Bladder cancer (BCa) is a prevalent genitourinary malignancy characterized by limited specific diagnostic and therapeutic options. Although hypoxia is known to drive tumor progression via exosome-mediated communication, the specific oncogenic roles of hypoxia-induced exosomal long non-coding RNAs (lncRNAs) remain poorly elucidated. Here, we profiled exosomes from normoxic and hypoxic BCa cells using high-throughput sequencing, identifying LNCOC1 as a significantly upregulated lncRNA under hypoxic conditions. Mechanistically, hypoxia-inducible factor 1α (HIF1A) directly binds to the LNCOC1 promoter to drive its transcription and subsequent exosomal encapsulation. Upon transfer to recipient cells, exosomal LNCOC1 promotes BCa cell proliferation, migration, and invasion. It acts as a nuclear scaffold, directly recruiting the transcription factor YBX1 to the PIK3CA promoter, thereby upregulating PIK3CA expression and hyperactivating the PI3K/AKT signaling pathway. Clinically, elevated LNCOC1 levels in tumor tissues and circulating plasma exosomes from 96 BCa patients positively correlated with advanced tumor grade, metastasis, and poor prognosis. Furthermore, circulating exosomal LNCOC1 demonstrated moderate diagnostic efficacy in distinguishing BCa patients from healthy controls (AUC = 0.789) and metastatic from non-metastatic cases (AUC = 0.765). Collectively, these findings elucidate a novel HIF1A/LNCOC1/YBX1/PIK3CA regulatory axis, highlighting circulating exosomal LNCOC1 as a preliminary candidate biomarker for BCa diagnosis that warrants further validation in independent cohorts.

BACKGROUND:The urosepsis after percutaneous nephrolithotomy (PCNL) is a critical health risk necessitating prompt medical identification and intervention. Nevertheless, a deficiency exists in the availability of a tool for precise and timely predictive analysis. The purpose is to establish a machine learning (ML) model using radiomic features and clinical data to predict urosepsis following PCNL. METHOD:This study retrospectively included 401 patients with kidney stones from two centers who underwent PCNL. To enhance the dataset's equilibrium, the synthetic minority over-sampling technique for regression with Gaussian noise (SMOGN) was used to resample the training set. The screening of radiomics features and the construction of radiomics scores were completed by applying the Absolute Shrinkage Selection Operator (LASSO). Subsequently, the critical clinical indicators for urosepsis were pinpointed through the application of a multivariate logistic regression. The performance of seven ML algorithms was compared for the combined dataset that incorporated clinical variables and radiomics scores. The efficacy of these models was assessed through the implementation of a fivefold cross-validation process. Ultimately, the Shapley Additive exPlanations (SHAP) methodology was utilized to provide a visual and interpretative analysis of the optimal model. RESULT:Among 401 patients, 30 cases (7.48%) were diagnosed with urosepsis. The radiomics score, established by 13 radiomics features, was combined with six important clinical features (including urine nitrite positivity, stone volume, mean intrarenal pressures, urine white blood cells, and operation time) to construct a combined dataset. Comparative analysis of seven machine learning (ML) models revealed that CatBoost demonstrated superior predictive performance. The model achieved area under the receiver operating characteristic curve (AUC-ROC) values of 0.88, 0.94, and 0.89 on the training, internal test, and external validation sets, respectively. Corresponding area under the precision-recall curve (AUC-PR) values were 0.92, 0.75, and 0.63. The SHAP value method identifies key features influencing prediction outcomes, with the radiomics score and urine nitrite positivity being the top contributors to the model. We deployed the optimal prediction model to a web for clinical application ( https://predictive-model-for-urosepsis.streamlit.app/ ). CONCLUSION:This study constructed a predictive model that incorporates clinical risk characteristics and radiomics scores to assess the risk of urosepsis after PCNL, with SHAP visualization for clinical physicians to formulate evaluation strategies.

