First-in-human study of PSMA-targeting agent, [18F]AlF-P16-093: dosimetry and initial evaluation in prostate cancer patients.

PURPOSE: This is a first-in-human study to evaluate the radiation dosimetry of a new prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical, [18F]AlF-P16-093, and also initial investigation of its ability to detect PSMA-positive tumors using PET scans in a cohort of prostate cancer (PCa) patients. METHODS: The [18F]AlF-P16-093 was automatically synthesized with a GE TRACERlab. A total of 23 patients with histopathologically proven PCa were prospectively enrolled. Dosimetry and biodistribution study investigations were carried out on a subset of six (6) PCa patients, involving multiple time-point scanning. The mean absorbed doses were estimated with PMOD and OLINDA software. RESULTS: [18F]AlF-P16-093 was successfully synthesized, and radiochemical purity was > 95%, and average labeling yield was 36.5 ± 8.3% (decay correction, n = 12). The highest tracer uptake was observed in the kidneys, spleen, and liver, contributing to an effective dose of 16.8 ± 1.3 µSv/MBq, which was ~ 30% lower than that of [68Ga]Ga-P16-093. All subjects tolerated the PET examination well, and no reportable side-effects were observed. The PSMA-positive tumors displayed rapid uptake, and they were all detectable within 10 min, and no additional lesions were observed in the following multi-time points scanning. Each patient had at least one detectable tumor lesion, and a total of 356 tumor lesions were observed, including intraprostatic, lymph node metastases, bone metastases, and other soft tissue metastases. CONCLUSIONS: We report herein a streamlined method for high yield synthesis of [18F]AlF-P16-093. Preliminary study in PCa patients has demonstrated its safety and acceptable radiation dosimetry. The initial diagnostic study indicated that [18F]AlF-P16-093 PET/CT is efficacious and potentially useful for a widespread application in the diagnosis of PCa patients.

Determining the optimal pharmacokinetic modelling and simplified quantification method of [18F]AlF-P16-093 for patients with primary prostate cancer (PPCa).

PURPOSE: This paper discusses the optimization of pharmacokinetic modelling and alternate simplified quantification method for [18F]AlF-P16-093, a novel tracer for in vivo imaging of prostate cancer. METHODS: Dynamic PET/CT scans were conducted on eight primary prostate cancer patients, followed by a whole-body scan at 60 min post-injection. Time-activity curves (TACs) were obtained by drawing volumes of interest for primary prostatic and metastatic lesions. Optimal kinetic modelling involved evaluating three compartmental models (1T2K, 2T3K, and 2T4K) accounting for fractional blood volume (Vb). The simplified quantification method was then determined based on the correlation between the static uptake measure and total distribution volume (Vt) obtained from the optimal pharmacokinetic analysis. RESULTS: In total, 17 intraprostatic lesions, 10 lymph nodes, and 36 osseous metastases were evaluated. Visually, the contrast of the tumor increased and showed the steepest incline within the first few minutes, whereas background activity decreased over time. Full pharmacokinetic analysis revealed that a reversible two-compartmental (2T4K) model is the preferred kinetic model for the given tracer. The kinetic parameters K1, k3, Vb, and Vt were all significantly higher in lesions when compared with normal tissue (P < 0.01). Several simplified protocols were tested for approximating comprehensive dynamic quantification in tumors, with image-based SURmean (the ratio of tumor SUVmean to blood SUVmean) within the 28-34 min window found to be sufficient for approximating the total distribution Vt values (R2 = 0.949, P < 0.01). Both Vt and SURmean correlated significantly with the total serum prostate-specific antigen (tPSA) levels (P < 0.01). CONCLUSIONS: This study introduced an optimized pharmacokinetic modelling approach and a simplified acquisition method for [18F]AlF-P16-093, a novel PSMA-targeted radioligand, highlighting the feasibility of utilizing one static PET imaging (between 30 and 60 min) for the diagnosis of prostate cancer. Note that the image-derived input function in this study may not reflect the true corrected plasma input function, therefore the interpretation of the associated kinetic parameter estimates should be done with caution.

