Publications by authors named "Chenwei Huang"

9 Publications

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Combination of Urine Exosomal mRNAs and lncRNAs as Novel Diagnostic Biomarkers for Bladder Cancer.

Front Oncol 2021 27;11:667212. Epub 2021 Apr 27.

Department of Clinical Laboratory, Peking University First Hospital, Beijing, China.

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.
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http://dx.doi.org/10.3389/fonc.2021.667212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111292PMC
April 2021

Clinical manifestation and genetic findings in three boys with low molecular Weight Proteinuria - three case reports for exploring Dent Disease and Fanconi syndrome.

BMC Nephrol 2021 01 11;22(1):24. Epub 2021 Jan 11.

Department of Clinical Laboratory, Peking University First Hospital, No.8 Xishiku St., Xicheng District, 100034, Beijing, China.

Background: Dent disease is an X-linked form of progressive renal disease. This rare disorder was characterized by hypercalciuria, low molecular weight (LMW) proteinuria and proximal tubular dysfunction, caused by pathogenic variants in CLCN5 (Dent disease 1) or OCRL (Dent disease 2) genes. Fanconi syndrome is a consequence of decreased water and solute resorption in the proximal tubule of the kidney. Fanconi syndrome caused by proximal tubular dysfunction such as Dent disease might occur in early stage of the disease.

Case Presentation: Three cases reported in this study were 3-, 10- and 14-year-old boys, and proteinuria was the first impression in all the cases. All the boys presented with LMW proteinuria and elevated urine albumin-to-creatinine ratio (ACR). Case 1 revealed a pathogenic variant in exon 11 of CLCN5 gene [NM_001127899; c.1444delG] and a nonsense mutation at nucleotide 1509 [p.L503*], and he was diagnosed as Dent disease 1. Case 2 carried a deletion of exon 3 and 4 of OCRL1 gene [NM_000276.4; c.120-238delGA] and a nonsense mutation at nucleotide 171 in exon 5 [p.E57*], and this boy was diagnosed as Dent disease 2. Genetic analysis of Case 3 showed a missense mutation located in exon 2 of HNF4A gene [EF591040.1; c.253C > T; p.R85W] which is responsible for Fanconi syndrome. All of three pathogenic variants were not registered in GenBank.

Conclusions: Urine protein electrophoresis should be performed for patients with proteinuria. When patients have LMW proteinuria and/or hypercalciuria, definite diagnosis and identification of Dent disease and Fanconi syndrome requires further genetic analyses.
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http://dx.doi.org/10.1186/s12882-020-02225-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802264PMC
January 2021

Microbial Distribution and Antibiotic Susceptibility of Lower Respiratory Tract Infections Patients From Pediatric Ward, Adult Respiratory Ward, and Respiratory Intensive Care Unit.

Front Microbiol 2020 30;11:1480. Epub 2020 Jun 30.

Department of Clinical Laboratory, Peking University First Hospital, Beijing, China.

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. was the dominant pathogen in both the adult respiratory ward ( = 156, 21.49%) and RICU ( = 975, 35.67%), whereas ( = 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 ( = 59, 47.20%) in the pediatric ward and ( = 10, 21.8%) in adult respiratory ward. However, Gram-negative bacteria were the main pathogens in the RICU, of which ( = 51, 27.57%) is the most prevalent. 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. 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.
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http://dx.doi.org/10.3389/fmicb.2020.01480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338583PMC
June 2020

Baseline Glycated Albumin Predicts the Renal Dysfunction in a Five-Year Prospective Population-Based Study.

Clin Lab 2020 Jul;66(7)

Background: Glycated albumin (GA) was reported to be associated with renal dysfunction in non-diabetic CKD population. This study assessed the correlation of GA and renal dysfunction and explored risk factors affecting renal progression in a general population-based study through a five-year follow-up.

Methods: Individuals who underwent a physical examination between September 2010 and September 2015 were enrolled. Multivariate linear regression was performed to assess the relationship between GA and eGFR change rate. The relationship between GA and renal progression was analyzed by multivariate logistic regression among 1,501 participants. Other risk factors were also explored and their predictive value was evaluated by ROC analysis, external validation was carried out in another 603 participants from the general population.

