Publications by authors named "Jian Guo Wen"

83 Publications

METTL3/N6-methyladenosine/ miR-21-5p promotes obstructive renal fibrosis by regulating inflammation through SPRY1/ERK/NF-κB pathway activation.

J Cell Mol Med 2021 Jun 24. Epub 2021 Jun 24.

Department of Urology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Renal fibrosis induced by urinary tract obstruction is a common clinical occurrence; however, effective treatment is lacking, and a deeper understanding of the mechanism of renal fibrosis is needed. Previous studies have revealed that miR-21 impacts liver and lung fibrosis progression by activating the SPRY1/ERK/NF-kB signalling pathway. However, whether miR-21 mediates obstructive renal fibrosis through the same signalling pathway has not been determined. Additionally, studies have shown that N6-methyladenosine (m A) modification-dependent primary microRNA (pri-microRNA) processing is essential for maturation of microRNAs, but its role in the maturation of miR-21 in obstructive renal fibrosis has not yet been investigated in detail. To address these issues, we employed a mouse model of unilateral ureteral obstruction (UUO) in which the left ureters were ligated for 3, 7 and 14 days to simulate the fibrotic process. In vitro, human renal proximal tubular epithelial (HK-2) cells were transfected with plasmids containing the corresponding sequence of METTL3, miR-21-5p mimic or miR-21-5p inhibitor. We found that the levels of miR-21-5p and m A modification in the UUO model groups increased significantly, and as predicted, the SPRY1/ERK/NF-kB pathway was activated by miR-21-5p, confirming that miR-21-5p plays an important role in obstructive renal fibrosis by enhancing inflammation. METTL3 was found to play a major catalytic role in m A modification in UUO mice and drove obstructive renal fibrosis development by promoting miR-21-5p maturation. Our research is the first to demonstrate the role of the METTL3-m A-miR-21-5p-SPRY1/ERK/NF-kB axis in obstructive renal fibrosis and provides a deeper understanding of renal fibrosis.
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http://dx.doi.org/10.1111/jcmm.16603DOI Listing
June 2021

Histamine H Receptor Signaling Regulates the NLRP3 Inflammasome Activation in C2C12 Myocyte During Myogenic Differentiation.

Front Pharmacol 2021 31;12:599393. Epub 2021 May 31.

Urodynamic Center and Department of Urology, Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

NLRP3 inflammasome has been implicated in impaired post-injury muscle healing and in muscle atrophy. Histamine receptors play an important role in inflammation, but the role of histamine H receptor (HR) in myocyte regeneration and in the regulation of NLRP3 inflammasome is not known. We studied the effects of HR signaling on C2C12 myocyte viability, apoptosis, and tumor necrosis factor alpha (TNFα)-induced NLRP3 inflammasome activation during striated myogenic differentiation at three time points (days 0, 3, and 6). Expression of , interleukin-1β (IL-1β), and myogenesis markers were determined. TNFα reduced overall viability of C2C12 cells, and exposure to TNFα induced apoptosis of cells at D6. Activation of HR had no effect on viability or apoptosis, whereas inhibition of HR increased TNFα-induced apoptosis. Stimulation of C2C12 cells with TNFα increased mRNA expression at D3 and D6. Moreover, TNFα reduced the expression of myogenesis markers MyoD1, Myogenin, and Myosin-2 at D3 and D6. HR attenuated TNFα-induced expression of and further inhibited the myogenesis marker expression; while HR -blockage enhanced the proinflammatory effects of TNFα and increased the myogenesis marker expression. TNFα-induced secretion of mature IL-1β was dependent on the activation of the NLRP3 inflammasome, as shown by the reduced secretion of mature IL-1β upon treatment of the cells with the small molecule inhibitor of the NLRP3 inflammasome (MCC950). The activation of HR reduced TNFα-induced IL-1β secretion, while the HR blockage had an opposite effect. In conclusion, the modulation of HR activity regulates the effects of TNFα on C2C12 myocyte differentiation and TNFα-induced activation of NLRP3 inflammasome. Thus, HR signaling may represent a novel target for limiting postinjury muscle inflammation and muscle atrophy.
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http://dx.doi.org/10.3389/fphar.2021.599393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202077PMC
May 2021

Mechanism and Priority of Botulinum Neurotoxin A versus Sacral Neuromodulation for Refractory Overactive Bladder: A Review.

Urol Int 2021 Jun 15:1-6. Epub 2021 Jun 15.

First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: The treatment of common overactive bladder (OAB) has reached a consensus, but there is not a clear answer to the treatment of refractory OAB (ROAB). ROAB is defined as nonresponsive to treatment with behavioural and oral therapies. The disease can influence the physical and mental health of patients, cause poor quality of life, and create an urgent socio-economic burden. With the advancement of medical treatment, the treatment of OAB has improved significantly in the last 2 decades, especially ROAB, by the usage of botulinum neurotoxin A (BoNT-A) and sacral neuromodulation (SNM). Many studies have demonstrated their effectiveness and safety. However, which therapy is the optimal method remains unclear for patients with ROAB, and the exact mechanism involved in the procedures is still unknown.

Summary: This review is to clarify the mechanisms, advantages, and disadvantages of SNM and BoNT-A in treatment of ROAB, and determine whether there is an order effect of SNM and BoNT-A in managing ROAB. Key Messages: BoNT-A and SNM mainly act on the peripheral nervous system and central nervous system, respectively. But BoNT-A and SNM may partly act on the central and peripheral nervous systems, separately. SNM may be a better choice than BoNT-A in the long time. At the same time, BoNT-A and SNM can treat the ROAB as the first and next steps, and the sequence of both would not affect the effectiveness of each other.
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http://dx.doi.org/10.1159/000515991DOI Listing
June 2021

Delayed elimination communication on the prevalence of children's bladder and bowel dysfunction.

Sci Rep 2021 Jun 11;11(1):12366. Epub 2021 Jun 11.

