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Introduction: Megalin plays an important role in proximal tubule uptake of filtered proteins. Downregulation and dysfunction of megalin were previously demonstrated in IgA nephropathy (IgAN); however, its relationship to IgAN progression remains unclear. Methods: We measured renal megalin mRNA and miR-148b, previously identified as a regulator of megalin, in a retrospective cohort of 417 IgAN patients at the time of biopsy, and evaluated their associations with chronic kidney disease (CKD) progression event, defined as end-stage renal disease or ≥40% decline in estimated glomerular filtration rate, using Cox proportional hazard models. Risk classification statistics were calculated for CKD progression. Results: During a median follow-up of 43 months, 121 (29.0%) patients reached the CKD progression event. Patients in the highest tertile of renal megalin mRNA had a lower risk for CKD progression than in the lowest tertile (hazard ratio (HR): 0.407, 95% confidence interval (CI) 0.231–0.719; p = 0.002). Log megalin mRNA was independent and negatively associated with CKD progression in IgAN (HR: 0.529, 95% CI 0.377–0.742; p < 0.001). The addition of renal megalin mRNA to a model with traditional risk factors improved risk prediction of disease progression (C statistic from 0.76 to 0.80; integrated discrimination index: 0.04 [95% CI: 0.02–0.07]). Moreover, patients in the highest tertile of renal miR-148b had a 2.3-fold higher risk for CKD progression compared with those in the lowest tertile. Conclusions: Lower renal megalin mRNA levels were associated with a greater risk of CKD progression in IgAN independent of clinical and pathological characteristics, suggesting that renal megalin could be an important prognostic factor for IgAN.

This study aimed to investigate the value of high-frequency ultrasound (HFUS) in differentiation of the seronegative rheumatoid arthritis (SNRA) and osteoarthritis (OA) and in the diagnosis of SNRA. 83 patients diagnosed with SNRA (SNRA group) and 40 diagnosed with OA (OA group) who received HFUS were retrospectively analyzed. The grayscale (GS) scores, power Doppler (PD) scores, and bone erosion (BE)scores were recorded, and added up to calculate the total scores of US variables. The correlations of the total scores of US variables with the 28-joint disease activity score (DAS28), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were analyzed. The diagnostic efficacy of the total scores of US variables for SNRA was assessed. In the SNRA group, the detection rate of abnormal US findings in the joints and tendons by GS and PD as well as BE was higher than those in the OA group. There were significant differences between the two groups in GS scores and PD scores of joints and tendons, and BE scores of joints (P P P > 0.05). Among different US variables, the diagnostic value of total PD scores of the joints was the highest for SNRA. HFUS could be used to differentiate SNRA from OA and make a diagnosis of SNRA based on joint and tendon synovial sheath assessment.

Few studies have reported the roles of the complement system in concomitant idiopathic membranous nephropathy and IgA nephropathy (IMN-IgAN). Complement factor B (CFB) is a crucial factor that involved in the alternative complement pathway. We aimed to evaluate the association between disease activity (eGFR, anti-PLA2R antibody levels and 24 h urinary protein excretion), progression and serum CFB levels of IMN-IgAN patients. In total, 39 IMN-IgAN patients (median follow-up, 46.6 months), 99 IMN patients and 92 IgAN patients participated in this study. The disease progression event was defined as end-stage renal disease (ESRD) or a 30% decline in estimated glomerular filtration rate (eGFR). The serum CFB concentration was measured by enzyme-linked immunosorbent assay. Serum CFB levels were lower in IMN-IgAN patients than in patients with IgAN only (P

To assess the efficacy of sacral neuromodulation (SNM) for neurogenic bladder (NB), guided by intraoperative three-dimensional imaging of sacral computed tomography (CT) and mobile C-arm fluoroscopy through video-urodynamics examination. We enrolled 52 patients with NB who underwent conservative treatment with poor results between September 2019 and June 2021 and prospectively underwent SNM guided by intraoperative three-dimensional imaging of sacral CT and mobile C-arm fluoroscopy. Video-urodynamics examination, voiding diary, quality of life questionnaire, overactive bladder symptom scale (OABSS) scoring, and bowel dysfunction exam were completed and recorded at baseline, at SNM testing, and at 6-month follow-up phases. Finally, we calculated the conversion rate from period I to period II, as well as the treatment efficiency and the occurrence of adverse events during the testing and follow-up phases. The testing phase of 52 NB patients was 18–60 days, with an average of (29.3 ± 8.0) days. Overall, 38 patients underwent SNM permanent electrode implantation, whose follow-up phase was 3–25 months, with an average of (11.9 ± 6.1) months. Compared with baseline, the voiding times, daily catheterization volume, quality of life score, OABSS score, bowel dysfunction score, maximum detrusor pressure before voiding, and residual urine volume decreased significantly in the testing phase. The daily voiding volume, functional bladder capacity, maximum urine flow rate, bladder compliance, and maximum cystometric capacity increased significantly in the testing phase. Besides, the voiding times, daily catheterization volume, quality of life score, OABSS score, bowel dysfunction score, maximum detrusor pressure before voiding, and residual urine volume decreased further from the testing to follow-up phase. Daily voiding volume, functional bladder capacity, maximum urine flow rate, bladder compliance, and maximum cystometric capacity increased further from testing to follow-up. At baseline, 10 ureteral units had vesicoureteral reflux (VUR), and 9 of them improved in the testing phase. Besides, there was 1 unit that further improved to no reflux during the follow-up phase. At baseline, 10 patients had detrusor overactivity (DO), and 8 of them improved in the testing phase. Besides, 1 patient’s symptoms further improved during the follow-up phase. At baseline, there were 35 patients with detrusor-bladder neck dyssynergia (DBND); 14 (40.0%) of them disappeared during the testing phase. Among 13 cases who had DBND in the testing phase, 6 (46.2%) disappeared during the follow-up phase. Of the 47 patients with detrusor-external sphincter dyssynergia (DESD) at baseline, 8 (17.0%) disappeared during the testing phase. Among 26 cases who had DESD in the testing phase, 6 (23.1%) disappeared during the follow-up phase. The effective rate of this study was 88.5% (46/52), and the conversion rate from phase I to phase II was 73.1% (38/52). Additionally, the efficacy in a short-term follow-up was stable. SNM guided by intraoperative three-dimensional imaging of sacral CT and mobile C-arm fluoroscopy is an effective and safe treatment option for NB in short time follow-up. It would be well improved in the bladder storage function, sphincter synergetic function and emptying efficiency by video-urodynamics examination in this study.Trial registration: Chinese Clinical Trial Registry. ChiCTR2100050290. Registered August 25 2021. http://www.chictr.org.cn/index.aspx.

