Development and validation of a CT-based deep learning radiomics nomogram to predict muscle invasion in bladder cancer.

Objective: This study aimed to develop a nomogram combining CT-based handcrafted radiomics and deep learning (DL) features to preoperatively predict muscle invasion in bladder cancer (BCa) with multi-center validation. Methods: In this retrospective study, 323 patients underwent radical cystectomy with pathologically confirmed BCa were enrolled and randomly divided into the training cohort (n = 226) and internal validation cohort (n = 97). And fifty-two patients from another independent medical center were enrolled as an independent external validation cohort. Handcrafted radiomics and DL features were constructed from preoperative nephrographic phase CT images. Least absolute shrinkage and selection operator (LASSO) regression was used to identify the most discriminative features in train cohort. Multivariate logistic regression was used to develop the predictive model and a deep learning radiomics nomogram (DLRN) was constructed. The predictive performance of models was evaluated by area under the curves (AUC) in the three cohorts. The calibration and clinical usefulness of DLRN were estimated by calibration curve and decision curve analysis. Results: The nomogram that incorporated radiomics signature and DL signature demonstrated satisfactory predictive performance for differentiating non-muscle invasive bladder cancer (NMIBC) from muscle invasive bladder cancer (MIBC), with an AUC of 0.884 (95 % CI: 0.813-0.953) in internal validation cohort and 0.862 (95 % CI: 0.756-0.968) in external validation cohort, respectively. Decision curve analysis confirmed the clinical usefulness of the nomogram. Conclusions: A CT-based deep learning radiomics nomogram exhibited a promising performance for preoperative prediction of muscle invasion in bladder cancer, and may be helpful in the clinical decision-making process.

A CT-based deep learning model predicts overall survival in patients with muscle invasive bladder cancer after radical cystectomy: a multicenter retrospective cohort study.

BACKGROUND: Muscle invasive bladder cancer (MIBC) has a poor prognosis even after radical cystectomy (RC). Postoperative survival stratification based on radiomics and deep learning (DL) algorithms may be useful for treatment decision-making and follow-up management. This study was aimed to develop and validate a DL model based on preoperative computed tomography (CT) for predicting postcystectomy overall survival (OS) in patients with MIBC. METHODS: MIBC patients who underwent RC were retrospectively included from four centers, and divided into the training, internal validation, and external validation sets. A DL model incorporated the convolutional block attention module (CBAM) was built for predicting OS using preoperative CT images. The authors assessed the prognostic accuracy of the DL model and compared it with classic handcrafted radiomics model and clinical model. Then, a deep learning radiomics nomogram (DLRN) was developed by combining clinicopathological factors, radiomics score (Rad-score) and deep learning score (DL-score). Model performance was assessed by C-index, KM curve, and time-dependent ROC curve. RESULTS: A total of 405 patients with MIBC were included in this study. The DL-score achieved a much higher C-index than Rad-score and clinical model (0.690 vs. 0.652 vs. 0.618 in the internal validation set, and 0.658 vs. 0.601 vs. 0.610 in the external validation set). After adjusting for clinicopathologic variables, the DL-score was identified as a significantly independent risk factor for OS by the multivariate Cox regression analysis in all sets (all P <0.01). The DLRN further improved the performance, with a C-index of 0.713 (95% CI: 0.627-0.798) in the internal validation set and 0.685 (95% CI: 0.586-0.765) in external validation set, respectively. CONCLUSIONS: A DL model based on preoperative CT can predict survival outcome of patients with MIBC, which may help in risk stratification and guide treatment decision-making and follow-up management.

Association of elastic power in mechanical ventilation with the severity of acute respiratory distress syndrome: a retrospective study.