BACKGROUND:Bladder cancer (BC), a prevalent genitourinary malignancy, poses a substantial threat to public health, particularly among middle-aged and elderly populations. Given the increasing life expectancy, understanding the BC burden in these demographic groups is imperative. METHODS:Based on the GBD 2021 dataset encompassing 371 diseases and injuries with 88 risk factors globally, this study analyzed bladder cancer data from 204 countries and territories (1990-2021) for populations aged ≥55 years, with core metrics including incidence, deaths, and disability-adjusted life years (DALYs). We used Joinpoint regression analysis to assess temporal trends, calculating the Annual Percentage Change (APC) and Average Annual Percentage Change (AAPC). We conducted a decomposition analysis to break down the changes in mortality rates into contributions from aging, population growth, and epidemiological changes. We performed a frontier analysis using the Socio-demographic Index (SDI) to evaluate the relationship between bladder cancer burden in people aged 55 and above and socio-demographic development. Among them, we further combined the National Health and Nutrition Examination Survey (NHANES) database for risk analysis related to bladder cancer. Finally, we used the Bayesian age-period-cohort (BAPC) model to project bladder cancer trends from 2022 to 2036. RESULTS:From 1990 to 2021, bladder cancer cases among adults ≥55 years increased by 113% (226 421 to 483 234), while crude incidence rates declined slightly. Mortality rates decreased from 16.83 to 14.11 per 100 000, and DALYs rates dropped from 337.59 to 257.76. High-income regions (North America: 76.85/100 000; Western Europe: 77.62/100 000) had the highest incidence but showed downward trends, whereas Central Europe experienced rising mortality. Males consistently bore a 3.8-fold higher incidence burden than females. Smoking (26.6%) and high fasting glucose (8.2%) were key risk factors. According to NHANES data, elevated fasting blood glucose levels and smoking are both associated with an increased risk of bladder cancer. Projections to 2036 suggest continued declines: incidence (-13.3%), mortality (-16.4%), and DALYs (-17.9%). Health inequality persisted but improved marginally. CONCLUSION:The current data and future prediction of this study show that the incidence rate, mortality and DALYs rate of bladder cancer in middle-aged and elderly people have declined. However, disparities in disease burden still exist across regions. Thus, tailored measures are needed to reduce inequalities in high-burden areas.

OBJECTIVE:To investigate the pharmacological mechanism of Compound Xuanju Capsule in the treatment of erectile dysfunction (ED) by using network pharmacology and molecular docking technology. METHODS:The active ingredients and targets of Compound Xuanju Capsule were screened using Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform (TCMSP). TTD, OMIM, DrugBank and GeneCards databases were used to obtain genes related to ED, and the union of the results was taken as the disease genes of ED. The common target of drug and disease was taken as the potential target of Compound Xuanju Capsule in ED, and the drug-disease interaction network was constructed by using Cytoscape software. The protein-protein interaction (PPI) network was constructed by using String database, which was then imported into Cytoscape to identify the key target. Based on the drug-disease intersection genes, GO and KEGG enrichment analyses were performed to predict the relevant signaling pathways and molecular mechanisms of Compound Xuanju Capsule for the treatment of ED. Autodock software was used to perform molecular docking between the active ingredients and the core targets. RESULTS:Forty chemical components of Compound Xuanju Capsule were screened, and 239 predicted targets were obtained. A total of 1 907 ED-related genes were screened, and 97 common targets were identified between Compound Xuanju Capsule and ED, among which the core targets included EGFR, ESR1, HIF1A, PTGS2, and STAT3. The signaling pathways obtained by KEGG enrichment analysis included calcium signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway, cGMP-PKG signaling pathway, relaxin signaling pathway, Serotonergic synapse signaling pathway. The molecular docking results showed that there were molecular binding sites between the key active ingredients and the core targets with strong binding activity. CONCLUSION:Compound Xuanju Capsule may treat ED through multi-target pathways such as anti-inflammatory and improving cellular oxidative stress.

To evaluate the feasibility, safety and efficacy of robot-assisted laparoscopic modified ureteroplasty using a lingual mucosa graft (LMG) or an appendiceal flap (AF) for complex ureteral strictures and summarize our experience. A total of 16 patients with complex ureteral strictures (range: 1.5–5 cm) who underwent robotic-assisted laparoscopic-modified ureteroplasty and were admitted to our hospital from May 2022-October 2023 were retrospectively analyzed. We used modified presuture methods in patients who needed the posteriorly augmented anastomotic technique to reduce anastomotic tension. Perioperative variables and outcomes were recorded for each patient. The operation under robot-assisted laparoscopy was successfully performed in all sixteen patients (12 with LMG ureteroplasty and 4 with AF ureteroplasty) without conversion to open surgery. The mean length of the ureteral structure was 2.90 ± 0.90 cm (range: 1.5–5 cm), the mean operation duration was 209.69 ± 26.74 min (range: 170–255 min), the median estimated blood loss was 75 (62.5) ml (range: 50–200 ml), and the duration of postoperative hospitalization was 10.44 ± 2.10 d (range: 7–14 d). The follow-up time in this group was 6 21 months. The success rate of the surgery was 100