Pediatric Urodynamic Center and Department of Urology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

To determine the prevalence of bladder and bowel dysfunction (BBD) and its relationship with delayed elimination communication (EC) in children. A cross-sectional study was carried out in kindergartens and primary schools in mainland China. A total of 10,166 children ranging from 4 to 10 years old were included. A total of 10,166 valid questionnaires were collected, and 409 children were diagnosed with BBD. The overall prevalence was 4.02% (409/10,166) and decreased with age, from 6.19% at age 4 to 1.96% at age 10. With the prolonged use of disposable diapers (DDs), the commencement of usage of EC in a child was significantly put off or delayed by parents, and the prevalence of BBD amongst these children increased (P < 0.001). The prevalence of BBD among children who stopped using DDs within the first 12 months and after more than 24 months was 2.79% and 4.38% respectively. Additionally, the prevalence among children who started EC within 12 months after birth and those who never engaged in EC was 1.36% and 15.71% respectively. Early introduction of EC and weaning of DD usage has a positive correlation with lower prevalence of BBD in children in China.
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http://dx.doi.org/10.1038/s41598-021-91704-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196082PMC
June 2021

Prevalence, Risk Factors, and Psychological Effects of Primary Nocturnal Enuresis in Chinese Young Adults.

Int Neurourol J 2021 Mar 31;25(1):84-92. Epub 2021 Mar 31.

First, Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.

Purpose: This study aimed to investigate the prevalence, risk factors, and effects of primary nocturnal enuresis (PNE) on physical and mental health in young adults in mainland China.

Methods: An anonymous questionnaire was used to collect information including the sociodemographic characteristics, history of PNE, family history, daytime voiding symptoms, Pittsburgh Sleep Quality Index (PSQI) scores, Self-Esteem Scale (SES), and Self-Rating Depression Scale (SDS). A total of 22,500 university students from 23 provinces and 368 cities in mainland China were included.

Results: In total, 21,082 questionnaires were collected, and 20,345 of them qualified for statistical analysis. The PNE prevalence was 1.17%, and the distribution of monosymptomatic nocturnal enuresis (MNE) and nonmonosymptomatic nocturnal enuresis (NMNE) was 66.1% and 33.9%, respectively. In total, 28% of respondents with PNE reported bedwetting daily, 31.6% between 1 and 7 times weekly, and 40.4% between 1 and 4 times monthly; 80% of PNE cases had no history of treatment. The prevalence of PNE in patients with a family history, frequency, urgency, urinary incontinence, and recurrent urinary tract infections was significantly higher than in those without these conditions (P<0.001). PNE was significantly correlated with the PSQI total score (sleep quality) (P=0.011). The SES score was lower and the SDS was higher (P<0.001) in the PNE group than in those without PNE.

Conclusion: In mainland China, the PNE prevalence among young adults was found to be high, and PNE had significant effects on physical and mental health. Risk factors included a family history, daytime voiding symptoms, and lack of treatment.
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http://dx.doi.org/10.5213/inj.2040398.149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022166PMC
March 2021

The TGF-β1 pathway is early involved in neurogenic bladder fibrosis of juvenile rats.

Pediatr Res 2021 Jan 19. Epub 2021 Jan 19.

Pediatric Urodynamic Center and Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China.

Background: This study investigated whole neurogenic bladder's progression changes, as well as the expression of TGF-β1 fibrosis pathway-related proteins in bilateral spinal nerve-amputated juvenile rats.

Methods: Sixty-four 8-week-old rats (32 bilateral L6 + S1 spinal nerve amputated and 32 sham operated) were selected. Cystometry was performed. General assessments, Masson, Sirius red, immunohistochemical staining, and western blotting of fibrosis and TGF-β1 pathway-related proteins were conducted using bladder tissues.

Results: Cystometry results showed that the basal intravesical pressures and bladder capacities in nerve-amputated rats were significantly higher than those in sham-operated ones. Compared to the sham-operated groups, the bladder size and wall thickness in the nerve-amputated groups increased initially but then decreased over time. However, bladder weight continuously increased over time. Disintegration, thickening, and hypertrophy of the bladder wall were found over time in the amputated rats. Moreover, there was a significant increase in collagen III, and the ratio of collagen III/I was higher in amputated rats (P < 0.01). Finally, the expression of TGF-β1, TGF-βRI, Smad2, and collagen III and I increased in amputated bladder tissues, while Smad6 decreased over time.

Conclusions: The main clinical features of pediatric neurogenic bladder (PNB) were detrusor paralysis and continuous intravesical pressure. Biological molecular findings are earlier than the pathophysiological findings. Therefore, early preventing bladder fibrosis by targeting TGF-β1/Smad pathway-related proteins once knowing the PNB diagnosis might be an alternative treatment for PNB.

Impact: The study found that the main clinical features of PNB were detrusor paralysis, continuous intravesical pressure, and increased TGF-beta/Smad signal proteins over time. The study makes contributions to the literature because it suggests biological molecular findings are earlier than the pathophysiological findings by various staining in PNB. The study investigated whole neurogenic bladder's progression changes, as well as the expression of TGF-β1 fibrosis pathway-related proteins in the spinal nerve-injured PNB juvenile rat models, which suggests that early prevention of bladder fibrosis by targeting TGF-β1/Smad pathway-related proteins once knowing the PNB diagnosis might be an alternative treatment for pediatric neurogenic bladder.
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http://dx.doi.org/10.1038/s41390-020-01329-xDOI Listing
January 2021

Disposable diaper overuse is associated with primary enuresis in children.

Sci Rep 2020 09 1;10(1):14407. Epub 2020 Sep 1.

Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, 13 Hangkong Rd, Wuhan, 430030, Hubei, China.

This research investigated the association between prolonged disposable diaper (DD) wearing in infancy and primary enuresis (PNE). As a case-control study, we collected data from 376 children with enuresis and 379 healthy children who were sex- and age-matched at three tertiary care institutions in mainland China from August 2017 to July 2018. The results of adjusted logistic regression showed the odds ratios (95% confidence intervals) for PNE across the categories of age of daytime DD use cessation were as follows: ≥ 25 months: 1.00, 18-24 months: 0.25 (0.17-0.37), and ≤ 17 months: 0.11 (0.06-0.20), independent of age, mother education, residence, toilet training approach, breastfeeding duration, UTI, constipation, anaphylactic disease and family history. After a similar multivariable adjustment, increased age of daytime DD use (per-month) had a positive correlation with PNE, OR = 1.17, 95% CI 1.13-1.20 and non-linear relationship was detected, whose point was 21 months (the effect sizes and the 95%CI on the left and right sides of inflection point were 1.04 (0.99-1.10), P = 0.131 and 1.25 (1.18-1.31), P < 0.001). Subgroup analysis found that the effect of duration of disposable diaper exposure for each additional month, those children had accepted assisted infant toilet training/elimination communication (AITT/EC) practice had a lower risk of PNE (OR = 1.08, 95% CI 1.04-1.12), compared with those without AITT/EC practice (OR = 1.20, 95% CI 1.14-1.27), P for interaction < 0.001. In conclusion, the children diagnosed with primary enuresis after age 5 stopped using disposable diapers at daytime later than the control group. Association between duration of DD exposure and the risk of childhood enuresis is modified by AITT/EC practice. Timely cessation use of disposable diaper and practice AITT/EC may shorten the time to nocturnal continence, and the prospective cohort studies are needed to verify the discoveries.
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http://dx.doi.org/10.1038/s41598-020-70195-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462848PMC
September 2020

EGFRvIII-specific CAR-T cells produced by piggyBac transposon exhibit efficient growth suppression against hepatocellular carcinoma.

