Association between single nucleotide polymorphisms on chromosome 17q and the risk of prostate cancer in a Chinese population

In European populations,7 single nucleotide polymorphisms(SNPs) on chromosome 17q,3 SNPs on 17q12,and 4 SNPs on 17q24.3 were recently identified to be closely related to the risk of prostate cancer by a genome-wide association study.In Japanese populations,the correlation between 2 SNPs on 17q and the risk of prostate cancer and tumor aggressiveness was also confirmed by a large-scale experiment.However,whether 17q is associated with prostate cancer and its clinical manifestations in Chinese populations is still unknown.Therefore,we conducted a case-control study in a northern Chinese population and tested 2 SNPs,rs4430796 and rs1859962,on 17q in 124 prostate cancer patients and 111 controls using polymerase chain reaction-high resolution melting curve(PCR-HRM) combined with sequencing.We analyzed the association of the 2 SNPs with the risk of prostate cancer as well as patients' lifestyles,onset ages,Gleason scores,PSA levels,and pathologic stages.We found a significant difference in the G allele of SNP rs1859962(P = 0.035,OR = 1.51,95% CI = 1.03-2.21) but not in the rs4430796 genotype frequency or allele frequency distribution between prostate cancer patients and the controls(P > 0.05).Neither of the SNPs was significantly associated with the onset age,Gleason score,PSA level,pathologic stage,or other clinical indicators of patients with prostate cancer(P > 0.05).Our results show that polymorphism of the G allele of SNP rs1859962 is associated with the risk of prostate cancer in a Chinese population.

Body mass index and serum lipid profile influence serum prostate-specific antigen in Chinese men younger than 50 years of age

This study is to assess the potential factors that could affect the serum prostate-specific antigen （PSA） level in healthy younger men. We evaluated the associations of age, body mass index （BMI） and serum lipid profile with serum PSA level in 6774 Chinese men （aged 20-49 years） who received a routine health examination. Eligible men were classified into 10-year age groups, BMI was categorized as underweight （〈18.5）, normal （18.5-22.9）, overweight （23.0-24.9）, obese （25.0-29,9） and very obese （〉30） according to the redefined World Health Organization （WHO） criteria for the Asia-Pacific region. PSA levels were compared among groups as well, In multiple linear regression analysis, PSA was positively correlated with age （P〈0.0001）. Negative correlations existed between PSA and BMI （P〈0.0001） and triglyceride level （P=0.01）. No relationship could be found between PSA and serum cholesterol （P=0.711） or high-density lipoprotein （HDL; P =0.665）. In addition, we found that serum PSA levels increased with age and decreased with BMI. Our study demonstrates that age, BMI and triglyceride levels influence the PSA level in men 〈50 years of age.

Rare primary lymphoepithelioma-like carcinoma of the renal pelvis

Lymphoepithelioma-like carcinoma(LELC)is a rare,malignant epithelial tumour which can arise within the upper urinary tract.This letter adds to a previous systematic review and cumulative analysis of 28 published upper urinary tract-LELC cases which provided insight into this disease;however,the current evidence does not provide clinicians with clear guidelines due to its rarity.Therefore,the aim was to report a new case of renal pelvis LELC presented in our hospital.In this instance,we were able to report treatment experience and longterm follow-up results.This patient presented with hypertension and haemturia which initiated further investigation.While ultrasound identified an hypechoic mass,no malignant cells were detected using cytological testing.Abdominal magnetic resonance imaging identified a slightly enhanced mass in the left renal pelvis with no evidence of lymph node metastasis.Ureteroscopic tumor biopsy suggested the existence of urothelial carcinoma,hence,laparoscopic radical left nephroureterectomy with bladder cuff excision was performed.Through patientpractitioner consultations,we decided to adopt a"watch and wait"approach after radical nephroureterectomy rather than administering chemotherapy.Although,we would encourage clinicians to record and publish cases to garner insight into this type of malignant disease.

