Impact of Left Renal Vein Ligation on Renal Function Following En Bloc Resection of Segmental Inferior Vena Cava and Right Kidney.

BACKGROUND: Renal function after left renal vein (LRV) ligation following en bloc resection of segmental inferior vena cava (IVC) and right kidney is understudied. We assessed the impact of LRV ligation on postoperative renal function following en bloc resection of segmental IVC and right kidney. METHODS: We retrospectively reviewed 28 patients who underwent LRV ligation during en bloc resection of segmental IVC and right kidney. Patient demographics, tumor characteristics, intraoperative factors, complications, length of hospital and intensive care unit (ICU) stay, and patient survival were collected. Pre- and postoperative renal function was retrospectively analyzed. RESULTS: Twenty patients underwent robot-assisted surgery and eight patients underwent open surgery. The median operative time was 162 min and estimated blood loss was 350 mL. Ten patients had normal renal function and 12 patients had an initial increase in creatinine but improved gradually. Six patients developed acute renal failure; five patients gradually recovered in 5-32 days after temporary hemodialysis. Renal replacement therapy significantly correlated with maximal anterior-posterior diameter of the LRV (p = 0.001). Complications were observed in 11 cases, four of which were Clavien-Dindo grades I-II. Thirteen patients were alive with no recurrence, nine patients were alive with metastasis, and six cases died during the follow-up period. CONCLUSIONS: LRV ligation following en bloc resection of segmental IVC and right kidney is feasible, with no significant long-term impact on renal function. The maximum anterior-posterior diameter of the LRV is a reliable method for predicting renal replacement therapy in the absence of collateral circulation.

Assessing the Feasibility and Safety of the Toumai® Robotic System in Urologic Surgery: Initial Experience.

Introduction: Robotic surgery using da Vinci surgical system has gained prominence in urology; emerging robotic platforms are expanding its applications and increasing affordability. We assess the feasibility and safety of a novel system, the Toumai® robotic system in various urological surgeries. Methods: This prospective study was conducted at the first affiliated hospital of Zhengzhou university. Twenty consecutive patients underwent renal and prostatic surgery with the Toumai. The study assessed technical feasibility (conversion rate) and safety (perioperative complications) of the procedures as primary outcomes. Secondary endpoints included key surgical perioperative outcomes: functional and oncologic results. The Endoscopic Surgical System operates within a master-slave protocol, comprising a Surgeon Console, Patient Platform, and Vision Platform. Results: Seventeen patients underwent various nephrectomy procedures and three underwent radical prostatectomy (RP). There was no conversion to alternative surgical approach; a single (Clavien-Dindo grade ≥3b) complication occurred, and no readmission was recorded within 30 days. The median operative time was 120, 140, and 210 minutes for partial nephrectomy (PN), radical nephrectomy, and RP, respectively. Off-clamp PN was performed in one case, and the warm ischemia time in the remaining two case was 18 minutes. The median docking time was 22 minutes for nephrectomy and 20 minutes for RP; no major robotic malfunction was encountered. At 3-month follow-up, no tumor recurrence was recorded, renal function was well preserved, and the continence status was satisfactory. Conclusions: We present the initial clinical utilization of an innovative robotic platform. Complex urological surgeries were successfully completed without conversions and with minimal complications. Further investigations are warranted to confirm these initial findings.

Laparoscopic placement of left renal vein extravascular stenting in treatment of nutcracker syndrome: Techniques and long-term outcomes.