Bladder cancer (BC) is one of the most common malignant neoplasms worldwide. Competing endogenous RNA (ceRNA) networks may identify potential biomarkers associated with the progression and prognosis of BC. The OCT4-pg5/miR-145-5p/OCT4B ceRNA network was found to be related to the progression and prognosis of BC. OCT4-pg5 expression was significantly higher in BC cell lines than in normal bladder cells, with OCT4-pg5 expression correlating with OCT4B expression and advanced tumor grade. Overexpression of OCT4-pg5 and OCT4B promoted the proliferation and invasion of BC cells, whereas miR-145-5p suppressed these activities. The 3' untranslated region (3'UTR) of OCT4-pg5 competed for miR-145-5p, thereby increasing OCT4B expression. In addition, OCT4-pg5 promoted epithelial-mesenchymal transition (EMT) by activating the Wnt/β-catenin pathway and upregulating the expression of matrix metalloproteinases (MMPs) 2 and 9 as well as the transcription factors zinc finger E-box binding homeobox (ZEB) 1 and 2. Elevated expression of OCT4-pg5 and OCT4B reduced the sensitivity of BC cells to cisplatin by reducing apoptosis and increasing the proportion of cells in G1. The OCT4-pg5/miR-145-5p/OCT4B axis promotes the progression of BC by inducing EMT via the Wnt/β-catenin pathway and enhances cisplatin resistance. This axis may represent a therapeutic target in patients with BC.

Objective To report the experience of partial inferior pubicectomy in the treatment of complex posterior urethral stricture after trauma. Methods A total of 46 patients with post-traumatic posterior urethral stricture admitted to the Department of Urology of our Hospital from January 2013 to September 2021 were selected as the research objects and underwent urethroplasty (including nine patients who had failed previous perineal repair surgery and adopted partial inferior pubicectomy approach). Retrograde urethrograph (RUG) and urine flow measurement were performed at 1, 3, 12 and 18 months after operation, and follow-up was performed when necessary. The clinical data during treatment were statistically analyzed. Results All 46 patients underwent urethroplasty successfully, of which nine were treated with partial pubicectomy, accounting for 19.57% of the total. The causes of the disease were motor vehicle accident in 4 cases, falling collision injury in 2 cases, and rolling injury of military exercise tank in 3 cases. Among the 9 patients, 2 were children (22.22%), aged 8 and 12 years, and 7 were adults (77.78%), aged 19–44 (28.42 ± 1.56) years. Among the 9 patients, 6 had erectile dysfunction, accounting for 66.67%. The length of posterior urinary tract stenosis was (5.12 ± 0.57) cm. The operation time was (290.34 ± 12.35) min from anesthesia induction to skin closure. Five patients received 2 U blood transfusion during operation and three patients received 3 U blood transfusion after operation. The average hospital stay was 12–16 (14.24 ± 1.25) days, and the follow-up was 12–24 (18.24 ± 1.35) months. After surgery, one patient developed HIP abscess, which was successfully treated conservatively. One patient had dysuria 1 month after operation and was successfully treated by transurethral dilatation. One case had postoperative infection and recovered after intravenous administration of potent antibiotics. Cystourethrography was performed 3 months after operation, and there was no difference between patients with wide, long or short anastomotic stretch defects. All patients met the criteria for surgical success. Conclusion Partial inferior pubicectomy is a good surgical procedure for the repair of complicated posterior urethral stricture after operation. It is safe and reliable, can better display the prostatic apex and surgical field, shorten the length of reconstructed urethra, and has good postoperative effect. It has no direct or long-term effect on the stability of pelvis or bladder. However, further studies in a larger cohort of patients with complex posterior urethral strictures after repair are needed to demonstrate the specific indications for partial pubicectomy.