To explore the value of ultrasound in the preoperative diagnosis of nonpalpable testis (NPT) in children. A retrospective study of 254 cases with NPT from May 2017 to December 2021. The preoperative ultrasound examination results were compared with the surgical exploration and pathological results. There were 254 cases (312 testes) NPT has got surgery in our centre. The surgical age were from 6 month to 12 years old, the median age was 2.33 years. There were 103 cases (136 testes) diagnosed as intra-abdominal testis (IAT) by preoperative ultrasound, and 80 cases (103 testes) of extra-abdominal testis (EAT), 71 cases (73 testes) of non-viable testis (NVT). There were 102 cases (135 testes) consistented as IAT by the diagnostic laparoscopy, the preoperative ultrasound’s coincidence of IAT was 99.02%. There were 80 cases (103 testes) consistented as EAT by the diagnostic laparoscopy, the preoperative ultrasound’s coincidence rate was100%. There were 62 cases (62 testes) consistented as NVT by the diagnostic laparoscopy, there were 9 cases (11 testes) misdiagnosed, the preoperative ultrasound’s coincidence rate was 84.9%. Ultrasound can provide valuable information for the preoperative diagnosis of children with nonpalpable testicles, and especially good at identifying the EAT and IAT with normal testicular morphology.

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.

Background Accumulating evidence have highlighted the importance of long noncoding RNAs (lncRNAs) in multiple cancers development and progression. Cancer susceptibility candidate 9 (CASC9) is a novel long non-coding RNA and plays important regulatory role in diverse biological processes of cancers. However, the clinical significance and molecular mechanism of CASC9 in bladder cancer is still unknown. Methods Comprehensive lncRNAs profiling analysis were conducted to identify lncRNAs profile alterations and uncover valuable lncRNA candidates for bladder cancer. The expression level of CASC9 was determined in a total of 106 patients with bladder cancer. Loss-of-function experiments were performed to identify the functions of CASC9 in tumor growth and metastasis of bladder cancer in vitro and in vivo. Bioinformatics analysis and further experiments were performed to explore the molecular mechanisms underlying the functions of CASC9. Results This study found that CASC9 expression was markedly upregulated in bladder cancer and related to histological grade, TNM stage and prognosis. Knockdown of CASC9 inhibited tumor growth and metastasis of bladder cancer in vitro and in vivo. Mechanistically, we found that CASC9 functions as a miRNA sponge to positively regulate FZD6 expression and subsequently activates Wnt/β-catenin signaling pathway, thus playing an oncogenic role in bladder cancer pathogenesis. Conclusion In summary, lncRNA CASC9 plays a critical regulatory role in bladder cancer. The CASC9/miR-497-5p/ FZD6 axis provides insights for regulatory mechanism of bladder cancer, and new strategies for clinical practice.

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 (χ2 trend = 88.899; P

Intercellular adhesion molecule 1 (ICAM-1) related long noncoding RNA (ICR) is on the antisense strand of ICAM-1 and regulates ICAM-1 expression. ICAM-1 is involved in renal tubulointerstitial injury; however, the expression and clinical implication of ICR are not determined in IgA nephropathy (IgAN). We compared renal ICR levels in 337 IgAN patients with those of 89 biopsy controls, and a markedly increased ICR level was observed in IgAN patients. By Cox proportional hazards models, higher levels of renal ICR were independently associated with disease progression event defined as end-stage renal disease or ≥ 40% decline in estimated glomerular filtration rate. Patients in the highest tertile of renal ICR had a 3.5-fold higher risk for disease progression compared with those in the lowest tertile. The addition of renal ICR to a model with traditional risk factors improved risk prediction of disease progression (net reclassification index: 0.31 [95% CI 0.01–0.50]; integrated discrimination index: 0.10 [95% CI 0.04–0.16]). Inhibition of ICR by transfection with plasmids containing ICR shRNA significantly reduced expression of collagen I and α-SMA, and phosphorylation of Akt and mTOR in TGF-β1- treated HK-2 cells. Our findings suggest that renal ICR might be an independent predictor of IgAN progression and contribute to renal fibrosis.

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

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 (m6A) 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 m6A 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 m6A 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‐m6A‐miR‐21‐5p‐SPRY1/ERK/NF‐kB axis in obstructive renal fibrosis and provides a deeper understanding of renal fibrosis.

Mycoplasmas are unique cell wall-free bacteria. Because they lack a cell wall and have resistance to β-lactam antibiotics, mycoplasma is the major pathogen that infects cultured cells in research laboratories. For rapid detection of mycoplasma-infected cells, we developed an ssDNA aptamer sequence composed of 40 nucleotides. Flow cytometry analysis showed that the synthetic aptamer probe selectively targeted mycoplasma-infected culture cells with high specificity identical to commercially available PCR-based assays. Additionally, fluorescent microscopy studies revealed that the aptamer probe rapidly stained mycoplasma-infected cells with higher sensitivity compared to Hoechst dye-mediated cellular DNA content stains. Moreover, confocal microscopy studies of trypsin-treated cells validated that the aptamer probes selectively targeted mycoplasma components on the surface of infected cells. Finally, preclinical studies of peripheral blood cells demonstrated that the aptamer probe was able to detect in vitro mycoplasma infection of primary lymphocytes. Taken together, these findings indicate that the aptamer probe will not only allow rapid detection of mycoplasma-infected culture cells for research purposes but also provide a simple method to monitor mycoplasma infection in primary cell products for clinical use.

