The Efficacy and Safety of Thrice vs Twice per Week Low-Intensity Pulsed Ultrasound Therapy for Erectile Dysfunction: A Randomized Clinical Trial.

BACKGROUND: A recent sham-controlled clinical study has shown that low-intensity pulsed ultrasound twice per week can safely and effectively treat patients with mild-to-moderate erectile dysfunction (ED). However, large-scale clinical trials are needed to verify its efficacy and safety and determine a reasonable treatment interval. AIM: To study whether low-intensity pulsed ultrasound therapy thrice per week is non-inferior to twice per week in patients with mild-to-moderate ED. METHODS: A randomized, open-label, parallel-group, non-inferiority clinical trial was conducted in 7 hospitals in China. A total of 323 patients with mild-to-moderate ED were randomized (1:1) into thrice per week (3/W) and twice per week (2/W) groups. Low-intensity pulsed ultrasound was applied on each side of the penis for 16 sessions. OUTCOMES: The primary outcome was response rate using the minimal clinically important difference in the International Index of Erectile Function (IIEF-EF) score at week 12. Secondary outcomes included Erection Hardness Score (EHS), Sexual Encounter Profile, Global Assessment Question, and Self Esteem and Relationship Questionnaire. RESULTS: Response rates in 3/W and 2/W groups were 62.0% and 62.5%, respectively. Treatment effect in the 3/W group was noninferior to that of the 2/W group, with rate difference lower bound of -0.01% [95% confidence interval -0.11 to 0.10%] within the acceptable margin (-14.0%). No significant difference was found among secondary outcomes. IIEF-EF score showed a significant increase from baseline in the 3/W group (16.8 to 20.7) and 2/W group (17.8 to 21.7), and the percentage of patients with EHS ≥3 increased in the 3/W (54.9% to 84.0%) and 2/W (59.5% to 83.5%) groups. There was no significant difference in response rate between the 2 groups after controlling for strata factors and homogeneous tests. No treatment-related adverse events were reported. CLINICAL IMPLICATIONS: Low-intensity pulsed ultrasound therapy displays similar efficacy and safety for mild-to-moderate ED when administered thrice or twice per week for 16 sessions. This study provides two options to suit patients' needs. STRENGTHS & LIMITATIONS: This is a large-sample, randomized, controlled, noninferiority trial study. Short-term follow-up and mostly younger patients are the main limitations. CONCLUSION: Low-intensity pulsed ultrasound therapy thrice and twice per week showed equivalent therapeutic effects and safety for mild-to-moderate ED in a young and generally healthy population. This therapy warrants further investigation of its potential value in rehabilitation of ED. Chen, H., Li Z., Li X., et al. The Efficacy and Safety of Thrice vs Twice per Week Low-Intensity Pulsed Ultrasound Therapy for Erectile Dysfunction: A Randomized Clinical Trial. J Sex Med 2022;19:1536-1545.

A multicenter observational study of the real-world use of docetaxel for metastatic castration-resistant prostate cancer in China.

AIM: To investigate the use of docetaxel for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in real-world clinical practice in China. METHODS: This single-arm, prospective, observational study was conducted at 32 study centers in China and included male patients aged ≥18 years with histologically confirmed prostate cancer who received ≥1 dose of docetaxel following failure of hormonal therapy (disease progression with serum testosterone <50 ng/dL). The primary aim was to investigate patterns of docetaxel treatment. RESULTS: Overall 403 patients were included between August 2011 and June 2016; patients initiated docetaxel after failure of first- (42.2% [170]), second- (31.0% [125]) and ≥third-line (12.7% [51]) hormonal therapy, estramustine (11.4% [46]) or other (2.7% [11]). The planned cycles of docetaxel therapy were completed by 30.8% of patients, and the mean (SD) number of cycles received was 4.4 (2.86). Median overall survival (mOS) was 22.4 (95% CI, 20.4-25.8) months and the prostate-specific antigen (PSA) response rate in patients with available data was 70.9% (168/237), with no differences in mOS and PSA response rates between treatment settings. Subgroup analysis revealed higher mOS in patients without visceral metastasis versus those with such metastases (22.9 vs. 17.4 months; P = 0.022). No new safety signals were observed and the most common adverse events associated with docetaxel were granulocytopenia (5%) and leukopenia (4.5%). CONCLUSION: Data from this study showed that around three-quarters of Chinese patients with mCRPC treated with docetaxel initiated treatment following first- or second-line hormonal therapy and no new safety signals were observed.

