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The conventional fault diagnosis of patient monitors heavily relies on manual experience, resulting in low diagnostic efficiency and ineffective utilization of fault maintenance text data. To address these issues, this paper proposes an intelligent fault diagnosis method for patient monitors based on multi-feature text representation, improved bidirectional gate recurrent unit (BiGRU) and attention mechanism. Firstly, the fault text data was preprocessed, and the word vectors containing multiple linguistic features was generated by linguistically-motivated bidirectional encoder representation from Transformer. Then, the bidirectional fault features were extracted and weighted by the improved BiGRU and attention mechanism respectively. Finally, the weighted loss function is used to reduce the impact of class imbalance on the model. To validate the effectiveness of the proposed method, this paper uses the patient monitor fault dataset for verification, and the macro F1 value has achieved 91.11%. The results show that the model built in this study can realize the automatic classification of fault text, and may provide assistant decision support for the intelligent fault diagnosis of the patient monitor in the future.
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Mineração de Dados , Fontes de Energia Elétrica , Humanos , Monitorização FisiológicaRESUMO
This study investigated the mechanism of action of ABT-263 in the treatment of neurogenic bladder fibrosis (NBF)and its protective effects against upper urinary tract damage (UUTD). Sixty 12-week-old Sprague-Dawley (SD) rats were randomly divided into sham, sham + ABT-263 (50 mg/kg), NBF, NBF + ABT-263 (25 mg/kg, oral gavage), and NBF + ABT-263 (50 mg/kg, oral gavage) groups. After cystometry, bladder and kidney tissue samples were collected for hematoxylin and eosin (HE), Masson, and Sirius red staining, and Western Blotting (WB) and qPCR detection. Primary rat bladder fibroblasts were isolated, extracted, and cultured. After co-stimulation with TGF-ß1 (10 ng/mL) and ABT-263 (concentrations of 0, 0.1, 1, 10, and 100 µmol/L) for 24 h, cells were collected. Cell apoptosis was detected using CCK8, WB, immunofluorescence, and annexin/PI assays. Compared with the sham group, there was no significant difference in any physical parameters in the sham + ABT-263 (50 mg/kg) group. Compared with the NBF group, most of the markers involved in fibrosis were improved in the NBF + ABT-263 (25 mg/kg) and NBF + ABT-263 (50 mg/kg) groups, while the NBF + ABT-263 (50 mg/kg) group showed a significant improvement. When the concentration of ABT-263 was increased to 10 µmol/L, the apoptosis rate of primary bladder fibroblasts increased, and the expression of the anti-apoptotic protein BCL-xL began to decrease.ABT-263 plays an important role in relieving NBF and protecting against UUTD, which may be due to the promotion of myofibroblast apoptosis through the mitochondrial apoptosis pathway.
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Bexiga Urinaria Neurogênica , Sistema Urinário , Ratos , Animais , Ratos Sprague-Dawley , FibroseRESUMO
OBJECTIVE: The purpose of this study was to investigate the mechanism of long noncoding RNA (lncRNA) prostate cancer antigen 3 (PCA3) in prostate cancer (PCa) via regulating the miR-218-5p/high mobility group box 1 (HMGB1) axis. METHODS: The Cancer Genome Atlas database was used to divide differentially expressed lncRNAs, microRNAs, and messenger RNA (mRNAs). The mRNA expressions of lncRNA PCA3, miR-218-5p, and HMGB1 were determined by reverse transcription polymerase chain reaction. Cell propagation was evaluated using the Cell Counting Kit-8 assay and the apoptotic rate was examined by flow cytometry. Cell migration and invasion were observed through the wound healing assay and transwell assay. Target relationships among PCA3, miR-218-5p, and HMGB1 were validated via dual-luciferase reporter gene assay. A nude mouse model in vivo was designed to evaluate the effect of PCA3 on prostate tumor growth. RESULTS: PCA3 and HMGB1 were high-expressed in PCa, whereas miR-218-5p was low-expressed. PCA3 knockdown or miR-218-5p overexpression suppressed PCa cell proliferation, migration, and invasion, but promoted apoptosis. Besides, targeted relationships and interactions on the expression between miR-218-5p and PCA3 or HMGB1 were elucidated. PCA3 weakened cell viability and mobility whereas induced apoptosis through binding with miR-218-5p. Meanwhile, miR-218-5p also inhibited PCa tumorigenesis via downregulation of HMGB1. Knockdown of PCA3 impeded tumor growth by downregulating its downstream gene HMGB1. CONCLUSIONS: lncRNA PCA3 facilitated PCa progression through sponging miR-218-5p and regulating HMGB1.