International Alliance of Urolithiasis (IAU) guideline on staghorn calculi management.

BACKGROUND: The stone burden based management strategy reported in the guidelines published by different associations is well known for a long time. Staghorn calculi, representing the largest burden and most complex stones, is one of the most challenging cases to practicing urologists in clinical practice. The International Alliance of Urolithiasis (IAU) has released a series of guidelines on the management of urolithiasis. PURPOSE: To develop a series of recommendations for the contemporary management management of staghorn calculi and to provide a clinical framework for urologists treating patients with these complex stones. METHODS: A comprehensive literature search for articles published in English between 01/01/1976 and 31/12/2022 in the PubMed, OVID, Embase and Medline database is performed. A series of recommendations are developed and individually graded following the review of literature and panel discussion. RESULTS: The definition, pathogenesis, pathophysiology, preoperative evaluation, intraoperative treatment strategies and procedural advice, early postoperative management, follow up and prevention of stone recurrence are summarized in the present document. CONCLUSION: A series of recommendations regarding the management of staghorn calculi, along with related commentary and supporting documentation offered in the present guideline is intended to provide a clinical framework for the practicing urologists in the management of staghorn calculi.

Asprosin aggravates nonalcoholic fatty liver disease via inflammation and lipid metabolic disturbance mediated by reactive oxygen species.

Asprosin (ASP) is a newly-identified adipokine and plays important roles in energy metabolism homeostasis. However, there is no report on whether and how ASP is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Therefore, in the study, we investigated the protective effects of ASP-deficiency on the liver in the NAFLD model mice and the detrimental effects of ASP treatment on the human normal hepatocytes (LO2 cell line). More important, we explored the underlying mechanism from the perspective of lipid metabolism and inflammation. In the in vivo experiments, our data showed that the ASP-deficiency significantly alleviated the high-fat diet-induced inflammation and NAFLD, inhibited the hepatic fat deposition and downregulated the expressions of fat acid synthase (FASN), peroxisome proliferator-activated receptor γ (PPARγ) and forkhead box protein O1 (FOXO1); moreover, the ASP-deficiency attenuated the inflammatory state and inhibited the activation of the IKK/NF-κBp65 inflammation pathway. In the in vitro experiments, our results revealed that ASP treatment caused and even exacerbated the injury of LO2 cells induced by FFA; In contrast, the ASP treatment upregulated the expressions of PPARγ, FOXO1, FASN, ACC and acyl-CoA oxidase 1 (ACOX1) and elevated the reactive oxygen species (ROS) levels. Accordingly, these results demonstrate that ASP causes NAFLD through disrupting lipid metabolism and promoting the inflammation mediated by ROS.

Extracellular vesicle-circEHD2 promotes the progression of renal cell carcinoma by activating cancer-associated fibroblasts.

BACKGROUND: The encapsulation of circular RNAs (circRNAs) into extracellular vesicles (EVs) enables their involvement in intercellular communication and exerts an influence on the malignant advancement of various tumors. However, the regulatory role of EVs-circRNA in renal cell carcinoma (RCC) remains elusive. METHODS: The in vitro and in vivo functional experiments were implemented to measure the effects of circEHD2 on the phenotype of RCC. The functional role of EVs-circEHD2 on the activation of fibroblasts was assessed by collagen contraction assay, western blotting, and enzyme-linked immunosorbent assay (ELISA). The mechanism was investigated by RNA pull-down assay, RNA immunoprecipitation, chromatin isolation by RNA purification, luciferase assay, and co-immunoprecipitation assay. RESULTS: We demonstrated that circEHD2 was upregulated in RCC tissues and serum EVs of RCC patients with metastasis. Silencing circEHD2 inhibited tumor growth in vitro and in vivo. Mechanistic studies indicated that FUS RNA -binding protein (FUS) accelerated the cyclization of circEHD2, then circEHD2 interacts with tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH), which acts as a bridge to recruit circEHD2 and Yes1-associated transcriptional regulator (YAP) to the promoter of SRY-box transcription factor 9 (SOX9); this results in the sustained activation of SOX9. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) regulates the package of circEHD2 into EVs, then EVs-circEHD2 transmits to fibroblasts, converting fibroblasts to cancer-associated fibroblasts (CAFs). Activated CAFs promote the metastasis of RCC by secreting pro-inflammatory cytokines such as IL-6. Furthermore, antisense oligonucleotides (ASOs) targeting circEHD2 exhibited a strong inhibition of tumor growth in vivo. CONCLUSIONS: The circEHD2/YWHAH/YAP/SOX9 signaling pathway accelerates the growth of RCC. EVs-circEHD2 facilitates the metastasis of RCC by converting fibroblasts to CAFs. Our results suggest that EVs-circEHD2 may be a useful biomarker and therapeutic target for RCC.

