Robot-assisted single-port retroperitoneal partial nephrectomy with a novel purpose-built single-port robotic system with deformable surgical instruments.

OBJECTIVE: To investigate the safety and feasibility of using a novel purpose-built single-port robotic system (the SHURUI Robotic Surgical System) with deformable surgical instruments to perform retroperitoneal single-port partial nephrectomy. MATERIALS AND METHODS: A prospective study was conducted to recruit patients with a single renal tumor no more than 4 cm. Robot-assisted single-port partial nephrectomy was performed by using the novel purpose-built single-port robotic system with deformable surgical instruments. Patients' demographics, tumor characteristics, and perioperative parameters were recorded and analyzed. RESULTS: Sixteen patients were recruited to the study. The median tumor size was 2.0 cm (IQR: 1.2-2.4 cm). The median R.E.N.A.L score was 6 (IQR: 4-4.5). In 3 cases, pure single-port surgery was carried out, and all the assistance was through the robotic port. Median docking time was 15.5 min (IQR: 14.25-22.25 min). Median operating time was 148.5 min (IQR: 178-238.5 min). Median console time was 107 min (IQR: 92.75-149.75 min). Median warm ischemic time was 26.5 min (IQR: 24.5-30 min). Median blood loss was 17.5 ml (IQR: 10-50 ml). CONCLUSIONS: Retroperitoneal partial nephrectomy can be safely performed with this novel purpose-built single-port robotic system (SHURUI) with deformable surgical instruments. Further studies are needed to fully evaluate the role of this new platform.

Initial experience of laparoendoscopic single-site radical prostatectomy with a novel purpose-built robotic system.

Objective: This prospective single-arm clinical trial aimed to evaluated the feasibility and safety of the application of the SHURUI system (Beijing Surgerii Technology Co., Ltd., Beijing, China), a novel purpose-built robotic system, in single-port robotic radical prostatectomy. Methods: Sixteen patients diagnosed with prostate cancer were prospectively enrolled in and underwent robotic radical prostatectomy from October 2021 to August 2022 by the SHURUI single-port robotic surgical system. The demographic and baseline data, surgical, oncological, and functional outcomes as well as follow-up data were recorded. Results: The mean operative time was 226.3 (standard deviation [SD] 52.0) min, and the mean console time was 183.4 (SD 48.3) min, with the mean estimated blood loss of 116.3 (SD 90.0) mL. The mean length of postoperative hospital stay was 4.50 (SD 0.97) days. Two patients had postoperative complications (Clavien-Dindo Grade II), and both patients improved after conservative treatment. All patients' postoperative prostate-specific antigen levels decreased to below 0.2 ng/mL 1 month after discharge. The mean prostate-specific antigen level further decreased to a mean of 0.0219 (SD 0.0641) ng/mL 6 months after surgery. Thirty days postoperatively, 12 out of 16 patients reported using no more than one urinary pad per day, and all patients reported satisfactory urinary control without the need for pads 6 months after surgery. Conclusion: The SHURUI system is safe and feasible in performing radical prostatectomy via both transperitoneal and extraperitoneal approaches. Tumor control and urinary continence were satisfying for patients enrolled in. The next phase involves conducting a large-scale, multicenter randomized controlled trial to thoroughly assess the effectiveness and safety of the new technology in a broader population.

Proxalutamide in metastatic castration-resistant prostate cancer: Primary analysis of a multicenter, randomized, open-label, phase 2 trial.

We aim to assess the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, for men with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter, randomized, open-label, phase 2 trial. In our study, the enrolled mCRPC patients were randomized to 100, 200 and 300 mg dose groups at 1:1:1. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and time to PSA and radiographic progression. Safety and pharmacokinetics were also assessed. Finally, there were 108 patients from 17 centers being enrolled. By week 16, there were 13 (35.1%), 12 (36.4%) and 15 (42.9%) patients with confirmed 50% or greater PSA decline in 100 mg (n = 37), 200 mg (n = 33) and 300 mg (n = 35) groups, respectively. Among the 19 patients with target lesions at study entry, three (15.8%) had a partial response and 12 (63.2%) had stable disease. The ORRs of 20.0%, 22.2%, 0% and DCRs of 80.0%, 88.9%, 60.0% were, respectively, achieved in 100, 200 and 300 mg groups. By the maximum follow-up time of 24 weeks, there were 42.6% and 10.2% of cases experiencing PSA progression and radiographic progression, respectively. Overall, adverse events (AEs) were experienced by 94.4% of patients, most of which were mild or moderate. There were 28 patients experiencing ≥grade 3 AEs. The most common AEs were fatigue (17.6%), anemia (14.8%), elevated AST (14.8%) and ALT (13.0%), decreased appetite (13.0%). These findings preliminarily showed the promising antitumor activity of proxalutamide in patients with mCRPC with a manageable safety profile. The proxalutamide dose of 200 mg daily is recommended for future phase 3 trial (Clinical trial registration no. CTR20170177).