Decreased expression of the renal aquaporin (AQP) protein family is associated with hydronephrosis in adult humans and animals. However, the expression of AQPs, especially subtypes AQP1–3, which play a core role in the urinary concentration function, in hydronephrotic human fetuses is not clear. The aim of this study is to investigate the expression of the AQP1–3 in normal and hydronephrotic human fetal kidneys. Twenty-one normal and six hydronephrotic kidney (HK) samples were harvested from abortive fetuses. Meanwhile, seven normal adult human kidney samples were collected as positive controls. Quantitative real-time PCR, western blotting, and immunohistochemistry were used to analyze the expression of AQP1–3. Both the protein and messenger mRNA expression levels of AQP1–3 increased with gestational age in the normal fetuses, but the levels were significantly lower than those in the adult tissues and significantly higher than those in the hydronephrotic fetuses at the same gestational age. The increased expression of AQP1–3 with gestational age in the fetal kidney may indicate maturation of the urinary concentrating ability. The lower expression of AQP1–3 in HKs may reflect a maturation obstacle with regard to urinary concentration in human hydronephrotic fetuses.

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-1 beta (IL-1 beta) 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-1 beta, and caspase-1 (P 0.05), while their protein levels were significantly decreased (P

Healthcare-associated infections (HAIs) not only bring additional medical cost to the patients but also prolong the length of stay (LOS). 2119 HAI case-patients and 2119 matched control-patients were identified in 68 hospitals in 14 primary sampling provinces of 7 major regions of China. The HAI caused an increase in stay of 10.4 days. The LOS due to HAI increased from 9.7 to 10.9 days in different levels of hospitals. There was no statistically significant difference in the increased LOS between different hospital levels. The increased LOS due to HAI in different regions was 8.2 to 12.6 days. Comparing between regions, we found that the increased LOS due to HAI in South China is longer than other regions except the Northeast. The gastrointestinal infection (GI) caused the shortest extra LOS of 6.7 days while the BSI caused the longest extra LOS of 12.8 days. The increased LOS for GI was significantly shorter than that of other sites. Among 2119 case-patients, the non-multidrug-resistant pathogens were detected in 365 cases. The average increased LOS due to these bacterial infections was 12.2 days. E. coli infection caused significantly shorter LOS. The studied MDROs, namely, MRSA, VRE, ESBLs-E. coli, ESBLs-KP, CR-E. coli, CR-KP, CR-AB, and CR-PA were detected in 381 cases (18.0%). The average increased LOS due to these MDRO infections was 14 days. Comparing between different MDRO infections, we found that the increased LOS due to HAI caused by CR-PA (26.5 days) is longer than other MDRO infections (shorter than 19.8 days).

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.

Apigenin as a natural flavonoid product has been proved previously to play a renoprotective effect during ischemia/reperfusion injury (IRI), but the particular mechanisms involving the positive effects of apigenin remain totally unclear. The study investigated apigenin's roles and underlying biological mechanisms in IR-induced acute kidney injury (AKI). Thirty-six mice received a right nephrectomy and clamping of the left renal artery for 30 minutes, and then perfusion for 24 h. Apigenin was loaded onto a biodegradable polymer carrier (nanoparticle) to enhance its bioavailability. Mice were subjected to intraperitoneally injection with apigenin (5, 10 or 20 mg/kg) for 24 h before surgery. For

Objective To investigate the clinical significance of immune-related long non-coding RNAs (lncRNAs) and their potential role in guiding the treatment of prostate cancer. Methods lncRNAs of prostate cancer were obtained from TCGA database. The immune-related gene sets were downloaded from Molecular Signatures Database. Gene-lncRNA co-expression was confirmed by Pearson correlation analysis, and univariate Cox regression and selected operator regression (Lasso) were performed to identify important and immune-related lncRNAs. "gglot package" and "survival package" of R software were used to evaluate the correlation between the lncRNAs and clinical characteristics and the prognostic value of the lncRNAs. lnc2RNA database was used to analyze the difference of lncRNAs between normal prostate tissue and prostate cancer tissue. Starbase and David database were used to determine the predict function of lncRNAs in prostate cancer. Results AL162586.1, AC138028.4, SLC25A25-AS1, AC002553.1, AC004816.1, LINC00641 and AC027796.4 were key immune-related lncRNAs, and their expression was positively associated with N stage; the expression levels of AL162586.1 and SLC25A25-AS1 increased with higher T stage. The expression levels of SLC25A25-AS1 and LINC00641 were significantly different in tumor tissues from that of normal tissues. The GO enrichment showed that SLC25A25-AS1 was mainly distributed in membrane, had negative regulation of mRNA splicing via spliceosome and by a nucleotide binding. KEGG pathway enrichment showed that targeted genes were mainly involved in spliceosome pathway. Conclusion lncRNA has become a new research direction in prostate cancer and SLC25A25-AS1 may affect the prognosis of patients through splicing pathway.

Monoclonal antibodies (mAb) have had a transformative impact on treating cancers and immune-disorders. However, their use is limited by high development time and monetary cost, manufacturing complexities, suboptimal pharmacokinetics, and availability of disease-specific targets. To address some of these challenges, we developed an entirely synthetic, multivalent, Janus nanotherapeutic platform, called Synthetic Nanoparticle-Antibodies (SNAbs). SNAbs, with phage-display identified cell-targeting ligands on one “face”, and Fc-mimicking ligands on the opposite “face”, were synthesized using a custom, multi-step, solid-phase chemistry method. SNAbs efficiently targeted and depleted myeloid-derived immune-suppressor cells (MDSCs) from mouse-tumor and rat-trauma models, ex-vivo. Systemic injection of MDSC-targeting SNAbs efficiently depleted circulating MDSCs in a mouse triple-negative breast cancer model, enabling enhanced T cell and Natural Killer cell infiltration into tumors. Our results demonstrate that SNAbs are a versatile and effective functional alternative to mAbs, with advantages of a plug-and-play, cell-free manufacturing process, and high-throughput screening (HTS)-enabled library of potential targeting ligands.

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 in vitro and in vivo. 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 in vitro and in vivo, providing basis for immunotherapy of HCC in future clinical use.