Int J Med Sci 2020 5;17(10):1406-1414. Epub 2020 Jun 5.

Key Laboratory of Immunology and Kidney Disease, People's Hospital of Henan Province, Zhengzhou University, Zhengzhou, 450003, China.

Adoptive cellular immunotherapy employing chimeric antigen receptors-modified T (CAR-T) cells has demonstrated promising antitumor effects in hematologic cancers. However, CAR-T therapy confront many challenges in solid tumors like immunosuppressive microenvironment, molecular heterogeneity, etc. The cancer genome atlas (TCGA) of hepatocellular carcinoma (HCC) revealed many genetic characteristic and molecular tumorigenesis. EGFRvIII is a tumor specific antigen widely expressed in a variety of cancers including HCC and an ideal therapeutic target for cancer therapy. The liver cancer cell line SMMC7721 express high level EGFRvIII and widely applied in HCC investigations. Herein, we developed EGFRvIII CAR-T cells by piggyBac transposon system, and detected its specific killing effect against SMMC7721 cells and . Results indicated that transduction efficiency of CAR reached 53.1%. Expression of CAR protein was verified by immunoblotting as a band of approximate 57KD. The killing effect of CAR-T cells against SMMC7721 was positively correlated with E/T ratio (E:T=5:1, 10:1, 20:1, 40:1), and exceeded 50% at 20:1 ratio. Significant increase in IFN-γ and TNF-α secretion were detected in the co-culture supernatant of CAR-T cells and SMMC7721, comparable to the level of exogenous EGFRvIII-expressing U87 cells. The killing activity and cytokine secretion were both dependent on the expression level of EGFRvIII in target cells. In HCC xenograft models, CAR-T cells could effectively suppress the growth of SMMC7721. In conclusion, EGFRvIII CAR-T cells demonstrated specific antitumor effect against SMMC7721 and , providing basis for immunotherapy of HCC in future clinical use.
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http://dx.doi.org/10.7150/ijms.45603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330669PMC
March 2021

Delayed in toilet training association with pediatric lower urinary tract dysfunction: A systematic review and meta-analysis.

J Pediatr Urol 2020 06 10;16(3):352.e1-352.e8. Epub 2020 Mar 10.

Department of Maternal and Childi Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430030, China. Electronic address:

Background: Globally, attitudes and practices towards toilet training have changed several decades ago and children are completing toilet training at a later age compared to previous generations. Concurrently, there has been an increase in the incidence of pediatric bladder bowel dysfunction (BBD), including lower urinary tract dysfunction (LUTD). Whether the fact of delayed toilet training may negatively impact the ability of children to obtain bladder and bowel control and cause LUT dysfunction remains controversial.

Objectives: To investigate the association between age at initiation of toilet training or approach to toilet training and the risks of lower urinary tract (LUT) dysfunction.

Methods: A comprehensive search of the CENTRAL, EMBASE and MEDLINE via Ovid SP, and CINAHL via EBSCO databases was conducted to identify RCTs, cohort or case-control studies investigating the association between age at initiation of toilet training, approach used for toilet training, and pediatric LUT dysfunction.

Results: A total of 10 studies with 24,121 participants (aged 5-17) were included for pooled analysis. Overall, the odds ratio (OR) with 95% confidence interval (95%CI) of LUT dysfunction in children who initiated toilet training at a younger age when compared to those who initiated toilet training at an older age, was 0.71 (0.63-0.81), P < 0.001), irrespective of the approach used for toilet training (Table). Subgroup analysis for day-time incontinence (persistent daytime wetting) was 0.77 (0.62-0.95), P = 0.014; although the outcomes for enuresis fluctuated, favorable results were still observed in the earlier training group (OR:0.63, 95%CI:0.43-0.94, P = 0.023). Subgroup analysis for age at initiating toilet training vs LUT dysfunction also showed favorable results in children who were trained earlier, i.e., before 24 months (OR:0.77, 95% CI 0.63-0.94, P = 0.009). Sensitivity analysis confirmed that the results were robust.

Discussion: Although the definition about the age of initial toilet training varied greatly in studies, findings from the current study suggested that the optimal time for initiating toilet training may be prior to the age of 24 months; if toilet training was initiated after 24 months or later, it may result in increased prevalence of LUT dysfunction. Since no RCTs studies were included in the current meta-analysis, well-designed longitudinal studies with larger sample size and from different cultural background are needed to confirm these results.

Conclusion: This meta-analysis presents preliminary findings that show the incidence of LUTD may be decreased by initiating toilet training in children at a younger age.
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http://dx.doi.org/10.1016/j.jpurol.2020.02.016DOI Listing
June 2020

Prevalence and risk factors of overactive bladder in Chinese children: A population-based study.

Neurourol Urodyn 2020 02 5;39(2):688-694. Epub 2019 Dec 5.

Pediatric Urodynamic Centre, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Aims: To investigate the prevalence of overactive bladder (OAB) and assess its risk factors in 5- to 14-year-old Chinese children.

Methods: A cross-sectional study of OAB prevalence was performed by distributing 11 800 anonymous self-administered questionnaires to parents in five provinces of mainland China from July to October 2018. The questionnaires included questions on sociodemographics, history of urinary tract infection (UTI), lower urinary tract symptoms (LUTS), family history of LUTS, bowel symptoms, and details about the elimination communication (EC) start time. OAB was defined as urgency and increased the daytime frequency with or without urinary incontinence.

Results: A total of 10 133 questionnaires qualified for statistical analysis. The overall prevalence of OAB was 9.01% and decreased with age, from 12.40% at 5 years to 4.55% at 14 years (χ trend = 88.899; P < .001). The proportion of dry OAB increased with age, whereas the proportion of wet OAB decreased. A late-onset of EC was associated with a high OAB prevalence (χ trend = 39.802; P < .001). Children with obesity, a history of UTI, nocturnal enuresis (NE), a family history of LUTS, constipation, and fecal incontinence had a higher prevalence of OAB than did normal children (P < .05).

