Integrated bacterial transcriptome and host metabolome analysis reveals insights into "Candidatus Liberibacter asiaticus" population dynamics in the fruit pith of three citrus cultivars with different tolerance.

"Candidatus Liberibacter asiaticus" (CLas), the causal agent of citrus Huanglongbing (HLB), is able to multiply to a high abundance in citrus fruit pith. However, little is known about the biological processes and phytochemical substances that are vital for CLas colonization and growth in fruit pith. In this study, CLas-infected fruit pith of three citrus cultivars ("Shatangju" mandarin, "Guanxi" pomelo, and "Shatian" pomelo) exhibiting different tolerance to CLas were collected and used for dual RNA-Seq and untargeted metabolome analysis. Comparative transcriptome analysis found that the activation of the CLas noncyclic TCA pathway and pathogenic-related effectors could contribute to the colonization and growth of CLas in fruit pith. The pre-established Type 2 prophage in the CLas genome and the induction of its CRISPR/cas system could enhance the phage resistance of CLas and, in turn, facilitate CLas population growth in fruit pith. CLas infection caused the accumulation of amino acids that were correlated with tolerance to CLas. The accumulation of most sugars and organic acids in CLas-infected fruit pith, which could be due to the phloem blockage caused by CLas infection, was thought to be beneficial for CLas growth in localized phloem tissue. The higher levels of flavonoids and terpenoids in the fruit pith of CLas-tolerant cultivars, particularly those known for their antimicrobial properties, could hinder the growth of CLas. This study advances our understanding of CLas multiplication in fruit pith and offers novel insight into metabolites that could be responsible for tolerance to CLas or essential to CLas population growth.IMPORTANCECitrus Huanglongbing (HLB, also called citrus greening disease) is a highly destructive disease currently threatening citrus production worldwide. HLB is caused by an unculturable bacterial pathogen, "Candidatus Liberibacter asiaticus" (CLas). However, the mechanism of CLas colonization and growth in citrus hosts is poorly understood. In this study, we utilized the fruit pith tissue, which was able to maintain the CLas at a high abundance, as the materials for dual RNA-Seq and untargeted metabolome analysis, aiming to reveal the biological processes and phytochemical substances that are vital for CLas colonization and growth. We provided a genome-wide CLas transcriptome landscape in the fruit pith of three citrus cultivars with different tolerance and identified the important genes/pathways that contribute to CLas colonization and growth in the fruit pith. Metabolome profiling identified the key metabolites, which were mainly affected by CLas infection and influenced the population dynamic of CLas in fruit pith.

7.5F Mini Flexible Ureteroscope in Retrograde Intrarenal Surgery: Initial Results from a Multicenter Randomized Clinical Trial.

Objective: To report the initial results of an randomized clinical trail comparing the safety and efficacy between 7.5F and 9.2F flexible ureteroscope (FUS) in the management of renal calculi <2 cm. Materials and Methods: Eighty patients were enrolled and received retrograde intrarenal surgery (RIRS) with a different size FUS. The operation results and complications were compared. Results: Two cases in the 7.5F group and four cases in the 9.2F group failed to insert the 12/14F ureteral access sheath (UAS), respectively, and no significant difference (p = 0.396) was noted. However, 10/12F UAS was inserted in the 7.5F group, but not available in the 9.2F group, and thus, the 10/12F UAS inserting rate in the 7.5F group was higher than in the 9.2F group (100% vs 0%, p = 0.014), and the UAS insertion failure rate in 9.2F group was higher than in the 7.5F group (10% vs 0%, p = 0.040). The operation time in 7.5F group was shorter than the 9.2F group (35.60 ± 7.86 vs 41.05 ± 8.14, p = 0.003). Less irrigation was required in 7.5F group (813.93 ± 279.47 mL vs 1504.18 ± 385.31 mL, p = 0.000). The postoperative fever rate in 9.2F group was higher than 7.5F group (20% vs 5%, p = 0.043). There was no significant difference in sepsis (0% vs 2.5%, p = 0.314) between the two groups. No significant difference was noted in hospital stay (0.93 ± 0.49 days vs 1.14 ± 0.64 days, p = 0.099) between the two groups. The final stone-free rate (SFR) in 7.5F group was higher than 9.2F group (95% vs 80%, p = 0.043). Conclusion: The latest 7.5F mini FUS was a reliable instrument in RIRS to keep a good visualization with low requirement of irrigation, low postoperative infection complication, and also a high SFR when compared with the conventional 9.2F FUS. Clinical Trial Registration: NCT05231577.