BACKGROUND:The common causes of adrenocorticotrophic hormone (ACTH)-dependent Cushing's syndrome (CS) include Cushing's disease (CD) and ectopic ACTH syndrome (EAS). The differential diagnosis and lesion location of CD and EAS often bring great difficulties to clinical diagnosis and treatment. This article reports the localization diagnosis, treatment, and follow-up results of two patients with ACTH-dependent CS with different causes and reviews the literature.CASE DESCRIPTION:Case 1: a 29-year-old female patient attended the clinic because of irregular menstruation, weight gain, and violaceous striae. The low dose dexamethasone suppression test (LDDST) was not suppressed, and the high dose dexamethasone suppression test (HDDST) suggested the results of serum cortisol and 24-h urine free cortisol were contradictory. Magnetic resonance imaging (MRI) indicated pituitary microadenoma, and bilateral inferior petrosal sinus sampling (BIPSS) indicated ACTH was centrally secreted. CD was diagnosed. The patient underwent transsphenoidal surgery, and the symptoms of CS were improved after the operation. A natural pregnancy occurred more than half a year after the surgery, and a healthy baby boy was delivered 9 months later. Case 2: a 29-year-old female patient complained of facial redness and elevated blood pressure. Examination showed refractory hypokalemia and abnormally elevated serum cortisol and ACTH. Androgens also increased. Neither LDDST nor HDDST was inhibited. Chest-to-pelvis computed tomography (CT) scan revealed a soft tissue mass in the anterior mediastinum, considered as a possible thymoma. EAS and thymoma were diagnosed. An anterior mediastinal mass resection was performed, and pathological results suggested thymic carcinoid weakly positive for ACTH. After the operation, hypertension and hypokalemia were relieved, and cortisol, ACTH and androgens returned to normal levels.CONCLUSIONS:The differentiation between CD and EAS should be comprehensively evaluated in combination with the medical history, function tests, pituitary MRI, and other tests. If the function test results are discordant or pituitary MRI shows the lesion diameter is less than 6 mm, BIPSS should be further performed to confirm the diagnosis. The lesions of EAS are complex and diverse, and it is necessary to pay attention to imaging examinations of the neck-to-pelvis to locate lesion and provide direction for subsequent treatment.

Abstract Background Airborne fine particulate matter (PM2.5) has been associated with lung cancer development and progression in never smokers. However, the molecular mechanisms underlying PM2.5-induced lung cancer remain largely unknown. The aim of this study was to explore the mechanisms by which PM2.5 regulated the carcinogenesis of non-small cell lung cancer (NSCLC). Methods Paralleled ribosome sequencing (Ribo-seq) and RNA sequencing (RNA-seq) were performed to identify PM2.5-associated genes for further study. Quantitative real time-PCR (qRT-PCR), Western blot, and immunohistochemistry (IHC) were used to determine mRNA and protein expression levels in tissues and cells. The biological roles of PM2.5 and PM2.5-dysregulated gene were assessed by gain- and loss-of-function experiments, biochemical analyses, and Seahorse XF glycolysis stress assays. Human tissue microarray analysis and 18F-FDG PET/CT scans in patients with NSCLC were used to verify the experimental findings. Polysome fractionation experiments, chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assay were implemented to explore the molecular mechanisms. Results We found that PM2.5 induced a translation shift towards glycolysis pathway genes and increased glycolysis metabolism, as evidenced by increased L-lactate and pyruvate concentrations or higher extracellular acidification rate (ECAR) in vitro and in vivo. Particularly, PM2.5 enhanced the expression of glycolytic gene DLAT, which promoted glycolysis but suppressed acetyl-CoA production and enhanced the malignancy of NSCLC cells. Clinically, high expression of DLAT was positively associated with tumor size, poorer prognosis, and SUVmax values of 18F-FDG-PET/CT scans in patients with NSCLC. Mechanistically, PM2.5 activated eIF4E, consequently up-regulating the expression level of DLAT in polysomes. PM2.5 also stimulated transcription factor Sp1, which further augmented transcription activity of DLAT promoter. Conclusions This study demonstrated that PM2.5-activated overexpression of DLAT and enhancement in glycolysis metabolism contributed to the tumorigenesis of NSCLC, suggesting that DLAT-associated pathway may be a therapeutic target for NSCLC.

This study explores the effect of silencing lysyl oxidase-like protein-2 (LOXL2) gene on TE-1 cells. TE-1 cells were transfected by LOXL2-siRNA. E-cadherin, LOXL2, and Snail were detected using Western blot and Real-time PCR. Transwell invasion and migration assay was performed. Flow cytometry detected apoptosis. Cell growth was analyzed with CCK-8 and colony formation. After48 h of transfection, compared with control groups, LOXL2 mRNA in the LOXL2-siRNA group (0.40±0.01) lowered significantly (P < 0.05). Consistently, LOXL2 protein in LOXL2-siRNA group was (0.48± 0.02), significantly lower than that in blank control (1.04± 0.03) and negative control (1.02± 0.02) (P < 0.05). After 72 h of cell culture, the absorbance of LOXL2-siRNA group was (0.43±0.04), which reduced significantly than blank control (0.81±0.05) and negative control (0.84±0.06) (P < 0.05). Similarly, cell clone number after LOXL2-siRNA transfection (72.3±4.2)increased significantly than the negative control (178.8±4.6) and blank control (167.3±3.5) (P < 0.05). However, LOXL2 silencing did not significantly affect cell apoptosis. Furthermore, LOXL2 silencing inhibited Snail while increased E-cadherin (P < 0.05). Conclusively, LOXL2 silencing may suppress the invasion and proliferation of esophageal cancer cells via down-regulating Snail, and up-regulating E-cadherin to inhibit EMT in esophageal cancer cells.

