1.The effect of curcumin on the differentiation and functions of Th17 cells
Diying WU ; Pengjie XU ; Haojie ZHANG ; Xudong CAI
Chinese Journal of Rheumatology 2011;15(7):476-480
Objective To establish a culture protocol for Th17 cells in vitro and evaluate the effect of curcumin on the differentiation and functions of Th17 cells and explore the related mechanisms. Methods Splenic CD4+CD25- T cells of C57BL/6 mice were isolated and purified with magnetic bead methods, and were co-cultured with plate-bound anti-CD3 and anti-CD28 antibodies and with transforming growth factor (TGF)-β, interleukin (IL)-6, IL-23, anti-interferon-γ antibody and anti-IL-2 antibody for Th17-polarization. The cultured Th17 cells were allocated into four groups: the control group, in which T cells were cultured on the basis of the above protocol; the low-concentration curcumin (CM-L, 5 μmol/L) and high-concentration (CM-H, 25 μmol/L) curcumin groups, and sirolimus (SRL, 100 ng/ml) group. The proportion of Th17 cells was detected with flow cytometry, and the mRNA expression of retinoic acid-related orphan receptor (ROR)γt, IL-17A, IL-21 was examined with real-time quantitative polymerase chain reaction. Finally, the protein expression of RORγt and the phosphorylation levels of signal transducer and activator of transcription (STAT) 3 were measured using western blotting analysis. Results The proportion of Th17 cells in the freshly isolated CD4+CD25- T cells was (3.1 ±0.4)%, whereas the proportion of the cells cultured with the protocol could get [(54.1±3.4)%, P<0.01]. As compared with the control group, the Th17 cells proportion in CM-L, CM-H and SRL groups was significantly decreased [CM-L (40.3±2.8)%, CM-H (25.8±2.3)%, SRL (25.0±2.0)%versus the control (54.1±3.4)%, t=6.15, 12.63, 12.97, P<0.01], and no marked difference was seen between CM-H group and SRL group (ft>0.05). Moreover, the mRNA levels of RORγt, IL-17A and IL-21, the protein expression of RORγt and the phosphorylation levels of STAT 3 in CM-L, CM-H and SRL groups were also lower than those in the control group (IL-17A mRNA: CM-L 0.81±0.05, CM-H 0.61±0.05, SRL 0.58±0.05, Control 1.01 ±0.11, t=4.81, 8.52, 8.89; IL-21 mRNA: CM-L 0.73±0.06, CM-H 0.49±0.03,SRL 0.59±0.03, Control 1.12±0.11, t=5.98, 9.22, 7.95, P<0.01). The mRNA level of IL-21 in the CM-H group was lower than that in the SRL group (P<0.05). Conclusion In vitro, curcumin can inhibit the differentiaton of splenic CD4+CD25- T cells into Th17 cells in the setting of Th 17-polarization and inhibit the expression of IL-17A and IL-21 mRNA, which is associated with the inhibitive effect of curcumin on RORγt expression and STAT 3 phosphorylation.