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 P for interaction

BACKGROUND Neurogenic bladder (NB) is a common pediatric urological disease caused by a variety of neurological pathologies. Clean intermittent catheterization (CIC) has been the preferred method to empty bladder. OBJECTIVE To investigate the effect of CIC on preserving bladder and upper urinary tract function in infants less than 1 year old with NB. METHODS A retrospective analysis was conducted on 76 infants with NB. Patients were divided into two groups according to treatment initiation: the early CIC group (ECG) ( 3 years old). RESULTS Bladder compliance (BC), safe bladder capacity (SBC) and maximum cystometric capacity (MCC) were significantly higher in the ECG than those in the LCG at 6 years of follow-up respectively (P < 0.05). The frequencies of vesicoureteral reflux (VUR) and urinary tract infection (UTI) in the ECG were significantly lower than those in the LCG (P < 0.05) at 6 years of follow-up. Two and nine patients exhibited mild renal damage in the ECG and LCG, respectively, resulting in a significant difference (P < 0.05) at 6 years of follow-up. CONCLUSION Early CIC plays an important role in preserving bladder function and preventing UTI and renal deterioration in infants with NB, especially in the first year of life.

This study aimed to investigate the exact regulatory mechanisms of retinoid-interferon-induced mortality 19 (GRIM-19) in renal carcinoma. Tumour tissue samples from patients with renal carcinoma (n = 30, there were seven cases of Stage I, eight cases of Stage II, eight cases of Stage III, seven cases of Stage IV) and control subjects were selected from adjacent normal tissue (n = 10). Real-time quantitative PCR and western blotting were used to assess the level of GRIM-19, signal transducer and activator of transcription-3 (STAT3) and its downstream molecules. CD31 was detected by immunohistochemistry. The MTT assay was used to measure cell proliferation. The amount of apoptosis cells was analysed by Flow cytometry. The results showed that expression of GRIM-19 was decreased in renal carcinoma. However, in tumour tissue, STAT3 and its downstream signalling molecules showed the higher expression compared with control. Overexpression of GRIM-19, inhibited tumour growth apoptosis by mediating activators of STAT3 signal. In addition, interferon-β and all-trans-retinoic acid inhibited the renal carcinoma cell growth and induced apoptosis, and effect of drug combinations was particularly evident. In conclusion, GRIM-19 expression is associated with hyperactivation of STAT3-induced gene expression in renal carcinoma.

To investigate the correlation between urethral instability (URI) and overactive bladder (OAB) in children. We retrospectively investigated 126 children with OAB and 36 children without OAB using synchro-cystourethrometry. The prevalence of detrusor overactivity (DO) and URI, and the diagnostic sensitivity of DO alone and DO combined with URI, was compared. The OAB children with URI voluntarily received transcutaneous electrical pudendal nerve stimulation with anisodamine (stimulation group, SG) or anisodamine alone (non-stimulation group, NSG). The effectiveness of treatment was evaluated. Average voided volume (AVV), maximum voided volume (MVV), and number of voids per day (NV) were collected and analyzed. In OAB children, the prevalence of DO and URI was 51.6 and 32.5%, respectively. The prevalence of URI was 5.6% in controls. The prevalence of URI was significantly higher in OAB children. The diagnostic sensitivity and Youden index of DO combined with URI were higher than DO alone. In SG, 45.7% of children were cured, with a ≥ 50% improvement rate of 82.9%, while no child was cured, with a ≥ 50% improvement rate of 36.8% in NSG. A significant increase in AVV and MVV together, with a decrease in NV, was seen in SG. There was a significant difference in visual analogue scale values between SG and NSG (P

Multiple myeloma (MM) is estimated to have 30,280 new cases and be associated with 12,590 deaths in 2017. However, quantitative analysis for survival, based on a large population, is lacking. Data were extracted from a total of 33,170 cases from nine registry sites in the Surveillance, Epidemiology, and End Results database. The current study shows that the incidence for MM remained relatively stable between 1981 and 2010, with 4.6, 4.7, and 4.7 per 100,000 persons in each decade. In addition, survival for MM improved each decade with a larger increment in the last two decades, with a narrowing survival gap among races and a widening gap among socioeconomic status (SES) groups. The survival gap changes in races and SES groups may guide clinicians to design better treatment protocols and call for the pressing need for health-care policy to fill the gap among SES groups.

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

// Bing Yao 1, * , Bingqian Liu 1, * , Lei Shi 1, * , Xiang Li 2 , Chuanchuan Ren 1 , Mingbo Cai 3 , Wen Wang 3 , Jianhua Li 1 , Yongde Sun 1 , Yudong Wu 1 , Jianguo Wen 1 1 Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China 2 Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China 3 Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China * These authors contributed equally to this work Correspondence to: Yudong Wu, email: yudongwu_zhd@163.com Jianguo Wen, email: wenjg_zhdu@163.com Keywords: platelet activating factor receptor, prostatic neoplasms, radiotherapy, autophagy, drug sensitivity Received: July 22, 2016 Accepted: January 03, 2017 Published: January 14, 2017 ABSTRACT Platelet-activating factor receptor (PAFR) promotes tumorigenesis, angiogenesis and metastasis. Here, we defined the PAFR as a yielding new inhibiting target to selectively enhance the sensitivity of prostate cancer (PCa) cells to radiation. The selective responding to PAFR inhibiter may be caused by the differential expression pattern of PAFR in PCa cells. In this study, we also determined PAFR as a molecular basis by which the radiation induces autophagy suppression independent of activating mTOR pathway. PAFR can bind to the autophagy-indispensable protein Beclin 1, leading to the disability in its serine phosphorylation. The PAFR antagonist Ginkgolide B (GB) can sensitize radiotherapy by disrupting the formation of PAFR/Beclin 1 complex in PC3 and LNCaP cells, which have elevated PAFR expression after radiation exposure. Most importantly, GB efficiently radiosensitized PC3 and LNCaP tumor xenografts in vivo , and significantly reduced tumor burden. Overall, our results elucidated a significant role of GB in selectively improving the outcomes of PCa receiving radiation therapy.