Results: The frequencies of subjects with renal progression increased obviously with the increment of baseline and mean GA according to quartile stratification (p for trend < 0.001). Baseline GA, age, and uric acid (p < 0.05) were identified as risk factors for renal dysfunction with a 30% or more decrease of eGFR. For every 1% increase of GA, the risk of deterioration of renal function increased to 1.585 in the population (95% CI, 1.299 - 1.935, p < 0.001). The predictive value of the model-building equation was confirmed by ROC analysis (AUC = 0.82, 95% CI: 0.773 - 0.832, p < 0.001) and in the validation group, predictive sensitivity and specificity were 85.7% and 73.5%.

Conclusions: Baseline GA is independently associated with renal dysfunction. Uric acid and age are also considered risk factors. GA combining with age, serum creatinine and uric acid can serve as predictive indicators for the progression of renal dysfunction.
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http://dx.doi.org/10.7754/Clin.Lab.2019.190634DOI Listing
July 2020

Crk1/2 and CrkL play critical roles in maintaining podocyte morphology and function.

Exp Cell Res 2020 09 11;394(1):112135. Epub 2020 Jun 11.

Department of Clinical Laboratory, Peking University First Hospital, Beijing, China. Electronic address:

Podocytes are actin-rich epithelial cells whose effacement and detachment are the main cause of glomerular disease. Crk family proteins: Crk1/2 and CrkL are reported to be important intracellular signaling proteins that are involved in many biological processes. However, the roles of them in maintaining podocyte morphology and function remain poorly understood. In this study, specific knocking down of Crk1/2 and CrkL in podocytes caused abnormal cell morphology, actin cytoskeleton rearrangement and dysfunction in cell adhesion, spreading, migration, and viability. The p130Cas, focal adhesion kinase, phosphatidylinositol 3-kinase/Akt, p38 and JNK signaling pathways involved in these alterations. Furthermore, knocking down CrkL alone conferred a more modest phenotype than did the Crk1/2 knockdown and the double knockdown. Kidney biopsy specimens from patients with focal segmental glomerulosclerosis and minimal change nephropathy showed downregulation of Crk1/2 and CrkL in glomeruli. In zebrafish embryos, Crk1/2 and CrkL knockdown compromised the morphology and caused abnormal glomerular development. Thus, our results suggest that Crk1/2 and CrkL expression are important in podocytes; loss of either will cause podocyte dysfunction, leading to foot process effacement and podocyte detachment.
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http://dx.doi.org/10.1016/j.yexcr.2020.112135DOI Listing
September 2020

The relationship between childhood trauma and adult depression: The mediating role of adaptive and maladaptive emotion regulation strategies.

Asian J Psychiatr 2020 Feb 19;48:101911. Epub 2019 Dec 19.

The Emotion & Cognition Lab, Faculty of Psychology and Mental Health, Naval Medical University, Shanghai, 200433, China. Electronic address:

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http://dx.doi.org/10.1016/j.ajp.2019.101911DOI Listing
February 2020

Expression patterns of genes critical for SHH, BMP, and FGF pathways during the lumen formation of human salivary glands.

J Mol Histol 2019 Jun 20;50(3):217-227. Epub 2019 Mar 20.

Fujian Key Laboratory of Developmental and Neural Biology, College of Life Sciences, Fujian Normal University, Fuzhou, 350108, Fujian, People's Republic of China.

Sjögren's syndrome or radiotherapy for head and neck cancer leads to the irreversible hypofunction of salivary gland (SG). The stem/progenitor cell-based regenerative strategy has been proven to be the most promising approach to repair the function of SG. The molecular mechanisms that regulate SG morphogenesis, especially during lumen formation, provide valuable hints for establishment of such regenerative strategies. It has been demonstrated that numerous growth factors particularly belonging to SHH, BMP, and FGF signaling pathway are involved in the regulation of lumen formation and have shown protective effects on the SG from irradiation in mouse models. However, it remains elusive whether the expression pattern and function of these signaling molecules are conserved in humans. In this study, we examined the expression patterns of the molecules critical for SHH, BMP, and FGF signaling cascades from the canalicular stage to the terminal bud stage, the key stages for lumen formation, in human SG and compared them with the expression data observed in mice. Our results manifested that genes involved in SHH signaling pathway showed identical expression patterns, while genes involved in BMP as well as FGF pathway exhibited similar but distinct expression patterns in humans to those in the mouse. We concluded that the expression patterns of genes involved in SHH, BMP, and FGF pathways in the development of human SG exhibit high similarity to that in the development of mouse SG during lumen formation, suggesting that the molecular mechanism regulating the morphogenesis of SG during lumen formation may be conserved in mice and humans. Our results will have an implication in the future establishment of stem-cell based approaches for the repair of SG function.
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http://dx.doi.org/10.1007/s10735-019-09819-xDOI Listing
June 2019

