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1.
World J Urol ; 40(9): 2347-2352, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35849171

RESUMO

PURPOSE: To compare a novel vacuum suction ureteroscopic laser lithotripsy (VS-URS) with traditional ureteroscopic laser lithotripsy (T-URS) for impacted upper ureteral stones and to better define the potential benefits of VS-URS. METHODS: Between May 2019 and March 2021, 158 patients with impacted upper ureteral stones underwent ureteroscopic holmium-YAG laser lithotripsy. Of these, 76 underwent VS-URS and 82 underwent T-URS. In VS-URS procedures, the vacuum suction device is composed of a 5F ureteral catheter and a tee joint. The ureteral catheter is linked to the vacuum aspirator by the sidearm of the tee joint, and a 200 µm fiber is inserted through the tee joint and the ureteral catheter into the stone site for lithotripsy. RESULTS: When compared to the T-URS group, the VS-URS group had a shorter mean operation time (38.18 ± 6.37 min vs. 46.65 ± 5.66 min; P = 0.000), lower fever rate (3.9% vs. 14.6%; P < 0.022), less stone retropulsion (5.3% vs. 18.3%; P = 0.012), lower extra management rate (6.58% vs. 21.95%; P = 0.006), and a higher stone-free rate of the first postoperative day (88.2% vs. 72.0%; P = 0.011). There were no significant differences in stone-free rates 1 month after surgery between groups (94.7% vs. 92.7%; P = 0.748). CONCLUSIONS: VS-URS is an effective modality for impacted upper ureteral stones, and has a shorter operating time, lower fever rate, less stone retropulsion, and a higher primary stone-free rate compared with T-URS.


Assuntos
Litotripsia a Laser , Litotripsia , Cálculos Ureterais , Humanos , Litotripsia/métodos , Litotripsia a Laser/métodos , Sucção , Resultado do Tratamento , Cálculos Ureterais/cirurgia , Ureteroscopia/métodos , Vácuo
2.
Urol Int ; 106(12): 1241-1245, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34515252

RESUMO

OBJECTIVES: This study aimed to describe a novel double-sheath vacuum suction minimally invasive percutaneous nephrolithotomy (mini-PCNL) to overcome the deficiencies of the conventional procedure. PATIENTS AND METHODS: Between March 2019 and December 2019, 65 patients (37 males and 28 females) with a mean age of 41 years (range 23-69) underwent mini-PCNL with double-sheath vacuum suction. It consisted of an F20 Y-shaped sheath as an outer sheath and an F16 Y-shaped sheath as an inner sheath, in which the inner sheath was longer than the outer sheath. The oblique arm of the outer sheath and the inner sheath was connected to the perfusion inflow and the vacuum suction, respectively. A 550-µm holmium-YAG laser was introduced for stone fragmentation through the working channel of the mini-nephroscope, which was no longer connected to the perfusion fluid. RESULTS: All procedures were successful. Mean operation time was 50.2 min (range 39-83). Mean hemoglobin decrease was 5.2 g/L (range 1.0-15.5), and no patient needed a blood transfusion. One patient (1.5%) with low fever (<38°C) at day 1 had returned to normal at day 2 without administration of antibiotics. There were no Clavien grade 2-4 complications. Mean postoperative hospital stay was 2.4 days (range 2-6). The initial stone-free rate of PCNL was 81.53% (53 of 65 patients). One month after surgery, the final stone-free rate increased to 90.77% (59/65 patients). CONCLUSIONS: The double-sheath vacuum suction mini-PCNL is a safe and effective modality for large renal stones, which might increase the efficiency of stone extraction with low intrapelvic pressure.


Assuntos
Nefrolitotomia Percutânea , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso
3.
J Cell Mol Med ; 25(7): 3258-3271, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33608980

RESUMO

The immunophenotype of bladder cancer plays a pivotal role in the prognosis of cancer, but the effect of different epigenetic factors on different immunophenotypes in bladder tumours remains unclear. This study used multi-omics data analysis to provide molecular basis support for different immune phenotypes. Unsupervised cluster analysis revealed distinct subclusters with higher (subcluster B2) or lower cytotoxic immune phenotypes (subcluster A1) related to PD-L1 and IFNG expression. Mutational landscape analyses showed that the mutation level of TP53 in subcluster B1 was highest than other subclusters, and subcluster B1 had a lower frequency of concurrent mutation than subcluster A2. A total of 2364 differentially expressed genes were identified between subclusters A2 and B1, and the main functions of the up-regulated genes in subcluster B1 were enriched in the activation of T cells and other related pathways. We found that STAT1 was a key gene in a gene regulatory network related to immune phenotypes in bladder cancer. Finally, we constructed a prognostic prediction model by LASSO Cox regression which could distinguish high-risk and low-risk cases significantly. In conclusion, the present study addressed a field synopsis between genetic and epigenetic events in immune phenotypes of bladder cancer.