Cognitive magnetic resonance imaging-ultrasound fusion transperineal targeted biopsy combined with randomized biopsy in detection of prostate cancer

BACKGROUND Prostate cancer(PCa)is one of the most common cancers among men.Various strategies for targeted biopsy based on multiparametric magnetic resonance imaging(mp-MRI)have emerged,which may improve the accuracy of detecting clinically significant PCa in recent years.AIM To investigate the diagnostic efficiency of a template for cognitive MRIultrasound fusion transperineal targeted plus randomized biopsy in detecting PCa.METHODS Data from patients with an increasing prostate-specific antigen(PSA)level but less than 20 ng/mL and at least one lesion suspicious for PCa on MRI from December 2015 to June 2018 were retrospectively analyzed.All patients underwent cognitive fusion transperineal template-guided targeted biopsy followed by randomized biopsy outside the targeted area.A total of 127 patients with complete data were included in the final analysis.A multivariable logistic regression analysis was conducted,and a two-sided P<0.05 was considered statistically significant.RESULTS PCa was detected in 66 of 127 patients,and 56 cases presented clinically significant PCa.Cognitive fusion targeted biopsy alone detected 59/127 cases of PCa,specifically 52/59 cases with clinically significant PCa and 7/59 cases with clinically insignificant PCa.A randomized biopsy detected seven cases of PCa negative on targeted biopsy,and four cases had clinically significant PCa.PSA density(OR:1.008,95%CI:1.003-1.012,P=0.001;OR:1.006,95%CI:1.002-1.010,P=0.004)and Prostate Imaging-Reporting and Data System(PI-RADS)scores(both P<0.001)were independently associated with the results of cognitive fusion targeted biopsy combined with randomized biopsy and targeted biopsy alone.CONCLUSION This single-centered study proposed a feasible template for cognitive MRIultrasound fusion transperineal targeted plus randomized biopsy.Patients with higher PSAD and PI-RADS scores were more likely to be diagnosed with PCa.

Advances in single-cell sequencing:insights from organ transplantation

Single-cell RNA sequencing(scRNA-seq)is a comprehensive technical tool to analyze intracellular and intercellular interaction data by whole transcriptional profile analysis.Here,we describe the application in biomedical research,focusing on the immune system during organ transplantation and rejection.Unlike conventional transcriptome analysis,this method provides a full map of multiple cell populations in one specific tissue and presents a dynamic and transient unbiased method to explore the progression of allograft dysfunction,starting from the stress response to final graft failure.This promising sequencing technology remarkably improves individualized organ rejection treatment by identifying decisive cellular subgroups and cell-specific interactions.

Oncological impact of different distal ureter managements during radical nephroureterectomy for primary upper urinary tract urothelial carcinoma

BACKGROUND The current standard surgical treatment for non-metastatic upper urinary tract urothelial carcinoma(UTUC)is radical nephroureterectomy(RNU)with bladder cuff excision(BCE).Typically,BCE techniques are classified in one of the following three categories:An open technique described as intrasvesical incision of the bladder cuff,a transurethral incision of the bladder cuff(TUBC),and an extravesical incision of the bladder cuff(EVBC)method.Even though each of these management techniques are widely used,there is no consensus about which surgical intervention is superior,with the best oncologic outcomes.AIM To investigate the oncological outcomes of three BCE methods during RNU for primary UTUC patients.METHODS We retrospectively analyzed the data of 248 primary UTUC patients,who underwent RNU with BCE between January 2004 to December 2018.Patients were analyzed according to each BCE method.Data extracted included patient demographics,perioperative parameters,and oncological outcomes.Statistical analyses were performed using chi-square and log-rank tests.The Cox proportional hazards regression model was utilized to identify independent predictors.P<0.05 was considered statistically significant.RESULTS Of the 248 participants,39.9%(n=99)underwent intrasvesical incision of the bladder cuff,38.7%(n=96)EVBC,and 21.4%(n=53)TUBC.At a median followup of 44.2 mo,bladder recurrence developed in 17.2%,12.5%,and 13.2%of the cases,respectively.Cancer-specific deaths occurred in 11.1%,5.2%,and 7.5%of patients,respectively.Kaplan-Meier survival curves with a log-rank test highlighted no significant differences in intravesical recurrence-free survival,cancer-specific survival,and overall survival among these approaches with P values of 0.987,0.825,and 0.497,respectively.Multivariate analysis showed that the lower ureter location appears to have inferior intravesical recurrence-free survival(P=0.042).However,cancer-specific survival and overall survival were independently influenced by tumor stage(hazard ratio[HR]=8.439;95%con
dence interval:2.424-29.377;P=0.001)and lymph node status(HR=14.343;95%CI:5.176-39.745;P<0.001).CONCLUSION All three techniques had comparable outcomes;although,EVBC and TUBC are minimally invasive.While based upon rather limited data,these findings will support urologists in blending experience with evidence to inform patient choices.However,larger,rigorously designed,multicenter studies with long term outcomes are still required.