Conclusion: Obesity, a history of UTI, NE, a family history of LUTS, and bowel symptoms are risk factors associated with OAB. Starting EC before 12 months of age might help reduce the prevalence of OAB in children.
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http://dx.doi.org/10.1002/nau.24251DOI Listing
February 2020

Changes in bladder function with time following cystostomy in rats.

Neurourol Urodyn 2020 02 29;39(2):565-575. Epub 2019 Nov 29.

Department of Urology, Pediatric Urodynamic Centre, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.

Aims: To investigate bladder function patterns following cystostomy and determine the best time window for cystometric evaluation of bladder function in conscious rats.

Materials And Methods: Cystostomy was performed in rats of the first seven groups; thereafter, cystometry was performed in the designed time interval. Noncystostomy rats of group 8 voided freely as control. Basal bladder pressure (P ), maximum bladder pressure (P ), bladder threshold pressure (P ), voiding interval (VI), bladder contraction duration (CD), bladder compliance (ΔC), voided volume (VV), postvoiding residual urine (PVR), and bladder capacity (BC) were recorded and compared with cystostomy groups, with VV, PVR, BC compared with the control values. Bladders were collected after the urodynamic study for weighing, hematoxylin-eosin, and Masson staining to investigate pathological changes.

Results: P , P , and P trended downward, while BC, VI, VV, and ΔC trended upward on days 1 to 5 postcystostomy. BC and VV significantly decreased on days 1 to 3 postcystostomy compared with control values; on days 5 to 15 postcystostomy, P , P , P , VI, VV, BC, and PVR were stable, and BC, VV, and PVR showed no significant differences from the control values. However, on day 21 postcystostomy, BC increased significantly compared with the controls. Bladder weight increased in the cystostomy groups compared with the controls. Pathological analysis showed severe acute bladder inflammation on days 1 to 3, mild inflammation on days 5 to 15, and increased collagen deposition in bladder tissue on day 21 postcystostomy.

Conclusion: Cystometric evaluation of bladder function in conscious rats is best performed on days 5 to 15 postcystostomy.
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http://dx.doi.org/10.1002/nau.24241DOI Listing
February 2020

Forskolin attenuates the NLRP3 inflammasome activation and IL-1β secretion in human macrophages.

Pediatr Res 2019 12 13;86(6):692-698. Epub 2019 May 13.

Pediatric Urodynamic Center and Department of Urology, Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China.

Background: The treatment of nucleotide-binding domain and leucine-rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome-mediated pediatric inflammatory diseases is challenging. Here we studied whether cyclic adenosine monophosphate (cAMP) elevator forskolin could attenuate the nigericin-induced NLRP3-inflammasome activation and interleukin-1β (IL-1β) secretion in human macrophages.

Methods: The proteins and messenger RNA (mRNA) levels of inflammasome structural proteins and proinflammatory cytokines were measured in forskolin-stimulated nigericin-activated human THP-1 macrophages and primary macrophages.

Results: Activation of THP-1 macrophages with nigericin increased the mRNA expression of NLRP3, IL-1β, and caspase-1 (P < 0.01). Forskolin stimulation had no effect on the mRNA expression of NLRP3, caspase-1, or IL-1β in nigericin-activated cells (P > 0.05), while their protein levels were significantly decreased (P < 0.05). Forskolin-mediated increase in cytoplasmic cAMP in non-activated cells was attenuated in nigericin-activated macrophages (P < 0.05). Basal IL-1β secretion increased from 584 to 2696 pg/mL (P < 0.01) in nigericin-activated macrophages; forskolin dose-dependently reduced the nigericin-induced secretion of mature IL-1β (P < 0.01). Forskolin also inhibited the IL-1β secretion from activated human primary macrophages.

Conclusions: Forskolin inhibits the NLRP3 inflammasome activation and the secretion of mature IL-1β, in human macrophages. Forskolin and other cAMP elevator drugs could represent a novel approach for treatment of diseases associated with excessive inflammasome activation, like pediatric inflammatory diseases.
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http://dx.doi.org/10.1038/s41390-019-0418-4DOI Listing
December 2019

The influence of delay elimination communication on the prevalence of primary nocturnal enuresis-a survey from Mainland China.

Neurourol Urodyn 2019 06 18;38(5):1423-1429. Epub 2019 Apr 18.

Pediatric Urodynamic Centre, Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Aims: A pilot survey shows that primary nocturnal enuresis (PNE) prevalence has increased significantly during the past decade in Mainland China. Whether it is related to the delay of elimination communication (EC) is unclear. This study retrospectively investigated the influence of delayed EC on the PNE prevalence in children and adolescents in mainland China.

Methods: A cross-sectional study of PNE prevalence was performed by distributing 19 500 anonymous self-administered questionnaires to parents in five provinces of mainland China from July 2017 to October 2017. The questionnaires included sociodemographic data, family caregivers' information, and details about the disposable diapers (DD) usage, EC commencement date, psychological disorders, lower urinary tract symptoms, and family history of PNE in children and adolescents. The 2017 PNE prevalence was compared with that of 2006 in Mainland China.

Results: The total response rate was 97.04% (18 631 of 19 500) and 92.39% (18 016 of 19 500) qualified for statistical analysis. The PNE prevalence in 2017 has increased significantly compared to that of 2006 (7.30% vs 4.07%, P < 0.001). The PNE prevalence in children with EC starting before 6 months of age was significantly lower than those who start after 12 months of age. The longer DD were used and the later the beginning of EC, the higher the PNE prevalence was found.

Conclusions: The PNE prevalence in Mainland China has increased significantly during the past 10 years. A longer use of DD and later onset of EC may be risk factors for PNE.
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http://dx.doi.org/10.1002/nau.24002DOI Listing
June 2019

International Continence Society (ICS) report on the terminology for nocturia and nocturnal lower urinary tract function.

Neurourol Urodyn 2019 02 15;38(2):499-508. Epub 2019 Jan 15.

University of Pennsylvania, Philadelphia, Pennsylvania.

Introduction: The terminology for nocturia and nocturnal lower urinary tract function is reviewed and updated in a clinically and practically-based consensus report.

Methods: This report has been created by a Working Group under the auspices and guidelines of the International Continence Society (ICS) Standardisation Steering Committee (SSC). All relevant definitions were updated on the basis of research over the last 16 years since the publication of the first nocturia standardization document in 2002. An extensive process of 16 rounds of internal and external reviews was involved to examine each definition exhaustively, with decision-making by collective opinion (consensus).