BACKGROUND: Mechanical power (MP) is the total energy released into the entire respiratory system per minute which mainly comprises three components: elastic static power, Elastic dynamic power and resistive power. However, the energy to overcome resistance to the gas flow is not the key factor in causing lung injury, but the elastic power (EP) which generates the baseline stretch of the lung fibers and overcomes respiratory system elastance may be closely related to the ARDS severity. Thus, this study aimed to investigate whether EP is superior to other ventilator variables for predicting the severity of lung injury in ARDS patients. METHODS: We retrieved patient data from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The retrieved data involved adults (≥ 18 years) diagnosed with ARDS and subjected to invasive mechanical ventilation for ≥ 48 h. We employed univariate and multivariate logistic regression analyses to investigate the correlation between EP and development of moderate-severe ARDS. Furthermore, we utilized restricted cubic spline models to assess whether there is a linear association between EP and incidence of moderate-severe ARDS. In addition, we employed a stratified linear regression model and likelihood ratio test in subgroups to identify potential modifications and interactions. RESULTS: Moderate-severe ARDS occurred in 73.4% (296/403) of the patients analyzed. EP and MP were significantly associated with moderate-severe ARDS (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.15-1.28, p < 0.001; and OR 1.15, 95%CI 1.11-1.20, p < 0.001; respectively), but EP showed a higher area-under-curve (95%CI 0.72-0.82, p < 0.001) than plateau pressure, driving pressure, and static lung compliance in predicting ARDS severity. The optimal cutoff value for EP was 14.6 J/min with a sensitivity of 75% and specificity of 66%. Quartile analysis revealed that the relationship between EP and ARDS severity remained robust and reliable in subgroup analysis. CONCLUSION: EP is a good ventilator variable associated with ARDS severity and can be used for grading ARDS severity. Close monitoring of EP is advised in patients undergoing mechanical ventilation. Additional experimental trials are needed to investigate whether adjusting ventilator variables according to EP can yield significant improvements in clinical outcomes.

Paraneoplastic syndrome in malignant lymphoma: A case report.

Hypercalcaemia associated with malignancy is a complication of advanced tumors. Lactic acidosis is also an extremely rare paraneoplastic syndrome of malignancy, and the presence of both usually indicates an extremely poor prognosis for the tumour. Diffuse large B-cell lymphoma is the most common type of non-Hodgkin's lymphoma and is also a common aggressive lymphoma. It is extremely rare for patients with diffuse large B-cell lymphoma to develop both hypercalcaemia and severe lactic acidosis. In this article, we report a case of CD5 positive diffuse large B-cell lymphoma with hypercalcaemic crisis and persistent lactic acidosis, in which calcium was rapidly reduced to normal after rehydration, diuresis, calcitonin and zoledronate, and continuous renal replacement therapy (CRRT). After correction of acidosis with sodium bicarbonate, diuresis, vitamin B1 and CRRT, the patient's lactate remained at a high level. The aim of this article is to analyse the experience of the combination of hypercalcaemia and intractable lactic acidosis, which should be considered as a serious electrolyte disorder possibly associated with abnormal metabolism of malignant tumors, and to identify and treat the primary lesion as early as possible.

[Based on the Hippo signaling pathway to explore the mechanism of autophagy in lung injury of acute respiratory distress syndrome induced by sepsis].

The systemic inflammatory response caused by various pathogenic factors is a key stage in the development of acute respiratory distress syndrome (ARDS). At present, suppression of the inflammatory response and symptomatic support are main methods for the treatment of ARDS. Alveolar epithelial autophagy has an important role in the regulation of the inflammatory response in ARDS. Autophagy is a normal immune mechanism in the body, and it is a metabolic process by which phagocytes degrade intracellular components with the help of lysosomes to maintain intracellular homeostasis. Current studies have shown that pathogenic factors both inside and outside the lung can cause alveolar epithelial cells to form an unfavorable internal environment of hypoxia, starvation, infection, and even apoptosis by triggering inflammatory responses, leading to autophagy dysfunction. Excessive autophagy activation can continue to aggravate inflammatory responses. Autophagy related proteins such as Beclin1, microtubule-associated protein 1 light chain 3 (LC3), mammalian target of rapamycin (mTOR), and p62 are common autophagic markers in current research, which play a crucial role in regulating the autophagic process and the development of lung injury. Therefore, the expression of cellular autophagy genes can be used as early markers and important mechanisms of lung injury in septic ARDS. The Hippo signaling pathway is derived from the protein kinase Hippo in Drosophila, and the Hippo and autophagy are two conserved pathways that are essential for the protection of homeostasis in vivo. The mutual regulation of Hippo signaling pathway and autophagy is currently a hot topic in the academic community. This paper reviews the relevant literature to explore whether the Hippo signaling pathway can regulate cellular autophagy to alleviate the inflammatory response in septic ARDS, so as to provide further research directions for the treatment of ARDS.

Stanniocalcin-1 secreted by human umbilical mesenchymal stem cells regulates interleukin-10 expression via the PI3K/AKT/mTOR pathway in alveolar macrophages.

