Construction of endothelial cell signatures for predicting the diagnosis, prognosis and immunotherapy response of bladder cancer via machine learning.

We subtyped bladder cancer (BC) patients based on the expression patterns of endothelial cell (EC) -related genes and constructed a diagnostic signature and an endothelial cell prognostic index (ECPI), which are useful for diagnosing BC patients, predicting the prognosis of BC and evaluating drug sensitivity. Differentially expressed genes in ECs were obtained from the Tumour Immune Single-Cell Hub database. Subsequently, a diagnostic signature, a tumour subtyping system and an ECPI were constructed using data from The Cancer Genome Atlas and Gene Expression Omnibus. Associations between the ECPI and the tumour microenvironment, drug sensitivity and biofunctions were assessed. The hub genes in the ECPI were identified as drug candidates by molecular docking. Subtype identification indicated that high EC levels were associated with a worse prognosis and immunosuppressive effect. The diagnostic signature and ECPI were used to effectively diagnose BC and accurately assess the prognosis of BC and drug sensitivity among patients. Three hub genes in the ECPI were extracted, and the three genes had the closest affinity for doxorubicin and curcumin. There was a close relationship between EC and BC. EC-related genes can help clinicians diagnose BC, predict the prognosis of BC and select effective drugs.

NCAPG2 promotes prostate cancer malignancy and stemness via STAT3/c-MYC signaling.

BACKGROUND: Prostate cancer (PCa) is the second leading cause of cancer-related mortality among men worldwide, and its incidence has risen substantially in recent years. Therefore, there is an urgent need to identify novel biomarkers and precise therapeutic targets for managing PCa progression and recurrence. METHODS: We investigated the clinical significance of NCAPG2 in PCa by exploring public datasets and our tissue microarray. Receiver operating characteristic (ROC) curve and survival analyses were performed to evaluate the correlation between NCAPG2 and PCa progression. Cell proliferation, wound healing, transwell, flow cytometry, cell cycle, tumor sphere formation, immunofluorescence (IF), co-immunoprecipitation (co-IP), and chromatin immunoprecipitation (ChIP) assays were conducted to further elucidate the molecular mechanism of NCAPG2 in PCa. Subcutaneous and orthotopic xenograft models were applied to investigate the effects of NCAPG2 on PCa proliferation in vivo. Tandem mass tag (TMT) quantitative proteomics was utilized to detect proteomic changes under NCAPG2 overexpression. RESULTS: NCAPG2 was significantly upregulated in PCa, and its overexpression was associated with PCa progression and unfavorable prognosis. Knockdown of NCAPG2 inhibited the malignant behavior of PCa cells, whereas its overexpression promoted PCa aggressiveness. NCAPG2 depletion attenuated the development and growth of PCa in vivo. TMT quantitative proteomics analyses indicated that c-MYC activity was strongly correlated with NCAPG2 expression. The malignancy-promoting effect of NCAPG2 in PCa was mediated via c-MYC. NCAPG2 could directly bind to STAT3 and induce STAT3 occupancy on the MYC promoter, thus to transcriptionally activate c-MYC expression. Finally, we identified that NCAPG2 was positively correlated with cancer stem cell (CSC) markers and enhanced self-renewal capacity of PCa cells. CONCLUSIONS: NCAPG2 is highly expressed in PCa, and its level is significantly associated with PCa prognosis. NCAPG2 promotes PCa malignancy and drives cancer stemness via the STAT3/c-MYC signaling axis, highlighting its potential as a therapeutic target for PCa.