Novel compound heterozygous pathogenic variants in the SLC3A1 gene in a Chinese family with cystinuria.

BACKGROUND: Cystinuria is an autosomal recessive disorder characterized by a cystine transport deficiency in the renal tubules due to mutations in two genes: SLC3A1 and SLC7A9. Cystinuria can be classified into three forms based on the genotype: type A, due to mutations in the SLC3A1 gene; type B, due to mutations in the SLC7A9 gene; and type AB, due to mutations in both genes. METHODS: We report a 12-year-old boy from central China with cystine stones. He was from a non-consanguineous family that had no known history of genetic disease. A physical examination showed normal development and neurological behaviors. Whole-exome and Sanger sequencing were used to identify and verify the suspected pathogenic variants. RESULTS: The compound heterozygous variants c.898_905del (p.Arg301AlafsTer6) is located in exon5 and c.1898_1899insAT (p.Asp634LeufsTer46) is located in exon10 of SLC3A1 (NM_000341.4) were deemed responsible for type A cystinuria family. The variant c.898_905del was reported in a Japanese patient in 2000, and the variant c.1898_1899insAT is novel. CONCLUSION: A novel pathogenic heterozygous variant pair of the SLC3A1 gene was identified in a Chinese boy with type A cystinuria, enriching the mutational spectrum of the SLC3A1 gene. We attempted to find a pattern for the association between the genotype of SLC3A1 variants and the manifestations of cystinuria in patients with different onset ages. Our findings have important implications for genetic counseling and the early clinical diagnosis of cystinuria.

Nanoscratch-induced formation of metallic micro/nanostructures with resin masks.

Metallic micro/nanostructures present a wide range of applications due to the small size and superior performances. In order to obtain high-performance devices, it is of great importance to develop new methods for preparing metallic micro/nanostructures with high quality, low cost, and precise position. It is found that metallic micro/nanostructures can be obtained by scratch-induced directional deposition of metals on silicon surface, where the mask plays a key role in the process. This study is focused on the preparation of keto-aldehyde resin masks and their effects on the formation of scratch-induced gold (Au) micro/nanostructures. It is also found that the keto-aldehyde resin with a certain thickness can act as a satisfactory mask for high-quality Au deposition, and the scratches produced under lower normal load and less scratching cycles are more conducive to the formation of compact Au structures. According to the proposed method, two-dimensional Au structures can be prepared on the designed scratching traces, providing a feasible path for fabricating high-quality metal-based sensors.

Association between sarcopenia and kidney stones in United States adult population between 2011 and 2018.

Purpose: To investigate the relationship between kidney stones and sarcopenia in United States adult population between 2011 and 2018. Materials and methods: We conducted a cross-section study based on the National Health and Nutrition Examination Survey (NHANES) including 39,156 individuals. Sarcopenia was assessed by the sarcopenia index. Association between kidney stones and sarcopenia verified by multiple logistic regression analysis and dose-response curves analysis using restricted cubic spline (RCS) regression. Meanwhile, propensity score matching (PSM) was performed to exclude the effect of confounding variables. Results: There were 9,472 participants in the study by our accurate enrollment screening process. The odds of kidney stones decreased significantly with the increase of sarcopenia index. Logistic regression analysis showed that sarcopenia expressed significant differences in the participants which suffered kidney stone before PSM (p < 0.001). In model 4, adjusting all relevant covariates shown that adjusted odds ratio (aOR) of the 95% confidence intervals for kidney stones in all participants, age <39 years and age ≥40 years, were, respectively, 1.286 (1.006-1,643), 1.697 (1.065-2.702), and 0.965 (0.700-1.330) for sarcopenia, and p values were 0.044, 0.026, and 0.827. After performing PSM, the aOR of the 95% in modal 4 for kidney stones in all participants and age <40 year were 2.365 (1.598-3.500) and 6.793 (2.619-17.6180), respectively (p < 0.01), and especially the aOR in participants (age ≥40) was 1.771(1.138-2.757) with p value being 0.011. Conclusion: Sarcopenia was positively related to the potential risk of kidney stones in the United States adult population.

Two-Dimensional Omnidirectional Wind Energy Harvester with a Cylindrical Piezoelectric Composite Cantilever.