OBJECTIVES: We aimed to assess the feasibility and efficacy of laparoscopic extravascular stent in treatment of nutcracker syndrome by transperitoneal or retroperitoneal approach. METHODS: Seventy-six patients with nutcracker syndrome were retrospectively enrolled from a tertiary referral center, and underwent transperitoneal (63 patients) or retroperitoneal (13 patients) laparoscopic extravascular stent from March 2011 to December 2020. Surgical parameters, complications, imaging and clinical outcomes were collected and analyzed. RESULTS: All procedures were successfully carried out without open conversion. The median operation time, estimated blood loss, and postoperative hospital day were 120 (interquartile range [IQR]: 90-144) min, 20 (IQR: 10-30) ml, and 7 (IQR: 6-9) days. At a median follow-up of 52 (range: 9-127) months, 60 (79%) patients had complete symptom resolution, 14 (18%) patients had significant symptom improvement, and 2 (3%) patients reported no symptom improvement. Ninety-four percent (50/53) of hematuria, 91% (30/33) of proteinuria, and 89% (25/28) of flank/abdominal pain resolved after extravascular LRV stenting. No significant differences were detected in surgery parameters and recovery rates of clinical symptoms between two approaches (each p > 0.05). However, patients with transperitoneal approach need longer to achieve complete recovery compared with retroperitoneal approach (8.7 vs. 1.5 months, p = 0.016). CONCLUSIONS: Laparoscopic extravascular stent performed either transperitoneally or retroperitoneally is a feasible and effective option in treatment of nutcracker syndrome. Retroperitoneal laparoscopic extravascular stent required shorter time to achieve complete recovery, which should be considered whenever possible in surgical decision-making.

The efficacy of modified binding technique for renorrhaphy during robotic partial nephrectomy: surgical and functional outcomes from single-center experience.

BACKGROUND: To compare the traditional single-layer and double-layer suture renorrhaphy with modified "Binding" suture renorrhaphy (whole rim of the wound was closed by the all-layer flow suture starting from the parenchyma cut edges to hilum, followed by the final defect closure) in robotic partial nephrectomy (RPN) for treating localized renal cell carcinoma in our large institutional experience. METHODS: We retrospectively reviewed clinical data of 406 consecutive patients who underwent RPN from May 2018 and December 2020 in our center. The demographic and oncologic outcome variables were compared between different renal reconstruction groups and the effect of these suture techniques on renal function outcomes was also evaluated. RESULTS: For the single-layer group, median operative time and warm ischemic time were significantly less than that of the double-layer and "Binding" groups (p < 0.001), while the significantly lower eGFR drop (p = 0.014) was also detected within postoperative 3 months from baseline, but this difference lost its statistical significance from 3th month to the last follow-up. The changes in postoperative creatinine values were clinically insignificant among the three groups. In a sub-analysis over 258 patients with moderate/high nephrometry score, those patients who underwent "Binding" suture had an undifferentiated warm ischemic time, estimated blood loss, and length of hospitalization stay with a decreased risk of Grade III complications (postoperative hemorrhage requiring intervention) and improved renal function recovery during the whole follow-up. CONCLUSION: Single-layer suture renorrhaphy may be associated with better renal functional preservation and could prove to be reliable in patients with low-complexity tumor (RENAL score ≤ 6). Patients with moderate/high-complexity tumor (RENAL score ≥ 7) might represent a subgroup of patients having a functional benefit after "Binding" suture renorrhaphy even in the long-term period.

Erythropoietin prevented the decreased expression of aquaporin1-3 in ureteral obstructive kidneys in juvenile rats.

BACKGROUND: Urinary tract obstruction is associated with impaired renal urinary concentration; even after the release of the obstruction, patients still suffer from polyuria. It has been reported that the decreased expression of aquaporins (AQPs) is associated with postobstructive polyuria, and erythropoietin (EPO) can promote the recovery of decreased AQP2 expression induced by bilateral ureteral obstruction. However, whether EPO can promote the recovery of the expression of AQP1-3 after the release of unilateral ureteral obstruction (UUO) has not yet been reported. AIMS: To investigate the effects of EPO treatment on the expression of renal AQP1-3 after the release of UUO. METHODS: UUO was established in rats by 24-h temporary unilateral obstruction of renal ureters. Three days following EPO treatment, the kidneys were removed to determine the expression levels of AQP1-3, NLRP3, caspase-1, and IL-1ß via semiquantitative immunoblotting and immunohistochemistry. RESULTS: EPO inhibited the expression of NLRP3, caspase-1, and IL-1ß; reduced plasma creatinine and urea; and promoted the recovery of AQP1-3 expression in UUO rats. CONCLUSIONS: EPO treatment prevented the decreased expression of renal AQPs and the development of impaired urinary concentration capacity after the release of UUO, which may partially occur by way of anti-inflammasome effects. IMPACT: EPO treatment could prevent the decreased expression of renal water transporter proteins AQP1-3 and the development of impaired renal functions, which may be associated with its anti-inflammasome effects. EPO regulated the expression of renal water transporter proteins AQP1-3, which could provide the potential for the treatment of postobstructive polyuresis. EPO treatment could be one of the effective methods by participating in multiple dimensions for patients with obstructive nephropathy.