Acute respiratory distress syndrome (ARDS) is a syndrome of acute respiratory failure caused by infection, trauma, shock, aspiration or drug reaction. The pathogenesis of ARDS is characterized as an unregulated inflammatory storm, which causes endothelial and epithelial layer damage, leading to alveolar fluid accumulation and pulmonary edema. Previous studies have shown the potential role of mesenchymal stem cells (MSC) in combating the inflammatory cascade by increasing the anti-inflammatory mediator interleukin-10 (IL-10). However, the involved mechanisms are unclear. Here we investigated whether a key immunomodulatory regulator, stanniocalcin-1 (STC-1), was secreted by MSC to activate phosphoinositide 3-kinase/protein kinase B (PI3K/AKT)/ mammalian target of rapamycin (mTOR) signaling pathway to increase IL-10 expression in alveolar macrophages. Lipopolysaccharide (LPS)-stimulated alveolar macrophages co-cultured with human umbilical mesenchymal stem cells (HUMSC) secreted high levels of IL-10. HUMSC co-cultured with alveolar macrophages expressed high STC-1 levels and increased PI3K, AKT and mTOR phosphorylation after LPS activation in alveolar macrophages. STC-1 knockdown in HUMSC decreased the phosphorylation of PI3K, AKT and mTOR and suppressed IL-10 expression in alveolar macrophages. Rapamycin (an mTOR inhibitor) reduced IL-10 secretion in alveolar macrophages. These results, together with our previous study and others, indicate that the PI3K/AKT/mTOR pathway is involved in the regulation of IL-10 production by STC-1 secreted by HUMSC in alveolar macrophages.

A two-sample mendelian randomization analysis excludes causal relationships between non-alcoholic fatty liver disease and kidney stones.

Objectives: Non-alcoholic fatty liver disease (NAFLD) has been linked to an increased risk of kidney stones in prior observational studies, However, the results are inconsistent, and the causality remains to be established. We aimed to investigate the potential causal relationship between NAFLD and kidney stones using two-sample Mendelian randomization (MR). Methods: Genetic instruments were used as proxies for NAFLD. Summary-level data for the associations of exposure-associated SNPs with kidney stones were obtained from the UK Biobank study (6536 cases and 388,508 controls) and the FinnGen consortium (9713 cases and 366,693 non-cases). MR methods were conducted, including inverse variance weighted method (IVW), MR-Egger, weighted median, and MR-PRESSO. MR-Egger Regression Intercept and Cochran's Q test were used to assess the directional pleiotropy and heterogeneity. Results: cALT-associated NAFLD did not exhibit an association with kidney stones in the Inverse variance weighted (IVW) methods, in both the FinnGen consortium (OR: 1.02, 95%CI: 0.94-1.11, p = 0.632) and the UKBB study (OR: 1.000, 95%CI: 0.998-1.002, p = 0.852). The results were consistent in European ancestry (FinnGen OR: 1.05, 95%CI: 0.98-1.14, p = 0.144, UKBB OR: 1.000, 95%CI: 0.998-1.002, p = 0.859). IVW MR analysis also did not reveal a significant causal relationship between NAFLD and the risk of kidney stone for the other three NAFLD-related traits, including imaging-based, biopsy-confirmed NAFLD, and more stringent biopsy-confirmed NAFLD. The results remained consistent and robust in the sensitivity analysis. Conclusions: The MR study did not provide sufficient evidence to support the causal associations of NAFLD with kidney stones.

[Transcriptomics analysis of key genes and signaling pathways in sepsis-related exogenous acute respiratory distress syndrome].