To improve the response-ability of the energy harvester to multidirectional wind, this paper proposes a wind energy harvester to scavenge wind-induced vibration energy. The harvester comprises a cylindrical beam instead of conventional thin rectangular cantilevers, a bluff body (square prism or circle cylinder), and a piezoelectric tube bonded to the bottom side of the beam for energy conversion. Benefiting from the symmetry of the cylindrical structure, this harvester can respond to airflow from every direction of the two-dimensional plane. The performance of the harvester under a wind speed range of 1.5-8 m/s has been tested. The results demonstrate that the proposed harvester can respond to the wind from all directions of the two-dimensional plane. It provides a direction for the future in-depth study of multidirectional wind energy harvesting.

International Alliance of Urolithiasis Guideline on Shockwave Lithotripsy.

Different international associations have proposed their own guidelines on urolithiasis. However, the focus is primarily on an overview of the principles of urolithiasis management rather than step-by-step technical details for the procedure. The International Alliance of Urolithiasis (IAU) is releasing a series of guidelines on the management of urolithiasis. The current guideline on shockwave lithotripsy (SWL) is the third in the IAU guidelines series and provides a clinical framework for urologists and technicians performing SWL. A total of 49 recommendations are summarized and graded, covering the following aspects: indications and contraindications; preoperative patient evaluation; preoperative medication; prestenting; intraoperative analgesia or anesthesia; intraoperative position; stone localization and monitoring; machine and energy settings; intraoperative lithotripsy strategies; auxiliary therapy following SWL; evaluation of stone clearance; complications; and quality of life. The recommendations, tips, and tricks regarding SWL procedures summarized here provide important and necessary guidance for urologists along with technicians performing SWL. PATIENT SUMMARY: For kidney and urinary stones of less than 20 mm in size, shockwave lithotripsy (SWL) is an approach in which the stone is treated with shockwaves applied to the skin, without the need for surgery. Our recommendations on technical aspects of the procedure provide guidance for urologists and technicians performing SWL.

Ningmitai capsule promotes calculi expulsion after RIRS for 10-20-mm upper urinary stones: a multicenter, prospective, randomized controlled trial.

To evaluate the efficacy and safety of the use of Ningmitai capsule as an adjunctive stone expulsion therapy after RIRS. All patients were diagnosed with upper urinary tract calculi measuring 10-20 mm. The patients who successfully underwent RIRS were randomly assigned to the NMT capsule group (Ningmitai capsule, 1.52 g, three times daily) or the control group for 4 weeks based on the random number table method. The primary endpoints were the stone expulsion rate (SER) and stone-free rate (SFR). The average stone expulsion time (SET), average stone-free time (SFT) and complications were recorded. Between July 2, 2019, and December 17, 2020, 220 participants successfully underwent RIRS across 6 centers; 123 of them were randomized according to the exclusion criteria, and 102 (83%) were included in the primary analysis. The SERs on the 3rd, 7th, 14th and 28th days were significantly increased in the NMT capsule group compared with the control group (78.95% vs. 31.11%, 92.98% vs. 55.56%, 94.74% vs. 64.44%, 100% vs. 82.22%, respectively, p < 0.05). The SFRs on the 3rd and 7th days were not different (p > 0.05), while those on the 14th and 28th days were higher in the NMT capsule group (63.16% vs. 24.44% and 92.98% vs. 68.89%, p < 0.05). The average SET and average SFT of the NMT capsule group were remarkably shorter than those of the control group (p < 0.001). During the follow-up period, there were no significant differences in urine RBC counts between the two groups (p > 0.05). The urine WBC counts of the NMT capsule group were significantly lower than those of the control group on the 14th day (p = 0.011), but there was no difference on the 3rd, 7th or 28th day (p > 0.05). The analgesic aggregate of the NMT capsule group was also much lower (p = 0.037). There were no significant differences in adverse events (p > 0.05), and they improved significantly without sequelae. This study indicated that NMT capsules can significantly promote stone clearance and are more effective and safer for upper urinary calculi after RIRS.Trial registration Chinese Clinical Trial Registration No. ChiCTR1900024151.Date of registration June 28, 2019.

Identification of evodiamine as a suppressor of prostate cancer progression by reducing AR transcriptional activity via targeting Src.