Alteration of N6-methyladenosine epitranscriptome profiles in bilateral ureteral obstruction-induced obstructive nephropathy in juvenile rats.

BACKGROUND: Urinary tract obstruction is a common cause of renal failure in children and infants, and the pathophysiological mechanisms of obstructive nephropathy are largely unclear. It has been reported that m6A modulation is involved in renal injury. However, whether m6A RNA modulation is associated with obstructive nephropathy has not yet been reported. The aim of this study was to investigate the m6A epitranscriptome profiles in the kidneys of bilateral ureteral obstruction (BUO) in young rats. METHODS: The total level of m6A in the kidneys was measured by liquid chromatography-tandem mass spectrometry. The mRNAs of related genes were detected by real-time PCR. Methylated RNA immunoprecipitation sequencing was performed to map the epitranscriptome-wide m6A profile. RESULTS: Global m6A levels were increased after BUO, and the mRNA expression levels of m6A methyltransferases and demethylases were significantly decreased in BUO group rat kidneys; the expression levels of EGFR and Brcal were significantly upregulated, while the mRNA expression levels of Notch1 were downregulated (P < 0.05). A total of 154 genes associated with 163 m6A peaks were identified. CONCLUSION: The m6A epitranscriptome was significantly altered in BUO rat kidneys, which is potentially implicated in the pathophysiological processes of obstructive nephropathy. IMPACT: The m6A RNA modification was associated with the process of renal injury in ureteral obstructive nephropathy by participating in multiple dimensions. The dysregulation of m6A methyltransferases and demethylases may be related to the pathophysiological changes of BUO-induced obstructive nephropathy. The m6A RNA modulation of the genes EGFR, Brca1, and Notch1 that were related to the regulation of aquaporin2 might be the potential mechanism for the polyuresis after ureteral obstruction.

[Expression and significance analysis of GDF3 in testicular cancer based on TCGA and GTEx databases].

OBJECTIVE: To investigate the expression and significance of GDF3 in testicular cancer through bioinformatics analysis. METHODS: Using the TCGA and GTEx databases, differential expression analysis and pan-cancer analysis were performed to identify the target gene GDF3, and the clinical relevance of GDF3 in testicular cancer was analyzed using the UALCAN database. Based on the R packages "org.Hs.eg.db" and "clusterProfiler," gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore the potential functions of GDF3 in testicular cancer. The correlation of GDF3 with immune chemokines and immune inhibitors in testicular cancer was investigated using the TISIDB database. RESULTS: The GDF3 was significantly upregulated in testicular cancer (P<0.001) and closely associated with clinical staging (P<0.05) and tumor subtypes (P<0.001). The immune-related analysis revealed that GDF3 was strongly correlated with immune chemokines CCL26 (rho=0.599, P<0.001), CCL7 (rho=0.525, P<0.001), immune inhibitor ADORA2A (rho=0.723, P<0.001), and PVRL2 (rho=0.585, P<0.001). CONCLUSION: The GDF3 is closely related to the occurrence, development, and immune microenvironment of testicular cancer.

Seroepidemiology of enterovirus A71 infection in prospective cohort studies of children in southern China, 2013-2018.

Enterovirus A71 (EV-A71)-related hand, foot, and mouth disease (HFMD) imposes a substantial clinical burden in the Asia Pacific region. To inform policy on the introduction of the EV-A71 vaccine into the National Immunization Programme, we investigated the seroepidemiological characteristics of EV-A71 in two prospective cohorts of children in southern China conducted between 2013 and 2018. Our results show that maternal antibody titres declined rapidly in neonates, with over half becoming susceptible to EV-A71 at 1 month of age. Between 6 months and 2 years of age, over 80% of study participants were susceptible, while one third remained susceptible at 5 years old. The highest incidence of EV-A71 infections was observed in children aged 5-6 months. Our findings support EV-A71 vaccination before 6 months for birth cohorts in southern China, potentially with a one-time catch-up vaccination for children 6 months-5 years old. More regionally representative longitudinal seroepidemiological studies are needed to further validate these findings.