OBJECTIVE: To analyze the differentially expressed gene (DEG) in rats with sepsis-induced exogenous acute respiratory distress syndrome (ARDS) and explore the early diagnosis and protective mechanism of sepsis-induced ARDS at the transcriptome level. METHODS: Twelve 6 to 8 weeks old male Sprague-Dawley (SD) rats were randomly divided into lipopolysaccharide (LPS) induced sepsis-induced ARDS model group (model group, intraperitoneal injection of LPS 15 mg/kg) and control group (intraperitoneal injection of the same volume of normal saline), with 6 rats in each group. RNA was extracted from the left lung tissue of the two groups, and the paired-end sequencing mode of the illumina Hiseq sequencing platform was used for high-throughput sequencing. The DESeq2 software was used to screen DEG with |log2 (fold change, FC)| ≥ 3 and P < 0.001. Gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on DEG. STRING and CytoScape software were used to construct a protein-protein interaction (PPI) network and screen key genes. The peripheral blood mononuclear cell (PBMC) of 20 septic patients admitted to the emergency and critical care medical department of Lianyungang First People's Hospital from March to November 2021 and 20 age-matched healthy people in the same period were isolated and extracted, and the key genes were verified by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). RESULTS: A total of 286 DEG were screened, including 202 up-regulated genes and 84 down-regulated genes. GO enrichment analysis showed that DEG was mainly involved in biological processes such as neutrophil chemotaxis migration, antibacterial humoral response, host immune response, and humoral immune response. KEGG analysis showed that DEG mainly played a biological role through interleukin-17 (IL-17) signaling pathway, tumor necrosis factor (TNF) signaling pathway, and chemokine signaling pathway. In PPI analysis, a total of 262 node proteins were screened, and the interaction relationship was 852 edges. The first 15 key genes were IL-6, TNF, IL-10, IL-1ß, chemokine ligand 1 (CXCL1), CXCL10, chemokine receptor 3 (CXCR3), CXCR2, CXCL9, chemokine ligand 7 (CCL7), CXCL11, CCL1, CXCL13, CCL12, and CCL22. Five representative key genes were performed on PBMC of blood samples from septic ARDS patients and healthy controls by RT-qPCR. The results showed that their expression was significantly higher than that in the healthy controls [IL-6 mRNA (2-ΔΔCt): 2.803±1.081 vs. 0.951±0.359, TNF mRNA (2-ΔΔCt): 2.376±0.799 vs. 1.150±0.504, CXCL10 mRNA (2-ΔΔCt): 2.500±0.815 vs. 1.107±0.515, CXCR3 mRNA (2-ΔΔCt): 1.655±0.628 vs. 0.720±0.388, CCL22 mRNA (2-ΔΔCt): 1.804±0.878 vs. 1.010±0.850, all P < 0.05], and the trends were consistent with the RNA-Seq results. CONCLUSIONS: Biological processes such as chemotactic migration and degranulation of inflammatory cells, cytokine immune response, and signal pathways such as CXCL10/CXCR3 and IL-17 play important roles in the occurrence and development of sepsis-related exogenous ARDS, which would provide new ideas and targets for further study of lung injury mechanisms and clinical prevention and treatment.

Whole Transcriptomic Analysis of Key Genes and Signaling Pathways in Endogenous ARDS.

Objective: To analyze the differentially expressed genes (DEGs) in rats with endogenous acute respiratory distress syndrome (ARDS) lung injury and explore the pathogenesis and early diagnostic molecular markers using whole transcriptomic data. Methods: Twelve 8-week-old male Sprague Dawley rats were selected and randomly and equally divided into ARDS lung injury group and normal control group. RNA was extracted from the left lung tissues of both the groups and sequenced using the paired-end sequencing mode of the Illumina Hiseq sequencing platform. The DEGs of miRNA, cirRNA, lncRNA, and mRNA were screened using DESeq2 software, and the ceRNA regulatory network was constructed using Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed using the mRNA DEGs. STRING and Cytoscape software were used to construct the protein interaction network and identify the 15 key genes, which were verified using quantitative real-time polymerase chain reaction (qRT-PCR). Results: Based on different screening conditions, and compared with the control group, the ARDS lung injury group showed 836 mRNA DEGs (386 upregulated and 450 downregulated), 110 lncRNA DEGs (53 upregulated and 57 downregulated), 19 circRNA DEGs (3 upregulated and 16 downregulated), and 6 miRNA DEGs (5 upregulated and 1 downregulated gene). GO showed that the DEGs of mRNA were mainly involved in biological processes, such as defense response to lipopolysaccharide and other organisms, leukocyte chemotaxis, neutrophil chemotaxis, and cytokine-mediated signaling. KEGG enrichment analysis showed that the DEGs played their biological roles mainly by participating in IL-17, TNF, and chemokine signaling pathways. The PPI analysis showed a total of 281 node proteins and 634 interaction edges. The top 15 key genes, which were screened, included Cxcl10, Mx1, Irf7, Isg15, Ifit3, Ifit2, Rsad2, Ifi47, Oasl, Dhx58, Usp18, Cmpk2, Herc6, Ifit1, and Gbp4. The ceRNA network analysis showed 69 nodes and 73 correlation pairs, where the key gene nodes were miR-21-3p, Camk2g, and Stx2. Conclusions: The chemotaxis, migration, and degranulation of inflammatory cells, cytokine immune response, autophagy, and apoptosis have significant biological functions in the occurrence and development of endogenous acute lung injury during ARDS. Thus, the camk2g/miR-21-3p/lncRNA/circRNA network, CXCL10/CXCR3, and IL-17 signaling pathways might provide novel insights and targets for further studying the lung injury mechanism and clinical treatment.

Preoperative red blood cell distribution width as an independent prognostic factor in metastatic renal cell carcinoma.