Assuntos
Redes Reguladoras de Genes , Fator de Transcrição STAT1/genética , Linfócitos T/imunologia , Neoplasias da Bexiga Urinária/genética , Biologia Computacional , Humanos , Mutação , Proteína Supressora de Tumor p53/genética , Neoplasias da Bexiga Urinária/imunologia
4.
Lancet ; 396(10249): 479-488, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32702299

RESUMO

BACKGROUND: This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an appropriate dose of the candidate vaccine for an efficacy study. METHODS: This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single centre in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 × 1011 viral particles per mL or 5 × 1010 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titres (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, NCT04341389. FINDINGS: 603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 × 1011 viral particles n=253; 5 × 1010 viral particles n=129) or placebo (n=126). In the 1 × 1011 and 5 × 1010 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2-749·2) and 571·0 (467·6-697·3), with seroconversion rates at 96% (95% CI 93-98) and 97% (92-99), respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8-22·7) and 18·3 (14·4-23·3) in participants receiving 1 × 1011 and 5 × 1010 viral particles, respectively. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were observed in 227 (90%, 95% CI 85-93) of 253 and 113 (88%, 81-92) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1 × 1011 viral particles dose group and one (1%) participant in the 5 × 1010 viral particles dose group. No serious adverse reactions were documented. INTERPRETATION: The Ad5-vectored COVID-19 vaccine at 5 × 1010 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunisation. FUNDING: National Key R&D Programme of China, National Science and Technology Major Project, and CanSino Biologics.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/efeitos adversos , Vacinas Virais/imunologia , Adenoviridae , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19 , Vacinas contra COVID-19 , China , Infecções por Coronavirus/imunologia , Método Duplo-Cego , Feminino , Vetores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T/imunologia , Vacinas Virais/administração & dosagem , Adulto Jovem
5.
World J Urol ; 39(11): 4255-4260, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34032912

RESUMO

PURPOSE: To compare double-sheath vacuum suction minimally invasive percutaneous nephrolithotomy (DS-mini-PCNL) with vacuum-assisted mini-PCNL (VS-mini-PCNL) and to better define the potential benefits of DS-mini-PCNL. METHODS: Between July 2019 and May 2020, 117 patients with large radiopaque renal stones underwent mini-PCNL. Of these, 63 underwent DS-mini-PCNL and 54 underwent VS-mini-PCNL. For VS-mini-PCNL, a F20 Y-shaped sheath was used and the oblique arm of the sheath was connected to the vacuum suction. For DS-mini-PCNL, the oblique arm of a F20 Y-shaped sheath (the outer sheath) and a F16 Y-shaped sheath (the inner sheath) was connected to the perfusion inflow and the vacuum suction, respectively. A 550-µm holmium-YAG laser was used for stone fragmentation. RESULTS: Compared with VS-mini-PCNL group, DS-mini-PCNL group had significantly shorter operative time (35.78 ± 7.77 min vs. 44.56 ± 13.19 min; P = 0.000) and significantly lower fever rate (1.6% vs. 11.1%; P = 0.048). It was not significantly different between the two groups despite the higher initial stone-free rate seen for DS-mini-PCNL group relative to VS-mini-PCNL group (87.7% vs. 81.5%, P = 0.346). Auxiliary procedure rates were 4.8% (three patients) in DS-mini-PCNL group and 16.7% (nine patients) in VS-mini-PCNL group, with a significant difference (P = 0.034). The difference in the final stone-free rate between the two groups was rendered insignificant (93.8% vs. 89.1%, P = 0.510). CONCLUSIONS: DS-mini-PCNL is a safe and effective modality for large renal stones, which could increase the efficiency of stone extraction and decrease infectious complications compared with VS-mini-PCNL.