Results: A clinically-based terminology report for nocturia and nocturnal lower urinary tract function, encompassing five key definitions divided into signs and symptoms has been developed. Clarity and user-friendliness have been key aims to make it interpretable by healthcare professionals and allied healthcare practitioners involved in the care of individuals with nocturnal lower urinary tract function.

Conclusion: A consensus-based terminology report for nocturia and nocturnal lower urinary tract function has been produced to aid clinical practice and research.
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http://dx.doi.org/10.1002/nau.23917DOI Listing
February 2019

[High-frequency ultrasonographic characteristics and clinical features of primary testicular lymphoma in children].

Zhonghua Nan Ke Xue 2018 Dec;24(12):1100-1105

Department of Urology, Shenzhen Children's Hospital, Shenzhen, Guangdong 518038, China.

Objective: To investigate the high-frequency ultrasonographic characteristics and clinical features of primary testicular lymphoma (PTL) in children.

Methods: We retrospectively analyzed the high-frequency ultrasonographic manifestations and clinical characteristics of 11 cases of PTL in children, all confirmed by postoperative pathology.

Results: Most of the PTL patients were school-age children, with painless testicular enlargement as the initial symptom. Preoperative grey-scale ultrasonography showed involvement of the unilateral testis in 8, bilateral testes in 3, and both the testis and epididymis in 2 of in the 11 children with PTL. Nine of the cases were displayed as diffuse lesion and the other 2 as nodular lesion, all with extremely low echogenicity. Color Doppler flow imaging (CDFI) revealed abundant blood flow signals but no liquefaction or calcification echo in the lesions. Follow-up ultrasonography after immunochemotherapy showed complete disappearance of the lesion in 3 cases, reduction in another 3, no significant change in 1, and enlargement in the other 4.

Conclusions: PTL in children has some specific ultrasonographic characteristics. A deeper insight into the ultrasonographic characteristics and clinical features of PTL may help improve ultrasonographic diagnosis of the disease.
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December 2018

The relationship between Aquaporin-2 protein levels in amniotic fluid and the fetal kidney in humans.

Biochem Biophys Res Commun 2018 11 23;506(3):585-589. Epub 2018 Oct 23.

Department of Pediatric Urodynamic Center& Henan Joint International Pediatric Urodynamic Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. Electronic address:

Objectives: Aquaporin-2 (AQP2) is an important water channel protein that is expressed in the renal collecting duct and plays a key role in urine concentration and body water homeostasis. It has been demonstrated that the urinary excretion of AQP2 correlates strongly with its expression in the kidney in adult humans and rats. However, there have been no studies on the urinary excretion of AQP2 in human fetuses during development. Fetal urine is the main source of the amniotic fluid; we speculate that the level of AQP2 in the amniotic fluid could reflect the expression level of the AQP2 protein in the fetal kidney. The purpose of the present study was to explore the relationship between AQP2 in the amniotic fluid and that in the fetal kidney.

Methods: In the present study, the concentration of the AQP2 protein in human amniotic fluid was measured by Enzyme-linked immunosorbent assay (ELISA) and its expression level in human fetal kidneys were examined by wastern blot and immunohistochemistry.

Results: Both the expression level of AQP2 in the fetal kidney (F = 195.9, P < 0.001) and the concentration of AQP2 in the amniotic fluid increased with gestational age (F = 1098, P < 0.001). Moreover, the concentration of AQP2 in the amniotic fluid was positively correlated with its expression level in the fetal kidney (r = 0.872, P < 0.0001).

Conclusions: Our research indicates that AQP2 levels in the amniotic fluid may be used as a marker for AQP2 expression in the fetal kidney.
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http://dx.doi.org/10.1016/j.bbrc.2018.10.097DOI Listing
November 2018

The renal protect function of erythropoietin after release of bilateral ureteral obstruction in a rat model.

Clin Sci (Lond) 2018 09 22;132(18):2071-2085. Epub 2018 Sep 22.

Department of Urology, Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China

Congenital urinary tract obstruction is one of the most frequent malformations in fetuses or neonates, which usually causes profound impairment of renal function including reductions in both glomerular filtration rate (GFR) and tubular handling of water and solutes. Although obstruction can be released by surgical operation, the child will suffer from diuresis for sometime. It has been reported that erythropoietin (EPO) could prevent the down-regulation of aquaporin-2 (AQP2) and urinary-concentrating defects induced by renal ischemia/reperfusion (I/R) injury. However, whether EPO could promote the recovery of renal function and AQP2 expression after releasing of ureteral obstruction has not been reported yet. The purposes of the present study were to investigate the effects of EPO on renal function and AQP2 expression after release of bilateral ureteral obstruction (BUO-R) in rats. The results showed that EPO could promote interleukin (IL) 10 (IL-10) expression; inhibit tumor necrosis factor-α (TNF-α), IL-6, and inducible nitric oxide synthase (iNOS) expressions; reduce the fractional excretion of sodium (FENa) and plasma creatinine (CREA) and urea; and promote the recovery of water and salt handling and AQP2 expression in BUO-R rats, especially in the high dose of EPO-treated group rats. In conclusion, EPO could promote the recovery of renal function and AQP2 expression in BUO-R rats, which may partially associate with its anti-inflammation effect.
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http://dx.doi.org/10.1042/CS20180178DOI Listing
September 2018

Reconstruction of bladder function and prevention of renal deterioration by means of end-to-side neurorrhaphy in rats with neurogenic bladder.

Neurourol Urodyn 2018 04 21;37(4):1272-1280. Epub 2017 Nov 21.

Pediatric Urodynamic Centre, Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Aims: To investigate the feasibility of restoring bladder function and prevention of renal deterioration by neurorrhaphy in rats with neurogenic bladder (NB).

Methods: Forty-two rats were assigned to the end-to-side nerve coaptation group (ECG, n = 16), no nerve coaptation group (NCG, n = 16), and control group (CG, n = 10). In the ECG, the left ventral root (VR) and dorsal root (DR) of L6 and S1 were transected, and the distal stump of L6VR was sutured to the lateral face of L4VR. In the NCG, the left VR and DR of L6 and S1 were transected, but coaptation was not performed. In the CG, no operation was performed. Nerve regeneration, bladder function, and renal function were evaluated by FluoroGold (FG) retrograde tract tracing, cystometry, electrical stimulation, MRI, histology and biochemical assays.