Clinical outcomes of sacral neuromodulation in non-neurogenic,non-obstructive dysuria:A 5-year retrospective,multicentre study in China

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 nonneurogenic,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,nonobstructive 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.

Lymphoepithelioma-like carcinoma of the upper urinary tract: A systematic review of case reports

BACKGROUND Lymphoepithelioma-like carcinomas(LELCs)are rare,malignant epithelial tumors,generally considered a subtype of squamous cell carcinoma.LELCs are undifferentiated and can occur in multiple tissues,although LELCs in the urinary tract are extremely rare.As such,evidence does not provide clinicians with guidelines for the best practices.Even though this is a rare disease,it is associated with high morbidity and mortality.Therefore,we must learn to differentiate LELC types and identify risk factors for early identification.AIM To develop an evidence base to guide clinicians treating primary LELCs of the upper urinary tract(UUT-LELC).METHODS We performed a systematic review of all reports on UUT-LELC from the first published case in 1998 until October 2019,according to the PRISMA.A database was then developed by extracting data from previously published reports in order to analyze interactions between clinical characteristics,pathological features,interventions and outcomes.Survival was analyzed using Kaplan–Meier estimates,which were compared using log rank tests.RESULTS A total of 28 previously published cases were identified for inclusion.The median age was 72 years with a male to female ratio of 4:3.Pure type LELCs were most common with 48.3%(n=14),followed by 37.9%(n=11)predominant LELCs and 3.4%(n=1)focal LELCs.Epstein-Barr virus testing was negative in all cases.Fourteen patients received radical nephroureterectomy(RNU)-based intervention.Twenty-three patients survived with no evidence of further metastasis,although six died before the median 18 mo follow-up point.Survival analysis suggests pure histological subtypes,and patients who receive complete tumor resection have more favorable prognoses.As always in cancer care,early identification generally increases the probability of interventional success.CONCLUSION The most effective treatment for UUT-LELC is RNU-based therapy.Since cases are few in number,case reporting must be enhanced and publishing encouraged to both save and prolong lives.

Evaluation of the Prostate Imaging Reporting and Data System for Magnetic Resonance Imaging Diagnosis of Prostate Cancer in Patients with Prostate-specific Antigen 〈20 ng/ml

