Prevalence of urolithiasis in China: a systematic review and meta-analysis.

OBJECTIVE: To estimate the pooled prevalence, as well as the spatial and temporal distribution, of urolithiasis among subjects in China. MATERIALS AND METHODS: We conducted a comprehensive search of both Chinese and English databases to retrieve literature pertaining to the prevalence of urolithiasis in the indigenous Chinese population. A random-effects meta-analysis model was employed to calculate the pooled prevalence of urolithiasis. Subgroup analyses were conducted based on factors such as time, region, gender, and sample size. Prevalence and spatial distribution maps were created based on provinces and latitude/longitude coordinates. RESULTS: A total of 46 studies conducted in 22 provinces across China were included in this meta-analysis and the pooled prevalence of urolithiasis, kidney stones, ureteric calculi, urethral and bladder stones were 8.1% (95% confidence interval [CI] 5.6-11.1%), 7.8% (95% CI 5.8-10.0%), 3.2% (95% CI 0.6-5.7%), 0.5% (95% CI 0.1-0.9%). Most of the urolithiasis prevalence screening in China was concentrated between 100° E and 120° E, with higher rates observed in low latitude areas. Subgroup analysis of kidney stones revealed that Guangdong (12.7%) and Guangxi (10.3%) had the highest prevalence, with the eastern developed area exhibiting higher rates compared to the west. The prevalence in males was higher than in females (odds ratio 1.67, 95% CI 1.46-1.92), although the gender gap has significantly reduced since 2006. Moreover, a greater sample size is associated with a decreased prevalence of urolithiasis. CONCLUSIONS: The prevalence of urolithiasis is increasing in China, and there are noteworthy regional or provincial disparities in occurrence. It is worth noting that the current number of screening studies in some areas is insufficient. Additional investigations with appropriate sample sizes should be supplemented in time.

PGE2 binding to EP2 promotes ureteral stone expulsion by relaxing ureter via the cAMP-PKA pathway.

BACKGROUND: This study investigated the relaxation effect of PGE2 on the ureter and its role in promoting calculi expulsion following calculi development. METHODS: By using immunofluorescence and Western blot, we were able to locate EP receptors in the ureter. In vitro experiments assessed the impact of PGE2, receptor antagonists, and agonists on ureteral relaxation rate. We constructed a model of ureteral calculi with flowable resin and collected ureteral tissue from postoperative side of the ureter after obstruction surgery. Western blot analysis was used to determine the protein expression levels of EP receptors and the PGE2 terminal synthase mPGES-1. Additionally, PGE2 was added to smooth muscle cells to observe downstream cAMP and PKA changes. RESULTS: The expression of EP2 and EP4 proteins in ureteral smooth muscle was verified by Western blot analysis. According to immunofluorescence, EP2 was primarily found on the cell membrane, while EP4 was found in the nucleus. In vitro, PGE2 induced concentration-dependent ureteral relaxation. Maximum diastolic rate was 70.94 ± 4.57% at a concentration of 30µM. EP2 antagonists hindered this effect, while EP4 antagonists did not. Obstructed ureters exhibited elevated mPGES-1 and EP2 protein expression (P < 0.01). Smooth muscle cells treated with PGE2 displayed increased cAMP and phosphorylated PKA. CONCLUSIONS: PGE2 binding to EP2 induces ureteral relaxation through the cAMP-PKA pathway. This will provide a new theoretical basis for the development of new therapeutic approaches for the use of PGE2 in the treatment of ureteral stones.

CancerMIRNome: an interactive analysis and visualization database for miRNome profiles of human cancer.

MicroRNAs (miRNAs), which play critical roles in gene regulatory networks, have emerged as promising diagnostic and prognostic biomarkers for human cancer. In particular, circulating miRNAs that are secreted into circulation exist in remarkably stable forms, and have enormous potential to be leveraged as non-invasive biomarkers for early cancer detection. Novel and user-friendly tools are desperately needed to facilitate data mining of the vast amount of miRNA expression data from The Cancer Genome Atlas (TCGA) and large-scale circulating miRNA profiling studies. To fill this void, we developed CancerMIRNome, a comprehensive database for the interactive analysis and visualization of miRNA expression profiles based on 10 554 samples from 33 TCGA projects and 28 633 samples from 40 public circulating miRNome datasets. A series of cutting-edge bioinformatics tools and machine learning algorithms have been packaged in CancerMIRNome, allowing for the pan-cancer analysis of a miRNA of interest across multiple cancer types and the comprehensive analysis of miRNome profiles to identify dysregulated miRNAs and develop diagnostic or prognostic signatures. The data analysis and visualization modules will greatly facilitate the exploit of the valuable resources and promote translational application of miRNA biomarkers in cancer. The CancerMIRNome database is publicly available at http://bioinfo.jialab-ucr.org/CancerMIRNome.