Bioinformatics analysis and experimental validation of cuproptosis-related lncRNA LINC02154 in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is common in urinary system tumors. Cuproptosis is a non-apoptotic cell death pathway. Copper binds to fatty acylated mitochondrial proteins and activates various forms of cell death. LncRNA LINC02154 is significantly highly expressed in cells and tissues of many types of tumors, and the risk signature of LINC02154 in some tumors has been validated for effectiveness. METHODS: We constructed a risk prognostic signature by obtaining differentially expressed long noncoding RNAs (lncRNAs) associated with ccRCC outcomes and cuproptosis from The Cancer Genome Atlas (TCGA). We used TCGA to construct training and testing sets to analyze the risk signature and the impact of LINC02154, and we performed relevant survival analyses. Tumor mutational burdens were analyzed in different LINC02154 expression groups and risk score groups. We next analyzed the immune microenvironment of LINC20154. We performed LINC20154-related drug sensitivity analyses. We also investigated the cellular function of LINC02154 in the ACHN cell line and performed CCK-8 assay, EdU, wound-healing assay, and Transwell assay. The essential genes FDX1 and DLST of cuproptosis were detected by western blot. RESULTS: We demonstrated that LINC02154's impact on outcomes was statistically significant. We also demonstrated the association of different ages, genders, stages, and grades with LINC02154 and risk models. The results showed a significant difference in tumor mutation burden between the groups, which was closely related to clinical prognosis. We found differences in immune cells among groups with different levels of LINC02154 expression and significant differences in immune function, immunotherapeutic positive markers, and critical steps of the immune cycle. The sensitivity analysis showed that differential expression of LINC02154 discriminated between sensitivity to axitinib, doxorubicin, gemcitabine, pazopanib, sorafenib, sunitinib, and temsirolimus. This difference was also present in the high-risk group and low-risk group. We demonstrated that the proliferation and migration of t ACHN cells in the LINC02154 knockdown group were inhibited. The western blot results showed that the knockdown of LINC02154 significantly affected the expression of FDX1 and DLST, critical genes of cuproptosis. CONCLUSION: Finally, we demonstrated that LINC02154 and our constructed risk signature could predict outcomes and have potential clinical value.

A modified triangular Double-J stent for retrograde intrarenal surgery improvement of free-stone rate, and quality of life: a randomized controlled, multiple centers, perspective trial.

PURPOSE: The goal of this study is to evaluate the efficacy and safety of modified triangular double-J (DJ) stent in 1-2 cm renal or ureter calculi after retrograde intrarenal surgery (RIRS) via a randomized, controlled clinical study. METHODS: A total of 196 patients with 1-2 cm renal or ureter calculi who were performed RIRS and received 7Fr modified triangular DJ stents (100 cases) or 6Fr normal DJ stents (96 cases). All operations were performed by experienced surgeons. The clinical characteristics and outcomes were analyzed. RESULTS: There were no significant differences between two groups in terms of age, gender, BMI, location, hydronephrosis, urea WBC, urea RBC, BUN, Cr, laser emission time, operation time, Hb loss, postoperative BUN, postoperative Cr. Patients who received modified triangular DJ stents were shown to have higher stone-free rate (p = 0.038), but lower general health (p = 0.004). CONCLUSION: The modified triangular 7Fr DJ stents were more efficient for patients underwent RIRS than 6Fr normal DJ stents.

Different lymph node dissection ranges during radical prostatectomy for patients with prostate cancer: a systematic review and network meta-analysis.

OBJECTIVE: The purpose of this network meta-analysis was to compare the effectiveness and adverse effects of limited, standard, extended, and super-extended pelvic lymph node dissection (PLND) following radical prostatectomy. METHODS: This study followed the PRISMA 2020 statement. Clinical trials were searched from three electronic databases, including PubMed, the Cochrane Library, and Embase from the database's inception to April 5, 2022. The lymph node-positive rate, biochemical recurrence-free rate, lymphocele rate, thromboembolic rate, and overall complication rate were compared by meta-analysis. Data analyses were performed using R software based on the Bayesian framework. RESULTS: Sixteen studies involving 15,269 patients were included. All 16 studies compared the lymph node-positive rate; 5 studies compared the biochemical recurrence-free rate; 10 studies compared the lymphocele rate; 6 studies compared the thromboembolic rate, and 9 studies compared the overall complication rate. According to Bayesian analysis, the lymph node-positive rate, lymphocele rate, and overall complication rate were significantly associated with the extension of the PLND range. The limited, extended, and super-extended PLND templates showed a similar but lower biochemical recurrence-free rate and a higher thromboembolic rate than the standard template. CONCLUSIONS: The extension of the PLND range is associated with an elevated lymph node-positive rate; however, it does not improve the biochemical recurrence-free rate and correlates with an increased risk of complications, especially lymphocele. The selection of the PLND range in clinical practice should consider the oncological risk and adverse effects. TRIAL REGISTRATION: PROSPERO (CRD42022301759).