Assuntos
Cálculos Renais/cirurgia , Nefrolitotomia Percutânea/instrumentação , Nefrolitotomia Percutânea/métodos , Sucção/instrumentação , Adulto , Desenho de Equipamento , Feminino , Humanos , Cálculos Renais/patologia , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Estudos Retrospectivos , Vácuo
6.
BMC Med Inform Decis Mak ; 21(1): 19, 2021 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446198

RESUMO

BACKGROUND: CPGs are not uniformly successful in improving care and several instances of implementation failure have been reported. Performing a comprehensive assessment of the barriers and enablers is key to developing an informed implementation strategy. Our objective was to investigate determinants of guideline implementation and explore associations of self-reported adherence to guidelines with characteristics of participants in China. METHODS: This is a cross-sectional survey, using multi-stage stratified typical sampling based on China's economic regional divisions (the East, the Middle, the West and the Northeast). 2-5 provinces were selected from each region. 2-3 cities were selected in each province, and secondary and tertiary hospitals from each city were included. We developed a questionnaire underpinned by recommended methods for the design and conduct of self-administered surveys and based on conceptual framework of guideline use, in-depth related literature analysis, guideline development manuals, related behavior change theory. Finally, multivariate analyses were performed using logistic regression to produce adjusted odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: The questionnaire consisted of four sections: knowledge of methodology for developing guidelines; barriers to accessing guideline; barriers to guideline implementation; and methods for improving guideline implementation. There were 1732 participants (87.3% response rate) from 51 hospitals. Of these, 77.2% reported to have used guidelines frequently or very frequently. The key barriers to guideline use were lack of education or training (46.2%), and overly simplistic wording or overly broad scope of recommendations (43.8%). Level of adherence to guidelines was associated with geographical regions (the northeast P < 0.001; the west P = 0.02; the middle P < 0.001 compared with the east), hospital grades (P = 0.028), length of practitioners' practice (P = 0.006), education background (Ph.D., P = 0.027; Master, P = 0.002), evidence-based medicine skills acquired in work unit (P = 0.012), and medical specialty of practitioner (General Practice, P = 0.006; Surgery, P = 0.043). CONCLUSION: Despite general acknowledgement of the importance of guidelines, the use of guidelines was not as frequent as might have been expected. To optimize the likelihood of adherence to guidelines, guideline implementation should follow an actively developed dissemination plan incorporating features associated with adherence in our study.


Assuntos
Medicina Baseada em Evidências , Fidelidade a Diretrizes , China , Estudos Transversais , Inquéritos e Questionários
7.
J Cell Mol Med ; 24(1): 655-670, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31691530

RESUMO

The antitumour effect of melittin (MEL) has recently attracted considerable attention. Nonetheless, information regarding the functional role of MEL in bladder cancer (BC) is currently limited. Herein, we investigated the effect of MEL on critical module genes identified in BC. In total, 2015 and 4679 differentially expressed genes (DEGs) associated with BC were identified from the GSE31189 set and The Cancer Genome Atlas database, respectively. GSE-identified DEGs were mapped and analysed using Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes analyses to determine BC-involved crucial genes and signal pathways. Coupled with protein-protein interaction network and Molecular Complex Detection analyses, Modules 2 and 4 were highlighted in the progression of BC. In in-vitro experiments, MEL inhibited the proliferation, migration, and invasion of UM-UC-3 and 5637 cells. The expression of NRAS, PAK2, EGFR and PAK1 in Module 4-enriched in the MAPK signalling pathway-was significantly reduced after treatment with MEL at concentrations of 4 or 6 µg/mL. Finally, quantitative reverse transcription-polymerase chain reaction and Western blotting analyses revealed MEL inhibited the expression of genes at the mRNA (ERK1/2, ERK5, JNK and MEK5), protein (ERK5, MEK5, JNK and ERK1/2) and phosphorylation (p-ERK1/2, p-JNK, and p-38) levels. This novel evidence indicates MEL exerts effects on the ERK5-MAK pathway-a branch of MAPK signalling pathway. Collectively, these findings provide a theoretical basis for MEL application in BC treatment.


Assuntos
Biomarcadores Tumorais/metabolismo , Movimento Celular , Proliferação de Células , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Meliteno/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Apoptose , Biomarcadores Tumorais/genética , Humanos , Invasividade Neoplásica , Prognóstico , Mapas de Interação de Proteínas , Células Tumorais Cultivadas , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
8.
Aging Male ; 23(5): 655-662, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30739562

RESUMO

OBJECTIVE: To investigate the correlation of clinical measurements on normal and abnormal fasting blood glucose (FBG) with benign prostatic hyperplasia (BPH). METHODS: From September 2016 to January 2018, 771 BPH patients were enrolled for further selection. The eligible patients were divided into normal FBG, impaired fasting glucose (IFG), and high risk of type 2 diabetes mellitus (HR-T2DM) groups. Then, relevant parameters were compared among these three groups using Pearson's correlation coefficient. RESULTS: Finally including 443 patients with normal FBG, 113 with IFG and 56 with HR-T2DM. Height, weight, body mass index, smoking status, hemoglobin, serum Na+, serum Cl-, and serum Ca2+ were significantly different between normal and abnormal FBG groups. In IFG/HR-T2DM group, obviously connections were demonstrated for weight with prostate volume (PV), for serum Na+, PV, and serum Cl- with total prostate-specific antigen (t-PSA), for FBG with international prostate symptom score (IPSS). In normal FBG group, significant correlations of age, weight, body mass index, hemoglobin, and serum Ca2+ with PV, of age, systolic blood pressure, PV, and serum Cl- with t-PSA; and of FBG, hemoglobin, and serum Na+ with IPSS were also observed. CONCLUSIONS: Our study suggests that FBG level probably plays an important role in BPH.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperplasia Prostática , Glicemia , Índice de Massa Corporal , Jejum , Humanos , Masculino
9.
Urol Int ; 104(9-10): 752-757, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32570250