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Antígenos de Neoplasias/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Proteína HMGB1/metabolismo , MicroRNAs/metabolismo , Neoplasias da Próstata/patologia , Animais , Antígenos de Neoplasias/genética , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Proteína HMGB1/genética , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Nus , MicroRNAs/genética , Neoplasias da Próstata/genética , RNA Longo não Codificante/genéticaRESUMO
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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Aquaporina 1/metabolismo , Aquaporina 3/metabolismo , Feto/metabolismo , Hidronefrose/metabolismo , Rim/metabolismo , Aquaporina 1/genética , Aquaporina 3/genética , Estudos de Casos e Controles , Humanos , Rim/embriologia , RNA Mensageiro/genéticaRESUMO
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.
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Antidiuréticos/uso terapêutico , Antagonistas Colinérgicos/uso terapêutico , Alarmes Clínicos , Desamino Arginina Vasopressina/uso terapêutico , Enurese Noturna/tratamento farmacológico , Criança , Humanos , Metanálise em Rede , Enurese Noturna/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Resultado do TratamentoRESUMO
Pancreatic ductal adenocarcinoma (PDAC) poses a formidable challenge in oncology due to its limited treatment options and poor long-term survival rates. Our previous work identified MG53, a member of the tripartite motif family protein (TRIM72), as a key player in tissue repair with potential applications in regenerative medicine. Despite the focus on MG53's cytosolic functions, its nuclear role in suppressing pancreatic cancer remains unknown. Through orthotopic and subcutaneous transplantation studies in mice, we observed enhanced tumor growth in MG53-deficient mice compared to wild-type counterparts. The overexpression of KIF11, a motor protein crucial for cell mitosis regulation, has been linked to the aggressive proliferation of pancreatic cancer cells. Confocal imaging confirmed MG53's presence in the nucleus of human pancreatic cancer cells, while functional assays demonstrated its impact on KIF11 expression and subsequent cell proliferation. Mechanistically, we revealed MG53's transcriptional control over KIF11, leading to cell cycle arrest. Our findings position MG53 as a promising tumor suppressor in PDAC, offering a novel avenue for therapeutic intervention by regulating KIF11 expression.
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The purpose of this study was to investigate the prevalence and relevant factors of nocturia and its impact on sleep quality in university students in Mainland China. A large-scale survey was conducted on 14,000 university students from 3 universities in Henan province, China by using an anonymous questionnaire. The questionnaire collected the information from the past six months. The relationships between the prevalence of nocturia and its relevant factors were evaluated. A total of 13,874 questionnaires were collected and 13,104 qualified for statistical analysis. A total of 659 students suffered from clinically relevant nocturia (CRN) (4.56% in male and 5.34% in female). Both univariate analysis and the logistic stepwise regression model showed that the prevalence of nocturia was significantly related to female, history of enuresis, ease of waking up, urgency, frequency and RUTI (P < 0.05). The sleep quality and the university entrance score of CRN group was significantly lower than that of control group (P < 0.05). Nocturia was common in Chinese university students and showed a negative impact on sleep and academic performance. Gender of female, history of enuresis, ease of waking up, urgency, frequency and RUTI were relevant factors for CRN.
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Noctúria , Qualidade do Sono , Estudantes , Humanos , Noctúria/epidemiologia , Feminino , Masculino , China/epidemiologia , Universidades , Prevalência , Adulto Jovem , Inquéritos e Questionários , Adulto , AdolescenteRESUMO
Impaired wound healing in diabetes results from a complex interplay of factors that disrupt epithelialization and wound closure. MG53, a tripartite motif (TRIM) family protein, plays a key role in repairing cell membrane damage and facilitating tissue regeneration. In this study, bone marrow-derived mesenchymal stem cells (BMSCs) were transduced with lentiviral vectors overexpressing MG53 to investigate their efficacy in diabetic wound healing. Using a db/db mouse wound model, we observed that BMSCs-MG53 significantly enhanced diabetic wound healing. This improvement was associated with marked increase in re-epithelialization and vascularization. BMSCs-MG53 promoted recruitment and survival of BMSCs, as evidenced by an increase in MG53/Ki67-positive BMSCs and their improved response to scratch wounding. The combination therapy also promoted angiogenesis in diabetic wound tissues by upregulating the expression of angiogenic growth factors. MG53 overexpression accelerated the differentiation of BMSCs into endothelial cells, manifested as the formation of mature vascular network structure and a remarkable increase in DiI-Ac-LDL uptake. Our mechanistic investigation revealed that MG53 binds to caveolin-3 (CAV3) and subsequently increases phosphorylation of eNOS, thereby activating eNOS/NO signaling. Notably, CAV3 knockdown reversed the promoting effects of MG53 on BMSCs endothelial differentiation. Overall, our findings support the notion that MG53 binds to CAV3, activates eNOS/NO signaling pathway, and accelerates the therapeutic effect of BMSCs in the context of diabetic wound healing. These insights hold promise for the development of innovative strategies for treating diabetic-related impairments in wound healing.