In silico development and experimental validation of a novel 7-gene signature based on PI3K pathway-related genes in bladder cancer.

Although bladder cancer (BLCA) is the 10th most common tumor worldwide, particularly practical markers and prognostic models that might guide therapy are needed. We used a non-negative matrix factorization algorithm to classify PI3K pathway-related genes into molecular subtypes. A weighted gene co-expression network analysis (WGCNA) was generated to identify co-expression modules. Univariate Cox regression, least absolute shrinkage sum selection operator-Cox regression, and multivariate Cox regression were utilized to develop a prognostic score model. Kaplan-Meier analysis and receiver operating characteristics were utilized to measure the model's effectiveness. A nomogram was constructed to improve the predictive ability of the model based on clinical parameters and risk. Decision curve analysis (DCA) was used to evaluate the nomogram. To evaluate the immune microenvironment, an estimate algorithm was used. Drug sensitivity was identified using the R package "pRRophetic." UM-UC-3 cell line was used to measure the effect of CDK6 in Western blotting, proliferation assay, and 5-ethynyl-20-deoxyuridine assay. Based on PI3K pathway-related genes, The Cancer Genome Atlas (TCGA)-BLCA and GSE32894 patients were divided into two subtypes. Twenty-five co-expression modules were established using the WGCNA algorithm. A seven-gene signature (CDK6, EGFR, IGF1, ITGB7, PDGFRA, RPS6, and VWF) demonstrated robustness in TCGA and GSE32894 datasets. Expression levels of CDK6 and risk positively correlated with M2 macrophages and IgG. Cisplatin, gemcitabine, methotrexate, mitomycin C, paclitaxel, and vinblastine are sensitive to different groups based on the expression of CDK6 and risk. Functional experiments suggested that CDK6 promotes the proliferation of UM-UC-3 cells. We constructed a seven-gene prognostic signature as an effective marker to predict the outcomes of BLCA patients and guide individual treatment.

Upregulation of SDHA inhibited proliferation, migration, and invasion of clear cell renal cell carcinoma cells via inactivation of the Wnt/ß-catenin pathway.

Clear cell renal cell carcinoma (ccRCC) is a common genitourinary malignancy with high mortality. Recent findings suggest that the succinate dehydrogenase complex subunit A (SDHA) is lowly expressed in many types of cancers and involved in tumorigenesis. However, the potential regulatory roles and molecular mechanisms by which SDHA affects the development and progression of ccRCC remain largely unknown. In this study, our results showed that there was significant downregulation of SDHA in ccRCC tissue relative to corresponding non-cancerous tissue, and low expression of SDHA was associated with Fuhrman pathological grade, tumor size, TNM stage, metastasis, and poor prognosis in ccRCC patients. Moreover, overexpression of SDHA inhibited the proliferation, invasion, and migration capacities of ccRCC cells. Mechanistically, SDHA impeded the proliferation and metastasis of ccRCC cells by inactivation of the Wnt/ß-catenin pathway. In vivo experiments, SDHA suppressed ccRCC growth in a nude mouse model. In conclusion, our study results indicated that SDHA may act as a new molecular marker for judging the occurrence and development of ccRCC and serve as a therapeutic target for the treatment of human ccRCC.