2.Clinical research on prophylactic pelviureteric instillation chemotherapy after endoscopic management of upper tract urothelial carcinoma
Fangyuan ZHANG ; Dong WEI ; Pengjie WU ; Xin CHEN ; Jianye WANG
Chinese Journal of Geriatrics 2015;34(8):878-880
Objective To investigate the effect of endoscopic management of upper tract urothelial carcinoma (UTUC),and evaluate the indication and clinical value of postoperative prophylactic pelviureteric instillation chemotherapy.Methods Patients who met the inclusion criteria included elderly patients,patients who could not tolerate radical surgery,patients with renal insufficiency or needed dialysis after removal of the kidney,patients with bilateral UTUC,patients with tumor≥3 cm in diameter but could be completely resectted under ureteroscopy who required to preserve renal function.Surgical procedure was successful.The ureteral stents were placed,and prophylactic ureteral infusion chemotherapy via the retrograde transvesical ureteric catheterisation was conducted 1-2 times one week at 2 days after surgery.40 milligram of pirarubicin hydrochloride or epirubicin hydrochloride was dissolved in 40 milliliter sterile water for the prophylactic infusion chemotherapy.These instillations were completed within 40 minutes.Results Totally,9 patients (3 males and 6 females) aged 60-86 years,mean age of (69.7±6.4) years,were enrolled in this study.The carcinoma of the renal pelvis was found in 2 cases and ureteral tumors in 7 cases.In pathological results,ureteral polyps was found in 1 case,papillary ureteral neoplasm with low malignant potential in 2 cases,urinary tract epithelial carcinoma in 4 cases (1 case with poorlydifferentiation,1 case with well-differentiation,2 cases with urinary tract epithelial cancer),and 2 cases were lack of pathological reports because of too few pathologic specimens.4 patients received adjuvant chemotherapy by instillation successfully,and lumbago,fever or other complications were not found.Patients were followed up for a mean period of 15 moths (4-31 months).Only 1 patient had recurrence of bilateral ureteral tumor 15 months after surgery,and no tumor recurrence was found in other patients.Conclusions Endoscopic management is a safe and effective in treating UTUC,which can preserve renal function by avoiding nephrorectomy in some patients.The instillation chemotherapy after endoscopic management is safe,which has a satisfactory effect,but further validation in a large clinical sample is needed.Patients with tumor resection under ureteroscopy who cannot obtain the pathology results need to be closely followed up.
3.Clinical efficacy and safety of docetaxel in the treatment of castration resistant prostate cancer patients over 75 years old
Hong MA ; Yaoguang ZHANG ; Pengjie WU ; Bin JIN ; Ben WAN
Chinese Journal of Urology 2021;42(1):6-11
Objective:To evaluate the efficacy and safety of docetaxel+ prednisone in the treatment of castrated resistant prostate cancer in patients over 75 years old.Methods:In this study, 118 metastatic castration resistant prostate cancer (mCRPC) patients over 60 years old treated in Beijing Hospital from February 2013 to December 2019 were retrospectively analyzed. The median age of the patients was 72 (65, 77)years, ECOG scores ≤2. All 118 cases had bone metastasis, 5 cases had visceral metastasis. A total of 40 patients chose docetaxel as the first-line treatment of mCRPC, and the remaining 78 patients chose docetaxel as second-line or third-line treatment. The study included 53 patients >75 years old and 65 patients aged 60-75 years. The age of patients in the two groups were 67 (63, 71) years old and 78 (76, 83) years old, the difference was statistically significant ( P<0.05). Among them, there were 24 cases with Gleason score ≤7 and 41 cases with Gleason score >7 in 60-75 years old group, and 30 cases with Gleason score ≤7 and 23 cases with Gleason score >7 in the group of >75 years old, with significant difference between the two groups ( P = 0.034). Sixty-one patients received endocrine therapy and 4 received orchiectomy in the 60-75 years old group; 43 patients received endocrine therapy and 10 received orchiectomy in the group of >75 years old, the difference was statistically significant ( P=0.035). There were 37 cases with ECOG 0 score, 25 cases with 1 scores and 3 cases with 2 scores in the group of 60-75 years old; there were 5 cases with ECOG 0 score, 38 cases with 1 score and 10 cases with 2 score in the group of >75 years old, with significant difference between the two groups ( P<0.05). There was no significant difference in PSA level[ 90 (35.5, 258) ng/ml vs. 115 (60, 296) ng/ml], G8 scale score [(14.3±2.1 vs. 13.6±1.1)], Mini-Cog score[3(2, 3) vs. 3(1, 3)], and visceral metastasis [2 cases (3.1%) vs. 3 cases (5.7%)]( P>0.05). The efficacy and safety of docetaxel in the two groups