A new histone deacetylase inhibitor remodels the tumor microenvironment by deletion of polymorphonuclear myeloid-derived suppressor cells and sensitizes prostate cancer to immunotherapy.

BACKGROUND: Prostate cancer (PCa) is the most common malignancy diagnosed in men. Immune checkpoint blockade (ICB) alone showed disappointing results in PCa. It is partly due to the formation of immunosuppressive tumor microenvironment (TME) could not be reversed effectively by ICB alone. METHODS: We used PCa cell lines to evaluate the combined effects of CN133 and anti-PD-1 in the subcutaneous and osseous PCa mice models, as well as the underlying mechanisms. RESULTS: We found that CN133 could reduce the infiltration of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), and CN133 combination with anti-PD-1 could augment antitumor effects in the subcutaneous PCa of allograft models. However, anti-PD-1 combination with CN133 failed to elicit an anti-tumor response to the bone metastatic PCa mice. Mechanistically, CN133 could inhibit the infiltration of PMN-MDSCs in the TME of soft tissues by downregulation gene expression of PMN-MDSC recruitment but not change the gene expression involved in PMN-MDSC activation in the CN133 and anti-PD-1 co-treatment group relative to the anti-PD-1 alone in the bone metastatic mice model. CONCLUSIONS: Taken together, our work firstly demonstrated that combination of CN133 with anti-PD-1 therapy may increase the therapeutic efficacy to PCa by reactivation of the positive immune microenvironment in the TME of soft tissue PCa.

International Alliance of Urolithiasis guideline on retrograde intrarenal surgery.

OBJECTIVES: To set out the second in a series of guidelines on the treatment of urolithiasis by the International Alliance of Urolithiasis that concerns retrograde intrarenal surgery (RIRS), with the aim of providing a clinical framework for urologists performing RIRS. MATERIALS AND METHODS: After a comprehensive search of RIRS-related literature published between 1 January 1964 and 1 October 2021 from the PubMed database, systematic review and assessment were performed to inform a series of recommendations, which were graded using modified GRADE methodology. Additionally, quality of evidence was classified using a modification of the Oxford Centre for Evidence-Based Medicine Levels of Evidence system. Finally, related comments were provided. RESULTS: A total of 36 recommendations were developed and graded that covered the following topics: indications and contraindications; preoperative imaging; preoperative ureteric stenting; preoperative medications; peri-operative antibiotics; management of antithrombotic therapy; anaesthesia; patient positioning; equipment; lithotripsy; exit strategy; and complications. CONCLUSION: The series of recommendations regarding RIRS, along with the related commentary and supporting documentation, offered here should help provide safe and effective performance of RIRS.

A case-based review of dietary management of calcium oxalate stones.