Primary monosymptomatic nocturnal enuresis (PMNE) is a heterogeneous disorder, which remains a difficult condition to manage due to lack of knowledge on the underlying pathophysiological mechanisms. Here we investigated the underlying neuropathological mechanisms of PMNE with functional MRI (fMRI), combining the amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and seed-based functional connectivity (seed-based FC) analyses. Compared to the control group, PMNE group showed decreased ALFF value in the left medial orbital superior frontal gyrus (Frontal_Med_Orb_L), and increased ReHo value in the left superior occipital gyrus (Occipital_Sup_L). With left thalamus as the seed, PMNE group showed significantly decreased functional connectivity to the left medial superior frontal gyrus (Frontal_Sup_Medial_L). We conclude that these abnormal brain activities are probably important neuropathological mechanisms of PMNE in children. Furthermore, this study facilitated the understanding of underlying pathogenesis of PMNE and may provide an objective basis for the effective treatment.

Long noncoding RNAs (lncRNAs) play an essential role in cancer development. However, the contribution of the lncRNA LINC00997 to kidney renal clear cell carcinoma (KIRC) has not been thoroughly elucidated to date. In this study, we examined the expression and biological effect of LINC00997 in KIRC development. We also investigated the potential mechanism underlying the observed effects. We found that LINC00997 is highly expressed in multiple carcinomas, being highest in stage IV KIRC in our RNA-Seq datasets. In addition, our data demonstrated that in KIRC patients, higher levels of LINC00997 are correlated with lower overall survival (OS) and disease-free survival (DFS) rates. In 18 cases of KIRC, we found that LINC00997 expression was greater in cancer tissues and metastases than in normal tissues. These results revealed that S100A11 is positively associated with LINC00997 in KIRC, which is positively correlated with metastasis-associated molecules VIM, MMP2 and MMP7. Our in vitro wound healing assay and Transwell tests demonstrated that interfering with either LINC00997 or S100A11 expression reduced migration of 786-O cells by inhibiting VIM, MMP2 and MMP7 expression. Importantly, we verified LINC00997 and STAT3 binding by RIP and determined that both LINC00997 and STAT3 bind to the S100A11 promoter, as shown by dual-luciferase reporter gene assay. In addition, inhibiting LINC00997 or STAT3 expression attenuated S100A11 levels. Consequently, the LINC00997-STAT3-S100A11 axis may promote the development of KIRC, and LINC00997 may represent a potential prognostic biomarker and therapeutic target for KIRC patients.

Natural Killer (NK) cells are a key component of the innate immune system as they can attack cancer cells without prior sensitization. However, due to lack of cell-specific receptors, NK cells are not innately able to perform targeted cancer immunotherapy. Aptamers are short single-stranded oligonucleotides that specifically recognize their targets with high affinity in a similar manner to antibodies. To render NK cells target-specificity, synthetic CD30-specific aptamers were anchored on cell surfaces to produce aptamer-engineered NK cells (ApEn-NK) without genetic alteration or cell damage. Under surface-anchored aptamer guidance, ApEn-NK specifically bound to CD30-expressing lymphoma cells, but did not react to off-target cells. The resulting specific cell binding of ApEn-NK triggered higher apoptosis/death rates of lymphoma cells compared to parental NK cells. Additionally, experiments with primary human NK cells demonstrated the potential of ApEn-NK to specifically target and kill lymphoma cells, thus presenting a potential new approach for targeted immunotherapy by NK cells.

Background To investigate the prognostic risk factors and postoperative recurrence of bladder cancer in patients with upper urinary tract urothelial carcinomas (UTUCs). Methods Data of 439 UTUC patients were retrospectively analyzed. Follow-up and analysis of smoking effects, consumption of traditional Chinese medicine containing aristolochic acid, history of bladder cancer, age, sex, presence or absence of diabetes mellitus (DM), metformin use, tumor characteristics (number, location, stage, grade), and open or laparoscopic surgery on the prognosis of UTUCs were performed. Cox proportional hazard regression analysis was performed to analyze the relationship between various factors and the postoperative survival rate. The survival rate was analyzed using the Kaplan-Meier method. Moreover, logistic regression analysis was performed to analyze the relationship between the above mentioned factors and postoperative recurrence of bladder cancer. Results Overall, 439 patients met, including 236 males (53.7%) and 203 females (46.3%), the criteria for the final statistical analysis, and the average age was 66.7 years. The 1-, 3-, and 5-year overall survival rates of 439 UTUC patients were 90.0, 76.4, and 67.7%, respectively. The 5-year survival rates of T1, T2, T3, and T4 patients were 90.2%, 78%, 43.8%, and 18.5%, respectively. Factors influencing the long-term survival rate of UTUC patients were smoking, taking traditional Chinese medicine containing aristolochic acid, history of bladder cancer, age, tumor size, tumor stage, tumor grade, and lymph node metastasis. The risk factors related to postoperative bladder cancer recurrence were advanced tumor stage, high grade tumor, preoperative ureteroscopy, ureteral urothelial carcinoma, no postoperative bladder perfusion chemotherapy and DM without metformin use. Conclusions Advanced tumor stage and presence of a high-grade tumor were risk factors for not only poor UTUC prognosis but also BC recurrence. In addition, preoperative ureteroscopy, ureteral urothelial carcinoma and DM without metformin use were high risk factors for BC recurrence, whereas regular postoperative bladder perfusion chemotherapy was a protective factor.

Healthcare associated infection (HAI) is known to increase the economic burden of patients while the medical cost due to MDRO HAI is even higher. Three hundred eighty-one multidrug resistance organisms (MDROs) healthcare associated infection (HAI) case-patients and three hundred eighty-one matched control-patients were identified between January and December in 2015. The average total hospitalization medical cost of the case group was $6127.65 and that of the control group was $2274.02. The difference between the case group and the control group was statistically significant (t = 21.07; P < 0.01). The attributable cost of MDRO HAI was $3853.63. The direct medical costs due to different MDRO infections were different. The increased medical costs of CR-AB, CR-KP, and CR-PA were significantly higher than that of MRSA, MRSE, ESBL E. coli, and ESBL Kp (P < 0. 05). Among the subitem expenses, the drug cost increased the most (the average cost was $1457.72), followed by the treatment fee and test fee; the differences were statistically significant (P < 0.01).