Exposure to heavy metal elements may significantly increase serum prostate-specific antigen levels with overdosed dietary zinc.

BACKGROUND: Serum prostate-specific antigen (PSA) is a primary metric for diagnosis and prognosis of prostate cancer (PCa). Exposure to heavy metals, such as lead, cadmium, mercury, and zinc can impact PSA levels in PCa patients. However, it is unclear whether this effect also occurs in men without PCa, which may lead to the overdiagnosis of PCa. METHOD: Data on a total of 5089 American men who had never been diagnosed with PCa were obtained from the National Health and Nutrition Examination Survey performed from 2003-2010. The relationship between serum PSA levels (dependent variable) and concentrations of lead (µmol/L), cadmium (nmol/L), and mercury (µmol/L) were investigated with dietary zinc intake being used as a potential modifier or covariate in a weighted linear regression model and a generalized additive model. A series of bootstrapping analyses were performed to evaluate sensitivity and specificity using these models. RESULTS: Regression analyses suggested that, in general, lead, cadmium, or mercury did not show an association with PSA levels, which was consistent with the results of the bootstrapping analyses. However, in a subgroup of participants with a high level of dietary zinc intake (≥14.12 mg/day), a significant positive association between cadmium and serum PSA was identified (1.06, 95% CI, P = 0.0268, P for interaction=0.0249). CONCLUSIONS: With high-level zinc intake, serum PSA levels may rise in PCa-free men as the exposure to cadmium increases, leading to a potential risk of an overdiagnosis of PCa and unnecessary treatment. Therefore, environmental variables should be factored in the current diagnostic model for PCa that is solely based on PSA measurements. Different criteria for PSA screening are necessary based on geographical variables. Further investigations are needed to uncover the biological and biochemical relationship between zinc, cadmium, and serum PSA levels to more precisely diagnose PCa.

Construction of a novel rabbit model of ureteral calculi implanted with flowable resin.

BACKGROUND: The purpose of this study was to characterize the pathophysiological changes of hydronephrosis caused by ureteral calculi obstruction in a new rabbit ureteral calculi model by implanting flowable resin. METHODS: Forty New Zealand rabbits were randomly divided into two groups: the calculi group and the sham control group. In the calculi group (n = 20), rabbits were operated at left lower abdomen and the left ureter was exposed. Then flowable resin (flowable restorative dental materials) was injected into the left ureter using a 0.45 mm diameter intravenous infusion needle. Then light-cured for 40 s by means of a dental curing light to form calculi. In the sham control group, normal saline was injected into the ureter. Rabbits underwent X-ray and routine blood and urine tests preoperatively, as well as X-ray, CT, dissection, HE staining and routine blood and urine tests on 1, 3, 5 and 7 days postoperatively. Stone formation was assessed by X-ray and unenhanced CT scan after surgery. The pathophysiological changes were evaluated through dissection, HE staining and routine blood and urine tests. RESULTS: Ureteral calculi models were successfully constructed in 17 rabbits. In calculi group, high-density shadows were observed in the left lower abdomen on postoperative day 1st, 3rd, 5th and 7th by X-ray and CT scan. Dissection found obstruction formation of the left ureters, dilatation of the renal pelvis and upper ureter during 7 days after surgery. The renal long-diameters of the left ureters increased only on the 1st postoperative day. HE staining found ureteral and kidney damage after surgery. In calculi group and sham group,the serum creatinine, urea nitrogen, white blood cells and urine red blood cells were raised at day 1 after surgery. However, the indicators returned to normal at day 3, 5, and 7. CONCLUSIONS: This is a stable, less complicated operation and cost-effective ureteral calculi model by implanting flowable resin. And this novel model may allow us to further understand the pathophysiology changes caused by ureteral calculi obstruction.