Prognostic Signatures and Therapeutic Value Based on the Notch Pathway in Renal Clear Cell Carcinoma.

The Notch family of genes encodes a group of highly conserved cell surface membrane receptors, which are involved in one of the key pathways that determine cell growth, differentiation, and apoptosis in embryonic tissues. Furthermore, abnormal expression of Notch genes is closely related to the occurrence and development of several cancers. To date, no specific treatment of RCC has been reported to relate to the Notch pathway. Therefore, we detected Notch pathway genes in series of tumors, as well as potential compounds targeting the Notch pathway, with a focus on the mechanism of Notch pathway action in kidney renal clear cell carcinoma (KIRC). Samples from KIRC patients were divided into three clusters based on the mRNA expression of Notch pathway genes. In addition, we investigated the potential targets of the Notch pathway, predicted the IC50 of several classical targeted therapies, and analyzed their correlation with the Notch pathway. Finally, LASSO regression analysis was performed to build a model to predict survival in KIRC patients. These results suggest that therapies targeting the Notch pathway could be more efficiently studied based on the Notch score and that we can predict the prognosis of patients with KIRC based on the expression of Notch pathway genes. Most importantly, these results may provide a solid theoretical basis for future research on therapeutic targets for patients with KIRC.

Evaluating Incidence, Location, and Predictors of Positive Surgical Margin Among Chinese Men Undergoing Robot-Assisted Radical Prostatectomy.

PURPOSE: To evaluate the incidence and locations of positive surgical margin (PSM) among Chinese men undergoing RARP and identify the preoperative predictors for PSM. METHODS: We retrospectively identified 393 patients who underwent RARP according to inclusion criteria by single surgeon in our hospital. PSM was defined as the presence of cancer adjacent to inked surface of the specimen and categorized into four groups based on locations: apex, posterolateral, base, and multifocal. Logistic regression analysis was performed to identify the predictors of overall and location-specific PSM. RESULTS: The overall PSM rate was 133/393 (34%). The PSM rates for pT2, pT3, and pT4 stage were 63/278 (23%), 50/89 (56%), and 20/26 (77%), respectively. The estimated rates for apical, posterolateral, basal, and multifocal PSM were 8%, 4%, 7%, and 14%, respectively. In univariate analysis, overall PSM related to tPSA, f/tPSA, percentage of positive needles, and Gleason score. Multifocal PSM correlated with smoking history, drinking history, tPSA, f/tPSA, percentage of positive needles, and Gleason score. In multivariate analysis, percentage of positive needles reminded the only independent predictor for overall (OR = 10.5, 95% CI: 2.58-44.4) and basal PSM (OR = 24.0, 95% CI: 3.22-179.4). The f/tPSA (OR = 2.59, 95% CI: 2.18-5.71) and percentage of positive needles (OR = 31.0, 95% CI: 3.17-303) were independent risk factors for multifocal PSM. CONCLUSION: The multifocal sites were the most common location of positive surgical margin, followed by apical and basal sites among Chinese patients undergoing RARP. The percentage of positive needles was an independent predictor for overall, basal, and multifocal PSM.

Developing Strategy to Predict the Results of Prostate Multiparametric Magnetic Resonance Imaging and Reduce Unnecessary Multiparametric Magnetic Resonance Imaging Scan.