OBJECTIVE: This study aimed to explore the prognostic value of preoperative red blood cell distribution width (RDW) in patients with metastatic renal cell carcinoma (mRCC). METHODS: Clinicopathological data of 230 patients with mRCC treated at the First Affiliated Hospital of Chongqing Medical University and the Chinese PLA General Hospital from January 2008 to December 2018 were retrospectively analyzed. Patients were stratified according to the optimal cut-off value of RDW calculated using X-tile software. The prognostic value of RDW was analyzed using the Kaplan-Meier curve with log-rank test and univariate and multivariate Cox proportional hazards models. RESULTS: A total of 230 patients were included. The optimal cut-off value of RDW obtained using X-tile software was 13.1%. The median Progression-free survival (PFS) and Overall survival (OS) of all populations were 12.06 months (IQR: 4.73-36.9) and 32.20 months (IQR: 13.73-69.46), respectively. Kaplan-Meier curves showed that patients with high RDW had worse PFS and OS than those with low RDW (median PFS of 9.7 months vs. 17.9 months, P = 0.002, and median OS of 27.8 months vs. 45.1 months, P = 0.012, respectively). Multivariate analysis showed that RDW was an independent risk factor for PFS (HR: 1.505; 95% CI: 1.111-2.037; P = 0.008) and OS (HR: 1.626; 95% CI: 1.164-2.272; P = 0.004) in mRCC after cytoreductive nephrectomy. CONCLUSION: Preoperative RDW was independently associated with PFS and OS in patients with mRCC and may be a potential predictor of survival outcomes in mRCC.

TRPM7 promotes lipopolysaccharide-induced inflammatory dysfunction in renal tubular epithelial cells.

BACKGROUND: Sepsis-associated acute kidney injury (S-AKI) has been reported to affect 30%-50% of all sepsis patients; this condition is associated with a notable fatality rate. Following lipopolysaccharide (LPS) stimulation, the expression of transient receptor potential cation channel subfamily M member 7 (TRPM7), a nonselective cation channel expressed by the renal tubular epithelial cells (RTECs) was found to be upregulated. We aimed to determine how TRPM7 functions in S-AKI. METHODS: To establish an in vitro model of S-AKI, RTECs were treated with LPS. The effect of TRPM7 knockdown on cell viability, lactate dehydrogenase (LDH) release, apoptosis, inflammation, and oxidative stress was studied. The binding site between Kruppel-like factor 2 (KLF2) and TRPM7 was predicted using JASPAR. The influence of KLF2 on the regulatory roles of TRPM7 in cells, as well as the effect of their knockdown on the MAPK signaling pathway, was investigated. RESULTS: TRPM7 was upregulated in LPS-treated cells, and knocking improved cell viability, reduced LDH levels, and minimized apoptosis, inflammation, and oxidative stress. KLF2 was shown to be associated with TRPM7 and its level decreased in LPS-treated cells. KLF2 knockdown increased TRPM7 expression and reversed the effects of TRPM7 knockdown in LPS-treated cells, including suppression of p38 MAPK, ERK1/2, and JNK activation. CONCLUSION: Taken together, our results show that TRPM7 is negatively regulated by KLF2 and promotes LPS-induced inflammatory dysfunction by activating the MAPK pathway in RTECs. The theoretical foundation for the prevention and management of S-AKI is laid out in this article.

Ectopic intrauterine device in the bladder causing cystolithiasis: A case report.

BACKGROUND: An intrauterine device (IUD) is a commonly used contraceptive among women in China. It is widely used because it is safe, effective, simple, economic, and reversible. Among the possible complications, an ectopic IUD in the bladder is rare. It occurs insidiously, has a long course, is associated with a high risk for injury, and is difficult to treat. CASE SUMMARY: A 44-year-old woman was admitted for repeated episodes of urinary frequency, urgency, and dysuria over three months. Laboratory tests revealed significantly elevated urine leukocytes and bacteria. Urine culture suggested colonization with Enterococcus faecalis. Abdominal computed tomography images suggested an abnormally positioned IUD that was protruding into the bladder. Cystoscopy revealed a metallic foreign body with multiple stones on its surface in the left posterior bladder wall. The foreign body measured approximately 1 cm. Hysteroscopy revealed the arm of a V-type metal IUD embedded in the middle and upper sections of the anterior wall of the cervical canal. The majority of the IUD was located in the uterine cavity. Cystoscopy was performed, and a holmium laser was utilized to break the stones attached to the portion of the IUD in the bladder. The IUD was then removed through hysteroscopy. CONCLUSION: Ectopic IUDs in the bladder can be diagnosed with thorough imaging and safely removed through cystoscopy or hysteroscopy.

SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain-dependent regulation of Wnt/ß-catenin signaling.