Molecular detection of Bartonella in ixodid ticks collected from yaks and plateau pikas (Ochotona curzoniae) in Shiqu County, China.

BACKGROUND: Bartonella bacteria have been associated with an increasingly wide range of human and animal diseases. These emerging pathogens have been identified as being globally dispersed. Ticks and small rodents are known hosts of Bartonella and play a significant role in the preservation and circulation of Bartonella in nature. This study investigated the occurrence of hoist spp. in ticks (Acari: Ixodidae) and plateau pikas (Ochotona curzoniae) in Shiqu County, which is located on the eastern Qinghai-Tibetan Plateau in China. Shiqu County is spread over approximately 26,000 km2, with an average altitude of above 4200 m and a vast area of pastureland. RESULTS: A total of 818 ticks (Dermacentor everestianus, 79.0%, 646/818; Haemaphysalis qinghaiensis, 21.0%, 172/818) were collected from yaks in 4 villages of Shiqu County. Only Bartonella melophagi was detected in tick samples, with a total prevalence of 30.1% (246/818). The infection rates of B. melophagi in ticks from Arizha, Maga, Derongma, and Changxgma were 4.8, 76.8, 12.5, and 18.0%, respectively. The infection rate of B. melophagi in Maga was higher (p < 0.01) than those in other villages. Regarding plateau pikas, the total infection rate of Bartonella spp. was 21.7% (62/286), with 16.7% (12/72), 30.9% (25/81), 13.8% (9/65), and 23.5% (16/68) in Arizha, Maga, Derongma, and Changxgma, respectively. Finally, B. queenslandensis and B. grahamii were detected in plateau pika. No significant difference was observed (p > 0.05) in the infection rates between these study sites. CONCLUSION: To date, only D. everestianus and H. qinghaiensis were found in Shiqu County with high infection of Bartonella spp. in the ticks and plateau pika. The threats of Bartonella species to public health should be closely monitored.

Is there a non-linear relationship between dietary protein intake and prostate-specific antigen: proof from the national health and nutrition examination survey (2003-2010).

BACKGROUND: Growing evidence demonstrated that dietary protein intake may be a risk factor for prostate cancer and elevate the level of prostate-specific antigen (PSA). However, proof for the correlation between dietary protein intake and PSA in American adults without prostate tumor history is limited. Our goal was to investigate the association of dietary protein intake with PSA using the National Health and Nutrition Examination Survey (NHANES) (2003-2010) database. METHODS: After the screening, 6403 participants were included in the study. The interested independent is the dietary protein intake, and the dependent variable is PSA levels, the covariates included demographic, dietary, biological data, and physical examination variables. A weighted linear model and a weighted linear regression model were used to examine the distribution of variables in the covariate differences between the different independent groups according to quartiles. Four models were used to survey the association between dietary protein intake and PSA. We also attempted to find a nonlinear relationship between dietary protein intake and PSA using the GAM model and the penalty spline method and further solved the nonlinear problem using weighted two-piecewise linear model. RESULTS: The weighted multivariate linear regression analysis demonstrated that dietary protein intake was not independently associated with PSA levels after adjusting potential confounders (ß = 0.015, 95%CI:-0.024, 0.055). However, we found the non-linear relationship between dietary protein intake and PSA, whose point was 18.18 g (per 10 g change). The magnitude and confidence intervals for the left and right inflection points are - 0.03 (- 0.09, 0.02) and 0.22 (0.07, 0.36), respectively. On the right side of the inflection point, one gram of increment in protein intake was associated with increased PSA levels by 0.22 (log2 transformation: 0.22, 95%CI: 0.07, 0.36). CONCLUSIONS: After adjusting for potential covariates, the non-linear correlation between dietary protein intake and PSA was observed. When dietary protein intake exceeded the threshold of 181.8 g, dietary protein intake was positively correlated with elevated PSA levels.

Detection of Theileria spp. in ticks, sheep keds (Melophagus ovinus), and livestock in the eastern Tibetan Plateau, China.