PURPOSE: The clinical utility of multiparametric magnetic resonance imaging (mpMRI) for the detection and localization of prostate cancer (PCa) has been evaluated and validated. However, the implementation of mpMRI into the clinical practice remains some burden of cost and availability for patients and society. We aimed to predict the results of prostate mpMRI using the clinical parameters and multivariable model to reduce unnecessary mpMRI scans. METHODS: We retrospectively identified 784 men who underwent mpMRI scans and subsequent prostate biopsy between 2016 and 2020 according to the inclusion criterion. The cohort was split into a training cohort of 548 (70%) patients and a validation cohort of 236 (30%) patients. Clinical parameters including age, prostate-specific antigen (PSA) derivates, and prostate volume (PV) were assessed as the predictors of mpMRI results. The mpMRI results were divided into groups according to the reports: "negative", "equivocal", and "suspicious" for the presence of PCa. RESULTS: Univariate analysis showed that the total PSA (tPSA), free PSA (fPSA), PV, and PSA density (PSAD) were significant predictors for suspicious mpMRI (P < 0.05). The PSAD (AUC = 0.77) and tPSA (AUC = 0.74) outperformed fPSA (AUC = 0.68) and PV (AUC = 0.62) in the prediction of the mpMRI results. The multivariate model (AUC = 0.80) had a similar diagnostic accuracy with PSAD (P = 0.108), while higher than tPSA (P = 0.024) in predicting the mpMRI results. The multivariate model illustrated a better calibration and substantial improvement in the decision curve analysis (DCA) at a threshold above 20%. Using the PSAD with a 0.13 ng/ml2 cut-off could spare the number of mpMRI scans by 20%, keeping a 90% sensitivity in the prediction of suspicious MRI-PCa and missing three (3/73, 4%) clinically significant PCa cases. At the same sensitivity level, the multivariate model with a 32% cut-off could spare the number of mpMRI scans by 27%, missing only one (1/73, 1%) clinically significant PCa case. CONCLUSION: Our multivariate model could reduce the number of unnecessary mpMRI scans without comprising the diagnostic ability of clinically significant PCa. Further prospective validation is required.

Development and head-to-head comparison of machine-learning models to identify patients requiring prostate biopsy.

BACKGROUND: Machine learning has many attractive theoretic properties, specifically, the ability to handle non predefined relations. Additionally, studies have validated the clinical utility of mpMRI for the detection and localization of CSPCa (Gleason score ≥ 3 + 4). In this study, we sought to develop and compare machine-learning models incorporating mpMRI parameters with traditional logistic regression analysis for prediction of PCa (Gleason score ≥ 3 + 3) and CSPCa on initial biopsy. METHODS: A total of 688 patients with no prior prostate cancer diagnosis and tPSA ≤ 50 ng/ml, who underwent mpMRI and prostate biopsy were included between 2016 and 2020. We used four supervised machine-learning algorithms in a hypothesis-free manner to build models to predict PCa and CSPCa. The machine-learning models were compared to the logistic regression analysis using AUC, calibration plot, and decision curve analysis. RESULTS: The artificial neural network (ANN), support vector machine (SVM), and random forest (RF) yielded similar diagnostic accuracy with logistic regression, while classification and regression tree (CART, AUC = 0.834 and 0.867) had significantly lower diagnostic accuracy than logistic regression (AUC = 0.894 and 0.917) in prediction of PCa and CSPCa (all P < 0.05). However, the CART illustrated best calibration for PCa (SSR = 0.027) and CSPCa (SSR = 0.033). The ANN, SVM, RF, and LR for PCa had higher net benefit than CART across the threshold probabilities above 5%, and the five models for CSPCa displayed similar net benefit across the threshold probabilities below 40%. The RF (53% and 57%, respectively) and SVM (52% and 55%, respectively) for PCa and CSPCa spared more unnecessary biopsies than logistic regression (35% and 47%, respectively) at 95% sensitivity for detection of CSPCa. CONCLUSION: Machine-learning models (SVM and RF) yielded similar diagnostic accuracy and net benefit, while spared more biopsies at 95% sensitivity for detection of CSPCa, compared with logistic regression. However, no method achieved desired performance. All methods should continue to be explored and used in complementary ways.

Genetic Variation of Multiple Serotypes of Enteroviruses Associated with Hand, Foot and Mouth Disease in Southern China.