RESUMO

OBJECTIVES: The aim of this study was to describe a novel negative-pressure laser lithotripsy device to overcome the deficiencies of the conventional procedure. PATIENTS AND METHODS: Between August 2018 and March 2019, 78 patients with a single ureteral stone underwent retrograde ureteroscopy with a Wolf 8F/9.8F rigid ureteroscope and a 200-µm holmium-YAG laser. The mean stone size was 11.8 mm, measured for the maximum length. The negative-pressure laser lithotripsy device consists of an F5 ureter catheter and a T joint. The closed tip of an F5 ureter catheter is cut off, and it is then inserted within one opening of the T joint. The 200-µm laser fiber is introduced into the ureteral catheter through the other opening of the T joint. The third opening of the T joint is connected to the negative-pressure pipe. The valve end of the Foley catheter is used for sealing the cap. Continuous suction and active irrigation throughout the lithotripsy could maintain adequate visibility. RESULTS: All ureteroscopic procedures were successful. The negative-pressure device showed good stone retention capabilities, with no observed stone migration. We did not observe any major complications. The stone-free rate was 97.44% (76/78), demonstrated on plain radiography of the kidney-ureter-bladder on the first postoperative day. The stone-free rate after 1 month was 100%. CONCLUSIONS: The negative-pressure ureteroscopic lithotripsy is easy and safe management for the ureteral stones. It might reduce the risk of stone fragment retropulsion, improve surgical vision, shorten the operative time, and decrease the renal pelvic pressure.


Assuntos
Lasers de Estado Sólido/uso terapêutico , Litotripsia a Laser/métodos , Cálculos Ureterais/terapia , Ureteroscópios , Ureteroscopia/métodos , Adulto , Idoso , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pressão , Adulto Jovem
10.
J Cell Mol Med ; 22(3): 1507-1516, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29266713

RESUMO

The bioactive lipid sphingosine-1-phosphate (S1P) regulates smooth muscle (SM) contractility predominantly via three G protein-coupled receptors. The S1P1 receptor is associated with nitric oxide (NO)-mediated SM relaxation, while S1P2 & S1P3 receptors are linked to SM contraction via activation of the Rho-kinase pathway. This study is to determine testosterone (T) modulating the expression and functional activity of S1P receptors in corpus cavernosum (CC). Adult male Sprague-Dawley rats were randomly divided into three groups: sham-operated controls, surgical castration and T supplemented group. Serum S1P levels were detected by high-performance liquid chromatography. The expression of S1P1-3 receptors and sphingosine kinases was detected by real-time RT-PCR. In vitro organ bath contractility and in vivo intracavernous pressure (ICP) measurement were also performed. T deprivation significantly decreased ICP rise. Meanwhile, surgical castration induced a significant increase in serum S1P level and the expression of S1P2-3 receptors by twofold (P < 0.05) but a decrease in the expression of S1P1 receptor. Castration also augmented exogenous phenylephrine (PE), S1P, S1P1,3 receptor agonist FTY720-P contractility and S1P2-specific antagonist JTE013 relaxation effect. T supplemented could restore the aforementioned changes. We provide novel data that castration increased serum S1P concentration and up-regulated the expression of S1P2-3 receptors in CC. Consistently, agonizing S1P receptors induced CCSM contraction and antagonizing mediated relaxation were augmented. This provides the first clear evidence that S1P system dysregulation may contribute to hypogonadism-related erectile dysfunction (ED), and S1P receptors may be expected as a potential target for treating ED.