Results: In the ECG, FG-labeled neurons were observed in the left ventral horn of L4 spinal cord. There was a significant increase in intravesical pressure upon stimulation of the left L4VR proximal to the coaptation. Maximum cystometric capacity, post-void residual urine, bladder compliance and weight, serum creatinine, blood urea nitrogen, and fibrotic area of bladder and kidney were lower in the ECG than in the NCG, but higher than the CG. Hydronephrosis was noticed in ECG and NCG rats. Maximum detrusor voiding pressure was higher in the ECG and CG than in the NCG.

Conclusions: End-to-side neurorrhaphy is a useful method for restoring bladder function and preventing renal injury in rats with NB.
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http://dx.doi.org/10.1002/nau.23456DOI Listing
April 2018

Low concentration of BPA induces mice spermatocytes apoptosis via GPR30.

Oncotarget 2017 Jul;8(30):49005-49015

Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.

Bisphenol A (BPA) acts as xenoestrogen and has a great impact on disorders of human reproductive system. However, the mechanism through which BPA can affect human testicular function remains to be identified. GPR30 is a novel membrane estrogen receptor with high-affinity and low-capacity binding to estrogens. We demonstrated that estrogen receptor α (ERα), estrogen receptor β (ERβ) as well as GPR30 are expressed in mouse spermatocyte-derived GC-2 cells using Real-time PCR. We treated the cells with different doses of BPA and found that even low doses of BPA can inhibit GC-2 cell growth using MTT assay. To make sure which receptor is responsible for the biological function of BPA, we used ER down-regulator ICI and indicated that BPA could bind to GPR30. We also observed that BPA was able to induce Erk1/2 phosphorylation in GC-2 cells and proved that this process was mediated by GPR30-related EGFR-MAPK pathway using western blot. By Real-time PCR, we found that the expression of c-Fos was up-regulated and Cyclin D1 gene was down-regulated, in the presence of BPA and ICI. The results of MTT assay, comet assay and flow cytometry indicated that the activation of GPR30 induced by BPA inhibited the cell growth and induced cell apoptosis and ICI, GPR30 siRNA, EGFR inhibitor (AG), and MAPK (PD) inhibitor could partially reverse this effect. Immunohistochemistry on the testis of BPA -damaged mice showed that BPA induced spermatocyte apoptosis without affecting the seminiferous tubules and spermatocyte. In conclusion, BPA triggered spermatocyte apoptosis via GPR30.
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http://dx.doi.org/10.18632/oncotarget.16923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564744PMC
July 2017

Role of silodosin as medical expulsive therapy in ureteral calculi: a meta-analysis of randomized controlled trials.

Urolithiasis 2018 Apr 1;46(2):211-218. Epub 2017 Apr 1.

Department of Urodynamic Centre and Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.

The objective of this study is to investigate the efficacy of silodosin in medical expulsive therapy (MET) for ureteral stones. We conducted a systematic review and meta-analysis to determine the efficacy and safety of silodosin in MET for ureteral calculi. We searched PubMed, Embase, Medline, Central (the Cochrane Library, Issue 1,2013), Google Scholar from the inception to March 2015 for randomized controlled trials (RCTs), comparing silodosin with tamsulosin or control on ureteral stone passage. Eight RCTs with a total of 1145 ureteral stone patients (300 patients in the control group, 287 patients in the tamsulosin group, 558 patients in the silodosin group) were included in this meta-analysis. When compared with control, silodosin significantly improved expulsion rate of distal ureteral stones (RR: 1.42; 95% CI, 1.21-1.67; P < 0.0001), while there was no significant difference between silodosin and the control in expulsion rate of proximal (RR: 0.99; 95% CI, 0.69-1.43; P < 0.97) or mid (RR: 1.13; 95% CI, 0.60-2.16; P < 0.0001) ureteral stones. There was no significant difference between silodosin and tamsulosin in terms of expulsion time (WMD: -2.47; 95% CI, -5.32 to 0.39; P = 0.09), analgesic use (WMD: -0.39; 95% CI, -0.91 to 0.13; P  = 0.14) and retrograde ejaculation rate (RR: 1.85; 95% CI, 0.95-3.59; P = 0.07) in MET for distal ureteral stones. However, silodosin provided a significantly higher expulsion rate (RR: 1.25; 95% CI, 1.13-1.37; P < 0.0001) than tamsulosin for distal ureteral stones. Silodosin significantly improved expulsion rate of distal ureteral stones and was clinically superior to tamsulosin. Silodosin was ineffective in MET for proximal and mid ureteral stones. More RCT studies are needed to compare the efficacy of silodosin versus tamsulosin in MET for distal ureteral stones.
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http://dx.doi.org/10.1007/s00240-017-0974-1DOI Listing
April 2018

Mitochondrial pyruvate carrier function is negatively linked to Warburg phenotype in vitro and malignant features in esophageal squamous cell carcinomas.

Oncotarget 2017 Jan;8(1):1058-1073

Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China.

Aerobic glycolysis is one of the emerging hallmarks of cancer cells. In this study, we investigated the relationship between blocking mitochondrial pyruvate carrier (MPC) with MPC blocker UK5099 and the metabolic alteration as well as aggressive features of esophageal squamous carcinoma. It was found that blocking pyruvate transportation into mitochondria attenuated mitochondrial oxidative phosphorylation (OXPHOS) and triggered aerobic glycolysis, a feature of Warburg effect. In addition, the HIF-1α expression and ROS production were also activated upon UK5099 application. It was further revealed that the UK5099-treated cells became significantly more resistant to chemotherapy and radiotherapy, and the UK5099-treated tumor cells also exhibited stronger invasive capacity compared to the parental cells. In contrast to esophageal squamous epithelium cells, decreased MPC protein expression was observed in a series of 157 human squamous cell carcinomas, and low/negative MPC1 expression predicted an unfavorable clinical outcome. All these results together revealed the potential connection of altered MPC expression/activity with the Warburg metabolic reprogramming and tumor aggressiveness in cell lines and clinical samples. Collectively, our findings highlighted a therapeutic strategy targeting Warburg reprogramming of human esophageal squamous cell carcinomas.
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http://dx.doi.org/10.18632/oncotarget.13717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352034PMC
January 2017

Melamine-contaminated milk formula and its impact on children.

Asia Pac J Clin Nutr 2016 Dec;25(4):697-705

Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.