were further observed. Results:The median follow-up time was 21.5 (6, 62) months. There was no significant difference in chemotherapy cycle [(6.1±1.3) vs. (6.8±1.7)] and chemotherapy dose [(70.3±4.3) mg/m 2 vs. (66.3±5.2) mg/m 2] between the 60-75 years old group and the >75 year old group ( P> 0.05). The PSA response rate [72.3%(47/65)vs.66.0%(35/53)], pain relief rate [45.0% (9/20) vs. 54.5% (6/11)], and median progression-free survival[6.1 (1.4, 11.2) months vs. 5.9 (2.0, 12.0) months] had no statistical significance ( P>0.05). There were no deaths in the two groups during chemotherapy. The median overall survival(OS) of patients aged 60-75 years and those >75 years old who received docetaxel as first-line treatment were 26.5 (16.1, 31.3) months and 24.8 (17.5, 28.4) months, respectively ( P=0.223). The median OS of the two groups were 17.3 (13.2, 20.5) months and 15.4 (12.3, 20.0) months with docetaxel treatment as second or third line treatment ( P=0.331). There were 3 cases (4.6%) and 5 cases (9.4%) of grade 3 adverse reactions in 60-75 years group and >75 years old group, respectively. Grade 3 leukopenia occurred in 1 case time (1.5%) and 2 cases (3.8%) respectively. Grade 3 neutropenia fever occurred in 1 case time in both groups. There was no significant difference in the incidence of above complications between the two groups ( P > 0.05). Conclusions:The efficacy and safety of docetaxel + prednisone chemotherapy for mCRPC patients >75 years old were similar to those of 60-75 years old. Age should not be the absolute contraindication of docetaxel for prostate cancer chemotherapy.
4.Efficacy and safety of RevoLix 2 micron continuous wave laser vaporesection in treatment for senile patients with benign prostatic hyperplasia
Jianlong WANG ; Leilei WANG ; Ming LIU ; Pengjie WU ; Yaoguang ZHANG ; Ben WAN ; Jianye WANG
Chinese Journal of General Practitioners 2017;16(7):551-553
The clinical efficacy and safety of RevoLix 2 μm continuous wave laser vaporesection in treatment of senile patients with benign prostatic hyperplasia (BPH) were retrospective evaluated.In 291 senile patients with BPH,213 received 2 μm continuous wave laser vaporesection (group A) and other 78 patients received transurethral resection of prostate (TURP, group B).Compared with group B the intraoperative blood loss was less, the bladder irrigation time, catheter time and hospitalization time were shorter in group A.The subjective or objective indexes were all significantly improved at 3 and 12 months after laser treatment.The improvements of international prostate symptom score (IPSS), IPSS-S, overactive bladder symptom score (OABSS) in patients of 70-79 were more marked than those of 80 or older.Patients with mild overactive bladder (OAB) had less improvement in IPSS and IPSS-S than those with moderate-severe OAB which suggest that the storage symptoms could be improved significantly by removing obstruction.
5.The value of serum IL-23 levels in predicting the progression of metastatic prostate cancer
Hong MA ; Bin JIN ; Pengjie WU ; Xin CHU ; Shuangyi ZHAO ; Ben WAN
Chinese Journal of Geriatrics 2021;40(1):107-111
Objective:To investigate the value of serum IL-23 in predicting the progression of prostate cancer at different stages of treatment.Methods:A total of 124 patients with metastatic prostate cancer diagnosed in Beijing Hospital from June 2018 to March 2019 were collected.Patients were TNM-staged according to the Prostate Cancer Guidelines of the European Association of Urology.Serum IL-23 levels were measured in patients with metastatic castration resistance prostate cancer(mCRPC), metastatic castration sensitive prostate cancer(mCSPC)and benign prostatic hyperplasia(BPH), respectively.Patients with mCRPC were subgrouped based on disease stability, and serum IL-23 levels were compared between the subgroups.Serum IL-23 levels in the groups were analyzed and compared with the Gleason score and the prostate-specific antigen(PSA)level.Results:The median value of serum IL-23 in the mCRPC group was 79.73(45.61, 95.63)μg/L, which was higher than that in the BPH group[30.88(15.01, 44.94)μg/L, Z=22.66, P=0.000]and the mCSPC group[46.10(35.27, 80.92)μg/L, Z=11.46, P=0.001]. Serum IL-23 levels were higher in the mCSPC group than in the BPH group( Z=7.17, P=0.007). Analysis for the subgroups showed that the median value of serum IL-23 was 110.25(88.47, 159.09)μg/L in mCRPC patients with unstable disease, which was higher than that in mCRPC patients with stable disease[46.52(44.97, 80.33)μg/L, Z=33.99, P=0.000]. There was no significant difference in serum IL-23 levels between mCRPC patients with stable disease and mCSPC patients[46.10(35.27, 80.92)μg/L]( Z=0.35, P=0.554). Conclusions:Serum IL-23 can be used as a potential biological indicator to predict the therapeutic effect of mCSPC and to predict tumor metastasis.