Abstract Background: Centrosomal protein 55 (CEP55) is implicated in the tumorigenesis of bladder cancer (BC) but the detailed molecular mechanisms are unknown. We aim to develop a potential competing endogenous RNA (ceRNA) network related with CEP55 in BC.Methods: We first extracted the expression profiles of RNAs from The Cancer Genome Atlas (TCGA) database and used bioinformatic analysis to establish ceRNAs in BC. Real-time quantity PCR (RT-qPCR) and immunohistochemical analysis were performed to measure CEP55 expression in different bladder cell lines and different grades of cancer. Bioinformatics analysis and luciferase assays were conducted to predict potential binding sites among miR-497-5p, CEP55, parathyroid hormone like hormone (PTHLH) and high mobility group A2 (HMGA2). Tumor xenograft model was used to show the effect of CEP55 3’-UTR on cisplatin therapy. Bioinformatics analysis, luciferase assays, and 5' rapid amplification of cDNA ends (5’RACE) were to explore the function of CEP55 3’-untranslated region (3’-UTR) on targeting miR-497-5p. Western blot and immunofluorescence assays were to detect the epithelial–mesenchymal transition (EMT) induction of CEP55 3’-UTR.Results: CEP55 expression as well as the expression levels of the oncogenic proteins PTHLH and HMGA2 were upregulated in BC cells while miR-497-5p was downregulated. Low miR-497-5p expression and high CEP55 and HMGA2 expression levels were associated with more advanced tumor clinical stage and pathological grade. Overexpression of the CEP55 3’-UTR promoted the proliferation, migration, and invasion of the EJ cell line in vitro and accelerated EJ-derived tumor growth in nude mice, while inhibition of the CEP55 3’-UTR suppressed all of these oncogenic processes. In addition, CEP55 3’-UTR upregulation reduced the cisplatin sensitivity of BC cell lines and xenograft tumors. Bioinformatics analysis, luciferase assays, and 5’RACE suggested that the CEP55 3’-UTR functions as a ceRNA targeting miR-497-5p, leading to miR-497-5p downregulation and disinhibition of PTHLH and HMGA2 expression. Further, CEP55 downregulated miR-497-5p transcription by promoting NF-kB signaling. In turn, PTHLH and HMGA2 activated p38MAPK and ERK 1/2 pathways, and induced EMT of BC cells. Conclusions: These results suggest that a ceRNA regulatory network involving CEP55 upregulates PTHLH and HMGA2 expression by suppressing endogenous miR-497-5p in bladder cancer.

Background Octamer-binding transcription factor 4 pseudogene 5 (OCT4-pg5) contributes to tumor progression in many cancer types, but contributions to bladder cancer (BC) have not been investigated. Methods Real-time quantity PCR ( RT-qPCR) was performed to measure OCT4-pg5 and OCT4B expressions in different bladder cell lines and different grades of cancer. The effects of OCT4-pg5, OCT4B and miR-145 on proliferation and metastasis were determined by in vitro and in vivo experiments. Luciferase reporter assay was carried out to reveal the interaction among OCT4-pg5, OCT4B and miR-145. Flow cytometry was performed to explore the effects of OCT4-pg5 and OCT4B expression on the cell cycle stage distribution of T24 cells. Results OCT4-pg5 expression was significantly increased in BC cell lines, which was correlated with OCT4B expression and advanced tumor grade. Overexpression of OCT4-pg5 and OCT4B promoted the proliferation and invasion of BC cells, while miR-145 suppressed these activities. Mechanically, OCT4-pg5 3’ untranslated region (3’UTR) competed for miR-145, thereby increasing OCT4B expression. In addition, OCT4-pg5 promoted EMT by activating the Wnt/β-catenin pathway and upregulating the expression levels of matrix metalloproteinases (MMPs) 2 and 9 as well as transcription factors zinc finger E-box binding homeobox (ZEB) 1 and 2. Furthermore, elevated expression of OCT4-pg5 and OCT4B reduced the sensitivity of BC cells to cisplatin by reducing apoptosis and increasing the proportion of cells in G1. Conclusions These findings indicate that OCT4-pg5/miR-145/OCT4B axis promotes the progression of BC by inducing EMT via Wnt/β-catenin pathway and enhances the cisplatin resistance. It could be prospect for the therapeutic approaches for BC.