Hierarchical task analysis for identification of interrelationships between ergonomic, external disruption, and internal disruption in complex laparoscopic procedures.

BACKGROUND: Traditionally, hierarchical task analysis (HTA) in surgery examines observable disruption in a predefined set of tasks as performed, rather than examining the ergonomics requirements, which may predispose surgical teams to act erroneously. This research aims to address this gap in the literature. It develops a HTA protocol taking into consideration surgical team actions, observable external disruption, internal disruption, and ergonomic goals required for safer conducting procedures. Laparoscopic radical prostatectomy (LRP) is selected as a case. METHODS: This research involved observations inside operating rooms (ORs) of three large teaching hospitals in Australia and China. Two rounds of observations are conducted: observations for developing HTA, and observations after presenting the developed HTA among surgical teams. The traditional HTA format is expanded to include two additional columns: technical considerations and ergonomics considerations. Two groups are formed from the observed LRPs. LRPs in the first group were conducted with no regard to the specified ergonomic goals and associated ergonomic features, and the second are conducted with the surgical teams attempting to follow specified ergonomic goals and features as prescribed in HTA. Careful attempt is required to select procedures such that the total operative times for both groups are approximately equal (± 5%). RESULTS: Between March 2016 and November 2017, a total of 29 LRPs were observed, and a HTA developed. The results reveal significant reduction (43%) in the total external disruptive events and approximately 58% reduction in the internal disruptive events in LRPs conducted with HTA requirements. CONCLUSIONS: The developed HTA appears to have some utility, but needs evaluation in larger studies. It can potentially be used as a training aid, and as a checklist for evaluating surgical performance.

Effects of microRNA-135a on the epithelial-mesenchymal transition, migration and invasion of bladder cancer cells by targeting GSK3ß through the Wnt/ß-catenin signaling pathway.

This study investigated the effects of microRNA-135a (miR-135a) targeting of glycogen synthase kinase 3ß (GSK3ß) on the epithelial-mesenchymal transition (EMT), migration and invasion of bladder cancer (BC) cells by mediating the Wnt/ß-catenin signaling pathway. BC and adjacent normal tissues were collected from 165 BC patients. Western blotting and quantitative real-time PCR were used to detect the expression of GSK3ß, ß-catenin, cyclinD1, E-cadherin, vimentin and miR-135a in BC tissues and cells. Cells were assigned to blank, negative control (NC), miR-135a mimics, miR-135a inhibitors, small interfering RNA (siRNA)-GSK3ß or miR-135a inhibitors+siRNA-GSK3ß groups. miR-135a, ß-catenin, cyclinD1 and vimentin expression increased, while GSK3ß and E-cadherin expression decreased in BC tissues compared with adjacent normal tissues. Compared with the blank and NC groups, the expression of miR-135a, ß-catenin, cyclinD1 and vimentin was higher, and cell proliferation, migration, invasion and tumor growth were increased in the miR-135a mimics and siRNA-GSK3ß groups. These groups showed an opposite trend in GSK3ß and E-cadherin expression and cell apoptosis. The miR-135a inhibitors group was inversely correlated with the blank and NC groups. It was concluded that miR-135a accelerates the EMT, invasion and migration of BC cells by activating the Wnt/ß-catenin signaling pathway through the downregulation of GSK3ß expression.

Ureteral double J stent displaced into vena cava and management with laparoscopy: A case report and review of the literature.