Assuntos
Lisofosfolipídeos/metabolismo , Ereção Peniana/efeitos dos fármacos , Isoformas de Proteínas/genética , Receptores de Lisoesfingolipídeo/genética , Esfingosina/análogos & derivados , Testosterona/farmacologia , Animais , Regulação da Expressão Gênica , Masculino , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Orquiectomia , Técnicas de Cultura de Órgãos , Tamanho do Órgão , Organofosfatos/farmacologia , Ereção Peniana/fisiologia , Pênis/efeitos dos fármacos , Pênis/metabolismo , Fenilefrina/farmacologia , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Próstata/efeitos dos fármacos , Próstata/metabolismo , Isoformas de Proteínas/agonistas , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/metabolismo , Pirazóis/farmacologia , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de Lisoesfingolipídeo/agonistas , Receptores de Lisoesfingolipídeo/antagonistas & inibidores , Receptores de Lisoesfingolipídeo/metabolismo , Transdução de Sinais , Esfingosina/metabolismo , Esfingosina/farmacologia , Receptores de Esfingosina-1-Fosfato , Testículo/cirurgia , Testosterona/metabolismo
11.
J Cell Mol Med ; 22(1): 576-588, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28990332

RESUMO

Benign prostatic hyperplasia (BPH) is mainly caused by increased prostatic smooth muscle (SM) tone and volume. SM myosin (SMM) and non-muscle myosin (NMM) play important roles in mediating SM tone and cell proliferation, but these molecules have been less studied in the prostate. Rat prostate and cultured primary human prostate SM and epithelial cells were utilized. In vitro organ bath studies were performed to explore contractility of rat prostate. SMM isoforms, including SM myosin heavy chain (MHC) isoforms (SM1/2 and SM-A/B) and myosin light chain 17 isoforms (LC17a/b ), and isoform ratios were determined via competitive RT-PCR. SM MHC and NM MHC isoforms (NMMHC-A, NMMHC-B and NMMHC-C) were further analysed via Western blotting and immunofluorescence microscopy. Prostatic SM generated significant force induced by phenylephrine with an intermediate tonicity between phasic bladder and tonic aorta type contractility. Correlating with this kind of intermediate tonicity, rat prostate mainly expressed LC17a and SM1 but with relatively equal expression of SM-A/SM-B at the mRNA level. Meanwhile, isoforms of NMMHC-A, B, C were also abundantly present in rat prostate with SMM present only in the stroma, while NMMHC-A, B, C were present both in the stroma and endothelial. Additionally, the SMM selective inhibitor blebbistatin could potently relax phenylephrine pre-contracted prostate SM. In conclusion, our novel data demonstrated the expression and functional activities of SMM and NMM isoforms in the rat prostate. It is suggested that the isoforms of SMM and NMM could play important roles in BPH development and bladder outlet obstruction.


Assuntos
Miosina Tipo II/metabolismo , Próstata/metabolismo , Miosinas de Músculo Liso/metabolismo , Sequência de Aminoácidos , Animais , Carbacol/farmacologia , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Masculino , Contração Muscular/efeitos dos fármacos , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Miosina Tipo II/química , Nitroprussiato/farmacologia , Especificidade de Órgãos , Fenilefrina/farmacologia , Cloreto de Potássio/farmacologia , Próstata/citologia , Isoformas de Proteínas/química , Isoformas de Proteínas/metabolismo , Ratos Sprague-Dawley , Miosinas de Músculo Liso/química
12.
Prostate ; 78(16): 1283-1298, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30073674

RESUMO

BACKGROUND: Benign prostatic hyperplasia (BPH) is mainly caused by increased prostatic smooth muscle (SM) tone and prostatic volume. At the molecular level, SM myosin II (SMM II) and non-muscle myosin II (NMM II) mediate SM tone and cell proliferation while testosterone (T) plays a permissive role in the development of BPH. AIMS: The novel objective of this study was to elucidate the effects of T on the proliferation and apoptosis of rat prostatic cells and SM contractility as well as related regulatory signaling pathways. MATERIALS AND METHODS: Briefly, 36 male rats were divided into three groups (sham-operated, surgically castrated, and castrated with T supplementation). In vitro organ bath studies, competitive RT-PCR, Western-blotting analysis, Masson's trichrome staining, and immunofluorescence staining were performed. RESULTS: Our data showed that castration dramatically increased prostatic SM contractility and SM MHC immunostaining revealed a relatively increased SM cell numbers in the stroma. T deprivation altered prostate SMM II isoform composition with upregulation of SM-B and SM2 but downregulation of LC17a, favoring a faster more phasic-type contraction. Moreover, protein expressions of MLCK, p-MLCP, RhoB, ROCK1, and ROCK2 increased in castrated rats. Meanwhile NMM II heavy chain isoforms A, B, and C (NMMHC-A, B, and C isoforms) were altered by castration which may be linked to decreased cell proliferation and increased apoptosis. CONCLUSION: Our novel data demonstrated T regulates SMM II and NMM II and their functional activities in rat prostate and T ablation not only decreases prostate size (static component) but also changes the prostatic SM tone (dynamic component).