Sex-determining region Y box (SOXs) are expressed in various cells and control cell fate and differentiation in a multitude of physiologic processes. SOX6, a main representative of SOXs, is involved in the regulation of carcinogenesis in various human malignancies. However, the role of SOX6 in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, SOX6 expression in ccRCC and its clinical significance were investigated. In vitro and in vivo assays were used to explore the tumor-related function and the underlying molecular mechanism of SOX6 in ccRCC. We confirmed that SOX6 was frequently downregulated in ccRCC tissues and cell lines. Besides, downregulation of SOX6 was significantly associated with larger tumor sizes, advanced tumor stage, higher Fuhrman grades, and its expression could act as an independent prognostic factor for ccRCC (hazards ratio = 0.590, P = .026). Gain/loss-of-function experiments demonstrated that SOX6 could remarkably inhibit tumor cell growth and foci formation in vitro and xenograft tumorigenesis in vivo, respectively. Mechanistically, SOX6 could influence cell cycle by regulating the G1/the S phase transition and had an inhibitory effect on Wnt/ß-catenin signaling as well as its target genes, c-Myc and cyclin D1. Interesting, the tumor-suppressive function of SOX6 was proved to be dependent on its specific high-mobility-group (HMG) domain. In general, our findings indicated that SOX6 was a novel tumor suppressor and prognostic biomarker in ccRCC. SOX6 could inhibit tumor growth by negatively regulating the Wnt/ß-catenin signaling pathway in an HMG domain-dependent manner in ccRCC, which might provide a novel therapeutic approach for ccRCC.

miR-363 suppresses the proliferation, migration and invasion of clear cell renal cell carcinoma by downregulating S1PR1.

BACKGROUND: MicroRNAs (miRNAs) serve as important regulators of the tumorigenesis and progression of many human cancers. Therefore, we evaluated the biological function and underlying mechanism of miR-363 in clear cell renal cell carcinoma (ccRCC). METHODS: The expression of miR-363 in ccRCC tissues compared with adjacent normal renal tissues was detected by quantitative real-time polymerase chain reaction, and the association between miR-363 levels and prognosis of ccRCC patients was analyzed. The candidate target gene of miR-363 was determined by in silico analysis and luciferase reporter assays. The effects of miR-363 on the proliferation, migration and invasion of ccRCC cells in vitro were determined by MTS assay, colony formation assay, Transwell assay and wound healing assay. We also investigated the roles of miR-363 in vivo by a xenograft tumour model. The mechanism of miR-363 on the proliferation, migration and invasion of ccRCC was determined by gain- and loss-of-function analyses. RESULTS: we demonstrated that miR-363 expression was obviously downregulated in ccRCC tissues and that reduced miR-363 expression was correlated with poor disease-free survival (DFS) in ccRCC patients after surgery. S1PR1 expression was inversely correlated with the level of miR-363 in human ccRCC samples. Luciferase reporter assays suggested that S1PR1 was a direct functional target of miR-363. miR-363 downregulated S1PR1 expression and suppressed the proliferation, migration and invasion abilities of ccRCC cells in vitro and suppressed xenograft tumour growth in vivo. Importantly, miR-363 exerted its biological function by inhibiting S1PR1 expression in ccRCC cells, leading to the repression of ERK activation. Moreover, we found that the levels of downstream effectors of ERK, including PDGF-A, PDGF-B, and epithelial-mesenchymal transition (EMT)-related genes, were decreased after miR-363 overexpression. CONCLUSIONS: Our results suggest that miR-363 acts as a tumour suppressor by directly targeting S1PR1 in ccRCC and may be a potential new therapeutic target for ccRCC.

Prediction of pentafecta achievement following laparoscopic partial nephrectomy: Implications for robot-assisted surgery candidates.

BACKGROUND: In clinical practice, objective basis for the choice between laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN) is scarce. To evaluate surgical outcomes, assess the individual benefit from LPN to RAPN, which can guide clinical decision-making. METHODS: Patients underwent LPN or RAPN for a localized renal mass in our center between Jan 2013 and Dec 2016 were included. The surgical outcome of LPN and RAPN was the pentafecta achievement. A multivariable model was fitted to predict the probability of pentafecta achievement after LPN. Model-derived coefficients were applied to calculate the probability of pentafecta achievement in case of LPN among patients treated with RAPN. Locally weighted scatterplot smoothing method was applied to plot the observed probability of pentafecta achievement against the predicted pentafecta probability in case of LPN. RESULTS: RAPN group had a significantly higher pentafecta achievement (54.6% vs. 41.1%, P < 0.001) than LPN. Multivariable analyses identified that tumor size, distance of the tumor to collecting system or sinus, and preoperative eGFR were independent predictors of pentafecta after LPN. When RAPN was chosen over LPN, the increase in the probability of pentafecta achievement was greatest in intermediate-probability patients. With the increase or decrease of the probability of pentafecta, the benefit of RAPN decreased. CONCLUSION: When pentafecta achievement are assessed, the benefit of RAPN over LPN varies from patient to patient. Patients at intermediate-probability of pentafecta achievement after LPN benefit the most from robotic surgery, which may be the potential ideal candidates for RAPN.