Background： The European Society of Urogenital Radiology has built the Prostate Imaging Reporting and Data System （PI-RADS） for standardizing the diagnosis of prostate cancer （PCa）. This study evaluated the PI-RADS diagnosis method in patients with prostate-specific antigen （PSA） 〈20 ng/ml. Methods： A total of 133 patients with PSA 〈20 ng/ml were prospectively recruited. T2-weighted （T2WI） and diffusion-weighted （DWI） magnetic resonance images of the prostate were acquired before a 12-core transrectal prostate biopsy. Each patient＇s peripheral zone was divided into six regions on the images; each region corresponded to two of the 12 biopsy cores. T2WI, DWI, and T2W1 ＋ DWI scores were computed according to PI-RADS. The diagnostic accuracy of the PI-RADS score was evaluated using histopathology of prostate biopsies as the reference standard. Results： PCa was histologically diagnosed in 169 （21.2%） regions. Increased PI-RADS score correlated positively with increased cancer detection rate. The cancer detection rate for scores 1 to 5 was 2.8%, 15.0%, 34.6%, 52.6%, and 88.9%, respectively, using T2W1 and 12.0%, 20.2%, 48.0%, 85.7%, and 93.3%, respectively, using DWI. For T2WI ＋ DWI, the cancer detection rate was 1.5% （score 2）, 13.5% （scores 3-4）, 41.3% （scores 5-6）, 75.9% （scores 7-8）, and 92.3% （scores 9-10）. The area under the curve for cancer detection was 0.700 （T2WI）, 0.735 （DWI） and 0.749 （T2WI ＋ DWI）. The sensitivity and specificity were 53.8% and 89.2%, respectively, when The summed score ofT2Wl ＋ DWI

Diagnosis and Treatment of Urinary Incontinence after Orthotopic Ileal Neobladder in China

INTRODUCTIONRadical cystectomy for bladder and urinary diversion is considered the gold standard for treatment of muscular invasive bladder cancer or high-risk nonmuscular invasive bladder cancer. Urinary diversion is usually classified into three types： orthotopic neobladder, ileal conduit or sigmoid conduit, and cutaneous ureterostomy Orthotopic neobladder is a better choice for urinary diversion than the other types because of its nonurinary diversion and better quality of life when this method is feasible for patients. One of the complications after creating an orthotopic neobladder is urinary incontinence. With an increasing amount of orthotopic neobladder procedures, more patients are suffering from urinary incontinence. Therefore, an article is required for diagnosis and treatment of urinary incontinence after the orthotopic ileal neobladder procedure.

Photoselective Vaporesection of the Prostate with an End-firing Lithium Triborate Crystal Laser

Background： Photoselective vaporization of the prostate is a technique that is widely used for the treatment of benign prostatic hyperplasia （BPH） and has pronounced advantages compared to the traditional transurethral resection of the prostate. Following the recent introduction of end-firing lithium triborate lasers, we have created a new technique called photoselective vaporesection of tile prostate （PVRP）. This study described our initial experience using the PVRP technique for the treatment of BPH. Methods： This prospective study included a total of 35 patients with BPH who underwent PVRP from August 2013 to July 2014. The chief clinical parameters were obtained and evaluated during the perioperative period and follow-up, including the International Prostate Symptom Score （IPSS）, quality of life （QoL） score, maximum urinary flow rate, and prostate volume. All variables were evaluated for statistically significant differences compared to baseline values using the analysis of variance. Results： The mean subgroup IPSS and QoL scores significantly improved during tbllow-up; the respective decreases in IPSS storage score, IPSS voiding score, IPSS nocturia score, and QoL score were 75.3%, 83.6%, 51.4%, and 71.7%, respectively （all P 〈 0.001 compared with baseline）. Three patients were diagnosed with prostate cancer based on postoperative pathological examinations. There were no serious perioperative complications. Conclusion： The PVRP technique demonstrates satisfactory short-term clinical outcomes and perioperative safety in the treatment of BPH.

Effect of pre-IVF incubation in maturation medium on oocyte maturity,fertilization,embryonic development,and clinical outcomes following embryo transfer