We reported displacement of a ureteral double J stent into the vena cava and laparoscopic management in a 69-year-old patient with a history of ureteral stent placement. Preoperative computed tomography and plain X-rays showed malpositioning of the double J stent and displacement into the inferior vena cava. The characteristics of stent misplacement precluded endovascular procedures and explorative laparoscopic surgery was performed. The intra- and postoperative periods were uneventful. Postoperative imaging demonstrated that the new double J stent was in the right position. The patient was discharged 7 d after the operation and was symptom free at the 4-mo follow-up.

CUL4B promotes bladder cancer metastasis and induces epithelial-to-mesenchymal transition by activating the Wnt/ß-catenin signaling pathway.

Increased expression of cullin 4B (CUL4B) is linked to progression in several cancers. This study aims to explore the effects of CUL4B on bladder cancer (BC) metastasis and epithelial-to-mesenchymal transition (EMT) and potential correlation to the Wnt/ß-catenin signaling pathway. We collected BC tissues and adjacent normal tissues from 124 BC patients. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were employed in order to detect the expression of Wnt/ß-catenin signaling pathway-related proteins and EMT markers. MTT and Transwell assays were used in order to measure cell proliferation, migration, and invasion. BC 5637 cells were transfected with control, siRNA scramble control (siRNA-NC), si-CUL4B, and CUL4B or Wnt inhibitory factor 1 (WIF-1) overexpression constructs. Levels of CUL4B mRNA and protein were increased in BC tissues in comparison with the adjacent normal tissues. CUL4B expression was negatively correlated with the expression of E-cadherin and positively correlated to the expression of N-cadherin and Vimentin. Compared to the control group, levels of ß-catenin, cyclinD1, c-myc, MMP7, and EMT markers were reduced, whereas phosphorylated GSK3ßSer9 and E-cadherin levels were increased in the si-CUL4B and WIF-1 groups. In addition, cell proliferation, migration, and invasion abilities were also increased. Increasing CUL4B expression had the opposite effect. These findings suggest that CUL4B induces EMT and promotes metastasis of BC by activating the Wnt/ß-catenin signaling pathway.

Ergonomics perspective for identifying and reducing internal operative flow disruption for laparoscopic urological surgery.

BACKGROUND: The aim of this study is to examine operative flow disruption that occurs inside the surgical field, (internal operative flow disruption (OFD)), during urological laparoscopies, and to relate those events to external ergonomics environment in terms of monitor location, level of instruments' handles, and location of surgical team members. According to the our best knowledge, this is the first study of its kind. METHODS: A combination of real and video-aided observational study was conducted in the operating rooms at hospitals in Australia and China. Brain storming sessions were first conducted to identify the main internal OFD events, and the observable reasons, potential external, and latent ergonomic factors were listed. A prospective observational study was then conducted. The observer's records and the related video records of internal surgical fields were analysed. Procedures were categorised into groups based on similarity in ergonomics environment. RESULTS: The mapping process revealed 39 types of internal OFD events resulted from six reasons. A total of 24 procedures were selected and arranged into two groups, each with twelve procedures. Group A was carried out under satisfactory ergonomics environment, while Group B was conducted under unsatisfactory ergonomics environment. A total of 1178 OFD events were detected delaying the total observed operative times (2966 min) by 220 min (7.43%). Average OFD/h in group A was less than 15, while in group B about 29 OFD/h. CONCLUSION: There are two main latent ergonomics factors affecting the surgeon's performance; non-physiological posture and long-period static posture. The delays and number of internal OFD were nearly doubled where procedures were conducted under unsatisfactory external ergonomics environment. Some events such as stopping operation and irrelevant conversations during long procedures may have a positive influence on the surgeon's performance.

Ureteroscopic management of asymptomatic and symptomatic simple parapelvic renal cysts.