A novel focal adhesion-related risk model predicts prognosis of bladder cancer -- a bioinformatic study based on TCGA and GEO database.

BACKGROUND: Bladder cancer (BLCA) is the ninth most common cancer globally, as well as the fourth most common cancer in men, with an incidence of 7%. However, few effective prognostic biomarkers or models of BLCA are available at present. METHODS: The prognostic genes of BLCA were screened from one cohort of The Cancer Genome Atlas (TCGA) database through univariate Cox regression analysis and functionally annotated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The intersecting genes of the BLCA gene set and focal adhesion-related gene were obtained and subjected to the least absolute shrinkage and selection operator regression (LASSO) to construct a prognostic model. Gene set enrichment analysis (GSEA) of high- and low-risk patients was performed to explore further the biological process related to focal adhesion genes. Univariate and multivariate Cox analysis, receiver operating characteristic (ROC) curve analysis, and Kaplan-Meier survival analysis (KM) were used to evaluate the prognostic model. DNA methylation analysis was presented to explore the relationship between prognosis and gene methylation. Furthermore, immune cell infiltration was assessed by CIBERSORT, ESTIMATE, and TIMER. The model was verified in an external GSE32894 cohort of the Gene Expression Omnibus (GEO) database, and the Prognoscan database presented further validation of genes. The HPA database validated the related protein level, and functional experiments verified significant risk factors in the model. RESULTS: VCL, COL6A1, RAC3, PDGFD, JUN, LAMA2, and ITGB6 were used to construct a prognostic model in the TCGA-BLCA cohort and validated in the GSE32894 cohort. The 7-gene model successfully stratified the patients into both cohorts' high- and low-risk groups. The higher risk score was associated with a worse prognosis. CONCLUSIONS: The 7-gene prognostic model can classify BLCA patients into high- and low-risk groups based on the risk score and predict the overall survival, which may aid clinical decision-making.

An 18-gene signature based on glucose metabolism and DNA methylation improves prognostic prediction for urinary bladder cancer.

BACKGROUND: Glucose metabolism and DNA methylation play important roles in cancers. We aimed to identify glucose metabolism-related genes that were DNA methylation associated to establish a prognostic signature of bladder cancer (BLCA). METHODS: With BLCA sample transcriptome data from The Cancer Genome Atlas (TCGA) and methylation data from TCGA 450 K microarray, glucose metabolism-related genes associated to prognosis and DNA methylation were identified and a prognostic signature was established. GSEA and WGCNA analysis were performed and two genes, UCHL1 and PYCR1, were selected for functional validations. RESULTS: 18 target genes were identified and the signature based on them was considered an effective and independent prognostic factor. Several pathways were enriched in the high-risk group by GSEA and three modules of genes were identified by WGCNA. UCHL1 and PYCR1 proliferated proliferation, migration and invasion ability of bladder cancer cells. CONCLUSIONS: The 18-gene signature is an independent prognostic factor for bladder cancer patients.

SNHG12 promotes carcinogenesis of human renal cell cancer via functioning as a competing endogenous RNA and sponging miR-30a-3p.

Small nucleolar RNA host gene 12 (SNHG12) has been indicated in the tumorigenesis of various human cancers, including clear cell renal cell carcinoma (ccRCC). However, the underlying mechanisms of SNHG12 driving progression of ccRCC remain incompletely understood. In the present study, we discovered that SNHG12 is up-regulated in ccRCC and that overexpression of SNHG12 predicted poor clinical outcome of ccRCC patients. SNHG12 knockdown notably inhibited proliferation and migration of RCC cells. Furthermore, we discovered that miR-30a-3p, a putative ccRCC inhibitor, was competitively sponged by SNHG12. Via the crosstalk network, SNHG12 was capable of up-regulating multiple target genes of miR-30a-3p, namely, RUNX2, WNT2 and IGF-1R, which have been identified to facilitate tumorigenesis of ccRCC. Taken together, our present study suggested a novel ceRNA network, in which SNHG12 could promote the malignancy of ccRCC although competitively binding with miR-30a-3p and consequently release the expression of its downstream cancer-related genes.