Enteroviruses (EVs) species A are a major public health issue in the Asia-Pacific region and cause frequent epidemics of hand, foot and mouth disease (HFMD) in China. Mild infections are common in children; however, HFMD can also cause severe illness that affects the central nervous system. To molecularly characterize EVs, a prospective HFMD virological surveillance program was performed in China between 2013 and 2016. Throat swabs, rectal swabs and stool samples were collected from suspected HFMD patients at participating hospitals. EVs were detected using generic real-time and nested reverse transcription-polymerase chain reactions (RT-PCRs). Then, the complete VP1 regions of enterovirus A71 (EV-A71), coxsackievirus A16 (CVA16) and CVA6 were sequenced to analyze amino acid changes and construct a viral molecular phylogeny. Of the 2836 enrolled HFMD patients, 2,517 (89%) were EV positive. The most frequently detected EVs were CVA16 (32.5%, 819), CVA6 (31.2%, 785), and EV-A71 (20.4%, 514). The subgenogroups CVA16_B1b, CVA6_D3a and EV-A71_C4a were predominant in China and recombination was not observed in the VP1 region. Sequence analysis revealed amino acid variations at the 30, 29 and 44 positions in the VP1 region of EV-A71, CVA16 and CVA6 (compared to the respective prototype strains BrCr, G10 and Gdula), respectively. Furthermore, in 21 of 24 (87.5%) identified EV-A71 samples, a known amino acid substitution (D31N) that may enhance neurovirulence was detected. Our study provides insights about the genetic characteristics of common HFMD-associated EVs. However, the emergence and virulence of the described mutations require further investigation.

The transfer and decay of maternal antibodies against enterovirus A71, and dynamics of antibodies due to later natural infections in Chinese infants: a longitudinal, paired mother-neonate cohort study.

BACKGROUND: Since 1997, epidemics of hand, foot, and mouth disease associated with enterovirus A71 (EV-A71) have affected children younger than 5 years in the Asia-Pacific region, including mainland China. EV-A71 vaccines have been licensed for use in children aged 6-71 months in China, but not for infants younger than 6 months. We aimed to assess the dynamics of maternal EV-A71 antibodies to inform choice of potential vaccination strategies to protect infants younger than 6 months, because they have a substantial burden of disease. METHODS: We did a longitudinal cohort study with mother-neonate pairs in local hospitals in southern China during 2013-18. We collected cord blood from neonates and venous blood from mothers at delivery. We followed up and collected blood samples from the children at ages 2, 4, 6, 12, 24, and 36 months and tested for the presence of neutralising antibodies against EV-A71 with virus neutralisation assays. Seropositivity, or protective titre, was defined as a neutralisation antibody titre of 16 or higher. We estimated the seroprevalence, geometric mean titre (GMT), and transfer ratio of maternal antibodies. We used a binomial distribution to derive the 95% CIs of seroprevalence. Seropositivity between mothers and neonates was compared by use of an agreement (κ), while GMTs were compared by use of paired Student's t tests. FINDINGS: Between Sept 20, 2013, and Oct 14, 2015, 1054 mothers with 1066 neonates were enrolled. The EV-A71 GMT was similar among pairs of neonates (22·7, 95% CI 20·8-24·9) and mothers (22·1, 95% CI 20·2-24·1; p=0·20). The mean transfer ratio of maternal antibodies was 1·03 (95% CI 0·98-1·08). Although 705 (66%) of 1066 neonates acquired protective concentrations of EV-A71 antibodies from mothers, these declined rapidly, with a half-life of 42 days (95% CI 40-44). The time to loss of protective immunity was extended to 5 months in neonates with mothers who had titres of 128 or higher. By age 30 months, 28% of children had become seropositive because of natural infection. INTERPRETATION: EV-A71 maternal antibodies were efficiently transferred to neonates, but declined quickly to below the protective threshold, particularly among those whose mothers had low antibody titres. Our findings suggest that maternal vaccination could be explored to provide neonatal protection against EV-A71 through maternal antibodies. Catch-up vaccination between ages 6 months to 5 years could provide protection to the approximately 30-90% of children that have not had natural EV-A71 infection by that age. FUNDING: National Science Fund for Distinguished Young Scholars, National Natural Science Foundation of China.

Multivariable Models Incorporating Multiparametric Magnetic Resonance Imaging Efficiently Predict Results of Prostate Biopsy and Reduce Unnecessary Biopsy.