PURPOSE: The purpose of this paper is to help patients with calcium oxalate stones to access prevention and treatment options with dietary management. METHODS: Typical cases in our hospital and other hospitals were selected for case review; combined with literature review through PubMed search, comprehensive analysis and suggestions were put forward. RESULTS: By retrieving the literature with sufficient evidence, selecting, and summarizing, analysis of dietary liquid, oxalate and oxalate precursors, calcium, protein, fruits and vegetables, salt, high dietary fiber, and other content with high evidence index was carried out, respectively. CONCLUSION: Through the retrospective analysis of typical cases and literature review, the importance of diet management in the prevention and treatment of calcium oxalate stones was emphasized again, and suggestions were put forward to promote the prevention and treatment of calcium oxalate stones.

Superselective renal arterial embolization for severe postpercutaneous nephrolithotomy haemorrhage: clinical characteristics and risk factors for initial failure.

OBJECTIVE: To identify the clinical characteristics of patients who underwent superselective renal arterial embolization (SRAE) after percutaneous nephrolithotomy (PCNL) and to explore the risk factors for failed initial SRAE after PCNL. MATERIALS AND METHODS: Patients who underwent SRAE for severe haemorrhage following PCNL between January 2014 and December 2020 were included in the study. The clinical data of those patients and the parameters and characteristics of the perioperative PCNL and SRAE procedures were collected and analysed. RESULTS: A total of 243 patients were included in this study. A total of 139 patients (57.2%) had a pseudoaneurysm, 25 (10.3%) had an arteriovenous fistula, 50 (20.6%) patients had both a pseudoaneurysm and an arteriovenous fistula, and 29 (11.9%) had an arterial laceration. In 177 patients with single percutaneous access, 125 (70.6%) patients exhibited nontract haemorrhage, and 55 (31.1%) patients exhibited multiple bleeding sites. In 66 patients with multiple percutaneous access, 44 (66.7%) patients exhibited nontract haemorrhage, and 32 (48.5%) patients exhibited multiple bleeding sites. The decrease in Hb before SRAE was 41.4 ± 19.8 g/L. The mean time between PCNL surgery and initial SRAE was 6.4 ± 4.9 days. Serum creatinine was increased after the SRAE procedure. Initial SRAE was successful in 229 (94.2%) patients and failed in 14 (5.8%) patients. Multivariate regression demonstrated that hydronephrosis < 20 mm, total ultrasonographic guidance, solitary kidney, previous ipsilateral renal surgery, PCNL duration > 90 min and multiple bleeding sites were potential risk factors for initial embolization failure. CONCLUSION: Percutaneous access was not the most important reason for post-PCNL severe haemorrhage. SRAE is effective for the treatment of severe haemorrhage following PCNL; however, several factors have an impact on the success of initial SRAE. Additionally, the SRAE procedure may affect renal function.

Current evidence for suction in endourological procedures: comprehensive review of literature.

PURPOSE OF REVIEW: To identify the latest advances on the utilization of suctioning devices in the surgical treatment of urinary stones. RECENT FINDINGS: Advances are being made to incorporate suction and pressure control capabilities in percutaneous and ureteroscopic lithotripsy. Multiple retrospective studies and few prospective studies have shown that suctioning with minimally invasive percutaneous nephrolithotomy, commonly referred to as Super MiniPerc, can lead to better stone-free rates (SFR) and shorter operative time with lower incidence of infectious complications. Suctioning during retrograde intrarenal surgery (RIRS) has mainly been achieved through suctioning ureteral access sheath. Here as well, the incorporation of suction improved the SFR, but most importantly, reduced the risk of postoperative infectious complications. SUMMARY: Theoretically suction in endourological procedures could facilitate stone debris removal and could reduce intrarenal pressure at the same time allowing for increased irrigation flow potentially decreasing operation time and infectious complications. These claims are supported in contemporary clinical studies, reporting superior SFR and reduced postoperative infectious complications in both percutaneous nephrolithotomy and RIRS.

The association between dairy products consumption and prostate cancer risk: a systematic review and meta-analysis.