Evodiamine (EVO) is a bioactive alkaloid that exerts antitumor activity in various cancers, including prostate cancer (PCa). In this paper, we further investigated the molecular mechanisms underlying the anti-PCa effect of evodiamine. In the present study, cell proliferation, colony formation, migration, and invasion were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, and transwell assays, respectively. Animal studies were used to evaluate the effect of evodiamine on the tumorigenicity of LNCaP cells in vivo. The expression levels of steroid receptor coactivator (Src), androgene receptor (AR), and prostate-specific antigen (PSA) were detected by western blot, quantitative real-time PCR (qRT-PCR) or ELISA assay. Association between Src and AR was examined by Co-Immunoprecipitation (CoIP). The impact of evodiamine on AR-mediated transcriptional activity was confirmed by dual-luciferase reporter assay. The results showed that evodiamine reduced LNCaP and 22Rv1 cell proliferation, colony formation, migration, and invasion induced by dihydrotestosterone (DHT) in vitro, as well as diminished tumor growth in vivo. Mechanistically, evodiamine directly targeted Src and reduced DHT-induced Src activation. Moreover, the restoration of Src activation abolished evodiamine-mediated suppression of proliferation, migration, and invasion of DHT-treated LNCaP and 22Rv1 cells. Furthermore, evodiamine inhibited DHT-induced AR transcriptional activity through targeting Src. As a conclusion, our findings demonstrate the antitumor property of evodiamine in PCa by blocking AR transcriptional activity through targeting Src and provide a rationale for developing evodiamine as a promising antitumor agent against PCa.

Effect of polyfluoroalkyl chemicals on the occurrence of urge urinary incontinence: a population-based study.

BACKGROUND: The artificial fluorinated group of compounds polyfluoroalkyl chemicals (PFCs) has been applied extensively in daily life for decades, and is present in food, drinking water, and indoor dust. The nephrotoxicity of PFCs has been widely studied for its characteristics of being mainly excreted through passing urine and affecting urodynamics. This work aimed to investigate the relationship between PFCs and the occurrence of urge urinary incontinence (UUI) in the United States (US) population. METHODS: There were 3157 eligible female participants retrieved from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2014. A logistic regression model was used to examine the relationship between UUI and eight kinds of PFCs. The dose-response relationship was investigated through restricted cubic spline analysis in this retrospective study. RESULTS: Of the 3157 eligible female participants, 913 self-reported a history of UUI. Total PFCs, perfluorohexane sulfonic acid (PFHS), 2-(N-methyl-perfluorooctane sulfonamido) acetate (MPAH), and perfluorononanoic acid (PFNA) correlated positively with the occurrence of UUI after adjusting for age, race, education, vigorous recreational activities, hypertension, diabetes, body mass index (BMI), creatinine, and estimated glomerular filtration rate (eGFR). Based on the results of sub-group analysis, the increasing tertiles contained odds ratios [OR; 95% confidence intervals (CI)] of 1.25 (95% CI, 1.03-1.51, p = 0.026) and 1.56 (95% CI, 1.29-1.89, p < 0.001) for total PFCs compared with the lowest tertile. The OR for PFHS, MPAH, and PFNA were 1.75, 1.71, and 1.41 respectively, in the highest tertile. CONCLUSION: This study investigated the relationship between PFCs and UUI in female and found total PFCs, PFHS, MPAH, and PFNA were positively correlated with the risk of UUI. The results will contribute to developing individualized treatment for female patients suffering UUI.

MicroRNA miR-145-5p inhibits Phospholipase D 5 (PLD5) to downregulate cell proliferation and metastasis to mitigate prostate cancer.

Prostate cancer (PCa), a frequently detected malignant tumor, is the fifth leading global cancer mortality cause in men. Although research has improved the PCa survival rate, significantly reduced survival occurs among patients at the metastatic stage. MiRNAs, which are short non-coding proteins, are crucial for several biological roles, essential for PCa proliferation, differentiation, multiplication, and migration. The investigation aimed to explore miR-145-5p and PLD5 association and clarify their function in regulating proliferation in PCa cell lines.The study used PC-3, LNCaP, DU-145 PCa, and RWPE-1 non-cancerous cell line, PCa, and BPH tissue specimens, and nude mice to validate results. MiR-145-5p and PLD5 manifestation were assessed through RT-qPCR. PLD5 and miR-145 binding was determined through dual-luciferase reporter gene assays. Validation of cell proliferation, migration, and invasion was assessed through MTT, scratch wound, and transwell assays, respectively.The results indicated a downregulation of miR-145-5p level in PCa cell lines and tissues in comparison to the non-cancerous controls. PLD5 overexpression exerted a cancerous effect while mimicking of miR-145-5p reversed the PLD5-oncogenic effects and significantly inhibited PCa cells proliferation, migration, invasion, and metastasis.In conclusion, the study revealed that miR-145-5p upregulated apoptosis and repressed migration, invasion, and metastasis of PCa via direct PLD5 modulation.