[Predictive value of lung ultrasound score on weaning outcome in patients with intro-abdominal infection undergoing mechanical ventilation].

OBJECTIVE: To evaluate the value of lung ultrasound score (LUS) on predicting weaning outcome in patients with intro-abdominal infection (IAI) undergoing mechanical ventilation. METHODS: Patients with IAI undergoing mechanical ventilation admitted to Research Institute of General Surgery of East War Zone Hospital and intensive care unit (ICU) of the First People's Hospital of Lianyungang from January to December in 2018 were included. The patients who satisfied weaning criteria were enrolled in the weaning process, which included spontaneous breathing trial (SBT) and extubation. They were divided into SBT success group and SBT failure group according to whether passed 120-minute SBT or not. LUS scores before and after SBT were compared between the two groups. The patients in the SBT success group were extubated, and they were divided into successful extubation group and failed extubation group for sub-group analysis according to whether re-intubation was needed in 48 hours after extubation. LUS score before extubation (at the end of SBT) and 48 hours after extubation (48 hours after extubation in the successful extubation group or before re-intubation in the failed extubation group) were compared. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of LUS score before SBT for SBT failure and LUS score before extubation for the failure. RESULTS: A total of 76 patients with IAI undergoing mechanical ventilation were included. Twenty-three patients had duration of mechanical ventilation less than 48 hours, severe chronic obstructive pulmonary disease (COPD), tracheotomy or automatic discharge were excluded, and 53 patients were enrolled. SBT was failed in 9 patients, and successfully performed in 44 patients, of whom 23 patients with successful extubation, and 21 with failed extubation. The LUS scores before and after SBT in the SBT failure group were significantly higher than those in the SBT success group (before SBT: 13.22±1.99 vs. 10.79±1.64, t = -3.911, P = 0.000; after SBT: 19.00±1.12 vs. 13.41±1.86, t = -8.665, P = 0.000). ROC curve analysis showed that the area under ROC curve (AUC) of LUS score before SBT for predicting SBT failure was 0.82 [95% confidence interval (95%CI) was 0.67-0.98, P = 0.002]. When the optimum cut-off value was 12.5, the sensitivity was 66.7%, and the specificity was 84.1%. Sub-group analysis showed that the LUS scores before and after extubation in the failed extubation group were significantly higher than those in the successful extubation group (before extubation: 14.19±1.60 vs. 12.69±1.81, t = -2.881, P = 0.006; after extubation: 16.42±1.59 vs. 12.78±1.54, t = -7.710, P = 0.000). ROC curve analysis showed that the AUC of LUS score before extubation for predicting the failure was 0.81 (95%CI was 0.69-0.92, P = 0.000). When the optimum cut-off value was 13.5, the sensitivity was 80.0%, and the specificity was 65.2%. CONCLUSIONS: LUS score can effectively predict SBT outcome, risk of re-intubation after extubation in patients with IAI undergoing mechanical ventilation.

Comparison of Robot-Assisted and Laparoscopic Partial Nephrectomy for Completely Endophytic Renal Tumors: A High-Volume Center Experience.

Objectives: To compare the perioperative, functional, and oncologic outcomes of robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) for completely endophytic renal tumors (three points for the "E" element of the R.E.N.A.L. scoring system). Materials and Methods: We retrospectively reviewed patients who underwent either RAPN or LPN between 2013 and 2016. Baseline characteristics, perioperative, functional, and oncologic outcomes were compared. Univariable and multivariable logistic analyses were performed to determine factors associated with pentafecta achievement (ischemia time ≤25 minutes, negative margin, no perioperative complication, return of estimated glomerular filtration rate [eGFR] to >90% from baseline, and no chronic kidney disease upstaging). Results: No significant differences between RAPN vs LPN were noted for operating time (105 minutes vs 108 minutes, p = 0.916), estimated blood loss (50 mL vs 50 mL, p = 0.130), renal artery clamping time (20 minutes vs 20 minutes, p = 0.695), rate of positive margins (3.3% vs 2.0%, p = 1.000), and postoperative complication rates (18.0% vs 21.6%, p = 0.639). RAPN was associated with a higher direct cost ($11240 vs $5053, p < 0.001). There were no significant differences in pathology variables, rate of eGFR decline for postoperative 12-month (9.8% vs 10.6%, p = 0.901) functional follow-up. Multivariate analysis identified that only RENAL score was independently associated with the pentafecta achievement. Conclusions: For completely endophytic renal tumors, both RAPN and LPN have excellent and similar results. Both operation techniques remain viable options in the management of these cases.