PURPOSE: We sought to develop diagnostic models incorporating mpMRI examination to identify PCa (Gleason score≥3+3) and CSPCa (Gleason score≥3+4) to reduce overdiagnosis and overtreatment. METHODS: We retrospectively identified 784 patients according to inclusion criteria between 2016 and 2020. The cohort was split into a training cohort of 548 (70%) patients and a validation cohort of 236 (30%) patients. Age, PSA derivatives, prostate volume, and mpMRI parameters were assessed as predictors for PCa and CSPCa. The multivariable models based on clinical parameters were evaluated using area under the curve (AUC), calibration plots, and decision curve analysis (DCA). RESULTS: Univariate analysis showed that age, tPSA, PSAD, prostate volume, MRI-PCa, MRI-seminal vesicle invasion, and MRI-lymph node invasion were significant predictors for both PCa and CSPCa (each p≤0.001). PSAD has the highest diagnostic accuracy in predicting PCa (AUC=0.79) and CSPCa (AUC=0.79). The multivariable models for PCa (AUC=0.92, 95% CI: 0.88-0.96) and CSPCa (AUC=0.95, 95% CI: 0.92-0.97) were significantly higher than the combination of derivatives for PSA (p=0.041 and 0.009 for PCa and CSPCa, respectively) or mpMRI (each p<0.001) in diagnostic accuracy. And the multivariable models for PCa and CSPCa illustrated better calibration and substantial improvement in DCA at threshold above 10%, compared with PSA or mpMRI derivatives. The PCa model with a 30% cutoff or CSPCa model with a 20% cutoff could spare the number of biopsies by 53%, and avoid the number of benign biopsies over 80%, while keeping a 95% sensitivity for detecting CSPCa. CONCLUSION: Our multivariable models could reduce unnecessary biopsy without comprising the ability to diagnose CSPCa. Further prospective validation is required.

Long non-coding RNA CASC9 promotes tumor growth and metastasis via modulating FZD6/Wnt/ß-catenin signaling pathway in bladder cancer.

BACKGROUND: Accumulating evidence have highlighted the importance of long noncoding RNAs (lncRNAs) in multiple cancers development and progression. Cancer susceptibility candidate 9 (CASC9) is a novel long non-coding RNA and plays important regulatory role in diverse biological processes of cancers. However, the clinical significance and molecular mechanism of CASC9 in bladder cancer is still unknown. METHODS: Comprehensive lncRNAs profiling analysis were conducted to identify lncRNAs profile alterations and uncover valuable lncRNA candidates for bladder cancer. The expression level of CASC9 was determined in a total of 106 patients with bladder cancer. Loss-of-function experiments were performed to identify the functions of CASC9 in tumor growth and metastasis of bladder cancer in vitro and in vivo. Bioinformatics analysis and further experiments were performed to explore the molecular mechanisms underlying the functions of CASC9. RESULTS: This study found that CASC9 expression was markedly upregulated in bladder cancer and related to histological grade, TNM stage and prognosis. Knockdown of CASC9 inhibited tumor growth and metastasis of bladder cancer in vitro and in vivo. Mechanistically, we found that CASC9 functions as a miRNA sponge to positively regulate FZD6 expression and subsequently activates Wnt/ß-catenin signaling pathway, thus playing an oncogenic role in bladder cancer pathogenesis. CONCLUSION: In summary, lncRNA CASC9 plays a critical regulatory role in bladder cancer. The CASC9/miR-497-5p/ FZD6 axis provides insights for regulatory mechanism of bladder cancer, and new strategies for clinical practice.

Using clinical parameters to predict prostate cancer and reduce the unnecessary biopsy among patients with PSA in the gray zone.

The gold standard for prostate cancer (PCa) diagnosis is prostate biopsy. However, it remines controversial as an invasive mean for patients with PSA levels in the gray zone (4-10 ng/mL). This study aimed to develop strategy to reduce the unnecessary prostate biopsy. We retrospectively identified 235 patients with serum total PSA testing in the gray zone before prostate biopsy between 2014 and 2018. Age, PSA derivates, prostate volume and multiparametric magnetic imaging (mpMRI) examination were assessed as predictors for PCa and clinically significant PCa with Gleason score ≥ 7 (CSPCa). Univariate analysis showed that prostate volume, PSAD, and mpMRI examination were significant predictors of PCa and CSPCa (P < 0.05). The differences of diagnostic accuracy between mpMRI examination (AUC = 0.69) and other clinical parameters in diagnostic accuracy for PCa were not statistically significant. However, mpMRI examination (AUC = 0.79) outperformed prostate volume and PSAD in diagnosis of CSPCa. The multivariate models (AUC = 0.79 and 0.84 for PCa and CSPCa) performed significantly better than mpMRI examination for detection of PCa (P = 0.003) and CSPCa (P = 0.036) among patients with PSA level in the gray zone. At the same level of sensitivity as the mpMRI examination to diagnose PCa, applying the multivariate models could reduce the number of biopsies by 5% compared with mpMRI examination. Overall, our results supported the view that the multivariate model could reduce unnecessary biopsies without compromising the ability to diagnose PCa and CSPCa. Further prospective validation is required.