Objective:Collected human cumulus-oocyte complexes(COCs)are usually inseminated after 4 to 6 hours in in vitro fertilization(IVF)laboratories.The purpose of this study was to determine the effect of short-term pre-IVF incubation in culture medium on subsequent oocyte maturation,fertilization,and embryonic development,as well as clinical outcomes.Methods:Sixty patients were divided randomly into 2 groups,pre-IVF incubation for 5 hours:1)with(+)the designed oocyte maturation medium;2)without(-)the designed oocyte maturation medium(transferred directly to fertilization medium for 5 hours before insemination).Oocyte maturation and fertilization were assessed,and the rate of cleavage and good quality embryos were evaluated between the 2 groups on days 2 and 3,respectively.Blastocyst development was based on the remaining number of embryos on day 3,continuously cultured to day 5 after embryo transfer or frozen on day 3,and was compared between the 2 groups.Clinical pregnancy,implantation,and miscarriage rates were also compared.Results:Oocyte maturation rates did not differ between groups(85.8±14.1%vs.90.7±9.1%).However,the range of oocyte maturation rates(58.3%-100.0%)for each patient was significantly higher in the(-)group than in the(+)pre-incubation group(71.4%-100.0%).There were no differences in fertilization rates(89.9±10.0%vs.86.5±12.2%)and good quality embryos(70.8±19.1%vs.62.1±23.7%)between groups;however,the blastocyst development rates were significantly different between groups(73.1±20.1%vs.58.8±18.2%,P<0.05).Nevertheless,clinical pregnancy(62.5%vs.61.1%)and implantation(46.9%vs.47.2%)rates did not differ between groups.Conclusions:These results indicate that a short pre-IVF incubation time in the designed culture medium promotes oocyte maturation and embryonic development,suggesting that short pre-IVF incubation of COCs in the designed culture medium may be important for subsequent final oocyte maturation and early embryonic development.

The sphingosine-1-phosphate/RhoA/Rho associated kinases/myosin light chain pathway in detrusor of female rats is down-regulated in response to ovariectomy

Background:Dysuria is one of the main symptoms of genitourinary syndrome of menopause,which causes serious disruption to the normal life of peri-menopausal women.Studies have shown that it is related to decrease of detrusor contractile function,but the exact mechanism is still poorly understood.Previous results have suggested that the sphingosine-1-phosphate(S1P)pathway can regulate detrusor contraction,and this pathway is affected by estrogen in various tissues.However,how estrogen affects this pathway in the detrusor has not been investigated.In this study,we detected changes of the S1P/RhoA/Rho associated kinases(ROCK)/myosin light chain(MLC)pathway in the detrusor of ovariectomized rats in order to explore the underlying mechanism of dysuria during peri-menopause.Methods::Thirty-six female Sprague-Dawley rats were randomly divided into SHAM(sham operation),OVX(ovariectomy),and E groups(ovariectomy+estrogen),with 12 rats in each group.We obtained bladder detrusor tissues from each group and examined the mRNA and protein levels of the major components of the S1P/RhoA/ROCK/MLC pathway using quantitative real-time polymerase chain reaction and Western blotting,respectively.We also quantified the content of S1P in the detrusor using an enzyme linked immunosorbent assay.Finally,we compared results between the groups with one-way analysis of variance.Results::The components of the S1P pathway and the RhoA/ROCK/MLC pathway of the OVX group were significantly decreased,as compared with SHAM group.The percent decreases of the components in the S1P pathway were as follows:sphingosine kinase 1(mRNA:39%,protein:45%)(both P<0.05),S1P(21.73±1.09 nmol/g vs.18.86±0.69 nmol/g)(P<0.05),and S1P receptor 2/3(S1PR2/3)(mRNA:25%,27%,respectively)(P<0.05).However,the protein expression levels of S1PR2/3 and the protein and mRNA levels of SphK2 and S1PR1 did not show significant differences between groups(P>0.05).The percent decreases of the components in the RhoA/ROCK/MLC pathway were as follows:ROCK2(protein:41%,mRNA:36%)(both P<0.05),p-MYPT1(protein:54%)(P<0.05),and p-MLC20(protein:47%)(P<0.05),but there were no significant differences in the mRNA and protein levels of RhoA,ROCK1,MYPT1,and MLC20(all P>0.05).In addition,all of the above-mentioned decreases could be reversed after estrogen supplementation(E group vs.SHAM group)(all P>0.05).Conclusion::In this study,we confirmed that ovariectomy is closely associated with the down-regulation of the S1P/RhoA/ROCK/MLC pathway in the rat detrusor,which may be one mechanism of dysuria caused by decreased contractile function of the female detrusor during peri-menopause.