Sustainable functional urethral reconstruction improves early urinary continence after robot-assisted radical prostatectomy: a randomised controlled trial.

OBJECTIVE: To evaluate the impact of sustainable functional urethral reconstruction (SFUR) on early recovery of urinary continence (UC) after robot-assisted radical prostatectomy. PATIENTS AND METHODS: Overall, 96 patients with primary prostate cancer were randomised into the SFUR or standard group (n = 48 each). The primary outcome was the 1-month UC recovery. Secondary outcomes included short-term (≤3 months) UC recovery, urinary function, micturition-related bother, perioperative complications, and oncological outcomes. Kaplan-Meier curves and Cox proportional hazard models were used to assess the 3-month UC recovery. Generalised estimating equations were used to compare postoperative urinary function and micturition-related bother. RESULTS: The 1-month UC recovery rates, median 24-h pad weights, and median operative time in the SFUR and standard groups were 73% and 49% (P = 0.017), 0 and 47 g (P = 0.001), and 125 and 103 min (P = 0.025), respectively. The UC recovery rates in the SFUR vs standard groups were 53% vs 23% at 1 week (P = 0.003), 53% vs 32% at 2 weeks (P = 0.038), and 93% vs 77% at 3 months (P = 0.025). The median time to UC recovery in the SFUR and standard groups was 5 and 34 days, respectively (log-rank P = 0.006); multivariable Cox regression supported this result (hazard ratio 1.73, 95% confidence interval 1.08-2.79, P = 0.024). Similar results were observed when UC was defined as 0 pads/day. Urinary function (P = 0.2) and micturition-related bother (P = 0.8) were similar at all follow-up intervals. The perioperative complication rates, positive surgical margin rates, and 1-year biochemical recurrence-free survival were comparable between both groups (all P > 0.05). CONCLUSION: SFUR resulted in earlier UC recovery without compromising postoperative urinary function. Long-term validation and multicentre studies are required to confirm the results of this novel technique.

Enzalutamide-resistant related lncRNA NONHSAT210528 promotes the proliferation and invasion of prostate cancer.

Background: As a new-generation androgen-receptor antagonist, enzalutamide is a first-choice drug for advanced prostate cancer (PCa) patients. However, secondary resistance to enzalutamide poses a new challenge in the treatment of cancer. Long non-coding RNA (lncRNA) regulates cell function through many levels and mechanisms, and also plays an important role in the biological behaviors of tumors. Methods: LncRNA microarrays were used to detect enzalutamide-resistant related lncRNA in Enzalutamide-resistant C4-2 (C4-2 ENZ-R) cells and corresponding parent cells. Cell Counting Kit 8, flow cytometry, and transwell assays were used to test the effect of lncRNA NONHSAT210528 on the function of PCa cells. RNA pulls down and the luciferase report gene was used to detect the competitive endogenous RNA (ceRNA) mechanism. The culture supernatant of C4-2 and C4-2b cells was transferred to the lower chamber for transwell assay of human umbilical endothelial cells (HUVECs). Results: The lncRNA microarray analysis showed that there were significant differences in the expression of many lncRNAs between the C4-2 ENZ-R and C4-2 cells. The real-time polymerase chain reaction (PCR) detection showed that the expression of lncRNA NONHSAT210528 was significantly higher in the C4-2 ENZ-R cells than the C4-2 cells. The Transwell assays showed that lncRNA NONHSAT210528 overexpression increased the invasion of the C4-2 and C4-2b cells. The cell-wound scratch and the transwell assays showed that the culture supernatant of C4-2 and C4-2b cells with overexpressed lncRNA NONHSAT210528 promoted the migration and invasion of HUVECs. Furthermore, lncRNA NONHSAT210528 regulated the expression of YOD1 dependent on miR-21. Conclusions: Enzalutamide-resistant related lncRNA NONHSAT210528 appears to promote the proliferation and invasion of PCa cells by functioning as a ceRNA and regulating the miR-21-5p/YOD1 signal pathway.

