Construction and validation of the nomogram predictive model for post-percutaneous nephrolithotomy urinary sepsis.

OBJECTIVE: This study aimed to construct and validate a simple and accurate clinical nomogram for predicting the occurrence of post-percutaneous nephrolithotomy sepsis, aiming to assist urologists in the early identification, warning, and early intervention of urosepsis, and to provide certain evidence-based medicine basis. METHODS: This study included patients who underwent PCNL surgery due to kidney or upper ureteral stones at the Department of Urology, Affiliated Hospital of Zunyi Medical University, from January 2019 to September 2022. This study utilized univariate and multivariate logistic regression analysis to screen and evaluate the risk factors for sepsis and construct a predictive model. An evaluation was performed using the receiver operating characteristic curve, calibration curve, and decision curve analysis curve. All statistical analyses were conducted using R version 4.2. RESULTS: A total of 946 patients who underwent post-PCNL were included in this study, among whom 69 patients (7.29%) developed post-PCNL urinary sepsis. Multiple-factor logistic regression analysis identified four independent risk factors associated with post-PCNL urinary sepsis, including positive urinary nitrite (OR = 5.9, P < 0.001), positive urine culture (OR = 7.54, P < 0.001), operative time ≥ 120 min (OR = 20.93, P = 0.0052), and stone size ≥ 30 mm (OR = 13.81, P = 0.0015). The nomogram model demonstrated good accuracy with an AUC value of 0.909, and in the validation cohort, the AUC value was 0.922. The calibration curve indicated a better consistency between the predictive line chart and the actual occurrence of post-PCNL urinary sepsis. The decision curve analysis curve showed favorable clinical utility. CONCLUSION: Preoperative positive urine culture, positive urinary nitrite, operative time ≥ 120 min, and stone size ≥ 30 mm are independent risk factors for developing post-PCNL urinary sepsis. The constructed line chart based on these factors effectively assesses the risk of urinary sepsis in patients after PCNL.

miR-33a-3p regulates METTL3-mediated AREG stability and alters EMT to inhibit pancreatic cancer invasion and metastasis.

Recent studies have shown that amphoteric regulatory protein (AREG), a member of the epidermal growth factor (EGF) family, is expressed in many cancers and is an independent prognostic indicator for patients with pancreatic cancer, but whether AREG is regulated at the epigenetic level to promote the development of pancreatic cancer (PC) has not been elucidated. Our results support the notion that AREG is overexpressed in pancreatic cancer tissues and cell lines. Functionally, the deletion of AREG impedes pancreatic cancer (PC) cell proliferation, migration, and invasion. In addition, we identified and validated that methyltransferase-like 3 (METTL3) induced the m6A modification on AREG and facilitated the stability of AREG mRNA after sequencing. Additionally, we obtained experimental evidence that miR-33a-3p targets and inhibits METTL3 from taking action, as predicted by using the miRDB and RNAinter. Remediation experiments showed that miR-33a-3p inhibits PC progression through METTL3. In summary, this research reveals that miR-33a-3p inhibits m6A-induced stabilization of AREG by targeting METTL3, which plays a key role in the aggressive progression of PC. AREG could be a potential target for PC treatment.

Linc00662 m6A promotes the progression and metastasis of pancreatic cancer by activating focal adhesion through the GTF2B-ITGA1-FAK pathway.

Recurrence and metastasis are major factors associated with the poor prognosis of pancreatic cancer (PC). Previous studies have indicated that METTL3-mediated N6-methyladenosine (m6A) modification is closely associated with PC progression and prognosis. However, its underlying regulatory mechanisms remain unclear. In this study, we found that METTL3 was upregulated in PC tissues and cells and was associated with malignant tumor progression and poor progression-free survival in PC. Linc00662 was screened as a m6A-enriched RNA that promoted tumor growth and metastasis in PC cells and mouse models and was associated with poor clinical prognosis. Four m6A motifs were identified in Linc00662, which maintained the stability of Linc00662 in an IGF2BP3-coupled manner and were closely associated with the pro-tumor properties of Linc00662 in vitro and in vivo. ITGA1 was identified as a downstream gene regulated by Linc00662. Linc00662 recruites GTF2B to activate the transcription of ITGA1 in a m6A-dependent manner and initiates the formation of focal adhesions through the ITGA1-FAK-Erk pathway, thereby promoting malignant behavior in PC cells. The FAK inhibitor-Y15 obviously repressed tumor progression in Linc00662-overexpressing PC cells in vitro and in vivo. This study proposes a novel regulatory mechanism of Linc00662 in oncogene activation in PC and indicates that Linc00662 and its downstream genes are potential targets for PC therapy.