In this study, we conducted a meta-analysis to estimate the relationship between the consumption of dairy products and the risk of prostate cancer. We searched PubMed, Embase and Cochrane databases for relevant articles and identified a total of thirty-three cohort studies between 1989 and 2020. The qualities of included studies were assessed using Newcastle-Ottawa scale. Pooled adjusted relative risks (RR) with 95 % CI were calculated. We performed subgroup analyses stratified by dairy type, prostate cancer type, follow-up years, treatment era, collection times, adjustment for confounders and geographic location. In the subgroup analysis stratified by prostate cancer type, the pooled RR were 0·98 (95 % CI 0·94, 1·03) in the advanced group, 1·10 (95 % CI 0·98, 1·24) in the non-advanced group and 0·92 (95 % CI 0·84, 1·00) in the fatal group. In the dose-response analysis, a positive association for the risk of prostate cancer was observed for total dairy products 400 g/d (RR: 1·02; 95 % CI 1·00, 1·03), total milk 200 g/d (RR: 1·02; 95 % CI 1·01, 1·03), cheese 40 g/d (RR: 1·01; 95 % CI 1·00, 1·03) and butter 50 g/d (RR: 1·03; 95 % CI 1·01, 1·05). A decreased risk was observed for the intake of whole milk 100 g/d (RR: 0·97; 95 % CI 0·96, 0·99). Our meta-analysis suggests that high intakes of dairy products may be associated with an increased risk of prostate cancer; however, since many of the studies were affected by prostate-specific antigen (PSA) screening bias, additional studies with an adjustment of PSA screening are needed.

Sexual violence against women remains problematic and highly prevalent around the world.

BACKGROUND: Sexual violence is far more prevalent in most societies than is usually suspected in daily life. However, no study has systematically summarized the global prevalence rate and the major outcomes of sexual violence against women. METHODS: We directed a wide-raging search in the PubMed, Embase, and Web of Science, catalogs since the beginning to December 2022 for relevant reports about the incidence of sexual fighting touching females. The occurrence frequency was assessed with a random-effects model. The heterogeneity was estimated with I 2 values. Differences by research features were assessed over subgroup evaluation and meta-regression. RESULTS: A total of 32 cross-sectional studies were included (a total of 19,125 participants). The pooled sexual violence rate was 0.29 (95% CI = 0.25-0.34). Subgroup analyses found that there was a higher rate of sexual violence against women in 2010-2019 period (0.33, 95% CI = 0.27-0.37), developing countries (0.32, 95% CI = 0.28-0.37), and interview (0.39, 95% CI = 0.29-0.49). The analysis found that more than half of women (0.56, 95% CI = 0.37-0.75) had post-traumatic stress disorder (PTSD) after experiencing sexual violence, and only a third of women considered seeking support (0.34, 95% CI = 0.13-0.55). CONCLUSIONS: Nearly one out of every three (29%) women around the world has been a victim of sexual violence in their life. This current study investigated the status and characteristics of sexual violence against women, which could provide an important reference for police and emergency health services management.

PET Imaging of Bromodomain and Extra-Terminal Domain Inhibitors for the Noninvasive Assessment of Metabolic Changes in the Liver and Brain of Early-Stage Alcoholic Liver Disease.

Alcoholic liver disease (ALD) has a significant impact on human health and is one of the leading causes of liver disease mortality. The early and exact diagnosis of ALD is very important since the early stage of disease progression can be reversible. Although ALD can be evaluated by ultrasound, CT, or MRI, there is still no imaging technique sufficient in the diagnosis of early-stage ALD. Of the current studies, epigenetic modulation plays a significant role in the development and progression of ALD. In this work, we evaluate whether BRDs play a vital role in the early-stage ALD using our new PET imaging probe of BET proteins, [11C]CW22. PET/CT imaging of [11C]CW22 and [18F]FDG was used to identify early-stage lesions of livers and brains in the mice model. We found that the average uptake values of livers and brains in early-stage ALD were significantly increased for [11C]CW22 PET/CT imaging but only slightly changed in [18F]FDG PET/CT imaging. Consistently, we also found that BRD 3, 4 protein expression levels were significantly higher in the liver and brain tissues of early-stage ALD. Furthermore, through Pmod software, we found that [11C]CW22 PET/CT uptakes in the brain stem, cerebellum, and midbrain were significantly up-regulated in the early-stage ALD. In conclusion, BRDs were important mediators of damage in early-stage ALD. [11C]CW22 PET/CT imaging can detect the early-phase alcohol-induced damage of livers and brains, which will likely lead to human trials in the future.