Theileria species, with a broad geographic distribution, infect a wide range of both domestic and wild animals and are transmitted by ixodid ticks. Currently, there is no comprehensive report regarding the distribution of Theileria spp. in the eastern Tibetan Plateau, especially in Ganze Tibetan autonomous prefecture (153,700 km2) and Ngawa Tibetan and Qiang autonomous prefecture (84,242 km2) of Sichuan province, China. In this study, we collected blood samples from yaks (n = 144) (Bos grunniens), Tibetan sheep (n = 92), and Tibet horses (n = 142) in Ganze and Ngawa.Theileria sinensis, T. luwenshuni, and T. equi were the dominant Theileria species detected in yaks, Tibetan sheep, and horses with the total infection rates of 25.7% (37/144), 75.0% (69/92), and 51.4% (73/142), respectively. For ectoparasites, T. luwenshuni was the only Theileria species detected in sheep keds (Melophagus ovinus) with an infection rate of 30.8% (8/26). The total infection rates of T. sinensis in Haemaphysalis qinghaiensis, Dermacentor everestianus, and Rhipicephalus microplus were 34.6% (36/104), 34.0% (17/50), and 51.3% (58/113), respectively. Theileria spp., belonging to T. sergenti/buffeli/orientalis group, were only detected in R. microplus collected in Danba county of Ganze with a total infection rate of 39.9% (19/48). Our results provide important data of the epidemiology of Theileria spp. in livestock and ectoparasites and will assist with the implementation of measures to control theileriosis transmission in eastern Tibetan Plateau, China.

Dietary phosphorus intake and serum prostate-specific antigen in non-prostate cancer American adults: A secondary analysis of the National Health and Nutrition Examination Survey (NHANES), 2003-2010.

BACKGROUND AND OBJECTIVES: Previous study has reported phosphorus intake is associated prostate cancer (PCa), but the association between phosphorus intake and serum prostate specific antigen (PSA) levels hasn't been reported in non-history of PCa population. Therefore, we performed a secondary data analysis based on existing data from the public Nutrition Examination Survey (NHANES) (2003-2010) database. METHODS AND STUDY DESIGN: Totally 6403 participants were selected from NHANES (2003-2010) database. The interested independent and dependent variables were considered as dietary phosphorus intake and PSA level, respectively. Covariates included demographic data, dietary data, physical examination data, and comorbidities. Weighted linear regression and generalized additive models were used to addressing the linear and non-linear link of phosphorus intake to PSA level. RESULTS: Linear association between phosphorus intake and PSA was not detected [ß=0.016 (95% Confidence Interval (CI) -0.012, 0.045)]. But we found an existing nonlinearity. By the recursive algorithm, the inflection point was 1151 mg. On the left side of the inflection point, we did not find the correlation between dietary phosphorus intake (per 100 change) and PSA level [ß=-0.04 (95% CI -0.11, 0.02), p=0.2155], while dietary phosphorus intake (per 100 change) positively associated with PSA [ß=0.05 (95% CI 0.01, 0.09) p=0.0293] on the right side of inflection point. CONCLUSIONS: There is a non-linear correlation between dietary phosphorus intake and PSA. Dietary phosphorus intake was positively associated with increased PSA when dietary phosphorus intake is beyond 1151 mg after adjusting other covariates. Over 1151 mg per day dietary phosphorus intake may be the risk factor for PSA increasing.

Systematic analysis of alternative splicing signature unveils prognostic predictor for kidney renal clear cell carcinoma.

There is growing evidence that alternative splicing (AS) plays an important role in cancer development. However, a comprehensive analysis of AS signatures in kidney renal clear cell carcinoma (KIRC) is lacking and urgently needed. It remains unclear whether AS acts as diagnostic biomarkers in predicting the prognosis of KIRC patients. In the work, gene expression and clinical data of KIRC were obtained from The Cancer Genome Atlas (TCGA), and profiles of AS events were downloaded from the SpliceSeq database. The RNA sequence/AS data and clinical information were integrated, and we conducted the Cox regression analysis to screen survival-related AS events and messenger RNAs (mRNAs). Correlation between prognostic AS events and gene expression were analyzed using the Pearson correlation coefficient. Protein-protein interaction analysis was conducted for the prognostic AS-related genes, and a potential regulatory network was built using Cytoscape (version 3.6.1). Meanwhile, functional enrichment analysis was conducted. A prognostic risk score model is then established based on seven hub genes (KRT222, LENG8, APOB, SLC3A1, SCD5, AQP1, and ADRA1A) that have high performance in the risk classification of KIRC patients. A total 46,415 AS events including 10,601 genes in 537 patients with KIRC were identified. In univariate Cox regression analysis, 13,362 survival associated AS events and 8,694 survival-specific mRNAs were detected. Common 3,105 genes were screen by overlapping 13,362 survival associated AS events and 8,694 survival-specific mRNAs. The Pearson correlation analysis suggested that 13 genes were significantly correlated with AS events (Pearson correlation coefficient >0.8 or <-0.8). Then, We conducted multivariate Cox regression analyses to select the potential prognostic AS genes. Seven genes were identified to be significantly related to OS. A prognostic model based on seven genes was constructed. The area under the ROC curve was 0.767. In the current study, a robust prognostic prediction model was constructed for KIRC patients, and the findings revealed that the AS events could act as potential prognostic biomarkers for KIRC.