BACKGROUND:Increasing evidences have underlined the importance of long non-coding RNAs (lncRNAs) in human malignancies. LINC00958 has been found involved in some cancers. However, the underlying mechanical performance of LINC00958 in lung adenocarcinoma (LAD) has not been explored yet.METHODS:The expression of relevant mRNA and protein were measured by qRT-PCR and western blot assays. EdU, colony formation, TUNEL and transwell assays were performed to investigate the function of LINC00958 on LAD progression. Luciferase reporter, RNA pull down and RIP assays were conducted to investigate the molecular mechanism of relevant RNAs.RESULTS:LINC00958 was found notably overexpressed in LAD, which was associated with the stimulation of its promoter activity induced by SP1. LINC00958 depletion dramatically inhibited LAD cell proliferation, migration and invasion capacities by acting as a miR-625-5p sponge. MiR-625-5p curbed LAD progression via targeting CPSF7 and down-regulating its expression. Mechanically, LINC00958 was identified as a competing endogenous RNA (ceRNA) and positively regulated the expression of CPSF7 via sponging miR-625-5p.CONCLUSIONS:LINC00958 might drive LAD progression via mediating miR-625-5p/CPSF7 axis, indicating the potential of targeting LINC00958 for the treatment of LAD.

Introduction: Extranodal natural killer/T-cell lymphoma (ENKTL) - nasal type is an aggressive form of malignant non-Hodgkin lymphoma with a very poor prognosis. Especially primary pulmonary ENKTL is a relatively rare form of non-Hodgkin lymphoma. Until now, the prevalence of primary pulmonary ENKTL is unknown. Since 2001, only 18 cases of primary pulmonary ENKTL have been published, in addition to the 2 cases reported here. Patient concerns: We describe 2 cases of primary pulmonary ENKTL. Both patients were male non-smokers, aged 61 and 49 years. Their main clinical symptoms included cold-like symptoms and intermittent fever (39.3 degrees C and 38.8 degrees C) for some days (40 days and 3 weeks). Both patients had no relevant personal or family medical history. Diagnosis: The patients were initially misdiagnosed with community-acquired pneumonia. Primary pulmonary ENKTL was confirmed by immunohistochemical staining of computed tomography-guided transthoracic needle biopsy specimens. Both cases were positive for CD56, CD3, and in situ hybridization for Epstein-Barr virus-encoded small RNA, but negative for CD20. Interventions: Initially, both patients were treated inadequately with intravenous moxifloxacin administration (unknown dosage and 400 mg q.d) in their local hospitals. Once diagnosed with primary pulmonary ENKTL in our hospital, they received 3 cycles of chemotherapy with combined regimens of dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE), and in the second patient, bone marrow transplantation was performed following the third chemotherapy cycle. Outcomes: Clinical follow-up after the chemotherapy showed that the condition of the first patient progressively deteriorated. He died 2 months following the initial diagnosis. However, the presence of the hemophagocytic lymphohistocytosis gradually improved in the second patient during chemotherapy. Ultimately, the second patient died of acute transplant rejection 6 months after the initial diagnosis. Conclusion: The diagnosis of ENKTL should be considered when patients present with fever and expansile consolidation of the lung not responding to antibiotics. The diagnosis depends on histopathology and immunophenotyping. Percutaneous transthoracic needle biopsy is a safe and effective biopsy method. Chemotherapy may improve the prognosis, but this should be confirmed by prospective multicenter studies.

Objective To investigate the effects of octamer-binding transcription factor 4 pseudogene 5 (OCT4-pg5) and octamer-binding transcription factor 4B (OCT4B) expression on cisplatin sensitivity of bladder cancer T24 cells. Methods The expression of OCT4-pg5 and OCT4B in bladder cancer cells and tissues were quantified by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR). To examine the effect of OCT4-pg5 and OCT4B on cisplatin sensitivity, cells were transfected with OCT4-pg5 si-RNA, OCT4B si-RNA and their control si-RNA by lipofectamine 2000 followed by a 48 h cisplatin treatment. CCK8 was used to assess the half-maximal inhibitory concentration (IC50) of cisplatin in T24 cells. OCT4-pg5 and OCT4B expression were detected by RT-qPCR or Western blot. Next, flow cytometry was used to examine the effects of OCT4-pg5 and OCT4B on T24 cells apoptosis and cell-cycle distribution. Results RT-qPCR results showed that OCT4-pg5 and OCT4B were highly expressed in bladder cancer cells and tissues. Moreover, OCT4-pg5 expression was positively correlated with OCT4B expression in 23 bladder cancer tissues. Cells transfected with OCT4-pg5 si-RNA or OCT4B si-RNA showed a much lower IC50 of cisplatin, compared with cells in the control group. RT-qPCR or Western blot results showed OCT4-pg5 or OCT4B expression was significantly down-regulated after being transfected with OCT4-pg5 si-RNA or OCT4B si-RNA in cisplatin treated T24 cells. The flow cytometry results showed that OCT4-pg5 suppression or OCT4B suppression of cisplatin treated T24 cells resulted in a significant increase of cell apoptosis and marked the transition from the S phase to G0/G1 phase. Conclusions Downregulating OCT4-pg5 and OCT4B could enhance the sensitivity of bladder cancer T24 cells to cisplatin. DOI: 10.11855/j.issn.0577-7402.2020.02.11