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Renal calculus is a common disease with complex etiology and high recurrence rate. Recent studies have revealed that gene mutations may lead to metabolic defects which are associated with the formation of renal calculus, and single gene mutation is involved in relative high proportion of renal calculus. Gene mutations cause changes in enzyme function, metabolic pathway, ion transport, and receptor sensitivity, causing defects in oxalic acid metabolism, cystine metabolism, calcium ion metabolism, or purine metabolism, which may lead to the formation of renal calculus. The hereditary conditions associated with renal calculus include primary hyperoxaluria, cystinuria, Dent disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis, Bartter syndrome, primary distal renal tubular acidosis, infant hypercalcemia, hereditary hypophosphatemic rickets with hypercalciuria, adenine phosphoribosyltransferase deficiency, hypoxanthine-guanine phosphoribosyltransferase deficiency, and hereditary xanthinuria. This article reviews the research progress on renal calculus associated with inborn error of metabolism, to provide reference for early screening, diagnosis, treatment, prevention and recurrence of renal calculus.

The long non-sacoding RNA TMEM147-AS1/miR-133b/ZNF587 axis regulates the Warburg effect and promotes prostatic carcinoma invasion and proliferation.

BACKGROUND: The Warburg effect is a characteristic tumor cell behavior regarded as one of the cancer hallmarks and promotes tumor progression by promoting glucose uptake and lactate production. Long non-coding RNAs (lncRNAs) had been reported to emerge as a vital function in cancer development. The present research is designed to investigate the underlying molecular mechanism of lncRNA TMEM147 antisense RNA 1 (TMEM147-AS1) on aerobic glycolysis in prostatic carcinoma. METHODS: lncRNA TMEM147-AS1, miR-133b and ZNF587 levels in prostatic carcinoma tissues and cells were detected by a polymerase chain reaction or western blot assays. Cell viability or invasion was determined by Edu (i.e. 5-ethynyl-2'-deoxyuridine), MTT (i.e. 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) or transwell assays. Hematoxylin and eosin and immunohistochemical staining were applied for histopathological examination. Tumor xenograft model was employed to investigate tumor growth in vivo. The combinative relationship between TMEM147-AS1 or ZNF587 and miR-133b was confirmed by a luciferase reporter assay. RESULTS: TMEM147-AS1 and ZNF587 were up-regulated in prostatic carcinoma tissues and cells. Knockdown of TMEM147-AS1 or ZNF587 within prostate cancer cells significantly restrained cell viability, invasion and aerobic glycolysis in vitro and suppressed the neoplasia of prostatic carcinoma in vivo. miR-133b was directly targeted in both TMEM147-AS1 and ZNF587. Overexpression of miR-133b restrained prostate cancer cell viability, invasion and aerobic glycolysis. TMEM147-AS1 competitively targeted miR-133b, therefore counteracting miR-133b-mediated repression on ZNF587. CONCLUSIONS: TMEM147-AS1 plays a tumor-promoting action in prostatic carcinoma aerobic glycolysis via affecting the miR-133b/ZNF587 axis, therefore regulating prostatic carcinoma cells invasion and proliferation. These outcomes implied that TMEM147-AS1 could be an effective treatment strategy for further study of prostatic carcinoma.

Misplaced drainage tube inserted in the vein in a percutaneous nephrostomy: a case series.