The efficacy and safety of retroperitoneoscopic renal pedicle ligation of lymphatic disconnection versus open surgery in the treatment of chyluria: A systematic review and meta-analysis
.

OBJECTIVE: The current meta-analysis was performed to evaluate the safety and efficacy of retroperitoneoscopic renal pedicle ligation of lymphatic disconnection (RRPLD) compared with open surgery (OS) in the treatment of chyluria. MATERIALS AND METHODS: Relevant studies were retrieved from MEDLINE, EMBASE, -SCOPUS, the Cochrane library and two Chinese literature database resources (Wanfang and CNKI) in March 2016. All eligible studies comparing RRPLD with OS for chyluria were included in this study. The main outcome including operative time, blood loss, postoperative (PO) intestinal recovery time, PO drainage duration, PO hospital stay, PO time of returning to work, PO bed time, and complications as well as rate of recurrence for RRPLD and OS were pooled using the Revman software. RESULTS: Twelve studies with a total of 620 patients were included in this meta-analysis. Of these patients, 365 and 255 had undergone renal pedicle lymphatic ligation via RRPLD and OS, respectively. There were significant reductions in operative time, PO intestinal recovery time, PO drainage duration, PO hospital stay, PO time of returning to work, and possible reductions in intraoperative blood loss intraoperative and PO complications for RRPLD compared to OS. However, other outcome variables, such as PO time in bed and PO recurrence, were not found to be statistically significant for either group. CONCLUSION: Compared with OS, RRPLD has several advantages such as shorter operative time, less intraoperative blood loss, and lower incidence of complications. Thus, it may be an efficacious and safe therapeutic modality for chyluria.

Super-Mini Percutaneous Nephrolithotomy Reduces the Incidence of Postoperative Adverse Events in Pediatric Patients: A Retrospective Cohort Study.

OBJECTIVE: To assess the safety of the super-mini percutaneous nephrolithotomy (SMP) versus the minimally invasive percutaneous nephrolithotomy (MPCNL) in the treatment of pediatric renal calculus. METHODS: We retrospectively reviewed the electronic records of pediatric patients who underwent treatment for renal stones by either SMP or MPCNL from May 2015 to May 2016. We compared the safety of the 2 surgical procedures in the treatment of renal calculus in children by using the generalized estimating equation (GEE) multivariate regression analysis, in which the exposures are the surgical procedures and postoperative adverse events (postoperative complications, fever, and WBC counts) are set as outcome variables. RESULTS: The study included 39 patients (26 boys and 13 girls), of which 22 underwent MPCNL and 17 underwent SMP, with a mean age of 110.05 ± 45.01 and 93.18 ± 41.72 months, respectively. In the univariate logistic regression model, the surgical procedures showed no significant association with postoperative complications (95% CI 0.0-1.5), fever (95% CI 0.1-2.1), postoperative peripheral WBC (95% CI 0.1-2.2). In the multiple logistic regression analysis, there was an insignificant association between surgical methods and postoperative complications (95% CI 0.28-1.1), fever (95% CI 0.1-1.2), and postoperative peripheral WBC (95% CI 0.03-1.8). While using GEE with multiple dependent variables and MPCNL as a reference, the OR of adverse events was 0.15 and the 95% CI were 0.04-0.55. CONCLUSIONS: Compared to MPCNL, SMP has a lower incidence of postoperative complications and appears to be a safer treatment for children with kidney stones.

Detection of Echinococcus multilocularis in domestic dogs of Shiqu County in the summer herding.