Preoperative antibiotic therapy exceeding 7 days can minimize infectious complications after percutaneous nephrolithotomy in patients with positive urine culture.

PURPOSE: To explore an appropriate duration of antibiotic therapy before percutaneous nephrolithotomy (PCNL) in patients with positive urine culture. METHODS: From March 2016 to May 2018, consecutive patients with positive urine culture undergoing PCNL were prospectively registered. Initial preoperative antibiotics were given empirically. If needed, antibiotics were upgraded or adjusted to susceptible antibiotic after obtaining antibiotic-sensitivity test. Postoperative systemic inflammatory response syndrome (SIRS) was the primary outcome. RESULTS: Among the 220 participants, the incidence of positive stone culture and SIRS were 85.5% and 36.8%. Escherichia coli (53.6%, 44.5%) and Proteus mirabilis (8.2%, 10.0%) were the top two bacteria in urine and stones. In univariable analysis, patients with postoperative SIRS had a higher rate of stone culture positivity (97.5% VS 78.4%, P < 0.001) and a shorter duration of preoperative antibiotics therapy (3.4 ± 2.7 days versus 4.2 ± 2.8 days, P = 0.037). The landscape of SIRS showed a declining trend as the elongation of preoperative antibiotics (P = 0.039). In a day-by-day comparison, SIRS was less prevalent in patients treated by pre-PCNL antibiotics ≥ 7 days than in those with antibiotics ≤ 6 days (21.7% VS 40.8%, P = 0.017). Multivariable logistic regression confirmed positive stone culture (P = 0.001, OR 11.115) as an independent risk factor and pre-PCNL antibiotics ≥ 7 days (P = 0.048, OR 0.449) as an independent protective factor for SIRS. Preoperative antibiotic ≥ 7 days decreased SIRS from 45.4 to 27.8% and from 9.1 to 0% in patients with a positive and negative stone culture, respectively. CONCLUSION: Exceeding seven days should be appropriate duration of antibiotic therapy before PCNL in patients with positive urine cultures.

Radical nephroureterectomy for UTUC conferred survival benefits irrespective of age and comorbidities.

PURPOSE: We investigated the effects of age, American Society of Anesthesiologists Physical Status Classification (ASA) grading and Charlson Comorbidity Index (CCI) on the survival outcomes of upper tract urothelial carcinoma (UTUC). METHODS: The CROES-UTUC registry was an international, multicenter study on patients with UTUC. Primary outcomes were overall survival (OS) and disease-free survival (DFS). Kaplan-Meier and multivariate Cox regression analyses were performed by stratifying patients according to their age (≤ 70 and > 70 years old) and ASA grade (I-II and III-V)/CCI (0-1 and ≥ 2). RESULTS: A total of 2352 patients were included in this study. Patients aged ≤ 70 years with ASA grading of I-II (p = 0.002), and patients aged ≤ 70 years with a CCI of 0-1 (p = 0.002) had the best OS. Upon multivariate analysis, both in patients aged ≤ 70 and > 70 years, ASA grading and CCI were not significantly associated with OS. Patients aged ≤ 70 years with ASA grading of III-IV (p = 0.024) had the best DFS. When stratified according to age and CCI, no significant difference in DFS was noted. Upon multivariate analysis, radical nephroureterectomy (RNU) was significantly associated with better DFS in patients aged ≤ 70 and > 70 years; CCI of ≥ 3 was significantly associated with worse DFS in patients ≤ 70 years; ASA grading was not associated with DFS in patients aged ≤ 70 and > 70 years. CONCLUSIONS: A high ASA grading and CCI should not be considered contraindications for RNU. RNU should be considered even in elderly patients when it is deemed feasible and achievable after a geriatric assessment.