Involvement of GPX4 in irisin's protection against ischemia reperfusion-induced acute kidney injury.

Ischemia reperfusion (I/R)-induced acute kidney injury (AKI) is a common and serious condition. Irisin, an exercise-induced hormone, improves mitochondrial function and reduces reactive oxygen species (ROS) production. Glutathione peroxidase 4 (GPX4) is a key regulator of ferroptosis and its inactivation aggravates renal I/R injury by inducing ROS production. However, the effect of irisin on GPX4 and I/R-induced AKI is still unknown. To study this, male adult mice were subjected to renal I/R by occluding bilateral renal hilum for 30 min, which was followed by 24 hr reperfusion. Our results showed serum irisin levels were decreased in renal I/R mice. Irisin (250 µg/kg) treatment alleviated renal injury, downregulated inflammatory response, improved mitochondrial function, and reduced ER stress and oxidative stress after renal I/R, which were associated with upregulation of GPX4. Treated with RSL3 (a GPX4 inhibitor) abolished irisin's protective effect. Thus, irisin attenuates I/R-induced AKI through upregulating GPX4.

Wnt pathway-related three-mRNA clinical outcome signature in bladder urothelial carcinoma: computational biology and experimental analyses.

BACKGROUND: The Wnt signaling pathway is core to the growth of bladder tumors. Epithelial-to-mesenchymal transition (EMT) is significant for bladder tumor metastasis. Nevertheless, the relationship between the Wnt signaling pathway, outcomes of bladder cancer (BLCA), and the specific mechanisms driving immune infiltration have not been studied. METHODS: We obtained Wnt pathway-related gene mRNA and clinicopathological data from the Cancer Genome Atlas (TCGA). We obtained 34 genes that were greatly correlated with outcome using univariate Cox regression analysis and conducted a completely randomized data t-test to perform clinical staging. According to the single-sample gene set enrichment analysis (ssGSEA), the weighted correlation network analysis (WGCNA) was applied to identify relevant biological functions. Various subtypes were identified using consensus cluster analysis. Univariate Cox regression and least absolute shrinkage sum selection operator-Cox regression algorithm analysis were conducted on TCGA and Gene Expression Omnibus data to identify risk characteristics. The Kaplan-Meier method and receiver running feature curves were adopted to calculate overall survival. Single-sample gene set enrichment analysis (ssGSEA) was adopted for the assessment of the degree of immune infiltration. Then, we demonstrated the relationship between PPP2CB and EMT function in two cell lines. RESULTS: Thirty-four Wnt signaling pathway-related genes were risk factors for BLCA outcome, and their expression levels differed by clinical stage. The co-expression of WGCNA showed the relationship between the Wnt signaling pathway and biological functions and was closely associated with EMT. We divided BLCA patients into two subtypes using consensus clustering. Survival curves and clinical analysis showed that the Wnt pathway enriched group had worse outcomes. The Wnt signature showed the significance of the outcome for MAPK10, PPP2CB, and RAC3. Based on these genes, the degree of immune infiltration was evaluated. Cell function experiments suggested that PPP2CB drives the proliferation and migration of BLCA cells. CONCLUSION: We found that Wnt signaling pathway-related genes can be used as prognostic risk factors for BLCA, and the Wnt signaling pathway is a cancer-promoting signaling pathway associated with EMT. We identified three critical genes: MAPK10, RAC3, and PPP2CB. The genes in these three Wnt signaling pathways are associated with tumor cell EMT and immune cell infiltration. The most important finding was that these three genes were independent prognostic factors for BLCA.

Genome instability-related long non-coding RNA in clear renal cell carcinoma determined using computational biology.