6.Effects of radical prostatectomy on survival in elderly patients aged 75 years and over
Xiaoxiao GUO ; Shengcai ZHU ; Huimin HOU ; Shengjie LIU ; Dalei ZHANG ; Pengjie WU ; Jianye WANG ; Ming LIU
Chinese Journal of Geriatrics 2019;38(3):278-282
Objective To investigate the effects of radical prostatectomy on the overall survival (OS)and tumor-specific survival in prostate cancer(PCa)patients aged 75 years and older.Methods Clinical data of patients aged 75 and older with localized PCa from Surveillance,Epidemiology,and End Results(SEER)Database from 2004 to 2016 were retrospectively analyzed.There were 17 899 cases of PCa undergoing radical prostatectomy and 3 648 cases of PCa without surgery in this study.The OS and prostate cancer-specific survival(PSS)were compared between the surgery group and the nonsurgery group.Results For 75-79-year-old patients with high-risk localized PCa,the OS and PSS in the surgery group were better than in the non-surgery group (OR =1.49,95 % CI:1.22 ~ 1.82,P < 0.01;OR=1.43,95%CI:1.09~2.04,P<0.05).For patients aged 75-79 years with low-risk PCa and patients aged 80 years and older with low-,middle-,or high-risk PCa,the OS was worse in the surgery group than in the non-surgery group(OR =0.54,95%CI:0.38~0.76,P<0.01;OR =0.47,95%CI:0.34~0.66,P<0.01;OR =0.58,95%CI:0.44~0.78,P<0.01;OR =0.59,95%CI:0.51 ~0.68,P<0.01).For patients aged 75-79 years with low-or medium-risk PCa and patients aged 80 years and older with medium-risk PCa,there was no statistical difference in PSS between the surgery and non-surgery groups(P>0.05).Conclusions Age limits for prostatectomy should be extended as a result of increasing average life expectancy.Patients aged 75-79 years with high-risk PCa can be considered for surgical treatment,while it should not be recommended for patients aged 75-79 years with low-or medium-risk localized PCa or aged more than 80 years.Many factors should be considered in making treatment decisions for prostate cancer.
7.Efficacy analysis of the single versus combination drug therapies for benign prostatic hyperplasia with overactive bladder
Xinghui LI ; Jianye WANG ; Pengjie WU ; Huiping YUAN ; Xiaoquan ZHU ; Liang SUN ; Na SUN ; Xiangwen LI ; Rongqiang ZHANG ; Qiling LIU ; Ze YANG
Chinese Journal of Geriatrics 2018;37(10):1092-1097
Objective To explore the efficacy of the single versus combination drug therapies for benign prostatic hyperplasia(BPH) combined with overactive bladder(OAB).Methods A total of 471 outpatients with BPH and OAB meeting the inclusion/exclusion criteria were enrolled in this prospective cohort study from March 2012 to October 2015.Patients were divided into two groups:(1) the single alpha-blocker treatment group (prostate volume < 30 ml),and (2) the 5 alpha reductase inhibitors(5-ARIs) plus alpha-blocker combination treatment group(prostate volume ≥ 30 ml).The 318 patients were treated with alpha blockers for 4 weeks,and then received a continuing alpha-blocker treatment for 8 weeks if IPSS score changes were less than 30% (i.e.single alpha-blocker treatment group).And 153 patients were treated with 5-ARIs for 12 weeks,then received 5-ARIs plus alpha-blocker combination treatment for another 4 weeks(a total of 16 weeks)if IPSS score changes were less than 30 % (i.e.combination treatment group).The improvements of post-voiding residual(PVR),PV,maximum urinary flow rate(Qmax),international prostate symptom score(IPSS),overactive bladder symptom score (OABSS),quality of life (QOL),urine storage period symptom score (USPSS) and voiding symptom score(VSS)were compared between the two groups.Results The values of IPSS,OABSS,QOL,USPSS and VSS index in the two groups were improved after treatment as compared with pre-treatment(all P≤0.05).Patients in combination treatment group had little improvement in PVR and Qmax after treatment.The OAB symptom remission rates of BPH patients with OAB in single alpha-blocker treatment group were 70.5% (206/292)and 78.6% (165/210)after 4 and 12 weeks of treatment respectively.The OAB symptoms remission rates of BPH patients with OAB in combination treatment group were 54.5 % (64/122) and 67.1% (53/79) after 12 and 16 weeks of treatment respectively.Conclusions Both single alpha-blocker treatment and alpha-blocker plus 5ARIs combination treatment,which identification was based on prostate volume,have good effects on BPH patients with OAB.The single alpha-blocker treatment can improve PVR and Qmax,and the alpha-blockers plus 5ARIs combination treatment can improve the prostate volume in BPH patients with OAB.