Urine afamin and afamin-creatinine ratio as biomarkers for kidney injury.

Biomark Med 2018 11 15;12(11):1241-1249. Epub 2018 Nov 15.

Department of Clinical Laboratory, Peking University First Hospital, 100034, Beijing, PR China.

Aim: The aim of this study was to evaluate the urine afamin (uAFM) and afamin-creatinine ratio (AfCR) levels in patients with glomerulonephritis.

Patients & Methods: We determined uAFM and AfCR of 247 healthy volunteers and 129 biopsy-proven glomerulonephritis patients.

Results: Analytical evaluation study revealed the assay is a reliable and robust test for measuring uAFM. For reference intervals, uAFM and AfCR values were different significantly between males and females. uAFM and AfCR levels were significantly increased in patients with primary membranous nephropathy, IgA nephropathy and minimal change disease compared with healthy volunteers. uAFM and AfCR were positively correlated with urine albumin and albumin-creatinine ratio, respectively.

Conclusion: Our study suggested that uAFM and AfCR may be attractive biomarkers for kidney injury.
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http://dx.doi.org/10.2217/bmm-2018-0126DOI Listing
November 2018

Electro-Acupuncture at Zusanli Acupoint (ST36) Suppresses Inflammation in Allergic Contact Dermatitis Via Triggering Local IL-10 Production and Inhibiting p38 MAPK Activation.

Inflammation 2017 Aug;40(4):1351-1364

Hubei Provincial Collaborative Innovation Center of Preventive Treatment by Acupuncture and Moxibustion, Hubei University of Chinese Medicine, 1 Huangjiahu West Road, Hongshan District, Wuhan, Hubei, 430065, China.

Acupuncture has shown beneficial effect in the treatment of multiple dermatologic conditions including dermatitis, pruritus, urticaria, and hyperhidrosis; however, the detailed mechanisms are still kept unclear. This study aimed to investigate if electro-acupuncture (EA) treatment prevents 2,4-dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis (ACD) in rats and explore its underlying mechanisms. ACD was induced by sensitizing and challenging with DNFB topically. Rats were treated daily following bilateral subcutaneous stimulation of EA at Zusanli acupoint (ST36) for 1 week. Ear swelling and serum IgE levels were measured. The ear biopsies were obtained for histology. Inflammatory cytokines on the dermatological ear and local acupoint tissue were assayed. Spleen lymphocytes and the homogenized supernatant of local acupuncture area were used to co-culture for flow cytology and immune analysis, respectively. EA treatment at ST36 notably inhibited ear swelling and inflammatory cell infiltration on DNFB-induced ACD. EA also decreased serum IgE concentrations and alleviated the production of inflammatory cytokines in dermatological ear. Additionally, EA treatment attenuated the percentage of CD4IFN-γ and CD4IL-4 T cells associated with ACD. Interestingly, secretion of interleukin (IL)-10 in the local acupoint tissue following EA stimulation was increased and showed suppressive function when co-cultured with the spleen lymphocytes from DNFB group. Lastly, EA treatment demonstrably suppressed p38 MAPK activation in DNFB-treated rats. Our findings suggest that EA treatment at ST36 may ameliorate inflammation associated with DNFB-induced ACD via triggering local IL-10 production and inhibiting p38 MAPK activation, which provide an alternative and promising therapy for ACD.
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http://dx.doi.org/10.1007/s10753-017-0578-5DOI Listing
August 2017