Albendazole induces an anti-tumor effect and potentiates PD-L1 blockade immunotherapy.

BACKGROUND: Previously, albendazole (ABZ) has been reported as an anti-parasitic drug rather than anti-tumor drug. Our study aim to investigate whether ABZ also has a potential anti-tumor effect by shaping the tumor immune microenvironment and interrogate whether ABZ could synergize with the PD-L1 blockade. METHODS: C57BL/6 mice (C57) were intravenously injected with B16F10-luciferase (B16-luc) cells to establish a lung metastatic melanoma model and subcutaneously inoculated with B16-luc cells to establish a subcutaneous tumor model. The tumor volume and tumor metastasis loci of the mice were measured by a vernier caliper and in vivo imaging. RNA sequencing was performed to analyze the different genes and pathways of immune cells in the tumors. Flow cytometry and immunofluorescence were used to analyze the different subsets of tumor-infiltrating immune cells. RESULTS: The results suggested that ABZ significantly inhibited lung melanoma metastasis with decreased fluorescence intensity and nodule score and mediated the regression of subcutaneous melanoma in mice with decreased tumor volume. Moreover, RNA sequencing results showed that ABZ regulated the gene expression levels and pathways of immune cells in the tumor microenvironment (TME). Meanwhile, flow cytometry and immunofluorescence showed that the number and percentage of CD8+ T cells, CD4+ T cells, and TH1 cells were enhanced in tumors after ABZ treatment. Furthermore, the combination of ABZ and anti-PD-L1 treatment significantly potentiated anti-tumor efficacy in both lung metastasis and subcutaneous melanoma models and mediated an increase in the percentage of CD8+ T cells, CD4+ T cells, and TH1 cells as compared to the control group. CONCLUSION: ABZ inhibits melanoma growth and metastasis. Moreover, ABZ synergized with PD-L1 blockade mediates tumor regression.

Autofluorescence spectral analysis for detecting urinary stone composition in emulated intraoperative ambient.

The prevalence and disease burden of urolithiasis has increased substantially worldwide in the last decade, and intraluminal holmium laser lithotripsy has become the primary treatment method. However, inappropriate laser energy settings increase the risk of perioperative complications, largely due to the lack of intraoperative information on the stone composition, which determines the stone melting point. To address this issue, we developed a fiber-based fluorescence spectrometry method that detects and classifies the autofluorescence spectral fingerprints of urinary stones into three categories: calcium oxalate, uric acid, and struvite. By applying the support vector machine (SVM), the prediction accuracy achieved 90.28 % and 96.70% for classifying calcium stones versus non-calcium stones and uric acid versus struvite, respectively. High accuracy and specificity were achieved for a wide range of working distances and angles between the fiber tip and stone surface in an emulated intraoperative ambient. Our work establishes the methodological basis for engineering a clinical device that achieves real-time, in situ classification of urinary stones for optimizing the laser ablation parameters and reducing perioperative complications in lithotripsy.

Reduced Ca2+ spark activity contributes to detrusor overactivity of rats with partial bladder outlet obstruction.

We tested whether or not altered Ca2+ spark activity accounted for detrusor overactivity (DO) of Wistar rats after partial bladder outlet obstruction (PBOO). We constructed a DO model through PBOO and studied the Ca2+ spark activity of detrusor. By way of using confocal microscopy and the patch-clamp technique, Ca2+ sparks and spontaneous transient outward currents (STOCs) in detrusor myocytes were measured respectively. Our results indicated that Ca2+ spark activity and STOCs were significantly reduced in the DO detrusor myocytes compared to unafflicted control cells, and both of these had levels that were remarkably increased by applications of caffeine (10 µM), a RyR agonist, in DO myocytes. In addition, measures of detrusor contractions were also recorded by using freshly isolated detrusor strips. These results indicated that the spontaneous contraction of DO detrusor was significantly enhanced, and that the effect of caffeine (10 µM) upon detrusor contractions was reversed by applications of iberiotoxin (100 nM) which is a BK channel blocker. Western blotting (WB) analyses indicated that the levels of expression of ryanodine receptor type 2 (RyR2) and FK506 binding protein 12.6 (FKBP12.6) in bladder muscle were respectively decreased and increased in the samples from DO rats. Thus, we considered in the rat DO model wherein PBOO, the reduced Ca2+ spark activity in detrusor myocytes partly contributed to overactive detrusor contractions. The impaired Ca2+ spark activity may have resulted from decreased RyR2 expression and increased FKBP12.6 expression. Such novel findings in our research might help to provide means for better treatment outcomes for patients afflicted by bladder dysfunction.