Objective To investigate octamer-binding transcription factor 4 pseudogene 5 (OCT4-pg5) expression in bladder cancer cell lines and its effect on T24 migration and invasion and the potential mechanism.Methods The real-time quantitative reverse transeriptase-polymerase chain reaction (RT-qPCR) was conducted to detect OCT4-pg5 expression in 5 kinds of bladder cancer cell lines (5637,EJ,BIU-87,T24,TCCSUP) and one normal Bladder epithelial cell line SV-HUC-1.Si-OCT4-pg5 vector and its control vector were transfected into T24 cells by Lipofectamine 2000,and OCT4-pg5 expression was detected by RT-qPCR.Next,wound healing assay and Transwell assay were used to examine the effects of OCT4-pg5 on T24 cell migration and invasion.Moreover,the possible mechanism by which OCT4-pg5 mediated T24 migration and invasion was explored using Western blotting and RT-qPCR.Results In comparison to SV-HUC-1,OCT4-pg5 levels were up-regulated in bladder cancer cell lines,especially in T24 cell (P ＜0.01).RT-qPCR results showed that OCT4-pg5 espression was obviously down-regulated after being translated with si-OCT4-pg5 vector.OCT4-pg5 down-expression in T24 cell could inhibit cell migration [(28.50 ± 4.08) ％ and (43.26 5.49) ％,P ＜ 0.01] and invasion [(104.50 ± 6.95) and (140.50 ± 8.90) cells,P ＜ 0.01].In addition,down-regulation of OCT4-pg5 significantly reduced Vimentin (0.60 ± 0.06) and β-catenin (0.70 ± 0.08)mRNA expression,and improved E-cadherin mRNA expression (1.50 ± 0.10) when compared with their contral groups (1.00 ± 0.02,1.00 ± 0.04 and 1.00 ± 0.05,respectively,P ＜ 0.01).Moreover,the same results were also obtained by western blotting.Conclusion OCT4-pg5 is overexpression in bladder cancer cells.And OCT4-pg5 down-expression in T24 cell could inhibit cell migration and invasion.OCT4-pg5 mediated T24 migration and invasion probably induced by regulating E-cadherin,Vimentin,β-catenin expression.

BACKGROUND Diabetes mellitus (DM) is a risk factor for renal failure and possibly for renal cell carcinoma (RCC). Post-transplantation DM occurs frequently after solid organ transplantation. We investigated whether new-onset diabetes after renal transplantation (NODAT) is a risk factor for RCC or renal failure. MATERIAL AND METHODS Data of 96,699 discharged patients with and without NODAT were extracted from the 2005-2014 Nationwide Inpatient Sample (NIS) database, after excluding patients with DM diagnosed at least 1 year prior to renal transplantation. Main outcomes were RCC diagnosis less than 1-year post-transplantation, RCC stage, and renal failure. Univariate and multivariate regression analyses were performed to identify demographic and clinical factors associated with post-transplantation RCC or renal failure. RESULTS Significant differences were found in age and race between patients with and without NODAT (both P<0.001). The renal failure rate was 0.8% (n=1) in NODAT patients and 0.3% (n=314) in those without NODAT. Older age (OR, 1.030; 95% CI: 1.023 to 1.036), male (OR, 1.872; 95% CI: 1.409 to 2.486), Black (OR, 2.199; 95% CI: 1.574 to 3.071) and hospitalization in urban teaching hospitals were associated with increased risk of RCC. CONCLUSIONS Analysis of over 90,000 NIS hospitalizations with diagnosis-coded kidney transplantation suggested that NODAT may not be an independent risk factor for RCC and renal failure.