Cerium oxide-based nanozyme suppresses kidney calcium oxalate crystal depositions via reversing hyperoxaluria-induced oxidative stress damage.

Oxidative stress damage to renal epithelial cells is the main pathological factor of calcium oxalate calculi formation. The development of medicine that could alleviate oxidative damage has become the key to the prevention and treatment of urolithiasis. Herein, porous nanorods CeO2 nanoparticles (CNPs) were selected from CeO2 with different morphologies as an antioxidant reagent to suppress kidney calcium oxalate crystal depositions with excellent oxidation resistance due to its larger specific surface area. The reversible transformation from Ce3+ to Ce4+ could catalyze the decomposition of excess free radicals and act as a biological antioxidant enzyme basing on its strong ability to scavenge free radicals. The protection capability of CNPS against oxalate-induced damage and the effect of CNPS on calcium oxalate crystallization were studied. CNPS could effectively reduce reactive oxygen species production, restore mitochondrial membrane potential polarity, recover cell cycle progression, reduce cell death, and inhibit the formation of calcium oxalate crystals on the cell surface in vitro. The results of high-throughput sequencing of mRNA showed that CNPs could protect renal epithelial cells from oxidative stress damage caused by high oxalate by suppressing the expression gene of cell surface adhesion proteins. In addition, CNPS can significantly reduce the pathological damage of renal tubules and inhibit the deposition of calcium oxalate crystals in rat kidneys while having no significant side effect on other organs and physiological indicators in vivo. Our results provide a new strategy for CNPS as a potential for clinical prevention of crystalline kidney injury and crystal deposition.

The antibiotic strategies during percutaneous nephrolithotomy in China revealed the gap between the reality and the urological guidelines.

BACKGROUND: Correct perioperative antibiotic strategies are crucial to prevent postoperative infections during percutaneous nephrolithotomy (PCNL). We aimed to compare the realistic antibiotic strategies applied in China with current urological guidelines. METHODS: Between April and May 2020, urologists from China were invited to finish an online cross-sectional survey. The questionnaire was designed according to the current urological guidelines and literatures. RESULTS: 3393 completed responses were received. 61.1% (2073/3393) respondents had urological experience of more than 10 years. 72.4% urologists chose multiple-dose antibiotics for patients with both negative urine culture (UC-) and negative urine microscopy (UM-) preoperatively. Respondents in central China (OR = 1.518; 95% CI 1.102-2.092; P = 0.011), east China (OR = 1.528; 95% CI 1.179-1.979; P = 0.001) and northeast China (OR = 1.904; 95% CI 1.298-2.792; P = 0.001) were more likely to prescribe multiple-dose antibiotic for UC-UM- patients. Notably, the respondents who finished PCNL exceeded 100 cases per year were in favor of single-dose administration (OR = 0.674; 95% CI 0.519-0.875; P = 0.003). There are only 8.3% urologists chose single-dose antibiotic for UC-UM+ patients, whereas 65.5% administered antibiotics for 1-3 days. Meanwhile, for UC+ patients, 59.0% of the urologists applied antibiotics shorter than 1 week, and only 26.3% of the urologists carried out routine re-examination of UC. Moreover, postoperative antibiotics were frequently prescribed for 3-6 days (1815; 53.5%). Finally, although 88.2% urologists considered stone culture important for management of postoperative antibiotics as the guideline recommended, only 18.5% performed it routinely. CONCLUSIONS: The antibiotic strategies are different between current practice in China and the urological guidelines. The dissimilarities suggested that further studies should be conducted to investigate the reasons of the differences and standardize the application of antibiotics.

Angiogenesis-Browning Interplay Mediated by Asprosin-Knockout Contributes to Weight Loss in Mice with Obesity.