The status and characteristics of urinary stone composition in China.

OBJECTIVES: To explore characteristics of urinary stone composition in China, and determine the effects of gender, age, body mass index (BMI), stone location, and geographical region on stone composition. PATIENTS AND METHODS: We prospectively used Fourier-transform infrared spectroscopy to analyse stones from consecutive patients presenting with new-onset urolithiasis at 46 hospitals in seven geographical areas of China, between 1 June 2010 and 31 May 2015. Chi-squared tests and logistic regression analyses were used to determine associations between stone composition and gender, age, BMI, stone location, and geographical region. RESULTS: The most common stone constituents were: calcium oxalate (CaOx; 65.9%), carbapatite (15.6%), urate (12.4%), struvite (2.7%), and brushite (1.7%). CaOx and urate stones occurred more frequently in males, whereas carbapatite and struvite were more common in females (P < 0.01). CaOx and carbapatite were more common in those aged 30-50 and 20-40 years than in other groups. Brushite and struvite were most common amongst those aged <20 and >70 years. The detection rate of urate increased with age, whilst cystine decreased with age. Obese patients were more likely to have urate stones than carbapatite or brushite stones (P < 0.01). CaOx, carbapatite, brushite, and cystine stones were more frequently found in the kidney than other types, whereas urate and struvite were more frequent in the bladder (P < 0.01). Stone composition varied by geographical region. CONCLUSIONS: The most common stone composition was CaOx, followed by carbapatite, urate, struvite, and brushite. Stone composition differed significantly in patients grouped by gender, age, BMI, stone location, and geographical region.

When is the best time to perform external physical vibration lithecbole (EPVL) after retrograde intrarenal surgery (RIRS): a multi-center study based on randomized controlled trials.

To determine the best time to perform EPVL treatment by evaluating the efficacy and safety of active stone extraction in treating residual fragments at different time points after RIRS. All participants had renal or upper ureteral stones preoperatively and still had residual stones after receiving RIRS. They were prospectively randomized into four groups: patients in group A received EPVL 3 days after RIRS; patients in group B received EPVL 7 days after RIRS; patients in group C received EPVL 14 days after RIRS; patients in group D did not receive EPVL after RIRS. Follow-up examinations were performed on all participants. The results, including stone size and location, stone-free rate (SFR) and complications, were compared among the groups. There were 176 patients in total. The SFR in groups A, B, C and D were 62.22%, 40.91%, 14.28% and 11.11%, respectively, 7 days after RIRS. At 14 days after RIRS, the SFR was 80%, 59.09%, 42.86% and 26.67% in groups A, B, C and D, respectively. At 28 days after RIRS, the SFR was 91.11%, 84.09%, 76.19% and 51.11% in groups A, B, C and D, respectively. Group A had the highest SFR from 7 to 28 days, and group C had a higher SFR at 28 days after RIRS than group D (P < 0.05). The side effects were less in groups A and B than in group D 28 days after RIRS (P < 0.05). We recommended that the best time to perform EPVL is 3 days after RIRS, because it could achieve a high SFR at any point in time and reduced complications.

Weighted gene co­expression network analysis for identifying hub genes in association with prognosis in Wilms tumor.

Wilms tumor (WT) is the most common type of renal malignancy in children. Survival rates are low and high­risk WT generally still carries a poor prognosis. To better elucidate the pathogenesis and tumorigenic pathways of high­risk WT, the present study presents an integrated analysis of RNA expression profiles of high­risk WT to identify predictive molecular biomarkers, for the improvement of therapeutic decision­making. mRNA sequence data from high­risk WT and adjacent normal samples were downloaded from The Cancer Genome Atlas to screen for differentially expressed genes (DEGs) using R software. From 132 Wilms tumor samples and six normal samples, 2,089 downregulated and 941 upregulated DEGs were identified. In order to identify hub DEGs that regulate target genes, weighted gene co­expression network analysis (WGCNA) was used to identify 11 free­scale gene co­expressed clusters. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were annotated using KEGG Orthology Based Annotation System annotation of different module genes. The Search Tool for the Retrieval of Interacting Genes was used to construct a protein­protein interaction network for the identified DEGs, and the hub genes of WGCNA modules were identified using the Cytohubb plugin with Cytoscape software. Survival analysis was subsequently performed to highlight hub genes with a clinical signature. The present results suggest that epidermal growth factor, cyclin dependent kinase 1, endothelin receptor type A, nerve growth factor receptor, opa­interacting protein 5, NDC80 kinetochore complex component and cell division cycle associated 8 are essential to high­risk WT pathogenesis, and they are closely associated with clinical prognosis.