Vessel and Tension-Free Reconstruction During Robot-Assisted Partial Nephrectomy for Hilar Tumors: "Garland" Technique and Midterm Outcomes.

Purpose: Robot-assisted partial nephrectomy (RAPN) is increasingly applied to renal hilar tumors. The present study aims to introduce our vessel and tension-free reconstruction technique and discuss the perioperative, functional, and midterm oncologic outcomes of RAPN for hilar tumors in a large cohort. Materials and Methods: We retrospectively reviewed clinical data of 286 consecutive patients with hilar tumors who underwent RAPN from June 2013 to December 2016 in our center. Our anatomy-based "Garland" technique specialized in protecting the large hilar vessels and minimizing the tension of suturing the defect via trans/retroperitoneal approaches for anterior/posterior lip hilar tumors, respectively. Results: "Garland" technique was effectively applied in 286 patients, and the warm ischemia time was 18.2 ± 4.1 minutes. Median estimated blood loss for RAPN was 100 mL (interquartile range [IQR]: 50-200 mL). Median operative time was 120 minutes (IQR: 90-150 minutes). No patient was converted to open surgery. Postoperative stay was 4.0 days (IQR: 4.0-5.0 days). Three patients (1.1%) had positive surgical margin. Two patients (0.7%) received blood transfusion. Complications occurred in 20 patients (7.0%), in which 18 patients were Clavien 1 and 2. Three patients (1.1%) had local recurrence. All patients were alive at a 48-month median follow-up (range: 24-66 months). Conclusions: "Garland" technique is safe and feasible for hilar tumor resection and kidney reconstruction. The trans/retroperitoneal approaches are options for anterior/posterior hilar tumors. Longer follow-up involving more patients is required.

Post ureteroscopic stone surgery ureteral strictures management: a retrospective study.

PURPOSE: To share experience in managing ureteral strictures following ureteroscopic lithotripsy. METHODS: Ninety five patients diagnosed as ureteral strictures after ureteroscopic lithotripsy between January 2013 and January 2018 were included. 53 received endourological treatment, 34 underwent reconstruction, 6 underwent nephrectomy for severe renal impairment, and 2 chose routine ureteral stent replacement. Therapeutic success was defined as absence of clinical symptoms and radiologic relief of obstruction. RESULTS: The follow-up time ranged from 13 to 57 months, with a median time of 24. It lasted more than 13 months in all patients, exception for 2 nephrectomies. Two patient groups including 69 endourological procedures and 37 reconstructions were used to compare therapeutic effects and complications. The overall success rate was 60.9% (42/69) in endourological intervention vs. 97.3% (36/37) in reconstruction (p < 0.001), while 74.4% (29/39) patients with stricture less than 1 cm and 68.8% (33/48) patients with mild-to-moderate hydronephrosis achieved success in endourological group. All except 1 failure appeared within the first year postoperatively. Subgroup analyses for endourological procedures revealed significant differences in the success rate of different stricture lengths and hydronephrosis (p = 0.004 and p = 0.043). Multivariate Cox regression analysis indicated that reconstruction was significantly related to a more successful outcome, compared with endourological procedures (HR 0.052, 95% CI 0.007-0.394, p = 0.004). CONCLUSION: Reconstruction performs better than endourological procedures in surgical outcome. Endourological procedure provides an acceptable success rate in patients with stricture shorter than 1 cm and slight hydronephrosis. Most stricture recurrence appeared within the first year postoperatively.

Identification of DDX58 and CXCL10 as Potential Biomarkers in Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is a devastating condition of acute inflammatory lung injury and causes high morbidity and mortality. Therefore, investigations on the effective biomarkers will be significant for the understanding of ARDS. In our research, the gene expression profiles of 27 samples from ARDS patients (n = 18) and healthy controls (n = 9) were analyzed and eight gene co-expression modules were identified by constructing weighted gene co-expression network. The correlation analysis of modules with phenotypes showed that genes in the yellow and black modules, which were significantly enriched in the ARDS-related pathways, such as TNF signaling pathway, Toll-like receptor signaling pathway, and NF-kappa B signaling pathway, were associated with the phenotype "time postinfection." Genes DDX58 and CXCL10, which were highly expressed after infection and significantly enriched in ARDS-related pathways, presented high score in protein-protein interaction analysis, indicating that they may be associated with ARDS and providing novel biomarkers for its diagnosis, treatment, and surveillance.