Percutaneous nephrostomy is a critical procedure for establishing surgical pathways from the skin to the renal collecting system. The drainage tube involved in the procedure rarely deviates into the renal vein. Herein, we report three cases in which the related drainage tube was mistakenly inserted into the renal vein and inferior vena cava after the renal vein was injured during percutaneous nephrostomy. In the three cases, the nephrostomy tube and double-J tube were gradually withdrawn from the renal pelvis or renal calyces under computed tomography (CT) monitoring. In case 1, the fistula tube was not completely withdrawn in time into the renal, causing multiple thromboses in the vein. The fistula was successfully withdrawn from the vena cava after the filter was placed. Finally, the stones were cleared in two cases and one case was discharged without complications after substantial renal function recovery. A safe and reliable approach is to gradually withdraw, within a short timeframe and under CT monitoring, an ectopic renal vein or inferior vena cava drainage tube into the renal pelvis. Removal of the catheter to the renal pelvis or calyces within 3 days can reduce thrombotic complications.

Cancer-derived exosomal circ_0038138 enhances glycolysis, growth, and metastasis of gastric adenocarcinoma via the miR-198/EZH2 axis.

This study aims to decipher the impact and downstream mechanisms of the bioinformatically identified circ_0038138 delivered by cancer-derived exosomes in gastric adenocarcinoma (GAC). Expression of circ_0038138 in clinical GAC tissues and exosomes (Exos) from clinical plasma samples (plasma-Exos) was predicted by bioinformatics analysis and validated by RT-qPCR. The binding affinity between circ_0038138, miR-198 and EZH2 was identified using luciferase activity, RIP, and RNA pull-down assays. GAC cells (AGS) were co-cultured with Exos isolated from GAC cell supernatant (GC9811-P). After co-culture, the behaviors of GAC cells including proliferation and glycolysis were assessed to identify the biological effect of exosomal circ_0038138. Also, in vivo effects of exosomal circ_0038138 on the tumorigenesis and lung metastasis of GAC cells were evaluated by developing nude mouse xenograft and metastatic models. circ_0038138 upregulation was detected in GAC tissues and plasma-Exos. Exos delivered circ_0038138 to GAC cells and potentiated the proliferative, migratory, invasive, and glycolytic potentials of GAC cells. Mechanistically, circ_0038138 competitively bound to miR-198, which in turn targeted EZH2 by binding to its 3'-UTR. Silencing of EZH2 promoted CXXC4 expression and inhibited Wnt/ß-catenin pathway activation, thus repressing the malignancy and glycolysis of GAC cells. In vivo assay confirmed that exosomal circ_0038138 induced tumorigenesis and lung metastasis by regulating the miR-198/EZH2 axis. Collectively, our work suggests that the Exo-mediated transfer of circ_0038138 potentially facilitates the glycolysis, growth and metastasis of GAC cells via miR-198/EZH2 axis, which offers a potential prognostic marker and a therapeutic target for GAC.

BATF3 promotes malignant phenotype of colorectal cancer through the S1PR1/p-STAT3/miR-155-3p/WDR82 axis.

Encouraging insight into novel underlying mechanisms targeting abnormal biological pathways in colorectal cancer (CRC) are currently under investigation, edging closer and closer to clinical use. Of note, basic leucine zipper ATF-like transcription factor 3 (BATF3) has been implicated with the tumorigenicity of CRC. The current study aimed to elucidate the oncogenic BATF3-mediated S1PR1/p-STAT3/miR-155-3p/WDR82 axis in CRC. Initially, clinical samples of CRC tissues as well as CRC cell lines were collected to evaluate the expression patterns of BATF3/S1PR1/p-STAT3/miR-155-3p/WDR82. Dual luciferase assay was employed to assess the binding affinity between miR-155-3p and WDR82. Artificial modulation of BATF3 (down- and overexpression) was conducted to measure the malignant phenotypes of CRC cells, while tumor-bearing mice were examined to determine the in vivo effects. BATF3 facilitated the proliferative, migratory, and invasive potential of CRC cells by upregulating S1PR1. Besides, the stimulatory effect of S1PR1 was realized via restored p-STAT3 expression. Furthermore, p-STAT3 was evidenced to heighten the expression of miR-155-3p and subsequently restrict the expression of its target gene WDR82. The in vivo assays provided data further substantiating the in vitro findings that inactivation of the BATF3/S1PR1/p-STAT3/miR-155-3p/WDR82 axis suppresses CRC tumor growth. Collectively, the results of the present study emphasize the oncogenic function of BATF3 illustrated by the reinforcement the biological processes of proliferation, invasion, as well as the metastatic capacity of CRC cells through activating the S1PR1/p-STAT3/miR-155-3p/WDR82 axis.