Super-mini percutaneous nephrolithotomy (SMP) vs retrograde intrarenal surgery for the treatment of 1-2 cm lower-pole renal calculi: an international multicentre randomised controlled trial.

OBJECTIVES: To compare the safety and effectiveness of super-mini-percutaneous nephrolithotomy (SMP) and retrograde intrarenal surgery (RIRS) for the treatment of 1-2 cm lower-pole renal calculi (LPC). PATIENTS AND METHODS: An international multicentre, prospective, randomised, unblinded controlled study was conducted at 10 academic medical centres in China, India, and Turkey, between August 2015 and June 2017. In all, 160 consecutive patients with 1-2 cm LPC were randomised to receive SMP or RIRS. The primary endpoint was stone-free rate (SFR). Stone-free status was defined as no residual fragments of ≥0.3 cm on plain abdominal radiograph of the kidneys, ureters and bladder, and ultrasonography at 1-day and on computed tomography at 3-months after operation. Secondary endpoints included blood loss, operating time, postoperative pain scores, auxiliary procedures, complications, and hospital stay. Postoperative follow-up was scheduled at 3 months. Analysis was by intention-to-treat. The trial was registered at http://clinicaltrials.gov/ (NCT02519634). RESULTS: The two groups had similar baseline characteristics. The mean (sd) stone diameters were comparable between the groups, at 1.50 (0.29) cm for the SMP group vs 1.43 (0.34) cm for the RIRS group (P = 0.214). SMP achieved a significantly better 1-day and 3-month SFR than RIRS (1-day SFR 91.2% vs 71.2%, P = 0.001; 3-months SFR 93.8% vs 82.5%, P = 0.028). The auxiliary procedure rate was lower in the SMP group. RIRS was found to be superior with lower haemoglobin drop and less postoperative pain. Blood transfusion was not required in either group. There was no significant difference in operating time, hospital stay, and complication rates, between the groups. CONCLUSIONS: SMP was more effective than RIRS for treating 1-2 cm LPC in terms of a better SFR and lesser auxiliary procedure rate. The complications and hospital stay were comparable. RIRS has the advantage of less postoperative pain.

How to accelerate the upper urinary stone discharge after extracorporeal shockwave lithotripsy (ESWL) for < 15 mm upper urinary stones: a prospective multi-center randomized controlled trial about external physical vibration lithecbole (EPVL).

OBJECTIVE: To asset the efficacy and safety of EPVL plus ESWL compared with ESWL alone for the treatment of simple upper urinary stones (< 15 mm). MATERIALS AND METHODS: All patients with upper urinary stones (< 15 mm) were prospectively randomized into two groups. In treatment group, patients were assigned to immediate EPVL after ESWL, while in control group, ESWL alone was offered. All patients were reexamined at 1, 2, and 4 weeks after ESWL. Stone size, stone location, stone-free rate (SFR), and complication rate were compared. RESULTS: 56 males and 20 females in treatment group were compared to 52 male and 25 females in control group (p = 0.404). Median ages were 42.9 ± 1.5 years in treatment group and 42.7 ± 1.3 years in control group (p = 0.943). Median stone size was 10.0 ± 0.4 mm (3-15 mm) in treatment group and 10.4 ± 0.4 mm (4-15 mm) in control group (p = 0.622). The stone clearance rate in treatment and control group at 1 week after ESWL was 51.3% (39/76) and 45.4% (35/77) (p > 0.05), at 2 weeks was 81.6% (62/76) and 64.9% (50/77) (p < 0.05), and at 4 weeks was 90.8% (69/76) and 75.3% (58/77) (p < 0.05), respectively. CONCLUSIONS: EPVL is a noninvasive, effective, and safe adjunctive treatment which increases and accelerates upper urinary stones discharge after ESWL treatment.

Efficacy and Safety of Tamsulosin in Medical Expulsive Therapy for Distal Ureteral Stones with Renal Colic: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial.