BACKGROUND: There is evidence that long non-coding RNA (lncRNA) is related to genetic stability. However, the complex biological functions of these lncRNAs are unclear. METHOD: TCGA - KIRC lncRNAs expression matrix and somatic mutation information data were obtained from TCGA database. "GSVA" package was applied to evaluate the genomic related pathway in each samples. GO and KEGG analysis were performed to show the biological function of lncRNAs-mRNAs. "Survival" package was applied to determine the prognostic significance of lncRNAs. Multivariate Cox proportional hazard regression analysis was applied to conduct lncRNA prognosis model. RESULTS: In the present study, we applied computational biology to identify genome-related long noncoding RNA and identified 26 novel genomic instability-associated lncRNAs in clear cell renal cell carcinoma. We identified a genome instability-derived six lncRNA-based gene signature that significantly divided clear renal cell samples into high- and low-risk groups. We validated it in test cohorts. To further elucidate the role of the six lncRNAs in the model's genome stability, we performed a gene set variation analysis (GSVA) on the matrix. We performed Pearson correlation analysis between the GSVA scores of genomic stability-related pathways and lncRNA. It was determined that LINC00460 and LINC01234 could be used as critical factors in this study. They may influence the genome stability of clear cell carcinoma by participating in mediating critical targets in the base excision repair pathway, the DNA replication pathway, homologous recombination, mismatch repair pathway, and the P53 signaling pathway. CONCLUSION SUBSECTIONS: These data suggest that LINC00460 and LINC01234 are crucial for the stability of the clear cell renal cell carcinoma genome.

A novel immune-related gene pair prognostic signature for predicting overall survival in bladder cancer.

BACKGROUND: Bladder cancer (BC) is the ninth most common malignant tumor. We constructed a risk signature using immune-related gene pairs (IRGPs) to predict the prognosis of BC patients. METHODS: The mRNA transcriptome, simple nucleotide variation and clinical data of BC patients were downloaded from The Cancer Genome Atlas (TCGA) database (TCGA-BLCA). The mRNA transcriptome and clinical data were also extracted from Gene Expression Omnibus (GEO) datasets (GSE31684). A risk signature was built based on the IRGPs. The ability of the signature to predict prognosis was analyzed with survival curves and Cox regression. The relationships between immunological parameters [immune cell infiltration, immune checkpoints, tumor microenvironment (TME) and tumor mutation burden (TMB)] and the risk score were investigated. Finally, gene set enrichment analysis (GSEA) was used to explore molecular mechanisms underlying the risk score. RESULTS: The risk signature utilized 30 selected IRGPs. The prognosis of the high-risk group was significantly worse than that of the low-risk group. We used the GSE31684 dataset to validate the signature. Close relationships were found between the risk score and immunological parameters. Finally, GSEA showed that gene sets related to the extracellular matrix (ECM), stromal cells and epithelial-mesenchymal transition (EMT) were enriched in the high-risk group. In the low-risk group, we found a number of immune-related pathways in the enriched pathways and biofunctions. CONCLUSIONS: We used a new tool, IRGPs, to build a risk signature to predict the prognosis of BC. By evaluating immune parameters and molecular mechanisms, we gained a better understanding of the mechanisms underlying the risk signature. This signature can also be used as a tool to predict the effect of immunotherapy in patients with BC.

Involvement of kindlin-2 in irisin's protection against ischaemia reperfusion-induced liver injury in high-fat diet-fed mice.