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Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Óxido Nítrico Sintase Tipo III , Óxido Nítrico , Transdução de Sinais , Cicatrização , Animais , Células-Tronco Mesenquimais/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Neovascularização Fisiológica , Células Cultivadas , Humanos , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Experimental/metabolismo , Diferenciação Celular , Proteínas de MembranaRESUMO
Ischemic heart disease is the leading cause of mortality in the United States. Progenitor cell therapy can restore myocardial structure and function. However, its efficacy is severely limited by cell aging and senescence. Gremlin-1 (GREM1), a member of the bone morphogenetic protein antagonist family, has been implicated in cell proliferation and survival. However, GREM1's role in cell aging and senescence has never been investigated in human cardiac mesenchymal progenitor cells (hMPCs). Therefore, this study assessed the hypothesis that overexpression of GREM1 rejuvenates the cardiac regenerative potential of aging hMPCs to a youthful stage and therefore allows better capacity for myocardial repair. We recently reported that a subpopulation of hMPCs with low mitochondrial membrane potential can be sorted from right atrial appendage-derived cells in patients with cardiomyopathy and exhibit cardiac reparative capacity in a mouse model of myocardial infarction. In this study, lentiviral particles were used to overexpress GREM1 in these hMPCs. Protein and mRNA expression were assessed through Western blot and RT-qPCR. FACS analysis for Annexin V/PI staining and lactate dehydrogenase assay were used to assess cell survival. It was observed that cell aging and cell senescence led to a decrease in GREM1 expression. In addition, overexpression of GREM1 led to a decrease in expression of senescence genes. Overexpression of GREM1 led to no significant change in cell proliferation. However, GREM1 appeared to have an anti-apoptotic effect, with an increase in survival and decrease in cytotoxicity evident in GREM1-overexpressing hMPCs. Overexpressing GREM1 also induced cytoprotective properties by decreasing reactive oxidative species and mitochondrial membrane potential. This result was associated with increased expression of antioxidant proteins, such as SOD1 and catalase, and activation of the ERK/NRF2 survival signal pathway. Inhibition of ERK led to a decrease in GREM1-mediated rejuvenation in terms of cell survival, which suggests that an ERK-dependent pathway may be involved. Taken altogether, these results indicate that overexpression of GREM1 can allow aging hMPCs to adopt a more robust phenotype with improved survival capacity, which is associated with an activated ERK/NRF2 antioxidant signal pathway.
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Antioxidantes , Células-Tronco Mesenquimais , Animais , Camundongos , Humanos , Idoso , Antioxidantes/metabolismo , Regulação para Cima/genética , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais , Células-Tronco Mesenquimais/metabolismo , Proteínas Morfogenéticas Ósseas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismoRESUMO
Sodium ion batteries (SIBs) attract most of the attention as alterative secondary battery systems for future large-scale energy storage and power batteries due to abundance resource and low cost. However, the lack of anode materials with high-rate performance and high cycling-stability has limited the commercial application of SIBs. In this paper, Cu7.2S4@N, S co-doped carbon (Cu7.2S4@NSC) honeycomb-like composite structure was designed and prepared by a one-step high-temperature chemical blowing process. As an anode material for SIBs, Cu7.2S4@NSC electrode exhibited an ultra-high initial Coulomb efficiency (94.9%) and an excellent electrochemical property including a high reversible capacity of 441.3 mAh g-1 after 100 cycles at 0.2 A g-1, an excellent rate performance of 380.4 mAh g-1 even at 5 A g-1, and a superior long-cycle stability with a capacity retention rate of approximately 100% after 700 cycles at 1A g-1.