LIM kinases modulate multiple aspects of cancer development, including cell proliferation and survival. As the mechanisms of LIMK‐associated tumorigenesis are still unclear, we analyzed the tumorigenic functions of LIM kinase 2 (LIMK2) in human bladder cancer (BC) and explored whether the newly identified LIMK2 3´‐UTR SNP rs2073859 (G‐to‐A allele) is correlated with clinical features. Expression levels of LIMK2 in 38 human BC tissues and eight cell lines were examined using quantitative real‐time PCR and immunohistochemistry. LIMK2 was overexpressed in most BC tissues (27/38, 71%) and BC‐derived cell lines (6/8), and was more frequently overexpessed in high‐grade than low‐grade BC (80% vs. 47%). The effects of LIMK2 on BC cell proliferation, survival and migration, were studied by overexpression and RNA interference approaches in vitro and in vivo. LIMK2 overexpression promoted proliferation, migration and invasion of BC cells, while LIMK2 depletion inhibited cell invasion and viability and induced growth arrest in vitro and in vivo. PCR‐Restriction Fragment Length Polymorphism (RFLP) was used to genotype LIMK2 SNP rs2073859 and multivariate logistic regression applied to assess the relationship between allele frequency and clinical features in 139 BC patients. Functional analyses localized SNP rs2073859 within the microRNA‐135a seed‐binding region and revealed significantly lower LIMK2 G allele expression. The frequency of A genotypes (AG + AA) was higher in the BC group than normal controls and correlated with risks of high‐grade and high‐stage BC. In conclusion, LIMK2 may function as an oncogene in human BC, while allele‐specific regulation by microRNA‐135a may influence disease risk.

Objective To observe the expression of microRNA-497 (miR-497) in bladder cancer cells and investigate its possible functions in epithelial-mesenchymal transition (EMT) of bladder cancer.Methods The expression of miR-497 in bladder cells and human normal bladder tissue were measured by real-time quantitative polymerase chain reaction (RT-qPCR).MiR-497 mimics and miR-497 inhibitor were transfected into bladder cancer EJ cells and RT-qPCR was used to analyze the effect of transfection.Then,morphological changes of cells were observed under the inverted microscope and the wound healing assay,transwell invasion assay were used to detect the cell migration and invasion of bladder cancer EJ cells transfected by miR-497 mimics and miR-497 inhibitor.cytometry.Finally,Western blotting was applied to detect the levels of EMT-related proteins.Results MiR-497 levels were obviously down-regulated in bladder cancer cells (5637,EJ,BIU-87,TCCSUP and T24) in comparison to human bladder pillon biochemical cell (SV-HUC-1),the difference was statistically significant (P =0.000).Compared with negative control,overexpression of miR-497 significantly suppressed EJ cells migration [(74.00 ± 3.61) ％ vs.(25.33 ± 6.11) ％] and invasion [(219 ± 17) cells vs.(109 ± 3) cells],and EJ ceils turned into epithelioid cells morphology,when compared with the control group.Moreover,opposite results were obtained when miR-497 inhibitor was transfected into EJ cells.Compared with mimics NC,the protein expression of E-cadherin was upregulated (P =0.000),while N-cadherin and vimentin downregulated (P =0.001,P =0.000) in miR-497 mimics transfection group.Conclusion MiR-497 may play an important role of EMT in bladder cancer.

Objective To explore the clinical effect of inlay labial mucosa graft urethroplasty (LMGU) forⅠperiod in the complexity hypospadias.Methods According to the digital table,30 patients with complexity hypospadias were randomly divided into control group and observation group,15 cases in each group.The control group took Ⅰ period operation.The observation group received surgery by stages to complete.Routine urinary diversion during operation was performed after bladder puncture and ostomy,and in the control group,the urethra was placed with self-made 10-14F lateral hole silica gel stent,which was extracted out in the middle of the perineum,left or right.After 12-14d removal postoperative,the urination was observed.The catheter in the observation group was removed after 10 d,the urethroplasty is performed 6 months later.The clinical effects of the two groups were compared.Results In the control group,postoperative urinary fistula in 2 cases(13.3%),urethral orifice in 1 case(6.7%).In the observation group,postoperative urinary fistula in 2 cases(13.3%),6 months postoperatively in patients with urinary fistula to repair fistula was successful,urethral mouth narrow pure line incision.The incidence rate of complication of the control group was 20.0%,which of the observation group was 13.3%,the difference was not significant between the two groups(P>0.05).All cases were followed up for 1 to 2 years,did not occur urinary tract stones,hair growth,oral ulcers,such as the limited mouth complications.The penis was straight,beautiful shape.Conclusion Inlay LMGU Ⅰperiod is suitable for multiple surgery led to the lack of local incidence,urethral plate dysplasia and with severe penis abnormalities such as complexity in patients with hypospadias.The postoperative complications,micturition,penile appearance have no obvious differences compared with the stage,it is worthy of clinical popularization and application.