Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial / 中华医学杂志(英文版)

BACKGROUND@#LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.@*METHODS@#We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels.@*RESULTS@#On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]).@*CONCLUSION@#LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT04563936.

Influencing factors of survival and prognosis of patients with bladder urothelial carcinoma after surgical treatment and recommendation of an artificial intelligence algorithm / 现代泌尿外科杂志

【Objective】 To explore the factors influencing the survival and prognosis of patients with bladder urothelial carcinoma (BUC) after surgical treatment, and to establish an artificial intelligence algorithm to predict the effects of different surgical regimens. 【Methods】 BUC patients treated with surgery during Jan.2007 and Jan.2019 in The Second Hospital of Dalian Medical University and Nanfang Hospital of Southern Medical University were enrolled. The complete clinical and follow-up data were collected. Deep neural network (DNN) was used to establish an artificial intelligence algorithm model. A prediction model of survival and prognosis was established, and the influencing factors of survival were explored and ranked by the artificial intelligence algorithm. 【Results】 A total of 832 patients were involved, including 438 (52.64%) treated in The Second Hospital of Dalian Medical University, and 394 (47.36%) treated in Nanfang Hospital of Southern Medical University. Of all cases, 579 (69.6%) were non-muscle invasive bladder cancer, and 253 (30.4%) were muscle invasive bladder cancer. Transurethral resection of bladder tumor was conducted in 539 (64.8%) cases, partial cystectomy in 66 (7.9%) cases, and total cystectomy in 227 (27.3%) cases. The data of patients treated in Second Hospital of Dalian Medical University were used for DNN modeling, and the data of patients treated in Nanfang Hospital of Southern Medical University were used for external verification after modeling. Finally, it was concluded that the factors affecting survival and prognosis were T stage, pathological grade, hypertension or cardiovascular and cerebrovascular disease, hemoglobin, blood calcium, smoking, albumin, lymphocytes, age, ratio of albumin/globulin, operation method, N stage, and creatinine clearance rate in descending order. The model could be used for preoperative prediction. 【Conclusion】 Through DNN modeling and external verification, the influencing factors of postoperative survival can be predicted for patients with bladder cancer, and the surgical effects can also be predicted before operation. The model can provide artificial intelligence algorithm support for the selection of surgical methods and postoperative follow-up plans.

Value of suprapubic cystostomy in bipolar transurethral resection of the prostate for benign prostatic hyperplasia below 80 gram / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the perioperative benefit of suprapubic cystostomy in bipolar transurethral resection of the prostate (B-TURP) for treatment of benign prostatic hyperplasia (BPH) below 80 g.</p><p><b>METHODS</b>This retrospective study was conducted in patients undergoing B-TURP for BPH below 80 g, who were stratified with respect of suprapubic cystostomy in B-TURP. The end points including the safety, efficiency, complications and nursing care were compared between the two groups.</p><p><b>RESULTS</b>A total of 585 patients were enrolled, including 366 in cystostomy group and 219 in non-cystostomy group. The two groups showed similar postoperative reduction of serum sodium (0.06 vs 0.54 mmol/L, P>0.05), hematocrict (2.44% vs 2.89%, P>0.05), and blood hemoglobin concentration (9.62 vs 10.42 g/L, P>0.05), with comparable weight of resected prostate (42.50 vs 43.76 g, P>0.05). The operation time was significantly longer in cystostomy group than in non-cystostomy group (90.75 vs 76.28 min, P<0.05), but the rate of blood transfusion and incidences of postoperative fever and catheter blocking were comparable between the two groups. Compared with the non-cystostomy group, cystostomy group had significantly longer time for bladder washing (3.15 vs 2.57 days, P<0.05), catheter indwelling time (5.19 vs 4.15 days, P<0.05), and hospital stay after the operation (7.36 vs 5.65 days, P<0.05).</p><p><b>CONCLUSIONS</b>In B-TURP for BPH below the weight of 80 g, suprapubic cystostomy is associated with a longer time for operation, bladder washing, catheter indwelling and postoperative hospital stay, and thus provides no obvious benefits for the patients.</p>