Alveolar echinococcosis (AE) is one of the most serious parasitic zoonosis in Asia. Shiqu County is the most important endemic area of AE in China. Our primary objective is to find out the risk factors for Echinococcus multilocularis infection in domestic dogs in Shiqu County during the summer herding period. A total of 120 fecal samples were collected from 60 ranchers in October 2016. Nested PCR (nPCR) was performed to amplify regions of the mitochondrial12S rRNA gene of E. multilocularis. The results showed that the infection rates of AE in dogs from Qiwu, Yiniu, Changshaganma, Derongma, Mengyi, and Xiazha villages were 5, 5, 10, 20, 10, and 5%, respectively. It should be stressed that the infected dogs will shed eggs through feces and may have a habit of preying on rodents, the intermediate host of the parasite, and become re-infected. This investigation confirmed the presence of E. multilocularis infection in dogs in Shiqu and revealed the risk factors associated with the infection during summer herding.

Role of GPR30 in estrogen-induced prostate epithelial apoptosis and benign prostatic hyperplasia.

Several studies have implicated estrogen and the estrogen receptor (ER) in the pathogenesis of benign prostatic hyperplasia (BPH); however, the mechanism underlying this effect remains elusive. In the present study, we demonstrated that estrogen (17ß-estradiol, or E2)-induced activation of the G protein-coupled receptor 30 (GPR30) triggered Ca2+ release from the endoplasmic reticulum, increased the mitochondrial Ca2+ concentration, and thus induced prostate epithelial cell (PEC) apoptosis. Both E2 and the GPR30-specific agonist G1 induced a transient intracellular Ca2+ release in PECs via the phospholipase C (PLC)-inositol 1, 4, 5-triphosphate (IP3) pathway, and this was abolished by treatment with the GPR30 antagonist G15. The release of cytochrome c and activation of caspase-3 in response to GPR30 activation were observed. Data generated from the analysis of animal models and human clinical samples indicate that treatment with the GPR30 agonist relieves testosterone propionate (TP)-induced prostatic epithelial hyperplasia, and that the abundance of GPR30 is negatively associated with prostate volume. On the basis of these results, we propose a novel regulatory mechanism whereby estrogen induces the apoptosis of PECs via GPR30 activation. Inhibition of this activation is predicted to lead to abnormal PEC accumulation, and to thereby contribute to BPH pathogenesis.

Association between single nucleotide polymorphism of vitamin D receptor gene FokI polymorphism and clinical progress of benign prostatic hyperplasia.

BACKGROUND: The aim of the study was to investigate the association between single nucleotide polymorphism (SNP) of vitamin D receptor (VDR) gene and clinical progress of benign prostatic hyperplasia (BPH) in Chinese men. METHODS: The DNA was extracted from blood of 200 BPH patients with operation (progression group) and 200 patients without operation (control group), respectively. The genotypes of VDR gene FokI SNP represented by "F/f" were identified by PCR-restriction fragment length polymorphism. The odds ratio (OR) of having progression of BPH for having the genotype were calculated. RESULTS: Our date indicated that the f alleles of the VDR gene FokI SNP associated with the progression of BPH (P = 0.009). CONCLUSION: For the first time, our study demonstrated that VDR gene FokI SNP may be associated with the risk of BPH progress.

Non-invasive preoperative prediction of Edmondson-Steiner grade of hepatocellular carcinoma based on contrast-enhanced ultrasound using ensemble learning.

Purpose: This study aimed to explore the clinical value of non-invasive preoperative Edmondson-Steiner grade of hepatocellular carcinoma (HCC) using contrast-enhanced ultrasound (CEUS). Methods: 212 cases of HCCs were retrospectively included, including 83 cases of high-grade HCCs and 129 cases of low-grade HCCs. Three representative CEUS images were selected from the arterial phase, portal vein phase, and delayed phase and stored in a 3-dimensional array. ITK-SNAP was used to segment the tumor lesions manually. The Radiomics method was conducted to extract high-dimensional features on these contrast-enhanced ultrasound images. Then the independent sample T-test and the Least Absolute Shrinkage and Selection Operator (LASSO) were employed to reduce the feature dimensions. The optimized features were modeled by a classifier based on ensemble learning, and the Edmondson Steiner grading was predicted in an independent testing set using this model. Results: A total of 1338 features were extracted from the 3D images. After the dimension reduction, 10 features were finally selected to establish the model. In the independent testing set, the integrated model performed best, with an AUC of 0.931. Conclusion: This study proposed an Edmondson-Steiner grading method for HCC with CEUS. The method has good classification performance on independent testing sets, which can provide quantitative analysis support for clinical decision-making.