8.Multivariate analysis of long-term outcomes of storage symptom improvement in elderly patients with benign prostatic hyperplasia after GreenLight laser vaporization
Jianlong WANG ; Yilai CHEN ; Leilei WANG ; Ming LIU ; Pengjie WU ; Yaoguang ZHANG ; Ben WAN ; Jianye WANG ; Xiaohu DENG
Chinese Journal of Geriatrics 2019;38(2):196-200
Objective To investigate the relationship between preoperative urodynamic parameters and the improvement of overactive bladder (OAB)symptoms after GreenLight laser vaporization,and to explore prognostic factors for improvement of OAB symptoms in the elderly.Methods A retrospective study was conducted in 100 benign prostatic hyperplasia (BPH)patients undergoing GreenLight laser vaporization at the Department of Urology of Beijing Hospital from July 2015 to March 2017.All patients completed a preoperative urodynamic examination and received GreenLight laser vaporization.Clinical data including age,prostate-specific antigen (PSA),prostate volume,international prognostic scoring system(IPSS),overactive bladder symptom score (OABSS),quality of life(QOL)and urodynamic parameters were collected.The related factors for improvement of OAB symptoms after GreenLight laser vaporization were analyzed by a binary Logistic regression analysis.Results All patients underwent surgery successfully and completed a 12-month follow-up.Both urinary storage and voiding symptoms improved at 3 and 12 months after GreenLight laser vaporization(P<0.05).The scores of IPSS,IPSS storage (IPSS-S),IPSS voiding (IPSS-V),OABSS and QOL and nighttime voiding frequency decreased and urinary storage and voiding symptoms improved at 3 and 12 months after GreenLight laser vaporization,compared with pre-surgery data(P<0.05).The success rates of storage symptom improvement at 3 and 12 months after GreenLight laser vaporization were 62.0 % (62/100) and 68.0 % (68/100) evaluated by IPSS-S and 68.0 % (68/100) and 75.0% (75/100)by OABSS,respectively.Multiple Logistic regression analysis showed that age,detrusor contractility,residual urine volume and nighttime voiding frequency were independent influencing factors for prognosis(OR =35.714,0.352,0.110 and 0.040,P =0.000,0.027,0.018 and 0.002).Conclusions GreenLight laser vaporization is an effective method in treating BPH with OAB.Age is an independent unfavorable factor and the residual urine volume,nighttime voiding frequency and detrusor contraction are independent influencing factors for prognosis.Enough attention should be paid to these related parameters before surgery.