Liver steatosis is associated with increased ischaemia reperfusion (I/R) injury. Our previous studies have shown that irisin, an exercise-induced hormone, mitigates I/R injury via binding to αVß5 integrin. However, the effect of irisin on I/R injury in steatotic liver remains unknown. Kindlin-2 directly interacts with ß integrin. We therefore suggest that irisin protects against I/R injury in steatotic liver via a kindlin-2 dependent mechanism. To study this, hepatic steatosis was induced in male adult mice by feeding them with a 60% high-fat diet (HFD). At 12 weeks after HFD feeding, the mice were subjected to liver ischaemia by occluding partial (70%) hepatic arterial/portal venous blood for 60 minutes, which was followed by 24 hours reperfusion. Our results showed HFD exaggerated I/R-induced liver injury. Irisin (250 µg/kg) administration at the beginning of reperfusion attenuated liver injury, improved mitochondrial function, and reduced oxidative and endoplasmic reticulum stress in HFD-fed mice. However, kindlin-2 inhibition by RNAi eliminated irisin's direct effects on cultured hepatocytes. In conclusion, irisin attenuates I/R injury in steatotic liver via a kindlin-2 dependent mechanism.

Irisin reverses intestinal epithelial barrier dysfunction during intestinal injury via binding to the integrin αVß5 receptor.

Disruption of the gut barrier results in severe clinical outcomes with no specific treatment. Metabolic disorders and destruction of enterocytes play key roles in gut barrier dysfunction. Irisin is a newly identified exercise hormone that regulates energy metabolism. However, the effect of irisin on gut barrier function remains unknown. The therapeutic effect of irisin on gut barrier dysfunction was evaluated in gut ischemia reperfusion (IR). The direct effect of irisin on gut barrier function was studied in Caco-2 cells. Here, we discovered that serum and gut irisin levels were decreased during gut IR and that treatment with exogenous irisin restored gut barrier function after gut IR in mice. Meanwhile, irisin decreased oxidative stress, calcium influx and endoplasmic reticulum (ER) stress after gut IR. Moreover, irisin protected mitochondrial function and reduced enterocyte apoptosis. The neutralizing antibody against irisin significantly aggravated gut injury, oxidative stress and enterocyte apoptosis after gut IR. Further studies revealed that irisin activated the AMPK-UCP 2 pathway via binding to the integrin αVß5 receptor. Inhibition of integrin αVß5, AMPK or UCP 2 abolished the protective role of irisin in gut barrier function. In conclusion, exogenous irisin restores gut barrier function after gut IR via the integrin αVß5-AMPK-UCP 2 pathway.

Effect of diabetes mellitus on short-term prognosis of 227 pyogenic liver abscess patients after hospitalization.

BACKGROUND: Pyogenic liver abscess (PLA) is an inflammatory disease with increasing incidence. When it occurs with diabetes mellitus (DM), the risk of recurrence and mortality may increase. However, the effect of DM on the short-term prognosis of PLA patients after hospitalization remained unknown. METHODS: Two hundred twenty-seven PLA patients who received treatment at the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to January 2018 were retrospectively enrolled. They were divided into two groups as the DM group (n = 61) and the Non-DM group (n = 166). In the DM group, HbA1C level < 7% was considered to be good-control of glycaemia (n = 23). The clinical characteristics and overall short-term survival were analyzed. RESULTS: The proportion of PLA patients with DM was 26.87%. In the DM group, there was a higher incidence of hypertension and Candida spp. infection. Conservative administration and percutaneous drainage were mainly used in patients with good- (60.87%) and poor-control (60.53%) of glycaemia, respectively. During follow-up, 24 (10.57%) died due to uncontrolled systemic infections and other serious complications. Compared with PLA patients without DM, patients in the DM group had significantly increased 6-month mortality rate after discharge (Log-Rank test, P = 0.021). Poor-control of glycaemia did not reduce the six-month survival, while the recurrence rate of PLA within 3 months showed an almost 3-fold increase (13.16% vs. 4.35%). Further multivariate analyses found that DM was the only independent risk factor for the PLA six-month survival (odds ratio [OR]: 3.019, 95% confidence interval [CI]: 1.138-8.010, P = 0.026). However, the blood glucose level had no significant effect on the short-term survival of PLA patients with DM (Log-Rank test, P = 0.218). CONCLUSIONS: In PLA patients, DM aggravated short-term mortality and blood glucose levels should be well controlled.