Asprosin (ASP) is a recently identified adipokine secreted by white adipose tissue (WAT). It plays important roles in the maintenance of glucose homeostasis in the fasting state and in the occurrence and development of obesity. However, there is no report on whether and how ASP would inhibit angiogenesis and fat browning in the mouse adipose microenvironment. Therefore, the study sought to investigate the effects of ASP-knockout on angiogenesis and fat browning, and to identify the interaction between them in the ASP-knockout mouse adipose microenvironment. In the experiments in vivo, the ASP-knockout alleviated the obesity induced by a high fat diet (HFD) and increased the expressions of the browning-related proteins including uncoupling protein 1 (UCP1), PRD1-BF-1-RIZ1 homologus domain-containing protein-16 (PRDM16) and PPAR gamma coactivator 1 (PGC1-α) and the endothelial cell marker (CD31). In the experiments in vitro, treatment with the conditional medium (CM) from ASP-knockout adipocytes (ASP-/--CM) significantly promoted the proliferation, migration and angiogenesis of vascular endothelial cells, and increased the expressions of vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR2) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/endothelial nitric oxide synthase (eNOS) pathway proteins. In addition, the treatment with CM from endothelial cells (EC-CM) markedly reduced the accumulation of lipid droplets and increased the expressions of the browning-related proteins and the mitochondrial contents. Moreover, the treatment with EC-CM significantly improved the energy metabolism in 3T3-L1 adipocytes. These results highlight that ASP-knockout can promote the browning and angiogenesis of WAT, and the fat browning and angiogenesis can interact in the mouse adipose microenvironment, which contributes to weight loss in the mice with obesity.

Global production of nursing research: A 10-year survey of subspecialty nursing journals.

AIM: This study aimed to investigate the characteristics of global productivity of nursing research in subspecialty nursing journals and to provide a general view of global nursing research. METHODS: On 10 January 2020, Web of Science was used for research collection. Publications in subspecialty nursing journals from 2015 to 2019 were analysed. RESULTS: A total of 34 275 publications were retrieved. The United States (15 155) ranked first, followed by Australia (2439), China (2076), Brazil (1803) and the United Kingdom (1602). High-income economies produced 82.26% of the total number of publications. Research production was not significantly correlated with the population (p = 0.113, r = 0.412), whereas it was positively correlated with gross domestic product (p = 0.030, r = 0.541). The United States had the highest number of total citations (46 297). The Netherlands ranked highest when analysing mean citations, followed by Finland and Australia. Sweden ranked highest after correcting for gross domestic product, followed by Australia and Finland. Australia was the most productive nation when adjusted by population, followed by Sweden and Norway. CONCLUSION: The United States is the leader in nursing research productivity. Countries with large economies tend to make greater contributions to global nursing research. Some European countries and Australia were found to be more prolific when stratified by population size and economic activity.

Glycine suppresses kidney calcium oxalate crystal depositions via regulating urinary excretions of oxalate and citrate.

An abnormal urine composition is a key reason for kidney stone formation, but little is known about the roles of small metabolites in the urine during kidney stone formation. Here, we found urine glycine in patients with kidney calcium oxalate (CaOx) stone was significantly lower than that in healthy people via 1 H NMR spectra detection, and investigated the role and underlying mechanism of glycine in the regulation of CaOx stone formation. Our results showed that glycine could significantly attenuate ethylene glycol-induced CaOx crystal depositions in rat kidney via decreasing urine oxalate and increasing urine citrate. Mechanism studies revealed that glycine could decrease urine oxalate through downregulating Slc26a6 expression, whereas increase urine citrate via inhibiting Nadc1 expression. Moreover, glycine decreased the protein expression of both Slc26a6 and Nadc1 via increasing the expression of miRNA-411-3p, which directly bound to the 3'-untranslated regions of Slc26a6 and Nadc1 messenger RNAs, in vitro and in vivo. Together, our results revealed a novel role of glycine in the regulation of kidney CaOx crystal formation and provided a potential target for the treatment of kidney CaOx stone.