Construction of full-length human bladder cancer-specific antibody libraries based on mammalian display technology / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct full-length human bladder cancer-specific antibody libraries for efficient display of full-length antibodies on the surface of mammalian cells.</p><p><b>METHODS</b>The total RNA was isolated from peripheral blood mononuclear cells from patients with bladder cancer. The repertoires of IgG1 heavy chain variable region (VH) and Kappa light chain were amplified by RT-PCR using specific primers. The antibody genes were inserted into the vector pDGB-HC-TM to construct the bladder-cancer-specific antibody libraries of heavy chains and light chains. Ten clones from each library were randomly picked for gene sequencing and transient transfection into FCHO cells to analyze antibody display on mammalian cell surface by flow cytometry after staining with corresponding fluorescent labeled antibodies.</p><p><b>RESULTS</b>The libraries of bladder-cancer-specific antibody heavy chain (IgG1) and light chain (LCk) were successfully constructed. Seven out of the 10 clones randomly selected from the heavy chain library and 9 out of the 10 clones from the light chain library showed correct open reading frame, coding for 7 unique VH and 9 unique LCk. The combinatory library size reached 3.32×10(11).</p><p><b>CONCLUSION</b>We have successfully constructed a full-length human bladder-cancer-specific antibody library with a combinatory diversity of 3.32×10(11) based on mammalian display technology, which can be used for screening monoclonal antibodies against bladder-cancer-associated antigens.</p>

A meta-analysis of fish intake and the risk of renal cell cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the association of fish intake with the risk of renal cancer.</p><p><b>METHODS</b>PubMed, Embase, CNKI and CA databases were searched for case-control studies or cohort studies examining the relationship between fish or fish products intake and renal cancer. Heterogeneity among the selected studies was assessed using I2 score, and the publication bias was assessed using funnel plots.</p><p><b>RESULTS</b>Seventeen articles were included in the analysis with a heterogeneity across the studies (P=0.003, I(2)=52.3%). A random-effects model was used to generate the pooled risk ratio (RR) and 95% confidence interval (CI), and no statistically significant association was found between the risk of renal cancer and fish intake (RR=0.90; 95% CI, 0.78-1.02). In subgroup analysis, no evidence was found that the study design, study region or publication date influenced the results; but in the gender subgroup analysis, fish intake we found to decrease the risk of renal cancer in men but not in women.</p><p><b>CONCLUSION</b>The results of meta-analysis do not support an association between fish intake and a lowered risk of renal cancer.</p>

Construction of dengue virus-specific full-length fully human antibody libraries by mammalian display technology / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct dengue virus-specific full-length fully human antibody libraries using mammalian cell surface display technique.</p><p><b>METHODS</b>Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) from convalescent patients with dengue fever. The reservoirs of the light chain and heavy chain variable regions (LCκ and VH) of the antibody genes were amplified by RT-PCR and inserted into the vector pDGB-HC-TM separately to construct the light chain and heavy chain libraries. The library DNAs were transfected into CHO cells and the expression of full-length fully human antibodies on the surface of CHO cells was analyzed by flow cytometry.</p><p><b>RESULTS</b>Using 1.2 µg of the total RNA isolated from the PBMCs as the template, the LCκ and VH were amplified and the full-length fully human antibody mammalian display libraries were constructed. The kappa light chain gene library had a size of 1.45×10(4) and the heavy chain gene library had a size of 1.8×10(5). Sequence analysis showed that 8 out of the 10 light chain clones and 7 out of the 10 heavy chain clones randomly picked up from the constructed libraries contained correct open reading frames. FACS analysis demonstrated that all the 15 clones with correct open reading frames expressed full-length antibodies, which could be detected on CHO cell surfaces. After co-transfection of the heavy chain and light chain gene libraries into CHO cells, the expression of full-length antibodies on CHO cell surfaces could be detected by FACS analysis with an expressible diversity of the antibody library reaching 1.46×10(9) [(1.45×10(4)×80%)×(1.8×10(5)×70%)].</p><p><b>CONCLUSION</b>Using 1.2 µg of total RNA as template, the LCκ and VH full-length fully human antibody libraries against dengue virus have been successfully constructed with an expressible diversity of 10(9).</p>

Construction of personalized full-length fully human mammalian display antibody library for children with systemic lupus erythematosus / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct a personalized full-length fully human antibody mammalian display library for children with systemic lupus erythematosus (SLE).</p><p><b>METHODS</b>The total RNA was isolated from the PBMCs of SLE children. The heavy chain variable region and kappa light chain (VH and LCκ) of the antibody genes were amplified by RT-PCR and inserted into the pDGB-HC-TM vector separately to construct the heavy chain and light chain libraries. The library DNAs were transfected into 293T cells and the expression of full-length fully human antibody on the surface of 293T cells was analyzed by flow cytometry.</p><p><b>RESULTS</b>Using 0.8 µg total RNA as the template, the VH and LCκ were amplified and the full-length fully human antibody mammalian display library was constructed. The VH and LCκ gene libraries had a size of 9.4×10(4) and 8.4×10(4), respectively. Sequence analysis of 10 clones randomly selected from the VH and LCκ gene libraries each showed that 8 heavy chain clones and 7 light chain clones contained correct open reading frames, and flow cytometry demonstrated that all the 15 clones express full-length antibodies on 293T cell surfaces. 293T cells co-transfected with the VH and LCκ gene libraries expressed the full-length antibodies on the cell surface.</p><p><b>CONCLUSION</b>The personalized full-length fully human antibody library for SLE children constructed allows display of the full-length antibodies on mammalian cell surfaces, thus providing a valuable platform for analyzing the autoantibodies, their etiological role, and their clinical implications in SLE.</p>