Assuntos
Músculo Liso/efeitos dos fármacos , Miosina Tipo II/metabolismo , Próstata/efeitos dos fármacos , Testosterona/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso/metabolismo , Próstata/metabolismo , Ratos , Ratos Sprague-Dawley
13.
Clin Sci (Lond) ; 132(20): 2189-2205, 2018 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-30279228

RESUMO

To investigate the effect of blebbistatin (BLEB, a selective myosin inhibitor) on regulating contractility and growth of prostate cells and to provide insight into possible mechanisms associated with these actions. BLEB was incubated with cell lines of BPH-1 and WPMY-1, and intraprostatically injected into rats. Cell growth was determined by flow cytometry, and in vitro organ bath studies were performed to explore muscle contractility. Smooth muscle (SM) myosin isoform (SM1/2, SM-A/B, and LC17a/b) expression was determined via competitive reverse transcriptase PCR. SM myosin heavy chain (MHC), non-muscle (NM) MHC isoforms (NMMHC-A and NMMHC-B), and proteins related to cell apoptosis were further analyzed via Western blotting. Masson's trichrome staining was applied to tissue sections. BLEB could dose-dependently trigger apoptosis and retard the growth of BPH-1 and WPMY-1. Consistent with in vitro effect, administration of BLEB to the prostate could decrease rat prostatic epithelial and SM cells via increased apoptosis. Western blotting confirmed the effects of BLEB on inducing apoptosis through a mechanism involving MLC20 dephosphorylation with down-regulation of Bcl-2 and up-regulation of BAX and cleaved caspase 3. Meanwhile, NMMHC-A and NMMHC-B, the downstream proteins of MLC20, were found significantly attenuated in BPH-1 and WPMY-1 cells, as well as rat prostate tissues. Additionally, BLEB decreased SM cell number and SM MHC expression, along with attenuated phenylephrine-induced contraction and altered prostate SMM isoform composition with up-regulation of SM-B and down-regulation of LC17a, favoring a faster contraction. Our novel data demonstrate BLEB regulated myosin expression and functional activity. The mechanism involved MLC20 dephosphorylation and altered SMM isoform composition.


Assuntos
Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Miosina Tipo II/metabolismo , Próstata/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Humanos , Técnicas In Vitro , Masculino , Músculo Liso/fisiologia , Miosina Tipo II/genética , Próstata/citologia , Próstata/fisiologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
14.
Med Sci Monit ; 24: 3113-3118, 2018 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-29752880

RESUMO

BACKGROUND The present study aimed to investigate the clinical relevance of fragile histidine triad protein (FHIT) in patients with bladder cancer (BC). MATERIAL AND METHODS Three independent BC microarray studies were collected and reanalyzed. The expression of FHIT was evaluated between BC samples and normal bladder tissues. The correlation between the expression of FHIT and clinicopathological features was analyzed using the chi-square test. Log-rank based survival analysis was conducted to detect the survival significance of FHIT in patients with BC. Gene set enrichment analysis (GSEA) was performed to identify the mechanisms. RESULTS FHIT was significantly downregulated in BC cells (p=0.0044). BC patients in the FHIT high expression group had better clinical characteristics (including invasiveness, tumor grade, disease progression, and T staging) than those in the FHIT low expression group (p<0.0001, p<0.0001, p=0.031, p<0.0001, and p=0.056, respectively). Patients in the FHIT high expression group had better cancer-specific survival (p<0.0001) and overall survival (p=0.0008) than those in the FHIT low expression. GSEA results indicated that BC samples in the FHIT low expression group were enriched in interferon alpha response, apoptosis, androgen response, interferon gamma response, heme metabolism, and transforming growth facto r(TGF) beta signaling. CONCLUSIONS FHIT predicts better clinical relevance for patients with BC, which may be a promising therapeutic target.


Assuntos
Hidrolases Anidrido Ácido/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Hidrolases Anidrido Ácido/genética , Neoplasias da Mama/genética , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Análise de Sobrevida , Neoplasias da Bexiga Urinária/genética
15.
BMC Anesthesiol ; 18(1): 93, 2018 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-30041610