Treatment of recurrent renal transplant lithiasis: analysis of our experience and review of the relevant literature.

BACKGROUND: Renal transplant lithiasis is a rather unusual disease, and the recurrence of lithiasis presents a challenging situation. METHODS: We retrospectively analyzed the medical history of one patient who suffered renal transplant lithiasis twice, reviewed the relevant literature, and summarized the characteristics of this disease. RESULTS: We retrieved 29 relevant studies with an incidence of 0.34 to 3.26% for renal transplant lithiasis. The summarized incidence was 0.52%, and the recurrence rate was 0.082%. The mean interval after transplantation was 33.43 ± 56.70 mo. Most of the patients (28.90%) were asymptomatic. The management included percutaneous nephrolithotripsy (PCNL, 22.10%), ureteroscope (URS, 22.65%), extracorporeal shockwave lithotripsy (ESWL, 18.60%) and conservative treatment (17.13%). In our case, the patient suffered from renal transplant lithiasis at 6 years posttransplantation, and the lithiasis recurred 16 months later. He presented oliguria, infection or acute renal failure (ARF) during the two attacks but without pain. PCNL along with URS and holmium laser lithotripsy were performed. The patient recovered well after surgery, except for a 3 mm residual stone in the calyx after the second surgery. He had normal renal function without any symptoms and was discharged with oral anticalculus drugs and strict follow-up at the clinic. Fortunately, the calculus passed spontaneously about 1 month later. CONCLUSIONS: Due to the lack of specific symptoms in the early stage, patients with renal transplant lithiasis may have delayed diagnosis and present ARF. Minimally invasive treatment is optimal, and the combined usage of two or more procedures is beneficial for patients. After surgery, taking anticalculus drugs, correcting metabolic disorders and avoiding UIT are key measures to prevent the recurrence of lithiasis.

Caspase recruitment domain family member 10 regulates carbamoyl phosphate synthase 1 and promotes cancer growth in bladder cancer cells.

Bladder cancer, which can be divided into non-muscle-invasive and muscle-invasive bladder cancer, is the most common urinary cancer in the United States. Caspase recruitment domain family member 10 (CARD10), also named CARD-containing MAGUK protein 3 (CARMA3), is a member of the CARMA family and may activate the nuclear factor kappa B (NF-κB) pathway. We utilized RNA sequencing and metabolic mass spectrometry to identify the molecular and metabolic feature of CARD10. The signalling pathway of CARD10 was verified by Western blotting analysis and functional assays. RNA sequencing and metabolic mass spectrometry of CARD10 knockdown identified the metabolic enzyme carbamoyl phosphate synthase 1 (CPS1) in the urea cycle as the downstream gene regulated by CARD10. We confirmed that CARD10 affected cell proliferation and nucleotide metabolism through regulating CPS1. We indicated that CARD10 promote bladder cancer growth via CPS1 and maybe a potential therapeutic target in bladder cancer.

Inhibition of stearoyl CoA desaturase-1 activity suppresses tumour progression and improves prognosis in human bladder cancer.

Urinary bladder neoplasm is one of the most common cancers worldwide. Cancer stem cells (CSCs) have been proven to be an important cause of cancer progression and poor prognosis. In the present study, we established bladder CSCs and identified the crucial differentially expressed genes (DEGs) between these cells and parental bladder cancer cells. Analyses of bioinformatics data and clinical samples from local hospitals showed that stearoyl CoA desaturase-1 (SCD) was the key factor among the DEGs. A significant correlation between SCD gene expression and poor prognosis among patients with bladder cancer was observed in our data. Loss-of-function experiments further revealed that the SCD inhibitor A939572 and SCD gene interference reduced cell proliferation and invasion. The above data suggest that SCD may serve as a novel marker for the prediction of tumour progression and poor prognosis in patients with bladder cancer.