Bladder cancer (BC) is a heterogeneous disease that characterized by genomic instability and a high mutation rate. Heterogeneity in tumor may partially explain the diversity of responses to targeted therapies and the various clinical outcomes. A combination of cytology and cystoscopy is the standard methodology for BC diagnosis, prognosis, and disease surveillance. However, genomics analyses of single tumor‐biopsy specimens may underestimate the mutational burden of heterogeneous tumors. Liquid biopsy, as a promising technology, enables analysis of tumor components in the bodily fluids, such as blood and urine, at multiple time points and provides a minimally invasive approach that can track the evolutionary dynamics and monitor tumor heterogeneity. In this review, we describe the multiple faces of BC heterogeneity at the genomic and transcriptional levels and how they affect clinical care and outcomes. We also summarize the outcomes of liquid biopsy in BC, which plays a potential role in revealing tumor heterogeneity. Finally, we discuss the challenges that must be addressed before liquid biopsy can be widely used in clinical treatment.

M-type phospholipase A2 receptor (PLA2R) is the major target antigen in primary membranous nephropathy (PMN). Previous studies have evaluated the diagnostic value of serum anti-PLA2R antibody. However, the correlation of serum anti-PLA2R antibody and glomerular PLA2R deposition, and their association with clinical characteristics need to be further evaluated. A total of 136 patients were involved as inception group because serum anti-PLA2R antibody and glomerular PLA2R antigen were simultaneously measured. We examined serum anti-PLA2R antibody by ELISA and glomerular PLA2R deposition by immunofluorescence assay. Positive serum anti-PLA2R antibody and glomerular PLA2R deposition were seen in 58.8% (80/136) and 95.6% (130/136) patients, respectively (P < .001). Proteinuria, serum total protein, serum albumin, serum creatinine, and estimated glomerular filtration rate (eGFR) had significant differences between patients with serum anti-PLA2R antibody and those without. Serum anti-PLA2R antibody levels were correlated with serum albumin, serum creatinine, eGFR, and proteinuria. Glomerular PLA2R deposition intensities were weakly correlated with proteinuria. Unexpectedly, there was a positive correlation rather than a negative correlation between glomerular PLA2R deposition intensity and eGFR. In conclusion, serum anti-PLA2R antibody is more closely correlated with disease activity and renal function than glomerular PLA2R deposition.

Background: The recent discovery of miRNAs and lncRNAs in urine exosomes has emerged as promising diagnostic biomarkers for bladder cancer (BCa). However, mRNAs as the direct products of transcription has not been well evaluated in exosomes as biomarkers for BCa diagnosis. The purpose of this study was to identify tumor progression-related mRNAs and lncRNAs in urine exosomes that could be used for detection of BCa. Methods: RNA-sequencing was performed to identify tumor progression-related biomarkers in three matched superficial tumor and deep infiltrating tumor regions of muscle-invasive bladder cancer (MIBC) specimens, differently expressed mRNAs and lncRNAs were validated in TCGA dataset (n = 391) in the discovery stage. Then candidate RNAs were chosen for evaluation in urine exosomes of a training cohort (10 BCa and 10 healthy controls) and a validation cohort (80 BCa and 80 healthy controls) using RT-qPCR. The diagnostic potential of the candidates were evaluated by receiver operating characteristic (ROC) curves. Results: RNA sequencing revealed 8 mRNAs and 32 lncRNAs that were significantly upregulated in deep infiltrating tumor region. After validation in TCGA database, 10 markedly dysregulated RNAs were selected for further investigation in urine exosomes, of which five (mRNAs: KLHDC7B, CASP14, and PRSS1; lncRNAs: MIR205HG and GAS5) were verified to be significantly dysregulated. The combination of the five RNAs had the highest AUC to disguising the BCa (0.924, 95% CI, 0.875–0.974) or early stage BCa patients (0.910, 95% CI, 0.850 to 0.971) from HCs. The expression levels of these five RNAs were correlated with tumor stage, grade, and hematuria degrees. Conclusions: These findings highlight the potential of urine exosomal mRNAs and lncRNAs profiling in the early diagnosis and provide new insights into the molecular mechanisms involved in BCa.

Introduction: Lower respiratory tract infections (LRTIs) account for significant morbidity and mortality in patients admitted to hospitals worldwide, especially in children and elderly. The prevalent microorganisms and antibiotic susceptibility were investigated among LRTI patients from the pediatric ward, adult respiratory ward, and respiratory intensive care unit (RICU) in order to achieve more efficient treatment protocols and better recovery. Methods: In this retrospective cross-sectional study (January 2016 to December 2019), 4,161 positive culture samples out of 18,798 different specimens (9,645 respiratory tract samples and 9,153 blood samples) from LRTI patients were analyzed for pathogen incidence and antibiotic sensitivity. Results: Among the respiratory tract cultures, the frequency of Gram-negative bacterial strains was higher than Gram-positive bacterial strains. Pseudomonas aeruginosa was the dominant pathogen in both the adult respiratory ward (n = 156, 21.49%) and RICU (n = 975, 35.67%), whereas Staphylococcus aureus (n = 66, 19.19%) was the most common bacterium in the pediatric ward. Among the blood cultures, Gram-positive bacteria remained the major microorganisms involved in LRTIs, and the most frequent pathogen was Staphylococcus epidermidis (n = 59, 47.20%) in the pediatric ward and Staphylococcus aureus (n = 10, 21.8%) in adult respiratory ward. However, Gram-negative bacteria were the main pathogens in the RICU, of which Klebsiella pneumoniae (n = 51, 27.57%) is the most prevalent. Pseudomonas aeruginosa of LRTI patients remained highly susceptible (>70%) to routine antibiotics in pediatric ward. However, it only had high susceptibility to amikacin, tobramycin, gentamicin in both the adult respiratory ward and RICU and its antibiotic sensitivity to meropenem and imipenem was moderate in the adult respiratory ward and mild (<30%) in the RICU. Staphylococcus aureus isolated from LRTI patients was highly susceptible to linezolid, daptomycin, teicoplanin, vancomycin, tigecycline, rifampicin, and trimethoprim/sulfamethoxazole in all three wards, moderately susceptible to gentamicin in both the adult respiratory ward and RICU and to clindamycin, oxacillin, moxifloxacin only in the adult respiratory ward. Conclusions: Microbial distribution and their patterns of antibiotic susceptibility revealed a high divergence among LRTI patients admitted to different wards in this hospital. Thus, different antibiotic therapies should be considered for distinct age groups.

Acute myeloid leukemia is the most common acute leukemia in adults, the barrier of refractory and drug resistance has yet to be conquered in the clinical. Abnormal gene expression and epigenetic changes play an important role in pathogenesis and treatment. A super-enhancer is an epigenetic modifier that promotes pro-tumor genes and drug resistance by activating oncogene transcription. Multi-omics integrative analysis identifies the super-enhancer-associated gene CAPG and its high expression level was correlated with poor prognosis in AML. CAPG is a cytoskeleton protein but has an unclear function in AML. Here we show the molecular function of CAPG in regulating NF-κB signaling pathway by proteomic and epigenomic analysis. Knockdown of Capg in the AML murine model resulted in exhausted AML cells and prolonged survival of AML mice. In conclusion, SEs-associated gene CAPG can contributes to AML progression through NF-κB.