Correlation of Reduced PTGER3 Expression with Prognosis and Immune Infiltration in Clear Cell Renal Carcinoma.

BACKGROUND: Prostaglandin E2 receptor 3 (PTGER3, EP3) is essential for many malignancies growth and metastasis. The role of PTGER3 in kidney renal clear cell carcinoma (KIRC) was assessed in terms of its prognosis and its association with immune infiltration. METHODS: Transcriptomic expression profiles of PTGER3 were acquired from The Cancer Genome Atlas (TCGA) database. Comparative analysis was performed to evaluate the disparity in PTGER3 expression between KIRC and normal tissues. The discriminative potential of PTGER3 as a distinguishing determinant was assessed through receiver operating characteristic (ROC) curves. Prognostic factors were evaluated employing COX regression and logistic models. Furthermore, the impact of PTGER3 on survival was ascertained utilizing the Kaplan-Meier method. A protein-protein interaction (PPI) network was constructed utilizing the STRING database. To investigate the correlation between immune infiltration levels and PTGER3 expression, a single-sample Gene Set Enrichment Analysis (GSEA) method was employed, employing the Gene Set Variation Analysis (GSVA) package and the Tumor Immune Estimation Resource (TIMER) database. RESULTS: Bioinformatics analysis unveiled a significant downregulation of PTGER3 expression in KIRC tissues compared to paraneoplastic tissues (p < 0.001). Furthermore, quantitative reverse transcription polymerase chain reaction (qRT-PCR) experiments demonstrated a reduction in PTGER3 expression in 786-O cells in contrast to paraneoplastic tissues (p < 0.01). The ROC curve, employing PTGER3 as a potential diagnostic biomarker, exhibited a substantial area under the curve (AUC) value of 0.929. According to the Kaplan-Meier survival analysis, reduced PTGER3 expression increased the chance of negative overall survival (OS) (p = 0.019). A PPI network was constructed, elucidating the interaction patterns between PTGER3 and the top 10 co-expressed genes. An examination of gene enrichment and immune infiltration levels found a link between PTGER3 transcription and immune infiltration levels. Notably, high B cell counts and low Mast cell counts were connected to a poor prognosis in KIRC patients. CONCLUSIONS: The expression of PTGER3 was found to be diminished in KIRC in comparison to paracancerous tissue. This observation exhibited a correlation with both prognosis and immune cell infiltration. As a result, our findings suggest that PTGER3 could be considered a promising biomarker to forecast KIRC prognosis and as a possible target for immunotherapy.

Long Noncoding RNA HAGLROS Promotes the Malignant Progression of Bladder Cancer by Regulating the miR-330-5p/SPRR1B Axis.

Bladder cancer (BC) is the most common genitourinary malignancy worldwide, and its aetiology and pathogenesis remain unclear. Accumulating evidence has shown that HAGLROS is closely related to the occurrence and progression of various cancers. However, the biological functions and underlying mechanisms of HAGLROS in BC remain unknown. In the present study, the expression of HAGLROS in BC was determined by public dataset analysis, transcriptome sequencing analysis, qRT-PCR and ISH assays. Gain- or loss-of-function assays were performed to study the biological roles of HAGLROS in BC cells and nude mouse xenograft model. Bioinformatic analysis, qRT-PCR, western blot, immunohistochemistry, FISH assays, subcellular fractionation assays and luciferase reporter assays were performed to explore the underlying molecular mechanisms of HAGLROS in BC. Here, we found that HAGLROS expression is significantly upregulated in BC tissues and cells, and elevated HAGLROS expression was related to higher pathologic grade and advanced clinical stage, which is significant for BC diagnosis. HAGLROS can enhance the growth and metastasis of BC in vitro and in vivo. Furthermore, miR-330-5p downregulation reversed the BC cells proliferation, migration and invasion inhibited by silencing HAGLROS. SPRR1B silencing restored the malignant phenotypes of BC cells promoted by miR-330--5p inhibitor. Mechanistically, we found that HAGLROS functions as a microRNA sponge to positively regulate SPRR1B expression by sponging miR-330-5p. Together, these results demonstrate that HAGLROS plays an oncogenic role and may serve as a potential biomarker for the diagnosis and treatment of BC.

