartoma arising from the median nerve at the level of the elbow. We report a case of a fibrolipomatous hamartoma in a 55-year-old woman that necessitated a surgical intervention because of its size and associated neurologic symptoms.

Objectives: The effect of p53 upregulated modulator of apoptosis (PUMA) in hypoxia/reoxygenation-induced cardiomyocyte injuries in rats was investigated., Methods: PUMA-targeting (si-PUMA) and scramble siRNAs were designed and transfected into primarily rat cardiomyocytes in vitro., Results: RT-PCR and Western blot analysis showed that 50 nmol/l of si-PUMA can specifically inhibit PUMA expression. MTT assay and lactate dehydrogenase activity detection showed that the cell survival rate in the si-PUMA group was enhanced and that the lactate dehydrogenase enzymatic activity dramatically decreased compared with the control group (p < 0.01). Spectrophotometry, as well as annexin V and propidium iodide staining, combined with flow cytometry, revealed that caspase-3 activity in the si-PUMA group was downregulated and the apoptotic rate was decreased (p < 0.01). RT-PCR also showed that Bax expression was downregulated and Bcl-2 expression was upregulated in the si-PUMA group, compared with the control group (p < 0.05). si-PUMA protects cardiomyocytes from apoptosis., Conclusion: PUMA mediates hypoxia/reoxygenation-induced cardiomyocyte apoptosis, which can be a potential target of gene therapy for ischemia/reperfusion cardiomyocyte injuries., (Copyright © 2012 S. Karger AG, Basel.)

Concurrent chemoradiotherapy begins to be more and more widely accepted as a standard adjuvant treatment in gastric cancer. And oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) also reveals to be a very effective regimen in gastric cancer. But the safety and the dosages of FOLFOX combining with radiotherapy are still unknown. This study was to determine the maximum-tolerated dose and the dose-limiting toxicity of FOLFOX with higher-dose concurrent radiotherapy (RT) as adjuvant treatment in patients with gastric cancer. Patients with Stage II/III gastric cancer after surgery were recruited. They received one cycle of induction chemotherapy (standard FOLFOX4). Then, they received 50.4 Gy in 1.8-Gy fractions in combination with two cycles of concurrent FOLFOX, and oxaliplatin among this regimen was administered with escalating doses. Dose-limiting toxicity including grade 3 or grade 4 hematologic and nonhematologic toxicities was investigated. Fifteen patients were enrolled at the following dose levels: oxaliplatin 55 mg/m(2) (3 patients), 65 mg/m(2) (6 patients), and 75 mg/m(2) (6 patients). Dose-limiting toxicity was observed in 1 patient at 65 mg/m(2) (grade 4 leukopenia) and in 3 patients at 75 mg/m(2) (1 patient had grade 4 leukopenia, 1 had grade 3 thrombocytopenia, and 1 had grade 3 stomatitis). Combination chemotherapy FOLFOX with oxaliplatin 65 mg/m(2), d 1; leucovorin 200 mg/m(2), 2 h, d1-2; 5-fluorouracil 400 mg/m(2), iv, d 1-2 and 600 mg/m(2) civ, 22 h, d 1-2 given concurrently with RT (50.4 Gy) can be recommended as a safer and preferable regimen for the adjuvant treatment of patients with gastric cancer.

Objective: A 3H-leucine (3H-Leu) single-injection method was proposed for determining the endogenous amino acid losses of broilers. This method was based on the hypothesis that the ratio of the specific radioactivity (SR) of endogenous Leu in excreta (SRe) to that of free Leu in trichloroacetic acid-soluble plasma (SRp) remains constant after a single subcutaneous injection of 3H-Leu into birds fed different diets., Methods: Two experiments were designed to clarify this hypothesis. In experiment 1, 40 female broilers were randomly divided into four groups and were force-fed a nitrogen-free diet (NFD), NFD plus enzyme-hydrolyzed casein (EHC), 5% crude protein (CP) and SBM (soybean meal), or 20% CP-SBM. In experiment 2, 24 broilers were randomly divided into four groups and were fasted or force-fed the NFD, 20% CP-SBM, or 20% CP and cottonseed meal (CSM) diet. After the forced feeding, broilers were administered 3H-Leu by a single subcutaneous injection at a rate of 30 μCi/kg of body weight. Blood samples were taken at 5 min, 30 min, 4 h, 24 h, 36 h, and 48 h after the injection. The excreta were totally collected and pooled over the 48-h experiment., Results: The ratios of SRe to SRp remained the same for the birds force-fed the NFD, NFD+EHC, and 5% CP-SBM diets in experiment 1 and for the birds fasted and force-fed the NFD diet in experiment 2. The proportions of endogenous Leu to total Leu in excreta were 72.8%, 61.4%, and 57.5% for birds force-fed with the 20% CP-SBM diet in experiment 1 and 20% CP-SBM and 20% CP-CSM diets in experiment 2, respectively. Broilers fed the 5% CP-SBM and 20% CP-SBM diets excreted more (P<0.05) endogenous Leu than those fed the NFD and NFD+EHC diets in experiment 1. Broilers fed the 20% CP-SBM diet excreted more (P<0.05) endogenous Leu than those fed the NFD diet and fasted and the 20% CP-CSM diet was intermediate (P>0.05) in experiment 2., Conclusion: The present study verified the hypothesis that the ratio of SRe to SRp remains constant after a single subcutaneous injection of 3H-Leu into broilers and proposes a new method to determine endogenous amino acid losses of broilers., (Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to explore the effects of varicocele on the morphology and function of Leydig cells in the rat testis. Forty male Sprague-Dawley rats were divided into two groups: the experimental group underwent surgery to create a left varicocele (VC), and the control group underwent a sham operation. Serum testosterone and intratesticular testosterone levels were measured using a radioimmunoassay after 4 and 8 weeks of operation. Leydig cells were studied for apoptosis and expression of steroidogenetic acute regulatory (StAR) protein mRNA levels. Serum testosterone levels declined after 4 and 8 weeks of operation but were not significant (P>0.05). However, the intratesticular testosterone levels after 8 weeks were significantly decreased compared with the control group (P<0.01). The mean apoptosis index of Leydig cells in the experimental group was significantly higher than that in the control group after 4 or 8 weeks (P<0.01). StAR mRNA levels in the Leydig cells of the experimental group were significantly lower compared to those of the control group (P<0.01). Our data show that varicocele did impair Leydig cell function by increasing apoptosis and suppressing the expression of the StAR protein.