The melamine contaminated milk powder contamination scandal occurred in China in 2008. Its main consequences so far have been urinary stone formation in children with associated renal damage and increased child mortality. Eight years have passed, but food safety issues still remain of concern in the daily lives of millions of Chinese. Vigilance is required to ensure no recurrence of such food safety problems. Ongoing studies focus on the early detection of food industry malpractice, mechanisms whereby these toxic substances induce disease and how its advent may be prevented and better managed. Melamine undergoes renal excretion, but is metabolized slowly and excreted largely unchanged in the urine. Urinary melamine measurement may provide a rapid and inexpensive way to identify exposure to melamine adulterated food items. Although most patients with melaminerelated urinary stones (MUS) have been responsive to conservative treatment, longer time follow-up is needed to assess chronic effects. Aside from MUS, melamine is a recognized carcinogen and can induce urinary tract tumours. Very little is known about the effects of excessive exposure to melamine contaminated milk powder in infants on growth, adolescent and adult health, although short-term effects have become apparent during the scandal.
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http://dx.doi.org/10.6133/apjcn.072016.01DOI Listing
December 2016

Sintokamide A Is a Novel Antagonist of Androgen Receptor That Uniquely Binds Activation Function-1 in Its Amino-terminal Domain.

J Biol Chem 2016 Oct 30;291(42):22231-22243. Epub 2016 Aug 30.

From the Department of Genome Sciences Centre, British Columbia Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada,

Androgen receptor (AR) is a validated drug target for all stages of prostate cancer including metastatic castration-resistant prostate cancer (CRPC). All current hormone therapies for CRPC target the C-terminal ligand-binding domain of AR and ultimately all fail with resumed AR transcriptional activity. Within the AR N-terminal domain (NTD) is activation function-1 (AF-1) that is essential for AR transcriptional activity. Inhibitors of AR AF-1 would potentially block most AR mechanisms of resistance including constitutively active AR splice variants that lack the ligand-binding domain. Here we provide evidence that sintokamide A (SINT1) binds AR AF-1 region to specifically inhibit transactivation of AR NTD. Consistent with SINT1 targeting AR AF-1, it attenuated transcriptional activities of both full-length AR and constitutively active AR splice variants, which correlated with inhibition of growth of enzalutamide-resistant prostate cancer cells expressing AR splice variants. In vivo, SINT1 caused regression of CRPC xenografts and reduced expression of prostate-specific antigen, a gene transcriptionally regulated by AR. Inhibition of AR activity by SINT1 was additive to EPI-002, a known AR AF-1 inhibitor that is in clinical trials (NCT02606123). This implies that SINT1 binds to a site on AF-1 that is unique from EPI. Consistent with this suggestion, these two compounds showed differences in blocking AR interaction with STAT3. This work provides evidence that the intrinsically disordered NTD of AR is druggable and that SINT1 analogs may provide a novel scaffold for drug development for the treatment of prostate cancer or other diseases of the AR axis.
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http://dx.doi.org/10.1074/jbc.M116.734475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064002PMC
October 2016

Generation of TALEN-mediated FH knockout rat model.

Oncotarget 2016 Sep;7(38):61656-61669

Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Transcription activator-like effector nucleases (TALENs) are valuable tools for precise genome engineering of laboratory animals. Here we utilized this technique for efficient site-specific gene modification to create a fumarate hydratase (FH) gene knockout rat model, in which there was an 11 base-pair deletion in the first exon of the FH gene in 111 rats. 18 live-born targeted mutation offsprings were produced from 80 injected zygotes with 22.5% efficiency, indicating high TALEN knockout success in rat zygots. Only heterozygous deletion was observed in the offsprings. Sixteen pairs of heterozygous FH knockout (FH+/-) rats were arranged for mating experiments for six months without any homozygous KO rat identified. Sequencing from the pregnant rats embryo samples showed no homozygous FH KO, indicating that homozygous FH KO is embryonically lethal. Comparatively, the litter size was decreased in both male and female FH+/- KO rats. There was no behaviour difference between the FH+/- KO and the control rats except that the FH+/- KO male rats showed significantly higher body weight in the 16-week observation period. Clinical haematology and biochemical examinations showed hematopoietic and kidney dysfunction in the FH+/- KO rats. Small foci of anaplastic lesions of tubular epithelial cells around glomeruli were identified in the FH+/- kidney, and these anaplastic cells were comparatively positive for Ki67, p53 and Sox9, and such findings are most probably related to the kidney dysfunction reflected by the biochemical examinations of the rats. In conclusion, we have successfully established an FH+/- KO rat model, which will be useful for further functional FH studies.
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http://dx.doi.org/10.18632/oncotarget.11429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308680PMC
September 2016

PDHA1 gene knockout in prostate cancer cells results in metabolic reprogramming towards greater glutamine dependence.

Oncotarget 2016 Aug;7(33):53837-53852

Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.

Alternative pathways of metabolism endowed cancer cells with metabolic stress. Inhibiting the related compensatory pathways might achieve synergistic anticancer results. This study demonstrated that pyruvate dehydrogenase E1α gene knockout (PDHA1 KO) resulted in alterations in tumor cell metabolism by rendering the cells with increased expression of glutaminase1 (GLS1) and glutamate dehydrogenase1 (GLUD1), leading to an increase in glutamine-dependent cell survival. Deprivation of glutamine induced cell growth inhibition, increased reactive oxygen species and decreased ATP production. Pharmacological blockade of the glutaminolysis pathway resulted in massive tumor cells apoptosis and dysfunction of ROS scavenge in the LNCaP PDHA1 KO cells. Further examination of the key glutaminolysis enzymes in human prostate cancer samples also revealed that higher levels of GLS1 and GLUD1 expression were significantly associated with aggressive clinicopathological features and poor clinical outcome. These insights supply evidence that glutaminolysis plays a compensatory role for cell survival upon alternative energy metabolism and targeting the glutamine anaplerosis of energy metabolism via GLS1 and GLUD1 in cancer cells may offer a potential novel therapeutic strategy.
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http://dx.doi.org/10.18632/oncotarget.10782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288225PMC
August 2016

Prevalence of Spina Bifida Occulta and Its Relationship With Overactive Bladder in Middle-Aged and Elderly Chinese People.

Int Neurourol J 2016 Jun 24;20(2):151-8. Epub 2016 Jun 24.

Urodynamic Centre, Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Purpose: To investigate the prevalence of spina bifida occulta (SBO) and its relationship with the presence of overactive bladder (OAB) in middle-aged and elderly people in China.