Interleukin-21 surface-modified MB49 cell vaccine for treatment of metastatic bladder in mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To develop a novel vaccine by immobilizing interleukin-21 (IL-21) on the surface of MB49 cells and evaluate its effect in inducing specific cytotoxic T lymphocytes (CTLs) and antitumor immunity in a mouse model of subcutaneous metastatic bladder cancer.</p><p><b>METHODS</b>SA-IL-21 was immobilized on the surface of 30% ethanol-fixed MB49 cells to prepare the cell vaccine. C57BL/6 mice with subcutaneous implantation of MB49 bladder cancer cells were randomized into 5 groups to receive treatments with IL-21/MB49 vaccine, soluble IL-21, GFP surface-modified MB49 cells, ethanol-fixed MB49 cells, or PBS. The tumor growth and CTL were examined to assess the antitumor efficacy of the vaccine.</p><p><b>RESULTS</b>IL-21 surface-modified MB49 cell vaccine significantly inhibited the tumor growth and generated a long-lasting memory response (P<0.05). At the same effector-target (E:T) ratio, the specific CTLs induced by IL-21/MB49 vaccine showed the most potent cytotoxicity against MB49 cells (P<0.05).</p><p><b>CONCLUSION</b>With the protein-anchor technique, IL-21 can be efficiently immobilized on the surface of MB49 cells to prepare IL-21/MB49 cells vaccine. The novel vaccine can maintain its biological activity and significantly enhance the cytotoxicity of CTLs against bladder cancer cells.</p>

"Street ketamine" associated urinary system dysfunction / 中华泌尿外科杂志

Objective To investigate the clinical, pathology, diagnosis and treatment of the lower urinary system dysfunction among chronic recreational ketamine abusers. Methods From 2000-2008, 20 ketamine abusers(14 men and 6 women; mean age, 22.3 years), from 3 hospitals in Guangzhou and Hongkong, and suffering from lower urinary tract dysfunction was reported. All of them had abused ketamine for 1 to 4 years, and presented with severe lower urinary tract symptoms. Complaint of severe frequency, urgency, urge incontinence, and painful haematuria was common. Urine cultures were negative. Six men suffered from severe dysuria. B ultrasound examination of 16 cases demonstrated the presence of bilateral hydronephrosis. Fourteen IVU and 10 CT investigations demonstrated the presence of bilateral hydronephrosis, bladder contraction, and 1 case showed papillary necrosis of the kidney. Different levels of abnormal liver function and chronic/acute renal failure were observed. All of the patients were required to withdraw the narcotics and the experimental medicine were given. Results The biopsies of 6 cases demonstrated the cystitis. Twelve cases' symptoms were reversible after these patients stopped or reduced the frequency and amount of ketamine abuse. Pentosan polysulfate sodium and sodium hyaluronate solution relieved the symptoms of 6 patients. Conclusions "Street ketamine" associated urinary system dysfunction might be a kind of in flammatory process involving the upper and lower urinary tract. Underlying aetiology and treatment methods necessitate further study.

Experience of intensive training of surgerical skills before clinical practice / 中华医学教育探索杂志

Clinical practice is quite important transition phase for medical students to become qualified doctors,and development of surgerical skills is the diffficult and key point in the clinical practice.Intensive training of surgerical skills before clinical practice can enhance the confidence and efficiency of medicine students during the course of clinical practice.Whihin limited time,the key of intensive training of surgerical skills is the training of aseptic technique and basic skills of surgery,and during the course of training,attention should be paid to both principle and details.

Influence of CO_2 pneumoperitoneum on hepatic functions, renal functions, and myocardial enzymogram during retroperitoneoscopy / 中国微创外科杂志

0.05). Conclusions Carbon dioxide pneumoperitoneum during retroperitoneoscopy has no obvious influence on hepatic functions, renal functions and myocardial enzymogram. It may not cause significant damage to patients with normal heart, hepatic, and renal functions.