BACKGROUND: To investigate feasibility and safety of treating simple parapelvic renal cysts using flexible ureteroscopy with the Holmium laser. METHODS: Between February 2010 and July 2013, a total of 21 patients, aging from 29 to 71 (49.00 ± 13.23), were diagnosed with parapelvic renal cysts by ultrasonography in combination with contrast-enhanced computer tomography (CT) and intravenous urography (IVU) in the Department of Urology Surgery, People's Hospital of the Zhejiang province. Fifteen patients were asymptomatic and 6 patients were symptomatic with flank pain. All patients underwent drainage of the cysts using flexible ureteroscopy with Holmium laser. Patients were followed up 1, 3 and 12 months after the operation. RESULTS: The intervention was successful in 20 patients and failed in 1 patient who, subsequently successfully underwent a laparoscopic cyst removal. There were no intra-operative and post-operative complications reported. The mean operation time was 27 min (range: 15 to 45 min). The mean hospital stay was 2.6 days (range: 1 to 5 days). Twenty patients were followed up until 15 months after surgery. After such ureteroscopic management, there were no renal cysts detected in 7 patients (35 %) and a reduction in size of the renal cysts was found in 13 patients (65 %). Flank pain subsided in all 6 (100 %) previously symptomatic patients. CONCLUSIONS: Flexible ureteroscopy with the Holmium laser may be a feasible and effective treatment option in selected patients with simple parapelvic renal cysts. Further prospective randomized studies that compare the procedure to laparoscopic treatments are needed.

Characterization of the roles of suppressor of cytokine signaling-3 in prostate cancer development and progression.

As negative feedback regulators of cytokine signaling, suppressor of cytokine signaling proteins are induced by interleukins and various peptide hormones and may prevent sustained activation of signaling pathways. In particular, suppressor of cytokine signaling-3 (SOCS-3) plays pivotal roles in the development and progression of various cancers and exerts pleiotropic effects on cell proliferation and apoptosis. In recent years, abnormal expression of SOCS-3 and its multiple functions have been extensively investigated in human carcinomas, particularly in prostate cancer. SOCS-3 can act as an oncogene or a tumor suppressor depending on the cellular context. In this review, we focus on the role of SOCS-3 in prostate cancer development and prognosis, as well as the potential of SOCS-3 as a therapeutic target and diagnostic marker.

Overactive bladder symptom score to evaluate efficacy of solifenacin for the treatment of overactive bladder symptoms.

BACKGROUND: Overactive bladder (OAB) is a series of symptoms with high prevalence in elderly people. This study was conducted using the overactive bladder symptom score (OABSS) to evaluate the efficacy of solifenacin succinate for the treatment of OAB. METHODS: This was a prospective, multicenter, single-arm, 12-week study that enrolled 241 OAB patients. The patients received 5-10 mg/day solifenacin. Changes in OABSS, symptoms from voiding diary, perception of bladder condition (PPBC) score, international prostate symptom score (IPSS) and quality of life (QOL) were evaluated at weeks 0, 4, and 12. The relationship between OABSS and PPBC score or parameters of voiding diary was also evaluated. RESULTS: At baseline, the mean OABSS for all patients was 9.41 ± 2.40, and was reduced significantly at week 12 (-3.76 points; 61.21%, P < 0.0001). The OABSS subscore, PPBC score, IPSS, and QOL were also significantly reduced during the study (P < 0.0001). The overall incidence of adverse events was 19.91% (44 cases). The gastrointestinal system was the most commonly affected (11.31%). Around 5.88% of the cases had adverse events related to the genitourinary system. There was a strong correlation between OABSS and urinary symptoms that was recorded in the 3-day voiding dairy. CONCLUSIONS: We showed that solifenacin was clinically effective for relieving OAB symptoms, considering the balance between efficacy, patients' well-being, and tolerability. OABSS integrates four OAB symptoms into a single score and can be a useful tool for research and clinical practice.

Atypical microorganisms in expressed prostatic secretion from patients with chronic prostatitis/chronic pelvic pain syndrome: microbiological results from a case-control study.