Methods: A cross-sectional community-based survey was carried out at 7 communities in Zhengzhou City, China from December 15, 2013 to June 10, 2014, where residents aged over 40 years were randomly selected to participate. All of the participants underwent lumbosacral radiographic analysis and relevant laboratory tests. A questionnaire including basic information, past medical history and present illness, and the OAB symptom score was filled out by all participants. Chi-square tests and logistic regression were used for data analysis with a P-value of <0.05 denoting statistical significance.

Results: A total of 1,061 subjects were qualified for the final statistical analysis (58.8±11.7 years; male, 471 [44.4%]; female, 590 [55.6%]). The overall prevalence of SBO was 15.1% (160 of 1,061): 18.3% (86 of 471) in men and 12.5% (74 of 590) in women. Among these subjects, 13.7% (145 of 1,061) had OAB: 13.2% (62 of 471) in men and 14.1% (83 of 590) in women. The results of logistic regression showed that age, SBO, history of cerebral infarction (HCI), and constipation were risk factors for OAB (P<0.05), while sex, history of childhood enuresis (HCE), body mass index (BMI), and diabetes mellitus (DM) were not (P>0.05). In men, age, SBO, and constipation were risk factors for OAB (P<0.05), while HCE, BMI, DM, HCI, and benign prostate hyperplasia were not (P>0.05). In women, age, SBO, and HCI were risk factors for OAB (P<0.05), while HCE, BMI, DM, vaginal delivery, and constipation were not (P>0.05).

Conclusions: The prevalence of SBO is high and it is related to OAB in middle-aged and elderly people in China.
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http://dx.doi.org/10.5213/inj.1630464.232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4932639PMC
June 2016

Feasibility and Usefulness of Intra-Cavitary Contrast-Enhanced Ultrasound in Percutaneous Nephrostomy.

Ultrasound Med Biol 2016 09 2;42(9):2180-8. Epub 2016 Jun 2.

Medical Clinic 2, Caritas-Krankenhaus Bad Mergentheim, Academic Teaching Hospital of the University of Wuerzburg, Wuerzburg, Germany; Sino-German Research Center of Ultrasound in Medicine, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address:

The aim of this study was to evaluate the feasibility and utility of intra-cavitary contrast enhanced ultrasound (ICCEUS) in guiding percutaneous nephrostomy (PCN) and assessing complications. Forty-five ultrasound-guided PCNs were performed in 35 patients with hydronephrosis resulting from urinary tract obstruction. Ultrasound contrast agent (0.1 mL diluted in 20-30 mL saline) was injected through the puncture needle and the drainage tube to precisely locate the device and obstruction, with the fluoroscopy results considered the gold standard. ICCEUS was performed again the next day to assess complications. All 45 PCNs were successfully performed under the guidance of ultrasound. With ICCEUS, we could confirm the correct insertion of needle and catheter and locate the obstruction in all 35 patients, with fluoroscopic results as the gold standard. Catheter dislodgement was diagnosed by administration of ultrasound contrast agent in 5 patients. Hematoma (1 patient) and urine leakage (1 patient) were also observed. With the advantages of lack of exposure to radiation, performance in real time and bedside availability, ICCEUS has the potential to become a new modality to guide PCN and assess catheter-related complications.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2016.04.015DOI Listing
September 2016

Inappropriate use of antibiotics in children in China.

Lancet 2016 Mar;387(10025):1273-4

The Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, China. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(16)30019-8DOI Listing
March 2016

Aldehyde Dehydrogenase-1 Expression Predicts Unfavorable Outcomes in Patients with Esophageal Squamous Cell Carcinoma.

Anticancer Res 2016 Jan;36(1):343-9

Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, University of Oslo, Montebello, Oslo, Norway Department of Pathology, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway

Background: Aldehyde dehydrogenase-1 (ALDH1) has been shown to be a potential cancer stem cell marker in different types of cancer. However, the role of its expression in tumor cells and the microenvironment in different types of cancer is still controversial.

Materials And Methods: ALDH1 protein was immunohistochemically investigated and analyzed in 157 samples of surgically dissected esophageal squamous cell carcinoma (ESCC) tissues.

Results: ALDH1 protein expression in ESCC tumor cells was significantly associated with poor differentiation (p<0.05) and strongly positive ALDH1 expression in tumor cells was related with shorter overall survival (p<0.05), while the expression of ALDH1 in ESCC stromal cells had no significant relationship with clinicopathological features (p>0.05).

Conclusion: High expression of cancer stem cell marker ALDH1 in ESCC cells may thus portend a poor prognosis. However, its expression in the tumor microenvironment did not appear to have a role in ESCC behavior. More studies are warranted to find out the mechanisms to explain this.
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January 2016

ILs-3, 6 and 11 increase, but ILs-10 and 24 decrease stemness of human prostate cancer cells in vitro.

Oncotarget 2015 Dec;6(40):42687-703

Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Henan, China.

Cancer stem cells (CSCs) are associated with cancer recurrence and metastasis. Prostate cancer cells often metastasize to the bone with a complex microenvironment of cytokines favoring cell survival. In this study, the cell stemness influence of a group of interleukins including IL-3, 6, 10, 11 and 24 on human prostate cancer cell lines LNCaP and PC-3 was explored in vitro. Sulforhodamine B(SRB) and 5-ethynyl-2'-deoxyuridine (EdU) assays were applied to examine the effect on cell proliferation, and wound healing and transwell assays were used for migration and invasion studies, in addition to colony formation, Western blotting and flowcytometry for the expression of stemness factors and chemotherapy sensitivity. We observed that ILs-3, 6 and 11 stimulated while ILs-10 and 24 inhibited the growth, invasion and migration of both cell lines. Interestingly, ILs-3, 6 and 11 significantly promoted colony formation and increased the expression of SOX2, CD44 and ABCG2 in both prostate cancer cell lines. However, ILs-10 and 24 showed the opposite effect on the expression of these factors. In line with the above findings, treatment with either IL-3 or IL-6 or IL-11 decreased the chemosensitivity to docetaxel while treatment with either IL-10 or IL-24 increased the sensitivity of docetaxel chemotherapy. In conclusion, our results suggest that ILs-3, 6 and 11 function as tumor promoters while ILs-10 and 24 function as tumor suppressors in the prostate cancer cell lines PC-3 and LNCaP in vitro, and such differences may attribute to their different effect on the stemness of PCa cells.
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http://dx.doi.org/10.18632/oncotarget.5883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767463PMC
December 2015
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