Antibiotic resistance of clinical isolates of Clostridioides difficile in China and its association with geographical regions and patient age.

It is known that antibiotic usage is associated with the development of Clostridioides difficile infection (CDI), especially clindamycin, third-generation cephalosporins, and fuoroquinolones. Antibiotic resistance rates to many antibiotics varies a lot by study. We performed a study focused on antibiotic resistance in clinical isolates of C. difficile from more widespread geographic regions across China. Of 319 C. difficile isolates tested against 11 antibiotics, 313 (98.1%) were resistant to at least one antibiotic. The highest rate of resistance was to ciprofloxacin, clindamycin, and erythromycin across all age groups, similar to previous studies. However, all isolates were susceptible to metronidazole and vancomycin. Overall the resistance rate to tested antibiotics was lower than other reports in China except for chloramphenicol and meropenem. Genotype ST37/RT017 in clade 4 was resistant to more antibiotics than other types. Unexpectedly, RT078 isolates in this study were susceptible to almost all tested antibiotics. In addition, the proportion of multi-drug resistant (MDR) isolates observed (17%) in this study was much lower than several European studies (up to 55%) and a previous study in China (78%). Although isolates from patients aged between 65 and 85 were more resistant to antibiotics in comparison to other age groups, MDR isolates were still detected in children below 2-years of age. The highest percentage of MDR isolates was determined in South China, an area that is most developed economically. The clade 4, RT017 (ST37) has been associated with outbreaks in Europe and North America and is responsible for most C. difficile infections (CDIs) in Asia. In addition, RT017 is often clindamycin and fluoroquinolone resistant. This study provided a relatively comprehensive description of antibiotic resistance of C. difficile in China, and further elucidates the epidemiology and antibiotic resistance of clinical isolates of C. difficile in China at a national level.

Polymorphism analysis of virulence-related genes among Candida tropicalis isolates.

BACKGROUND: Adhesion, biofilm formation, yeast-hyphal transition, secretion of enzymes, and hemolytic activity are all considered important factors in Candida tropicalis infection. However, DNA sequence data for this pathogen are limited. In this study, the polymorphism and heterogeneity of genes agglutinin-like sequences (ALS)2, Lipase (LIP)1, LIP4, and secretory aspartyl proteinase tropicalis (SAPT)1-4 as well as the relationship between phenotype and genotype were analyzed. METHODS: This study started in August 2013, and ended in July 2017. The complete length of ALS2, LIP1, LIP4, and SAPT1-4 of 68 clinical C. tropicalis isolates was sequenced. Single nucleotide polymorphisms (SNPs) as well as insertions and deletions (indels) were identified within these genes. In addition, phenotypic characteristics of the virulent factors, including adhesion and the secretion of aspartyl proteinases and phospholipases, were determined. RESULTS: There were 73, 24, 17, 16, 13, and 180 SNPs in the genes LIP1, LIP4, SAPT1, SAPT2, SAPT3, and SAPT4, respectively. Furthermore, 209 SNPs were identified in total for the gene ALS2. Interestingly, large fragment deletions and insertions were also found in ALS2. Isolate FXCT 01 obtained from blood had deletions on all 4 sites and showed the lowest adhesion ability on the polymethylpentene surface. In addition, isolates with deletions in the regions 1697 to 1925 and 2073 to 2272 bp displayed relatively low abilities for adhesion and biofilm formation, and this phenotype correlated with the deletions found in ALS2. LIP1, SAPT4, and ALS2 displayed great heterogeneity among the isolates. Large deletions found in gene ALS2 appeared to be associated with the low ability of adhesion and biofilm formation of C. tropicalis. CONCLUSION: This study might be useful for deeper explorations of gene function and studying the virulent mechanisms of C. tropicalis.