OBJECTIVES: To investigate the microorganisms in expressed prostatic secretions (EPS) of both chronic prostatitis patients and normal young male adults and to determine which microorganisms are associated with the degree of intraprostatic inflammation. METHODS: Specific polymerase chain reaction (PCR) technology was performed to confirm Neisseria gonorrhoeae, Mycobacterium tuberculosis, Mycoplasma and Chlamydia trachomatis as well as human papilloma virus (HPV), herpes simplex virus type 2 (HSV-2) and cytomegalovirus (CMV). Universal primer PCR technology was carried out to detect 16S bacteria rDNA, followed by cloning and sequencing of the entire 16S rDNA product. RESULTS: The total number of bacteria and/or viruses detected by PCR assays was significantly associated with disease severity (p < 0.001). The white blood cell count and lecithin level was significantly correlated with the number of detected bacteria and/or viruses (p = 0.001 and p = 0.046, respectively). 17 bacterial isolates were identified from 14 EPS samples by 16S rDNA sequencing. CONCLUSIONS: Various microorganisms including Ureaplasma urealyticum, C. trachomatis, CMV, HPV and HSV-2 were identified in the EPS from patients with type III prostatitis. HPV infection may be associated with the degree of intraprostatic inflammation.

Pyloric resection and delayed gastric liquid emptying in rats.

BACKGROUND: Surgical resection of the distal stomach impairs gastric emptying. Generally, pylorus and the antrum are removed in the distal gastrectomy, however, the pylorus is removed individually under specific circumstances. We focus on the relation between the pyloric resection and the gastric liquid emptying. AIMS: The present investigation aimed to explore the pylorectomy how to influence gastric liquid emptying in rats. METHODS: Pylorectomy and end-to-end gastroduodenal anastomosis were conducted in rats. Electrodes were implanted in the gastrointestinal serosal surface near the stoma. Total stomach, proximal stomach, distal stomach and duodenal liquid emptying, myoelectricities in the gastrointestinal tract near the stoma, and structures were examined with scintigraphy, electrode recording in vivo, and electron microscopy, respectively. RESULTS: Delayed total stomach and distal stomach emptying were found in pylorectomy rats (p<0.001). However, there was no difference in the proximal stomach and the duodenal liquid emptying compared to the controls (p>0.05). The myoelectricity of 3-5 cpm (cycles/min) in antrum and 10-12 cpm in duodenum were found in the controls and no retrograde or antegrade myoelectricities were recorded in the duodenum and antrum. High-frequency myoelectricities (tachygastria) were recorded in the antrum near the stoma (p<0.01), the retrograde and antegrade myoelectricities propagating through the stoma were recorded, and the regenerated interstitial cells of Cajal were found in stoma under electron microscope observation in pylorectomy rat. CONCLUSIONS: The gastroduodenal incoordination and abnormal myoelectricity related to impaired contraction in the antrum caused the delayed liquid gastric emptying in pylorectomy rats.

[Impact of abnormal myoelectricity at gastroduodenal anastomosis on gastric emptying in rats].

OBJECTIVE: To explore the impact of abnormal myoelectricity at gastroduodenal anastomosis on gastric emptying in rats. METHODS: Rats were randomly divided into experimental group (n=16) and control group (n=16). Pylorectomy and end-to-end gastroduodenal anastomosis were performed in the experimental group and electrodes were implanted in the serosal surface adjacent to the anastomosis. Slow waves were recorded by the implanted electrode in vivo. Gastric emptying was examined by scintigraphy. RESULTS: At the first week after surgery, antral slow-wave frequency was significantly lower in the experimental group (0.8±1.4 vs. 3.3±1.2, P<0.01), as was the duodenal slow-wave frequency (2.1±0.6 vs. 11.1±0.7, P<0.01). There was no consecutive slow-waves transduction across the pylorus or the anastomosis. Within 12-16 weeks after operation, antral slow-wave frequency in the experimental group and the control group were (8.7±0.6) cpm and (4.0±0.4) cpm, respectively (P<0.01), and duodenal slow-wave frequency were (11.1±0.8) cpm and (10.8±0.7) cpm, respectively (P>0.05). Retrograde and antegrade myoelectricity transduction through the anastomosis were detected. The mean semi-emptying time in the proximal stomach was 14.7 min in the experimental group and 13.6 min in the control group (P>0.05). Radionuclide retention rate was 25.4% in the experimental group and 39.4% in the control group (P>0.05). The mean semi-emptying time in the distal stomach was 25.3 min in the experimental group and 10.5 min in the control group (P<0.01). Radionuclide retention rate was 46.4% in the experimental group and 18.7% in the control group (P<0.01). CONCLUSION: The abnormal myoelectricity in the region of gastroduodenal stoma may delay liquid gastric emptying in pylorectomy rats.