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.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.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).Our research indicates that AQP2 levels in the amniotic fluid may be used as a marker for AQP2 expression in the fetal kidney.

The aim was to investigate the function of fibroblast growth factor receptor 4 (FGFR4) in gastric cancer (GC) and explore the treatment value of agent targeted to FGFR4. Function assays in vitro and in vivo were performed to investigate the discrepancy of biological features among the GC cells with different expression of FGFR4. GC cells were treated with the single and combination of PD173074 (PD, an inhibitor of FGFR4) and 5-fluorouracil (5-Fu). The invasion ability were stronger, and the apoptosis rates were lower in MGC803 and BGC823 cells treated with FGFR4-LV5 (over-expression of FGFR4 protein) (P

To clarify the role of fibroblast growth factor receptor 4 (FGFR4) in gastric cancer (GC) and explore the therapeutic value of BGJ398 targeted to FGFR4. We constructed lentivirus vectors to stably knockdown FGFR4 expression in GC cells. Function assays in vitro and in vivo, treated with 5-fluorouracil (5-Fu) and BGJ398, were performed to study the change of biological behaviors of GC cells and related mechanism. The proliferation and invasive ability of HGC27 and MKN45 significantly decreased while the apoptosis rate of GC cells obviously increased in shRNA group (P

Summary 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 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. Summary Table . Summarized effect estimates for composite outcome assessed for association between age of toilet training (TT) and LUT dysfunction Outcome assessed Number of studies Odds ratio 95% confidence interval P value Composite earlier vs late TT with LUT dysfunction (pooled-effects estimate) 8 0.71 0.63–0.81 0.001 Subgroup Day-time incontinence 4 0.77 0.62–0.95 0.014 Enuresis 4 0.63 0.43–0.94 0.023 Initial TT before age of 24 months vs after 24 months 7 0.77 0.63–0.94 0.009

Objective To assess the efficacy of desmopressin, alarm, desmopressin plus alarm, and desmopressin plus anticholinergic agent (AA) therapy in the management of paediatric monosymptomatic nocturnal enuresis (MNE) using a network meta-analysis. Materials and methods We searched the electronic databases PubMed, Cochrane Library, EMBASE and Web of Science from inception to 1 March 2018. Randomized controlled trials (RCTs) that compared desmopressin, alarm, desmopressin plus alarm, and desmopressin plus AAs were identified. The network meta-analysis was conducted with software R 3.3.2 and STATA 14.0. Results Eighteen RCTs with a total of 1 649 participants were included. The meta-analysis results showed that complete response (CR) and success rates with desmopressin plus AAs were higher than with desmopressin or alarm monotherapy. Success rates for desmopressin plus alarm therapy were higher than for alarm monotherapy. No obvious difference was observed between desmopressin plus AAs and desmopressin plus alarm therapy with regard to CR rate and success rate. The relapse rate with alarm monotherapy was much lower than with desmopressin monotherapy. Adverse events seemed to be infrequently and tolerable for all treatments. The ranking probability results were as follows: desmopressin plus AA ranked first for the outcomes of CR and success, desmopressin plus alarm therapy ranked first for mean number of wet nights per week, and alarm therapy had the lowest relapse rate. Conclusions The network meta-analysis showed that desmopressin had similar efficacy to alarm therapy but a higher relapse rate. Desmopressin plus AA therapy was associated with better efficacy than and a similar relapse rate to desmopressin monotherapy. Desmopressin plus alarm therapy was similar to both desmopressin and alarm monotherapy in efficacy. All treatments, including desmopressin plus AAwere associated with tolerable adverse events; however, additional high-quality studies are needed for further evaluation of these treatments.

This study investigated the effect of muscle-derived stem cells (MDSCs) and adipose tissue-derived stem cells (ADSCs) in the treatment of stress urinary incontinence (SUI) and their differences in a rat model. MDSCs and ADSC were isolated from rats (n = 10), examined for their properties, and labeled with enhanced green fluorescent protein (EGFP) and β-galactosidase (β-gal) gene. Rats received bladder-neck and transurethral sphincter injection of EGFP-labeled MDSCs and β-gal gene-labeled ADSC and injection of D-Hanks as a control (n = 24 each group). At 0, 15, 30, and 60 days after cells injection, urinary voiding function was assessed by urine dynamics detector. The rats were killed to harvest their urethras for tracking of MDSCs and ADSC. Western blotting and quantitative real-time reverse transcription PCR (qRT-PCR) was performed to detect smooth muscle contents. Urodynamic test showed that MDSCs and ADSC improved the function of urination in rats with intrinsic sphincter deficiency (ISD), and effect of MDSCs-treatment was more pronounced. In addition, histologic analysis showed that the MDSCs and ADSC-treated groups had significantly higher myosin and α-smooth muscle actin (α-SMA) content than the control group. Compared with ADSC-treated groups, the MDSCs-treated groups in myosin and α-SMA content showed the tendency of increase. In summary, MDSCs and ADSCs have obvious effects in the treatment and/or prevention of ISD and transplantation of MDSCs is more effective than ADSC. © 2018 IUBMB Life, 70(10):976-984, 2018.

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.

Cordycepin is an active component extracted from Traditional Chinese medical herb Cordyceps militaris. Many reports demonstrated that cordycepin harbors antitumor activity in a broad spectrum of cancer types. In this study the actions and the underneath molecular mechanisms of cordycepin were investigated in renal cell carcinoma Caki-1 cell line. Results showed that cordycepin induced apoptotic cell death and inhibited cell migration in Caki-1 cells. Quantitative real-time PCR results and western blot analyses indicated cordycepin dose-dependently decreased microRNA-21 expression and Akt phosphorylation levels in Caki-1 cells, but increased PTEN phosphatase levels. Block of cordycepin-induced microRNA-21 decrease or PTEN increase in Caki-1 cells by transfection of microRNA-21 mimic or PTEN siRNA significantly attenuated cordycepin-induced cell death and inhibition of cell migration. Taken together, findings in present study suggested that cordycepin induced apoptotic cell death in renal cell carcinoma through regulation of microRNA-21 and PTEN phosphatase. Furthermore, present study also firstly illustrated that cordycepin inhibited cell migration of renal cell carcinoma, which also involved microRNA-21 and PTEN phosphatase.