RESUMO

BACKGROUND: Current evidence regarding the efficacy of ethanol locks in preventing catheter-related bloodstream infection (CRBI) is inconclusive. METHODS: Electronic databases, including PubMed, Web of Science, Embase, and the Cochrane Library (until April 2018),were systematically searched for relevant studies. Two reviewers independently screened the retrieved records and identified RCTs that met the inclusion criteria. Relevant data were extracted for pooled analyses using Review Manager 5.3 software. Subgroup analysis was performed according to the study quality, duration of the ethanol lock, disease type and CRBI definition. Eggs' method was applied to detect publication bias. Sensitivity analysis was conducted to check the stability of the meta-analysis results. RESULTS: Ten RCTs involving 2760 patients were included in the analysis. The overall pooled result indicated that ethanol locks significantly reduced the incidence of CRBI (RR 0.66, 95% CI 0.51-0.86). Subgroup analysis suggested that an ethanol lock significantly decreased the incidence of CRBI in patients with hematological diseases (RR 0.50, 95% CI 0.31-0.80). An ethanol lock significantly reduced the incidence of CRBI in a2-hour ethanol lock group (RR 0.49, 95% CI 0.33-0.73). The meta-analysis showed that an ethanol lock significantly reduced the incidence of CRBI according to analysis of high-(RR 0.66, 95% CI 0.47-0.94) or low-(RR 0.66, 95% CI 0.46-0.95) quality studies. Meta-analysis of studies with a strict CRBI definition showed that an ethanol lock can significantly prevent CRBI (RR 0.61, 95% CI 0.42-0.89). The results of sensitivity analysis suggested that the pooled result was stable. Meta-analysis of adverse events showed that an ethanol lock did not increase the incidence of thrombosis (RR 1.05, 95% CI 0.51-2.18) or mortality (RR 0.99, 95% CI 0.90-1.08) but did result in increased nausea (RR 1.54, 95% CI 1.01-2.35), dizziness (RR 4.21, 95% CI 2.40-7.39),elevated blushing rates (RR 3.27, 95% CI 2.05-5.22) and altered taste rates (RR 2.61, 95% CI 1.93-3.54). CONCLUSIONS: An ethanol lock may play a role in the prevention of CRBI, especially in immunocompromised patients with hematological diseases.


Assuntos
Catéteres/efeitos adversos , Etanol/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Esterilização/métodos , Anti-Infecciosos Locais/uso terapêutico , Humanos
16.
J Neurosci Res ; 93(6): 922-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25597854

RESUMO

This study investigates the role of oxidative stress in surgical cavernous nerve (CN) injury in a rat model. Eighty-four male Sprague-Dawley rats were randomly divided into three groups: group 1, sham-operated rats; group 2, bilateral CN-crushed rats; and group 3, bilateral CN-transection-and-sutured-immediately rats. Oxidative stress was evaluated by malondialdehyde levels, super oxide dismutase (SOD) activities, and glutathione peroxidase (GPX) activities in serum. Erectile function was assessed by CN electrostimulation at 3 months with mean maximal intracavernous pressure (ICP) and maximal ICP per mean arterial pressure. Nerve injury was assessed by toluidine blue staining of CNs and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining of penile tissue. GPX protein expression and nitrotyrosine-3 (NT-3) levels in penile tissue were measured. Erectile function and the number of myelinated axons of CNs and NADPH-diaphorase-positive nerve fibers were statistically decreased between groups, from sham to crush to transection. For markers, both nerve-injury groups showed increased oxidative stress markers at early time points, with the transection group showing greater oxidative stress than the crushed group and values normalizing to sham levels by week 12. GPX expression and NT-3 levels in penile tissue were in concordance with the results of SOD and GPX. These results show that oxidative stress plays an important role in injured CNs, and different methods of CN injury can lead to different degrees of oxidative stress in a rat model.


Assuntos
Modelos Animais de Doenças , Estresse Oxidativo/fisiologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Análise de Variância , Animais , Glutationa Peroxidase/metabolismo , Masculino , Malondialdeído/metabolismo , NADPH Desidrogenase/metabolismo , Ereção Peniana , Traumatismos dos Nervos Periféricos/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
18.
Mol Biol Rep ; 41(10): 6713-7, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24990700