[Transperineal laparoscopic nephrectomy in live-donors].

OBJECTIVE: To evaluate the feasibility and safety of transperitoneal laparoscopic nephrectomy in live-donors. METHODS: Two cases of live-donor underwent laparoscopic nephrectomy in May and August 2008 respectively and both were followed up. RESULT: In two cases the operation time was 130, 10 min; blood loss was 50 ml; warm ischemic time was 30 s and 2 min; the length of artery was 4.0 cm and 3.5 cm; the length of vein was 3.0 cm. The grafted kidneys started to produce urine at 30 s and 10 s after blood supply. Renal function of donor returned to normal after two days. The donors were discharged at 7th day after the operation. Renal function of recipient was normal after 3 days. CONCLUSION: Transperitoneal laparoscopic nephrectomy in live-donor is a safe and effective procedure, which provides kidney with satisfactory blood vessels and ureter for graft.

[Development of oligoneucleotide arrays for HLA-DR53-associated group genotyping].

OBJECTIVE: To develop a method performed on an oligonucleotide array for HLA-DR53 group genotyping. METHODS: According to the specific allelic frequency and sequence of HLA-DRB loci in Chinese Han population, HLA-DR53 group typing probes which were immobilized on a glass supports were synthesized. A pair of group-special primers labeled by the Cy5-dCTP were designed, and the primers were used in the PCR, thus the PCR products were labeled with Cy5. The labeled PCR products were hybridized with array. The signals were scanned by scanner and analyzed by image software. The typing results were confirmed by standard DNA and PCR-SSO. One hundred and eleven samples were typed by this array. RESULTS: There were 72 HLA-DR53 group loci typed by oligonucleotide array. Among them, 34 loci were DR9, 25 were DR4, and 13 were DR7. No false positive or false negative typing results were observed. The specificity and reproducibility were 100% and the overall time of genotyping was 5 hours. CONCLUSION: The oligonucleotide array technique is a precise, rapid molecular method for HLA-DR53 genotyping, suited for clinical practice.

[Genotyping of HLA-DRB by oligonucleotide arrays in Han populations in southern China].

OBJECTIVE: To develop an oligoneucleotide array for HLA-DRB typing and evaluate its function in comparison with that of PCR-SSP typing. METHODS: According to the specific allele sequences of HLA-DRB loci in Han populations in Southern China, 44 synthesized typing probes were immobilized on a glass supports. A pair of group-specific primers was designed according to the sequence of HLA-DRB exon2, then the primers and Cy5-dCTP were used in PCR, thus the PCR products were labeled with Cy5. The labeled PCR products were hybridized with the probes in the array, and the signals were scanned by scanner and then analyzed by Image software.110 samples of DNA of the lymphocytes from the spleens or peripheral blood of kidney recipients and unrelated donors were typed by this array and the results were compared with those of PCR-SSP typing. RESULTS: All the samples except for one without PCR product had been genotyped by HLA array successfully. Ten samples were identified differently by these 2 methods. PCR-SSO verified the correctness of the array in 7 samples among which 6 samples were identified as homozygous by PCR-SSP and heterozygous by array and 1 sample was identified as heterozygous by PCR-SSP and homozygous by the array; and proved that among the remaining 3 samples the results of 2 samples identified by PCR-SSP and 1 sample identified by the array were wrong. CONCLUSION: The HLA-DRB oligoneucleotide array technique is a precise, rapid molecular method for HLA-DRB genotyping. Compared with PCR-SSP method, the genotyping chip is more sensitive and specific and can test several samples at a time.