Retroperitoneal laparoscopic ureterolithotomy: Report of 34 cases / 中国微创外科杂志

Objective To evaluate the clinical efficacy of retroperitoneal laparoscopic ureterolithotomy.Methods A total of 34 cases(38 sides) of middle(5 sides) or upper(33 sides) ureteral calculus were treated by retroperitoneal laparoscopic ureterolithotomy.The stones were(0.8 cm?1.0 cm)~(1.5 cm?3.0 cm) in size.Twenty cases had been previously treated by unsuccessful extracorporeal shock wave lithotripsy(ESWL).Results The operation was successfully completed in 33 cases and a conversion to open surgery was required in 1 case because of extensive adhesion and blood oozing.The operating time was 45~190 min(mean,85.5 min),the intraoperative blood loss was 10~50 ml(mean,20.6 ml),and the postoperative hospitalization,3~7 d(mean,4.3 d).Postoperative recovery was uneventful.No complication was observed during a 3~24 months(mean,9.7 months) of follow-up.Conclusions Retroperitoneal laparoscopic ureterolithotomy is micro-invasive,simple to perform,and safe.

Self-designed single J tube and medical nylon string for the prevention and treatment of child traumatic posterior urethral stricture / 中华泌尿外科杂志

Objective To improve the prevention and treatment level of child traumatic posterior urethral stricture. Methods This series included 22 male children (mean age 9 years) with pelvic fracture complicated by posterior urethral disruption.A medical nylon string was indwelled after uretheral reunion operation.Urethral stricture recurred in 9 patients 3 months after the operation,and they were all cured by performance of urethra dilatation with self-designed single J tube under the guidance of the medical nylon string. Results All of the 9 were doing well during the operation.The medical nylon string was not taken out until dysuria disappeared completely.The cure rate was 100%.All the cases were followed up for a mean period of 15 months(range,3 to 24 months).All had normal urination. Conclusions Application of self-designed single J tube and medical nylon string is effective,simple and economical for the treatment of child traumatic posterior urethral stricture.It is easy both for the doctors' training and for the children's cooperation.Thus,it provides a new approach for the prevention and treatment of child traumatic posterior urethral stricture.

Clinical analysis of differential diagnosis between renal cell carcinoma and benign space-occupying mass / 中华泌尿外科杂志

Objective To improve the differential diagnosis between benign renal mass and renal cell carcinoma(RCC) so as to lower the misdiagnosis rate. Methods This study included 12 cases of renal mass,whose age ranged from 35 to 69 years with a mean of 52 years.Among the 12 cases,flank pain occurned in 9,2 of whom had gross hematuria.Three clinically asymptomatic cases were detected incidentally by ultrasound in physical examination.All the 12 cases underwent imaging examinations such as B-ultrasound and CT scan,and all of them were preoperatively diagnosed as RCC. Results All the cases were surgically treated.Seven underwent enucleation or simple nephrectomy because of the diagnosis of benign renal mass by intraoperative frozen section.Five underwent radical nephrectomy.None developed recurrence during follow-up of 1 to 3 years. Conclusions Clinicians should not overestimate the diagnostic significance of imaging examinations such as CT and ultrasonography.For cases who have no definite diagnosis,surgical exploration can be performed.Intraoperative frozen section by pathologic study can increase correct diagnostic rate. Most of the misdiagnosed benign renal masses have different imaging features from those of RCC.

Pedicled greater omentum displacement for treatment of complex posterior urethral stricture(report of 6 cases) / 中华泌尿外科杂志

Objective To study the therapeutic effects of pedicled greater omentum displacement for complex posterior urethral stricture. Methods This study included 6 cases (all males) of complex posterior urethral stricture.Their age ranged from 14 to 45 years with a mean of 26 years.In these cases,traffic accident injury occurred in 5 and falling injury in 1.The course of diseases ranged from 6 months to 5 years with a mean of 2.5 years.The length of stricture segment was from 3.0 to 5.5 cm.All cases were surgically treated via transpubic approach and pedicled greater omentum displacement. Results Good operative results were achieved in all 6 cases.Each of them could urinate when the catheter was taken out 4 weeks later,and no urinary incontinence,urinary tract infection were observed.All were followed up for a median period of 26 months (ranged from 6 to 38 months).4 patients had normal micturition with no need of urethral dilatation and 2 patients reencountered dysuria in 3 months and were all cured by the administration of urethral dilatation for 3 to 24 months. Conclusions This procedure has a higher success rate.It is suitable for those with complicated posterior urethral stricture,such as longer posterior urethral stricture,urethra-rectal fistula, false passage, and especially those having experienced failure of urethra repair via perineal approach. It can be regarded as one of the ideal and effective therapeutic methods for complex posterior urethral stricture.