9.Comparison of single-course versus multiple course prophylactic intravesical instillation chemotherapy for bladder tumor recurrence after radical nephroureterectomy for upper tract urothelial carcinoma: a systematic review and meta-analysis
Pengjie WU ; Dong WEI ; Hong MA ; Bin JIN ; Yaqun ZHANG ; Shuangyi ZHAO ; Xin CHU ; Jianye WU ; Ben WAN ; Jianye WANG
Chinese Journal of Geriatrics 2023;42(10):1254-1258
Objective:To examine whether multiple-course prophylactic intravesical instillation chemotherapy is superior to single-course chemotherapy in preventing bladder tumor recurrence after radical nephroureterectomy(RNU)for primary upper tract urothelial carcinoma(UTUC).Methods:A comprehensive literature search was performed using the PubMed, Wanfang Data and China National Knowledge Infrastructure and all publications before March 2021 about clinical trials comparing the effects of single-course and multiple-course prophylactic intravesical instillation chemotherapy after RNU for UTUC were retrieved.Analysis was performed using Stata/SE 12.0.Results:Seven trials included a total of 998 patients, with 473 participants receiving multiple-course and 525 receiving single-course intravesical instillation chemotherapy.Bladder cancer recurrence occurred in 69 out of 473 patients(14.6%)with multiple-course chemotherapy and in 123 out of 525 patients(23.4%)with single-course chemotherapy.The absolute risk reduction was 8.8% and the relative risk reduction was 37.6%.Compared with a single-course instillation, the pooled OR of bladder cancer recurrence was 0.55(95% CI: 0.40-0.76, P<0.001)for multiple-course instillations.No serious adverse events were reported. Conclusions:Compared with single-course instillation chemotherapy, multiple-course prophylactic intravesical instillation chemotherapy significantly decreases the risk of bladder cancer recurrence in primary UTUC patients treated with RNU, indicating multiple intravesical instillation chemotherapy is superior to single instillation chemotherapy.
10.Evaluation of curative effect of kidney-sparing surgery in elderly patients with upper urinary tract urothelial tumors
Sen XU ; Pengjie WU ; Dong WEI ; Xin CHEN ; Jianye WANG ; Ben WAN
Chinese Journal of Geriatrics 2019;38(8):893-896
Objective To evaluate the value of kidney-sparing surgery in the treatment of upper urinary tract urothelial tumors by retrospectively analyzing and comparing the clinical data of elderly patients with upper urinary tract urothelial tumors between patients undergoing kidney-sparing surgery and nephroureterectomy in our hospital during the same period.Methods Thirty elderly patients with upper urinary tract urothelial tumors were treated with kidney-sparing surgery(ureteroscopy,segmental ureteral resection)and followed up from April 2004 to July 2017.One hundred and fortynine patients who underwent nephroureterectomy during the same period were selected as the control group.The survival rate and local recurrence rate were compared between the two groups.Results In the kidney-sparing group,23 cases were pathologically diagnosed as tumors,3 cases as inflammatory polyps and 4 cases without pathological findings.There were no statistically significant differences between kidney-sparing surgery and nephroureterectomy in bladder recurrence[4 cases(13.3%)vs.24 cases(16.1%),x2 =0.011,P =0.915],pelvic orthotopic recurrence [3 cases (10.0%) vs.6 cases (4.0%),x2 =0.825,P=0.364],cancer-specific death rate[2 cases(6.7%)vs.16 cases(10.7%),x2=0.118,P=0.731]and overall survival rate[4 cases(13.3%)vs.22 cases(14.8%),x2 =0.410,P =0.550].There were no significant differences between kidney-sparing surgery versus nephroureterectomy among postoperative 1-year,5-year and 10-year in the overall survival rates (100.0 %vs.95.1%、85.9 % vs.84.1%、80.5 % vs.60.8 %,P =0.156),tumor-specific survival rates (100.0 % vs.95.1%,85.7 % vs.87.6 %,85.7 % vs.76.8 %,P =0.380) and progression-free survival rates(100.0%vs.100.0%,90.9%vs.96.0%,90.9% vs.79.7%,P =0.680).Conclusions Elderly patients have poor physical conditions and poor tolerance to radical surgery with a significant damage on postoperative renal function.Kidney-sparing surgery(ureteroscopy,segmental ureteral resection) as the treatment of upper urinary tract tumors can minimize the risk of surgery and optimize the quality of life.The individual assessment based on individual conditions,postoperative complications,and the recovery of renal function should be conducted and the operation with the greatest benefit should be adopted.