Myelodysplastic syndromes are a heterogeneous group of clonal disorders of hematopoietic progenitors and have potentiality to progress into acute myelogenous leukemia. Development of effective treatments has been impeded by limited insight into pathogenic pathways. In this study, we applied RNA-seq technology to study the transcriptome on 20 MDS patients and 5 age-matched controls, and developed a pipeline for analyzing this data. After analysis, we identified 38 mutated genes contributing to MDS pathogenesis. 37 out of 38 genes have not been reported previously, suggesting our pipeline is critical for identifying novel mutated genes in MDS. The most recurrent mutation happened in gene IFRD1, which involved 30% of patient samples. Biological relationships among these mutated genes were mined using Ingenuity Pathway Analysis, and the results demonstrated that top two networks with highest scores were highly associated with cancer and hematological diseases, indicating that the mutated genes identified by our method were highly relevant to MDS. We then integrated the pathways in KEGG database and the identified mutated genes using our novel rule-based mutated driver pathway scoring approach for detecting mutated driver pathways. The results indicated two mutated driver pathways are important for the pathogenesis of MDS: pathway in cancer and in regulation of actin cytoskeleton. The latter, which likely contributes to the hallmark morphologic dysplasia observed in MDS, has not been reported, to the best of our knowledge. These results provide us new insights into the pathogenesis of MDS, which, in turn, may lead to novel therapeutics for this disease.

BACKGROUND: Determining the expression and functions of aquaporins (AQPs) in the adult kidney has generated important information about the roles of this protein family in the renal regulation of water homeostasis. However, limited information describes the expression of AQPs in fetal kidneys, and most reports on fetal renal AQPs originate from animal studies. Although there are the maturation and regulation of the renal-concentrating mechanism, the ways in which changes in the expression of AQPs contribute to the formation of urine during the perinatal period remain unclear.DATA SOURCES: This review summarizes current knowledge about the spatial and temporal expression patterns of AQP1, AQP2, AQP3, and AQP4 in the fetal and postnatal kidneys in different animal species and in human beings.RESULTS: AQP1 and AQP2 expression can be detected earlier in gestation in human beings and sheep compared with mice and rats. AQP1 expression is detected earlier in the proximal tubules than the expression of AQP2, AQP3, and AQP4 in the collecting ducts.CONCLUSION: Further studies investigating the regulation of AQPs during kidney development may provide insights into normal water-handling mechanisms and the pathophysiology of fetal kidneys, which may determine new directions for the clinical treatment of kidney diseases.

Aims Stress urinary incontinence (SUI) is a common problem worldwide. Mainstream surgical procedures include tension-free vaginal tape (TVT), transobturator tape (TOT), tension-free vaginal tape-obturator (TVT-O), tension-free vaginal tape SECUR (TVT-S), and adjustable single-incision sling (Ajust). The aim of this study was to compare the efficacy and safety of these surgical procedures and assess which surgery is most optimal for SUI by adopting a network meta-analysis (NMA). Methods Electronic databases including PubMed, Cochrance Library, and Embase database were researched systematically, until March 21, 2017. The randomized controlled trials (RCTs) that compared the efficacy and safety of TVT, TOT, TVT-O, TVT-S, and Ajust were identified. The studies were included in the analysis when met the predefined inclusion criteria. After demographic and outcome data extraction, a network meta-analysis was conducted with software R 3.3.2 and STATA 14.0. Objective cure rate, subjective cure rate, postoperative complication rate, bladder perforation, tape erosion, urinary retention, and postoperative pain were considered as outcomes, and the outcomes were displayed as odds ratios (ORs) and 95% credible intervals (CrI). The consistency of direct and indirect evidence was assessed by node splitting. The ranks based on probabilities of intervention for the different endpoints were performed. Results Fourty-five RCTs with 7295 participants were analyzed. The NMA results revealed that, TVT, TOT, and Ajust had a higher objective cure rate than TVT-O and TVT-S (TVT-O: OR = 0.76, 95%CI [0.61, 0.94]; TVT-S: OR = 0.41, 95%CI [0.28, 0.60]). TVT, TOT, and TVT-O had a superior subjective cure rate than TVT-S and Ajust (Ajust: OR = 0.45, 95%CI [0.20, 0.91]; TVT-S: OR = 0.29, 95%CI [0.15, 0.56]). With TVT as the reference, TVT-S had a statistically lower postoperative complication rate (TVT-S: OR = 0.39, 95%CI [0.16, 0.89]). TVT-O, TVT-S, and TOT had a significantly lower bladder perforation rate (TOT: OR = 0.076, 95%CI [0.0060, 0.37]; TVT-O: OR = 4.1e-17, 95%CI [6.1e-48, 0.0032]; TVT-S: OR = 3.8e-17, 95%CI [1.8e-48, 0.0052]). There were no obvious differences between the five treatments for tape erosion. TVT-O exhibited a less postoperative retention (TVT-O: OR = 0.35, 95%CI [0.16, 0.74]). Probabilities of ranking results indicated that TOT was the treatment with best ranking in efficacy and a relatively high safety. Conclusions Our study recommend TOT as the optimal regimen for SUI with high efficacy and moderate safety when compared with TVT, TVT-O, TVT-S, and Ajust interventions. However, with the limitation of our study, additional high-quality studies are needed to further evaluate the outcomes.

Background Sickle cell disease (SCD) is a disorder of red blood cells (RBCs) expressing abnormal hemoglobin-S (HbS) due to genetic inheritance of homologous HbS gene. However, people with the sickle cell trait (SCT) carry a single allele of HbS and do not usually suffer from SCD symptoms, thus providing a rationale to treat SCD. Methods To validate gene therapy potential, hematopoietic stem cells were isolated from the SCD patient blood and treated with CRISPR/Cas9 approach. To precisely dissect genome-editing effects, erythroid progenitor cells were cloned from single colonies of CRISPR-treated cells and then expanded for simultaneous gene, protein, and cellular function studies. Results Genotyping and sequencing analysis revealed that the genome-edited erythroid progenitor colonies were converted to SCT genotype from SCD genotype. HPLC protein assays confirmed reinstallation of normal hemoglobin at a similar level with HbS in the cloned genome-edited erythroid progenitor cells. For cell function evaluation, in vitro RBC differentiation of the cloned erythroid progenitor cells was induced. As expected, cell sickling assays indicated function reinstitution of the genome-edited offspring SCD RBCs, which became more resistant to sickling under hypoxia condition. Conclusions This study is an exploration of genome editing of SCD HSPCs. Electronic supplementary material The online version of this article (doi:10.1186/s13045-017-0489-9) contains supplementary material, which is available to authorized users.