RESUMO

The association between vitamin D receptor (VDR) gene polymorphisms and risk of benign prostatic hyperplasia (BPH) has been investigated in numerous publications, but published results remain inconclusive. Hence, we conducted this meta-analysis to derive a more precise conclusion. Four polymorphisms (Taq-I, Bsm-I, Apa-I, and Fok-I) of the VDR gene with risk of BPH from six case-control studies and one cohort study involving 2,248 individuals were identified from PubMed and China National Knowledge Internet databases up to November 20, 2013 (updated on March 5, 2014). After data extraction, the meta-analysis was performed using Comprehensive Meta-Analysis software. All four VDR polymorphisms were not associated with the risk of BPH [Taq-I: OR 0.61, 95 % CI (0.38-1.24) for tt vs. TT; Bsm-I: OR 1.27, 95 % CI (0.96-1.69) for bb vs. BB; Apa-I: OR 1.26, 95 % CI (0.64-2.46) for aa vs. AA; Fok-I: OR 0.95, 95 % CI (0.60-1.50) for ff vs. FF]. Subgroup analysis according to ethnicity for Taq-I polymorphism also showed that the polymorphism was not associated with risk of BPH for either Caucasians [OR 0.74, 95 % CI (0.31-1.78) for tt vs. TT] or Asians [OR 0.35, 95 % CI (0.11-1.11) for tt vs. TT]. However, results of this meta-analysis should be treated with caution because this meta-analysis has several limitations. We propose to conduct a high-quality study with large sample size to further identify the association between VDR gene polymorphisms and BPH susceptibility.


Assuntos
Polimorfismo Genético , Hiperplasia Prostática/genética , Receptores de Calcitriol/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Masculino , Razão de Chances , Polimorfismo de Fragmento de Restrição , Viés de Publicação , Risco
19.
Mol Biol Rep ; 41(6): 3621-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24510389

RESUMO

The association between xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism and bladder cancer (BC) susceptibility was investigated by two meta-analyses, however, their results were contrary. We conjecture the reason might be the sample size, thus we performed this updated and cumulative meta-analysis using the Comprehensive Meta-Analysis software. We searched PubMed up to August 25th, 2013 and yielded 20 published articles with 21 case-control trails including 6,836 BC patients and 8,251 controls. The meta-analysis results showed that XPD Lys751Gln polymorphism was borderline significantly associated with BC susceptibility for overall population [Gln vs. Lys: OR 1.07, 95% CI 1.01-1.12, P = 0.01; Gln/Gln vs. Lys/Lys: OR 1.15, 95% CI 1.03-1.29, P = 0.01; Gln/Gln vs. (Lys/Gln + Lys/Lys): OR 1.13, 95% CI 1.02-1.26, P = 0.02]. The cumulative meta-analysis according to the publication year showed the CI became increasingly narrower and tended to have statistical significance for the studies incessantly accumulated. In the subgroup analysis according to ethnicity, there was a significant association in Asian population and no association in Caucasian population. There was no publication bias detected. However, due to the limitations and cumulative analysis result of this meta-analysis, more well-designed and larger studies with risk factors adjusted are suggested to be performed to obtain a conclusive result on this topic.


Assuntos
Predisposição Genética para Doença , Neoplasias da Bexiga Urinária/genética , Proteína Grupo D do Xeroderma Pigmentoso/genética , Estudos de Casos e Controles , Suscetibilidade a Doenças , Estudos de Associação Genética , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/patologia , População Branca/genética
20.
Urology ; 187: 1-5, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38373576

RESUMO

OBJECTIVE: To evaluate the clinical efficacy of a novel negative pressure ureteroscopic lithotripsy (NP-URL) compared to standard ureteroscopic lithotripsy (S-URL) for treating ureteral stones. METHODS: A total of 284 patients diagnosed with ureteral stones and who underwent ureteroscopic lithotripsy between December 2020 and May 2022 at our hospital were included in the study. Among them, 146 cases underwent NP-URL and 138 cases underwent S-URL. The negative pressure device used in NP-URL consists of a 5F ureteric catheter and a tee joint. We evaluated the operative duration, stone-free rate, incidence of postoperative complications, stone retropulsion rate, and adjunct procedure rate between the two groups. RESULTS: The mean operative duration was significantly shorter in the NP-URL group compared to the S-URL group (30.17 ± 5.84 minutes vs 34.84 ± 6.62 minutes; P<.05). Additionally, the NP-URL group had a lower incidence of postoperative fever (1.4% vs 8.7%; P<.05), reduced stone retropulsion rate (3.4% vs 11.6%; P<.05), and a statistically lower rate of adjunct procedures (5.5% vs 14.5%, P<.05). The NP-URL group also demonstrated a higher primary stone-free rate (91.8% vs 81.9%; P<.05). However, there was no significant difference in the final stone-free rate between the NP-URL and S-URL groups (P>.05). CONCLUSION: NP-URL potentially reduces operative duration, significantly decreases the incidence of postoperative complications, and achieves better primary stone-free rates compared to S-URL.


Assuntos
Litotripsia , Duração da Cirurgia , Cálculos Ureterais , Ureteroscopia , Humanos , Cálculos Ureterais/terapia , Cálculos Ureterais/cirurgia , Ureteroscopia/métodos , Masculino , Feminino , Litotripsia/métodos , Litotripsia/instrumentação , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
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