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Both PD1/PD-L1 and CD47 blockades have demonstrated limited activity in most subtypes of NHL save NK/T-cell lymphoma. The hemotoxicity with anti-CD47 agents in the clinic has been speculated to account for their limitations. Herein we describe a first-in-class and rationally designed bispecific antibody (BsAb), HX009, targeting PD1 and CD47 but with weakened CD47 binding, which selectively hones the BsAb for tumor microenvironment through PD1 interaction, potentially reducing toxicity. In vitro characterization confirmed: (1) Both receptor binding/ligand blockade, with lowered CD47 affinity; (2) functional PD1/CD47 blockades by reporter assays; (3) T-cell activation in Staphylococcal-enterotoxin-B-pretreated PBMC and mixed-lymphocyte-reaction. In vivo modeling demonstrated antitumor activity in Raji-B and Karpass-229-T xenograft lymphomas. In the humanized mouse syngeneic A20 B-lymphoma (huCD47-A20) HuGEMM model, which has quadruple knocked-in hPD1xhPD-L1xhCD47xhSIRPα genes and an intact autologous immune-system, a contribution of effect is demonstrated for each targeted biologic (HX008 targeting PD1 and SIRPα-Fc targeting CD47), which is clearly augmented by the dual targeting with HX009. Lastly, the expression of the immune-checkpoints PD-L1/L2 and CD47 seemed co-regulated among a panel of lymphoma-derived-xenografts, where HX009 maybe more effective in those with upregulated CD47. Our data warrants HX009's further clinical development for treating NHLs.
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Anticorpos Biespecíficos , Linfoma não Hodgkin , Neoplasias , Camundongos , Animais , Humanos , Antígeno B7-H1 , Leucócitos Mononucleares/metabolismo , Anticorpos Monoclonais/uso terapêutico , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Antígeno CD47 , Neoplasias/metabolismo , Microambiente TumoralRESUMO
OBJECTIVE: To explore the surgical approaches, efficacy and safety of percutaneous nephroscopic 2 µm laser incision and drainage in the treatment of peripelvic renal cysts. METHODS: The peripelvic renal cysts were punctured percutaneously. A 1.5 - 4.0 cm incision was made at thin avascular area between cyst and pelvis by the 2 µm laser to connect the cyst with the renal collecting system with the help of injecting methylene blue solution into renal pelvis through ureteral catheter. The double-J tube was placed for drainage. RESULTS: The operations were successful in all cases. There were 16 males and 15 females with a mean age of 49 years old. The operative durations ranged from 25 to 120 minutes. And no severe complications occurred. The patients were followed up for an average of 12 months (range: 3 - 36). Among them, cysts disappeared in 18 cases and diminished over 1/3 in 13 cases. There was no recurrence of peripelvic renal cyst. CONCLUSION: Percutaneous nephroscopic 2 µm laser incision and drainage for peripelvic renal cyst is safe, effective and mini-invasive.
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Doenças Renais Císticas/cirurgia , Pelve Renal , Laparoscopia/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
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 in vitro experiments, mouse renal tubular epithelial cells (mRTECs) and miR-140-5p mimic/inhibitor transfected mRTECs were subjected to hypoxia/reoxygenation in the presence or absence of apigenin. In vitro, we uncovered that hypoxia/reoxygenation stimulation caused inflammatory injury in mRTECs. Apigenin reduced the hypoxia/reoxygenation-induced cell inflammatory injury and NF- B p65 nuclear translocation from cytoplasm and activation. Moreover, apigenin reduced hypoxia/reoxygenationtriggered miR-140-5p down-regulation. What's more, the luciferase reporter system revealed that miR-140-5p negatively regulates CXCL12, which is its direct target of action. CXCL12 exhibited an inhibitory effect on the apigenin-induced inactivation of NF- B signaling pathway. Furthermore, we observed that apigenin pretreatment attenuated the IR-triggered up-regulation of serum creatinine and blood urea nitrogen, elevation of pro-inflammatory cytokines secretion and tubular cell apoptosis, enhancement of CXCL12 and decline of miR-140-5p in vivo. Our studies show that apigenin protects against IR-triggered renal cell inflammatory injury in vivo and in vitro by miR-140-5p up-regulation and CXCL12 downregulation via quenching the NF- B pathway activation. Apigenin may be an encouraging therapeutic agent for patients with IR-associated kidney injury.