Intervening embolization for congenital renal arteriovenous malformation / 中华泌尿外科杂志

ObjectiveTo evaluate transcatheter arter ia l embolization(TAE) on congenital renal arteriovenous malformation(RAVM).MethodsFive cases of RAVM,diagnosed on digital substraction a ngiography have been treated between March 1995 and May 2002 by transarterial em bolization (TAE) with different embolic agents (ethanol,iodised oil,gelform part icles or metalic coils).The efficacy was evaluated.ResultsIn all the 5 cases,gross hematuria was controlled immediately after TAE,th e urine turned clear in 24 h and urinalysis became normal in 7 days.The patients have been followed up for 6～12 months with an average of 10 months with hematu r ia well controlled in all.There has been no hypertension or apparent renal funct ion damage.Bilateral renal emission computed tomography (ECT) reveated only some local loss of the renal cortical function on the concerned side.ConclusionsAt present renal arteriography is still the most reliable method in the diagnosis of RAVM.TAE has the benefits of less inva sive, a low incidence of complications, early resumption of normal activities an d shorter hospital stay,and can avoid renal resection and correlative surgical c omplications.The renal function could be well protected from harm.

Sarcoma of prostate (report of 7 cases) / 中华泌尿外科杂志

Objective To call attention to the diagnosis and treatment of prostate sarcoma. Me thods From Jan 1984 to May 2000,7 cases of prostate sarcoma were treated,2 cases by radical cystoprostatectomy and detenia cecocolon continent urinary reservoir,1 case by suprapubic prostatectomy,3 cases by radiotherapy whereas 1 case underwent needle biopsy only. Results Of the 2 cases underwent radical cystoprostatectomy,one has been still surviving after 5 years whereas the other one died of lung metastases after 9 months.The other 5 patients all died within 13 months. Conclusions Early dignosis and radical cystoprostatectomy are mandatory to prolong survival.

Study on the cloning, expression and identification of the renal cell carcinoma-associated antigen G250/MN/CA Ⅸ / 中华泌尿外科杂志

Objective To report the cloning, expression and identification of the tumor-associated antigen G250/MN/CA Ⅸ. Methods The total RNA was extracted from renal cell carcinoma tissue samples from 54 male patients. Gene fragments encoding G250 was obtained by RT-PCR,and was cloned into prokaryotic expression vector pET22b(+) and expressed in E.coli BL21(DE3);and the results were examined by SDS-PAGE gel electrophoresis. The recombinant protein was studied by Western blot test. Results DNA sequence analysis showed that the obtained sequence was the same as that showed in GenBank.Gene of G250 was expressed in E.coli BL21 successfully. Western blot analysis showed that the recombinant protein could be specially recognized by monoclonal antibody. It had better antigenicity and specificity. Conclusions This study provides experimental basis for the purification of G250/MN/CA Ⅸ protein and the further study of G250/MN/CA Ⅸ function and preparation of antibody.

Adenovirus-mediated TK gene combined with ?-IFN in treatment of nude mice transplanted with human renal clear-cell carcinoma / 第二军医大学学报

Objective:To investigate the inhibitory effect of adenovirus-mediated herpes simplex virus-thymidine kinase (TK) gene combined with ?-IFN on renal clear-cell carcinoma. Methods: Adenovirus containing suicide gene TK, in combination with GCV or ?-IFN, was used to treat human renal clear-cell carcinoma cell line 786-0, and the in vitro cytotoxic effects against 786-0 were evaluated using MTT method. The subcutaneous transplantation model of 786-0 cells was established with nude mice. Adenovirus containing TK gene was injected intratumorally and the GCV (50 mg/kg) was injected intraperitoneally; ?-IFN (104 U/L) was injected intratumorally in combined therapy. The growth of tumors was observed after treatments. Results: The survival rate of 786-0 cells was (35.07?1.43)% in the TK+GCV+?-IFN group, (68.57?1.41)% in the TK+GCV group and (68.65?1.45)% in the ?-IFN group ( P=0.000). There was an obvious synergic effect between Ad-TK and ?-IFN in inhibiting 786-0 cells. Ad-TK combined with GCV and ?-IFN significantly suppressed the growth of 786-0 cells growth in nude mice model.Conclusion: Adenovirus-mediated TK plus prodrug GCV combined with ?-IFN has obvious therapeutic effect in treatment of human renal clear-cell carcinoma.