The prognosis of extranodal nature killer (NK)/T cell lymphoma (ENKL) is dismal because of its aggressive course and multidrug resistance. Currently, for patients with relapsed/refractory ENKL, L-asparaginase-based regimens such as L-asparaginase, ifosfamide, methotrexate, etoposide, and dexamethasone (SMILE) or L-asparaginase, methotrexate, and dexamethasone (AspaMetDex) are recommended. We retrospectively investigated the efficacy and safety of gemcitabine, pegaspargase, cisplatin, and dexamethasone (DDGP) combination chemotherapy in the treatment of 17 relapsed/refractory ENKL patients. Clinical data from these patients were collected and analyzed. The primary end point was overall response rate (ORR). All patients were subjected to 2 to 6 cycles of DDGP chemotherapy, and the median number of cycles of DDGP regimen administrated was four. The ORR was 88.2 % (15/17), with nine patients (52.9 %) achieved complete response (CR) and six patients (35.3 %) achieved partial response (PR). The median follow-up time was 17 months (range 2-28 months). The 1-year overall survival (OS) rate and 1-year progression-free survival (PFS) were 82.4 and 64.7 %, respectively. For those CR responders, the median PFS was 17 months. Grade 3/4 neutropenia occurred in nine patients (52.9 %) and grade 3/4 thrombocytopenia occurred in six patients (35.3 %). DDGP combination chemotherapy produces favorable outcomes in relapsed/refractory ENKL, and more attention should be paid to treatment-related myelosuppression. Further prospective trials are expected to define the efficacy.

Summary Multiple myeloma (MM) stem cells, proposed to be responsible for the tumourigenesis, drug resistance and recurrence of this disease, are enriched in the cancer stem cell-like side population (SP). Cancer testis antigens (CTA) are attractive targets for immunotherapy because they are widely expressed in cancers but only in limited types of normal tissues. We designed a high throughput assay, which allowed simultaneous relative quantifying expression of 90 CTA genes associated with MM. In the three MM cell lines tested, six CTA genes were over-expressed in two and LUZP4 and ODF1 were universally up-regulated in all three cell lines. Subsequent study of primary bone marrow (BM) from eight MM patients and four healthy donors revealed that 19 CTA genes were up-regulated in SP of MM compared with mature plasma cells. In contrast, only two CTA genes showed a moderate increase in SP cells of healthy BM. Furthermore, knockdown using small interfering RNA (siRNA) revealed that LUZP4 expression is required for colony-forming ability and drug resistance in MM cells. Our findings indicate that multiple CTA have unique expression profiles in MM SP, suggesting that CTA may serve as targets for immunotherapy that it specific for MM stem cells and which may lead to the long-term cure of MM.

Aim To evaluate the effect of serious periventricular white matter injury (PWMI) on the voiding patterns of preterm infants. Methods Free voiding was continuously observed for eight hours in 19 preterm infants with serious PWMI and 16 infants without PWMI. The infants had a gestational age of 32–35 weeks and a postnatal age of 9–15 days. Voiding frequency, voided volume, postvoid residual volume, empty voiding, awake voiding and interrupted voiding were recorded and compared between the two groups of infants. Results The voiding frequency ((5.1 ± 1.0) vs. (7.0 ± 1.1)), awake voiding percentage ((23 ± 11)% vs. (42 ± 7)%) and empty voiding percentage (lower quartile = 16% vs. 28%, median = 20% vs. 33%, upper quartile = 28% vs. 40%) were significantly lower, while the voided volume ((19.9 ± 6.6) mL vs.(15.9 ± 5.3) mL)and postvoid residual volume (lower quartile = 1 mL. vs. 0 mL., median = 3 mL. vs. 2 mL., upper quartile = 3 mL. vs. 2 mL.) were significantly higher in the injured preterm infants, compared with the healthy infants (p

As a “chemical antibody”, oligonucleotide aptamers can specifically bind to their target molecules. However, clinical potential of aptamers in disease diagnosis is not yet fully explored. Using a tumor cell-based selection protocol, we developed single-stranded DNA aptamers for Hodgkin lymphoma (HL) tumor cells. The aptamers specifically bound to HL cells with a high affinity, reaching maximal cell binding at 10 nM final concentration. Importantly, the aptamers were able to selectively detect HL cells and did not react to other tumor or blood cells in mixed samples, indicating that the aptamers can be used as a specific probe for in vitro analysis of HL cells. Moreover, due to the inherent properties of DNA, the aptamers were stable in human serum, suggesting potential for in vivo detection of HL tumor cells.

Context.—Cancer stem cells (CSCs) comprise a minor cell population in a tumor; however, they possess self-renewal capacity and are responsible for tumor recurrence and the emerging issue of tumor resistance. Despite recent advances in the study of pathogenesis and mechanisms of CSC-mediated disease recurrence and multidrug resistance, many questions remain unanswered. Objectives.—To provide an overview of CSC theory and to describe major methods of CSC detection and isolation, with the emphasis on those techniques that are potentially relevant in clinical laboratory practice. Particular attention is given to CSC markers, such as cancer testis antigens, which could become promising targets in the development of immunotherapy in settings of minimal residual disease. Data Sources.—The review is based on analysis of peer-reviewed literature cited in PubMed, as well as preliminary results of studies conducted in our laboratory. Conclusions.—Despite a lack of consensus in the scientific community on research methodology, CSCs have demonstrated significant potential as therapeutic targets in the treatment of cancer. Further research of CSC biology and markers will eventually lead to the development of novel therapeutic approaches for targeting these cells to treat resistant and recurrent tumors and minimal residual disease.