Phase I clinical trial of HC-1119 soft capsule in Chinese healthy adult male subjects: Pharmacokinetics and safety of single-dose proportionality and effects of food.

BACKGROUND: Preclinical studies showed that HC-1119, a deuterated version of enzalutamide, could competitively inhibit androgen binding to androgen receptor by blocking the transmission of androgen receptor signaling pathway as enzalutamide, inducing apoptosis of prostate cancer cells and reducing the proliferation of prostate cancer cells. Animal pharmacokinetic studies also show that deuterization of enzalutamide as HC-1119 could retain the basic properties of mother drug, increases the stability of compounds to metabolic enzymes and the drug exposure in vivo, prolong the half-life and reduce the production of metabolites, which may lead to a better efficacy and safety of HC-1119 compared with enzalutamide. METHODS: To evaluate the pharmacokinetics and safety of HC-1119 and the effects of food on pharmacokinetics in healthy adult Chinese men after single-dose administration of HC-1119. A total of 47 Chinese healthy adult male subjects received HC-1119 soft capsule at a single oral dose of 40, 80, or 160 mg followed on fasting or 160 mg after high-fat meal respectively. HC-1119 prototype and its metabolites M1 and M2 in plasma were collected individually in a total 23 time points. Pharmacokinetics were determined by sensitive LC/MS/MS for dose-proportionality study. RESULTS: In subjects taking HC-1119 soft capsules on fasting, Cmax of HC-1119 prototype increased dose-dependently. Either Cmax and AUC0-∞ of M1 or Cmax of M2 showed statistically significant difference. Dose-proportionality evaluation showed linear pharmacokinetic characteristics in Cmax of HC-1119 prototype, Cmax and AUC0-∞ of M2 in dose range of 40-160 mg. Cmax of HC-1119 was significantly different between the two groups as 160 mg HC-1119 on fasting or after a high-fat diet respectively, while the other parameter were not. HC-1119 and its metabolites M1 and M2 showed a linear dynamic trend. CONCLUSIONS: HC-1119 is expected to have lower clinical dose than the similar drug enzalutamide. The absorption of HC-1119 and the main pharmacokinetic parameters of HC-1119 and its metabolites M1 and M2 were not affected by high-fat diet. The clinical application of HC-1119 soft capsule in the later stage can be recommended for both fasting and postprandial. The safety and tolerance were good in this population.

Baicalin attenuates diet-induced obesity partially through promoting thermogenesis in adipose tissue.

BACKGROUND: Adipose tissues have essential roles on energy homeostasis and the development of metabolic syndrome and obesity, they have become critical targets for treating obesity and metabolic disorders. Baicalin is a flavonoid that derived from the root of Scutellaria baicalensis, and it has been reported to take part in the regulation of adipocyte function. All these highlighted the potential of baicalin in the regulation of fat accumulation and obesity. Yet the impact of baicalin on thermogenic function of adipocytes remains to be deciphered. OBJECTIVE: This study aims to explore the anti-obesity effects of baicalin. MATERIALS & METHODS: The level of mRNA was detected by qRT-PCR and the protein expression level was examined by western blot. H&E staining was used for the observation of the structure of adipose tissue. Serum triglyceride and insulin levels were detected by commercial test kits. RESULTS: Our data demonstrated that baicalin up-regulates the expression of UCP1 and PGC1a in a dose-dependent manner in vitro. Baicalin also increases ERK phosphorylation, and the increased expression of UCP1 and PGC1a in adipocytes could be inhibited by an ERK inhibitor, U0126. Moreover, dietary baicalin ameliorates high fat diet (HFD)-induced obesity without affecting food intake. In addition, dietary baicalin inhibits adipocyte hypertrophy and enhances thermogenic gene program in sWAT and intrascapular brown adipose tissue (iBAT) in vivo. DISCUSSION & CONCLUSION: Baicalin prevents HFD-induced obesity partially through promoting adipocyte thermogenesis. Baicalin may be a promising compound against human obesity and related metabolic diseases.