BACKGROUND: Recent large high-quality trials have questioned the clinical effectiveness of medical expulsive therapy using tamsulosin for ureteral stones. OBJECTIVE: To evaluate the efficacy and safety of tamsulosin for distal ureteral stones compared with placebo. DESIGN, SETTING, AND PARTICIPANTS: We conducted a double-blind, placebo-controlled study of 3296 patients with distal ureteral stones, across 30 centers, to evaluate the efficacy and safety of tamsulosin. INTERVENTION: Participants were randomly assigned (1:1) into tamsulosin (0.4mg) or placebo groups for 4 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point of analysis was the overall stone expulsion rate, defined as stone expulsion, confirmed by negative findings on computed tomography, over a 28-d surveillance period. Secondary end points included time to stone expulsion, use of analgesics, and incidence of adverse events. RESULTS AND LIMITATIONS: Among 3450 patients randomized between September 1, 2011, and August 31, 2013, 3296 (96%) were included in the primary analysis. Tamsulosin benefits from a higher stone expulsion rate than the placebo (86% vs 79%; p<0.001) for distal ureteral stones. Subgroup analysis identified a specific benefit of tamsulosin for the treatment of large distal ureteral stones (>5mm). Considering the secondary end points, tamsulosin-treated patients reported a shorter time to expulsion (p<0.001), required lower use of analgesics compared with placebo (p<0.001), and significantly relieved renal colic (p<0.001). No differences in the incidence of adverse events were identified between the two groups. CONCLUSIONS: Our data suggest that tamsulosin use benefits distal ureteral stones in facilitating stone passage and relieving renal colic. Subgroup analyses find that tamsulosin provides a superior expulsion rate for stones >5mm, but no effect for stones ≤5mm. PATIENT SUMMARY: In this report, we looked at the efficacy and safety of tamsulosin for the treatment of distal ureteral stones. We find that tamsulosin significantly facilitates the passage of distal ureteral stones and relieves renal colic.

The impact of metformin use on survival in prostate cancer: a systematic review and meta-analysis.

BACKGROUND: Metformin has been implicated to reduce the risk of prostate cancer (PCa) beyond its glucose-lowering effect. However, the influence of metformin on prognosis of PCa is often controversial. RESULTS: A total of 13 cohort studies encompassing 177,490 individuals were included in the meta-analysis. Data on overall survival (OS) and cancer-specific survival (CSS) was extracted from 8 and six studies, respectively. Comparing metformin users with non-metformin users, the pooled hazard ratios (HRs) for OS and CSS were 0.79 (95% confidence interval [CI] 0.63-0.98) and 0.76 (95% CI 0.57-1.02), respectively. Subgroup analyses stratified by baseline charcteristics indicated significant CSS benefits were noted in studies conducted in USA/Canada with prospective, large sample size, multiple-centered study design. Five studies reported the PCa prognosis for recurrence-free survival (RFS) and metformin use was significantly associated with patient RFS (HR 0.74, 95% CI, 0.58-0.95). METHODS: Relevant studies were searched and identified using PubMed, Embase and Cochrane databases from inception through January 2017, which investigated associations between the use of metformin and PCa prognosis. Combined HRs with 95% CI were pooled using a random-effects model. The primary outcomes of interest were OS and CSS. CONCLUSIONS: Our findings provide indication that metformin therapy has a trend to improve survival for patients with PCa. Further prospective, multi-centered, large sample size cohort studies are warranted to determine the true relationship.

An integrated analysis for long noncoding RNAs and microRNAs with the mediated competing endogenous RNA network in papillary renal cell carcinoma.

Papillary renal cell carcinoma (PRCC) is the second most common subtype of renal cell carcinoma, and it lacks effective therapeutic targets and prognostic molecular biomarkers. Attention has been increasingly focused on long noncoding RNAs (lncRNAs), which can act as competing endogenous RNA (ceRNA) to compete for shared microRNAs (miRNAs) in the tumorigenesis of human tumors. Therefore, to clarify the functional roles of lncRNAs with respect to the mediated ceRNA network in PRCC, we comprehensively integrated expression profiles, including data on mRNAs, lncRNAs and miRNAs obtained from 289 PRCC tissues and 32 normal tissues in The Cancer Genome Atlas. As a result, we identified 2,197 differentially expressed mRNAs (DEmRNAs) and 84 differentially expressed miRNAs (DEmiRNAs) using a threshold of |log2 (fold change)| >2.0 and an adjusted P-value <0.05. To determine the hub DEmRNAs that could be key target genes, a weighted gene co-expression network analysis was performed. A total of 28 hub DEmRNAs were identified as potential target genes. Seven dysregulated DEmiRNAs were identified that were significantly associated with the 28 hub potential target genes. In addition, we found that 16 differentially expressed lncRNAs were able to interact with the DEmiRNAs. Finally, we used Cytoscape software to visualize the ceRNA network with these differently expressed molecules. From these results, we believe that the identified ceRNA network plays a crucial role in the process of PRCC deterioration, and some of the identified genes are strongly related to clinical prognosis.