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MicroRNAs , Nanopartículas , Traumatismo por Reperfusão , Animais , Apigenina/farmacologia , Apoptose , Quimiocina CXCL12 , Humanos , Isquemia , Rim , Camundongos , MicroRNAs/genética , NF-kappa B/metabolismo , Reperfusão , Traumatismo por Reperfusão/tratamento farmacológico , Transdução de SinaisRESUMO
In this work, coral-like CuO dendrites were successfully synthesized by a solvothermal method in the mixed solvent of distilled water and ethanol with assistance of dodecyl trimethyl ammonium bromide (DTAB). The products were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Brunauer-Emmett-Teller (BET) analysis techniques, to investigate their structure and morphology. The coral-like CuO dendrites were about 1 µm in length, with many dendrites pointing to a common center. The influence of experimental conditions on morphology, such as volume ratio of water to ethanol, surfactant DTAB and molar ratio of Na2CO3 and Cu(CH3COO)2, was also discussed. Time-dependent experiment was carried out to explore the formation mechanism while a "particle-sheet-dendrite (PSD)" mechanism was proposed to explain the growth process. The as-prepared CuO dendrites were used to degrade methylene blue (MB) under visible light irradiation in the presence of H2O2, where over 98% of methylene blue (MB) was degraded in 1 h. Results from the study demonstrated that the as-prepared coral-like CuO dendrites exhibited enhanced photocatalytic performance and excellent stability and reusability.
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OBJECTIVE: To evaluate the curative efficacy of transurethral 2 microm thulium laser urethrotomy in the treatment of urethral stricture and atresia. METHODS: 192 patients suffering from urethral stricture (n = 179) or atresia (n = 13), all male, aged 45.4 (38-56), underwent transurethral 2 microm thulium laser urethrotomy. The maximum flow rate (MFR) was measured before operation, immediately after removing the catheter, and 3 and 6 months postoperatively. RESULTS: All the patients got fluent urination immediately after the catheter removal with the mean MFR of (16.7 +/- 3.1) ml/s, significantly higher than that before the operation [(3.2 +/- 0.3) ml/s, P < 0.01]. 157 patients got permanent fluent urination without recurrence; 35 patients got recurrence 1 to 3 weeks after the catheter removal and got final cure 3 months later after periodic urethra dilatation. Besides, 6 patients encountered incontinence and all finally got convalescence after physical therapy and exercise. The mean MFR of all the patients 3 months and 6 months postoperatively were (18.7 +/- 3.1) ml/s and (19.2 +/- 2.8) ml/s respectively, both significantly higher than that before operation (both P < 0.01). CONCLUSION: Transurethral 2 microm thulium laser urethrotomy is a safe and efficient method in the treatment of urethral stricture and atresia.
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Terapia a Laser/métodos , Uretra/cirurgia , Obstrução Uretral/cirurgia , Estreitamento Uretral/cirurgia , Adulto , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Túlio , Resultado do TratamentoRESUMO
Megalin is essential for proximal tubule reabsorption of filtered proteins, hormones, and vitamins, and its dysfunction has been reported in IgA nephropathy (IgAN). miR-148b has been shown to regulate renal megalin expression in vitro and in animal models of kidney disease. We examined a potential role of miR-148b and other miRNAs in regulating megalin expression in IgAN by analyzing the association between megalin and miR-148b, miR-21, miR-146a, and miR-192 expression. Quantitative PCR (qPCR) analysis identified a marked increase in renal levels of several miRNAs, including miR-148b, miR-21, miR-146a, and a significant decrease in megalin mRNA levels in IgAN patients when compared with normal controls. By multiple linear regression analysis, however, only renal miR-148b was independently associated with megalin mRNA levels in IgAN. Proximal tubule megalin expression was further evaluated by immunofluorescence labeling of biopsies from the patients. The megalin expression was significantly lower in patients with highest levels of renal miR-148b compared with patients with lowest levels. To examine the direct effects of the miRNAs on megalin and other membrane proteins expression, proximal tubule LLC-PK1 cells were transfected with miR-148b, miR-21, miR-146a, or miR-192 mimics. Transfection with miR-148b mimic, but not the other three miRNA mimics inhibited endogenous megalin mRNA expression. No significant effect of any of the four miRNA mimics was observed on cubilin or aquaporin 1 (AQP1) mRNA expression. The findings suggest that miR-148b negatively regulates megalin expression in IgAN, which may affect renal uptake and metabolism of essential substances.