Asymptomatic versus symptomatic solid pseudopapillary tumors of the pancreas: clinical and MDCT manifestations.

BACKGROUND: To delineate the features of multi-detector computed tomography (MDCT) images and clinical characteristics of pancreatic solid pseudopapillary tumors (SPTs) of the pancreas in asymptomatic patients and compare these features and characteristics between asymptomatic and symptomatic patients. METHODS: This work is a retrospective study approved by our institutional review board. MDCT images and clinical data of 109 patients with pathologically proven SPTs obtained from October 2008 to October 2016 were reviewed. Patients were categorized into two groups: asymptomatic patients and patients with symptomatic disease. Cases were reviewed to determine the reason for detection, intervention, shape, diameter, location, calcification, encapsulation, internal composition, CT attenuation, enhancement pattern, and tumor pathology. Clinical factors and imaging features were also compared between groups. Statistical analysis was performed using χ2 and t-tests. RESULTS: Data from 49 asymptomatic and 60 symptomatic patients were collected. Asymptomatic SPTs were identified most frequently during routine health examination (18 patients, 36.7%), various screening purposes (12 patients, 24.5%), and traumatic injury (9 patients, 18.4%). Except for a smaller tumor size (5.8 cm in asymptomatic SPTs vs. 7.4 cm in symptomatic SPTs, P = 0.023), the clinical factors or imaging features of asymptomatic patients were very similar to those of symptomatic patients. CONCLUSIONS: The current research is the first single-center study to characterize SPTs in asymptomatic patients. Asymptomatic SPTs are gradually being identified with greater frequency. Although generally smaller in size than that in symptomatic patients, an asymptomatic pancreatic mass with the typical imaging features of SPT may be found, the treatment for which is similar to that for symptomatic patients. Evaluating asymptomatic SPTs requires further systematic and multi-center trials.

PETModule: a motif module based approach for enhancer target gene prediction.

The identification of enhancer-target gene (ETG) pairs is vital for the understanding of gene transcriptional regulation. Experimental approaches such as Hi-C have generated valuable resources of ETG pairs. Several computational methods have also been developed to successfully predict ETG interactions. Despite these progresses, high-throughput experimental approaches are still costly and existing computational approaches are still suboptimal and not easy to apply. Here we developed a motif module based approach called PETModule that predicts ETG pairs. Tested on eight human cell types and two mouse cell types, we showed that a large number of our predictions were supported by Hi-C and/or ChIA-PET experiments. Compared with two recently developed approaches for ETG pair prediction, we shown that PETModule had a much better recall, a similar or better F1 score, and a larger area under the receiver operating characteristic curve. The PETModule tool is freely available at http://hulab.ucf.edu/research/projects/PETModule/.

Clinicopathological and prognostic significance of myofibrillogenesis regulator-1 protein expression in pancreatic ductal adenocarcinoma.

Myofibrillogenesis regulator-1 (MR-1) expression was detected in different malignancies and is associated with poor prognosis. However, its role in pancreatic ductal adenocarcinoma (PDAC) has not been fully elucidated. Thus, the aim of this study was to investigate the association of MR-1 expression with clinicopathologic features and prognosis in patients with PDAC. Immunohistochemistry was performed to investigate the protein expression of MR-1 and epithelial (E)-cadherin in 87 patients with PDAC. Results showed that MR-1 expression was correlated with histologic grade, tumor stage, and lymph node metastasis (all P <0.05). In addition, MR-1 expression showed a significant inverse correlation with E-cadherin expression (P = 0.002). Furthermore, the variables associated with prognosis were analyzed by Cox's proportional hazards model. Kaplan-Meier analysis was used to plot survival curves according to different expression levels of MR-1. Kaplan-Meier analysis revealed that MR-1 expression was significantly associated with worse disease-free survival (DFS) and overall survival (OS) rates in patients with PDAC (both P <0.001). Finally, multivariate analysis demonstrated that MR-1 expression, together with histologic grade, tumor stage, lymph node metastasis, was an independent prognostic factor for both DFS and OS rates in patients with PDAC. MR-1 overexpression was tightly associated with more aggressive tumor behavior and a poor prognosis, indicating that MR-1 is a valuable molecular biomarker for PDAC progression.