Disposable circumcision suture devices versus Shang ring circumcision for management of redundant prepuce or phimosis: a systematic review and meta-analysis / Dispositivos de sutura de circuncisón desechables y circuncisión del anillo Shang para el manejo del prepucio redundante o fimosis: una revisión sistemática y metaanálisis

Objective. To evaluate the clinic efficacy and safety of the disposable circumcision suture device (DCSD) and Shang ring circumcision (SRC) in the treatment of redundant prepuce or phimosis with a meta-analysis. Material and methods. Electronic databases including PubMed, Embase, Wan Fang, VIP, CNKI and CBM database were researched from inception to August 30, 2016 for relevant RCTs and prospective studies, the reference lists of the included studies were also searched manually. The risk ratios (RR) or mean difference (MD) with 95% confidence intervals (CI) as the effect sizes were calculated by the Revman 5.3 and stata 12.0 software. Results. Twelve RCTs or prospective studies were included with 3345 patients among which 1661 cases received DCSD treatment and 1684 SRC. Compared to the Shang ring circumcision treatment, the disposable circumcision suture device provided a significantly shorter operation time [MD=−0.94, 95%CI (-1.76, -0.12), P=0.02], lower pain scores [MD=-1.89, 95%CI (-2.72, -1.07), P<0.001], no stitch removal pain, better postoperative penile appearance [RR=1.10, 95%CI (1.04, 1.17), P=0.001], fewer complications [RR=0.42, 95%CI (0.32, 0.56), P<0.001] and shorter wound healing time [MD=-8.92, 95%CI (-10.79, -7.05), P<0.001]. Meanwhile, there is more intraoperative blood loss [MD=0.12, 95%CI (0.02, 0.22), P=0.02], and more treatment cost [MD=877.57, 95%CI (737.94, 1017.20); P<0.001]. Conclusions. Based on the results of our meta-analysis, DCSD is more effective and safer than SRC. Thus, it has the advantages of shorter operation time, lower pain scores, better postoperative penile appearance, fewer complication and shorter wound healing time. However, the results need additional high-quality multicenter RCTs to evaluate in the future (AU)

Objetivo. Evaluar la eficacia clínica y la seguridad en el tratamiento del prepucio redundante o fimosis con los dispositivos de sutura de circuncisión desechable (DCSD) y la circuncisión del anillo Shang (SRC). Material y métodos. Se investigaron las bases de datos en línea, como PubMed, Embase, Wan Fang, VIP, CNKI y CBM desde el inicio hasta el 30 de agosto de 2016 para ensayos controlados aleatorios y estudios prospectivos relevantes, así como las listas de referencias de los estudios incluidos. Las relaciones de riesgo (RR) o la diferencia de medias (MD) con intervalos de confianza (IC) del 95% (IC 95%) así como los tamaños del efecto se calcularon con el software Revman 5.3 y stata 12.0. Resultados. Se incluyeron 12 ECA o estudios prospectivos con 3.345 pacientes, de los cuales 1.661 fueron tratados con el DCSD y 1.684 con SRC. En comparación con el tratamiento con SRC, el DCSD proporcionó un tiempo de operación más corto (MD=-0,94; IC 95% [-1,76, -0,12], p=0,02), sin dolor al extraer las puntadas (MD=−1.89; IC 95% [-2,72, -1,07], p<0,001), y mejor recuperación después de la cirugía (RR=1,10; IC 95% [1,04; 1,17], p=0,001), menos complicaciones (RR=0,42; IC 95% [0,32; 0,56], p<0,001)] y menor tiempo de cicatrización (MD=-8,92; IC 95% (-10,79, -7,05), p<0,001]. Mientras tanto, hay más pérdidas sanguíneas intraoperatorias (MD=0,12; IC 95% [0,02; 0,22]; p=0,02) y más costo de tratamiento (MD=877,57, IC 95% [737,94; 1.017.20]; p<0,001). Conclusión. El DCSD es más eficaz y más seguro que SRC según el resultado del metaanálisis. Por lo tanto, tiene las ventajas de un menor tiempo de operación, menores puntuaciones de dolor, mejor aspecto postoperatorio del pene, menor complicación y menor tiempo de cicatrización de la herida. Se necesitan ECA multicéntricos adicionales de mejor calidad en la evaluación debido a los límites de esta revisión sistemática (AU)