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Glomerulonefrite por IGA/genética , Túbulos Renais Proximais/metabolismo , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , MicroRNAs/genética , Adulto , Animais , Aquaporina 1/genética , Linhagem Celular , Feminino , Regulação da Expressão Gênica/genética , Glomerulonefrite por IGA/patologia , Humanos , Rim/metabolismo , Túbulos Renais Proximais/patologia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Receptores de Superfície Celular/genética , Suínos/genética , TransfecçãoRESUMO
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) (<1 year old) and the late CIC group (LCG) (>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 (Pâ< â0.05). The frequencies of vesicoureteral reflux (VUR) and urinary tract infection (UTI) in the ECG were significantly lower than those in the LCG (Pâ< â0.05) 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 (Pâ< â0.05) 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.
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Cateterismo Uretral Intermitente/métodos , Bexiga Urinaria Neurogênica/terapia , Feminino , Humanos , Lactente , Masculino , Bexiga Urinaria Neurogênica/reabilitaçãoRESUMO
PURPOSE: To investigate the correlation between urethral instability (URI) and overactive bladder (OAB) in children. METHODS: 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. RESULTS: 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 < 0.01). CONCLUSIONS: Urethral instability plays an essential role in the pathogenesis and progression of OAB in children. Synchro-cystourethrometry is a useful urodynamic technology to precisely diagnose OAB, and transcutaneous electrical pudendal nerve stimulation may be an effective treatment for OAB children induced by URI.
Assuntos
Agonistas alfa-Adrenérgicos/uso terapêutico , Alcaloides de Solanáceas/uso terapêutico , Estimulação Elétrica Nervosa Transcutânea , Doenças Uretrais/terapia , Bexiga Urinária Hiperativa/diagnóstico , Bexiga Urinária Hiperativa/terapia , Criança , Terapia Combinada , Feminino , Humanos , Masculino , Nervo Pudendo , Estudos Retrospectivos , Doenças Uretrais/complicações , Doenças Uretrais/fisiopatologia , Bexiga Urinária/fisiopatologia , Bexiga Urinária Hiperativa/etiologia , Bexiga Urinária Hiperativa/fisiopatologia , Micção , UrodinâmicaRESUMO
BACKGROUND: Immunophilin ligands are neuroregenerative agents binding to FK506 binding proteins, by which stimulate recovery of neurons in a variety of injury nerves. FK1706 is a novel immunophilin ligand which has neuroprotective and neuroregenerative effects but without immunosuppressive activity. At present, most reports about FK1706 in ameliorating nerve injury and functional recovery are limited to cavernous nerve injury and erectile function recovery. This study aimed to demonstrate the effects of FK1706 on nerve regeneration and bladder function recovery following an end-to-side neurorrhaphy in rat models. METHOD: The numbers of regenerated myelinated axons of the pelvic parasympathetic nerve (PPN) in the three groups' rats (FK1706 + ETS, ETS and control groups) were evaluated. Their intravesical pressure (IVP), S100ß and growth associated protein 43 (GAP43) expressions were also compared. RESULTS: In FK1706 + ETS group, 90% the rats showed that the frequency of FG labeled neurons was larger than the 3.5 cutoff value, 100% the rats showed that the frequency of FG-FB double-labeled neurons was larger than the 5.5 cutoff value. The average maximum of IVP in FK1706 + ETS group reached 76.3% of the value in control group. Their average number of myelinated axons of regenerated PPN reached 80% of the amount in control group. The nerve regeneration-associated markers data indicated that the expression level of S100ß and GAP43 in FK1706 + ETS group was approximately 2-fold higher than that of ETS group (P < 0.05). CONCLUSIONS: After end-to-side neurorrhaphy, FK1706 effectively enhanced the nerve regeneration and bladder function recovery.
RESUMO
Long non-coding RNAs (LncRNAs) have been reported to serve roles in various types of malignancy, including human renal cell carcinoma (RCC), which is among the most common types of kidney cancer worldwide. The present study aimed to investigate the effects of a newlydiscovered LncRNA, Z38, on cell proliferation and metastasis in RCC cells. Reverse transcriptionquantitative polymerase chain reaction analysis was used to detect the transcription levels of Z38 in clinical RCC tissues and cultured RCC cells. The expression of Z38 was notably increased in patients with stage III and IVRCC compared with patients with stage I and II. Knockdown of Z38 with specific short hairpin RNAs notably decreased the proliferation rate of A498 and ACHIN cells. In addition, a colony formation assay was included to investigate the role of Z38 in cell proliferation. Transwell assays demonstrated that Z38 deprivation inhibited the migratory and invasive capability of RCC cells. The association between Z38 and the epithelialmesenchymal transition process was investigated using western blot analysis. The results of the present study demonstrated that Z38 may serve as an important biomarker in the diagnosis and treatment of RCC in the clinic.