Genome-Wide CRISPR-Cas9 Screening and Identification of Potential Genes Promoting Prostate Cancer Growth and Metastasis.

OBJECTIVE: Identification and validation of genes that functionally account for the growth and metastasis of prostate cancer. METHODS: DU145-KO cell line was constructed by transfecting DU145 cells with lentivirus packaged with the genome-wide knock-out library. The DU145-KO cells were transplanted into the armpits of immunocompromised Nu/Nu mice, followed by the tissue collection from the lung at week 3 (early lung tissue) or week 7 (late lung tissue with micro-metastasis), as well as from primary tumor site at week 7 (late primary tumor) after inoculation. Lung metastasis was retrieved at various time points for DNA sequencing analysis to identify enriched sgRNAs, thus candidate genes/miRNAs. Further bioinformatics analysis and limited functional validation studies were carried out. RESULTS: DU145-KO cells promoted the formation of transplanted tumors in mice and promoted the growth and metastasis of primary tumors, compared to the controls (DU145-NC cells). The analysis of sequence data showed that the abundance of sgRNAs significantly changed in the primary tumor and micro-metastasis site. Fifteen target genes (C1QTNF9B, FAM229A, hsa-mir-3929, KRT23, TARS2, CRADD, GRIK4, PLA2G15, LOXL1, SLITRK6, CDC42EP5, SLC2A4, PTGDS, MYL9 and ACOX2 for the enriched sgRNAs) have been selected for experimental validation, which showed that knock-out of any of these genes led to the enhanced potential of invasion and metastasis of DU145 cells. CONCLUSION: Genome-wide CRISPR-Cas9 knock-out screening technology combined with highthroughput sequencing analysis identified genes that potentially relate to prostate tumor invasion and metastasis. Analysis of these genes provided insights into biological pathways relevant to the disease and disclosed innovative markers for diagnosis or prognosis as well as potential targets for therapy.

ZFP36 Inhibits Tumor Progression of Human Prostate Cancer by Targeting CDK6 and Oxidative Stress.

Background: The expression of ZFP36 in previous study was reduced in prostate cancer (PCa) tissues as compared to benign prostate tissues, indicating the potential of ZFP36 as an auxiliary marker for PCa. Further evaluation was conducted in clinical samples for in vitro and in vivo experiments, to prove the potential possibility that ZFP36 dysregulation participated in the malignant phenotype of PCa, to determine its potential mechanism for tumor regulation, and to provide a new theoretical basis for gene therapy of PCa. Methods: First, the expression of ZFP36 in prostate tissue and PCa tissue was explored, and the relationship between ZFP36 and clinical features of PCa patients was illustrated. Subsequently, the impact of ZFP36 on the biology of PCa cells and relevant downstream pathways of ZFP36's biological impact on PCa were elucidated. Finally, whether oxidative stress mediated the regulation of ZFP36 in PCa was verified by the determination of oxidative stress-related indicators and bioinformatics analysis. Results: The downregulation of ZFP36 in PCa tissue had a positive correlation with high Gleason scores, advanced pathological stage, and biochemical recurrence. ZFP36 was identified as an independent prognostic factor for PCa patients' BCR-free survival (P = 0.022) by survival analysis. Following a subsequent experiment of function gain and loss, ZFP36 inhibited the proliferation, invasion, and migration in DU145 and 22RV1 cells and inhibits tumor growth in the mouse model. Additionally, high-throughput sequencing screened out CDK6 as the downstream target gene of ZFP36. Western blot/Q-PCR demonstrated that overexpression of ZFP36 could reduce the expression of CDK6 at both cellular and animal levels, and the dual-luciferase experiment and RIP experiment proved that CDK6 was the downstream target of ZFP36, indicating that CDK6 was a downstream target of ZFP36, which mediated tumor cell growth by blocking cell cycle at the G1 stage. Furthermore, ZFP36 inhibited oxidative stress in PCa cells. Conclusions: In PCa, ZFP36 might be a tumor suppressor that regulated growth, invasion, and migration of PCa cells. The lately discovered ZFP36-CDK6 axis demonstrated the molecular mechanism of PCa progression to a certain extent which might act as a new possible therapeutic target of PCa therapy.