Comparative study of wire-integrated urethral catheter versus wire-assisted urethral catheter in difficult male urethral catheterization: a single-center experience.

BACKGROUND: This study reports the clinical experience of the wire-integrated urethral catheter (WIUC) versus wire-assisted urethral catheter (WAUC) in difficult male urethral catheterization. METHODS: The clinical data of 116 male patients undergoing urinary catheterization with WIUC or WAUC after a failed attempt catheterization in Southwest Hospital from June 2018 to June 2019 were retrospectively analyzed. The time spent during urinary catheterization, cost of consumables, experience rating of catheterization methods and materials assessed by medical staff were compared between WIUC group (n=58) and WAUC group (n=58). RESULTS: The catheterization succeeded in all 116 patients. The time spent of urinary catheterization was (4.0±1.6) min in WIUC group and (15.4±3.3) min in WAUC group, and the cost of consumables wasï¿¥400 in WIUC group andï¿¥706.2 in WAUC group. The medical staff's experience rating results were 9.0±0.8 vs. 7.8±0.7 for the catheterization method and 9.3±0.8 vs. 8.0±0.7 for the materials, respectively, in the WIUC group and WAUC group. CONCLUSIONS: WIUC is reasonably designed and easy to operate and can be used for a variety of clinical situations.

Procalcitonin as an early diagnostic and monitoring tool in urosepsis following percutaneous nephrolithotomy.

To evaluate the value of procalcitonin (PCT) as an early marker for diagnosis and differentiation of without urosepsis, urosepsis, severe urosepsis, and uroseptic shock following PCNL and the ability of PCT to assess the effectiveness of antibiotic therapy in patients with urosepsis. From June 2012 to August 2013, 267 patients undergoing PCNL for renal calculi, and who fulfilled selection criteria, were recruited into our study. The patients' medical records were reviewed retrospectively. One of selection criteria was the scores of PCT and WBC were collected at operative day, postoperative day one, day two, day three, day five and day seven. The area under the ROC curve for the prediction of urosepsis was 0.960 for PCT and 0.634 for WBC. PCT concentrations were higher in patients with uroseptic shock versus severe urosepsis versus urosepsis versus without urosepsis following PCNL. WBC values showed no significant difference between patients with urosepsis, severe urosepsis and uroseptic shock following PCNL. With time, in patients with successfully treated urosepsis following PCNL, the PCT concentrations significantly declined and kept decreasing from postoperative day two to postoperative day seven and the WBC scores showed no significant change over the first postoperative 2 days and were decreased only after postoperative day three. PCT appears to be a useful early marker to diagnosis and discriminate urosepsis, severe urosepsis and uroseptic shock following PCNL. Daily PCT measurements may be a valuable tool in monitoring the effectiveness of antibiotic therapy in urosepsis following PCNL.

Selective transurethral resection of the prostate combined with transurethral incision of the bladder neck for bladder outlet obstruction in patients with small volume benign prostate hyperplasia (BPH): a prospective randomized study.

PURPOSE: Transurethral resection of the prostate (TURP) has a high failure rate in patients with small volume benign prostate hyperplasia (BPH) with bladder outlet obstruction (BOO). We describe and report the results of an alternative surgical method, selective transurethral resection of the prostate (STURP) in combination with transurethral incision of the bladder neck (TUIBN). METHODS: Patients were randomized to receive TURP or STRUP+TUIBN in combination with TUIBN. Maximum urinary flow rate (Qmax), voided volume, and post voiding residual volume (PVR) were assessed at baseline and at 1, 3, and 6 months after surgery. Efficacy of treatment was assessed by lower urinary tract symptoms and IPSS. RESULTS: Sixty three patients received STRUP+TUIBN and 61 received TURP. Surgical time, amount of prostate tissue resected, and blood loss was the same in both groups (all, p>0.05). The mean duration of follow-up was 9.02 and 8.53 months in patients receiving TURP and STRUP+TUIBN, respectively. At 6 months postoperatively, IPSS was 4.26±1.22 and 4.18±1.47 in patients receiving TURP and STRUP+TUIBN, respectively (p>0.05), and the Qmax in patients receiving STRUP+TUIBN was markedly higher than in those receiving TURP (28.28±6.46 mL/s vs. 21.59±7.14 mL/s; p<0.05). Bladder neck contracture and urinary tract infections were observed in 3 and 5 patients receiving TURP, respectively, and none in STURP. CONCLUSIONS: STRUP+TUIBN may offer a more effective and safer alternative to TURP for small volume BPH patients.