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1.
Artigo em Inglês | MEDLINE | ID: mdl-38976496

RESUMO

Objectives: The primary objective of this study was to evaluate the safety and efficacy of the enhanced recovery after surgery (ERAS) protocol in cholecystectomy, comparing it with standard care. Methods: A comprehensive literature search was conducted in December 2023, using globally recognized databases such as PubMed, Embase, and the Cochrane Library. Various parameters were compared using Review Manager software. This study was duly registered with PROSPERO (CRD420223). Results: The meta-analysis included nine studies, encompassing a total of 1920 patients. The findings revealed that the ERAS group, in comparison to traditional care, experienced shorter hospitalization periods (weighted mean difference [WMD]: -1.23, 95% confidence interval [CI]: -1.98 to -0.47; P = .001), lower visual analog scale at 24 hours (WMD: -1.10, 95% CI: -1.30 to -0.90; P < .00001), faster time to first flatus (WMD: -4.48, 95% CI: -4.50 to -4.46; P < .00001), and reduced operative times (WMD: -9.94, 95% CI: -17.88 to -0.96; P = .03). In addition, there was a notable decrease in instances of postoperative nausea and vomiting (odds ratio [OR]: 0.46, 95% CI: 0.28 to 0.74; P = .002). No significant differences were observed in readmission rates, blood loss, postoperative complications, or bile leakage between the two care methods. Conclusions: This study substantiates that the ERAS protocol is an advantageous perioperative care strategy for patients undergoing cholecystectomy. It significantly outperforms traditional care in reducing the length of stay, decreasing the likelihood of postoperative nausea/vomiting, alleviating postoperative pain, and accelerating the time to the first flatus. These findings highlight the effectiveness of ERAS in enhancing patient outcomes in cholecystectomy.

2.
Medicine (Baltimore) ; 103(18): e37524, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701298

RESUMO

PURPOSE: There is still controversy regarding the safety and efficacy of cold knife visual internal urethrotomy and laser incisions for the treatment of urethral stricture. This study aims to compare the results of postoperative long-term and short-term maximum urinary flow rates (Qmax), surgical time, postoperative complications, and 1-year recurrence rates between the cold knife and laser surgery. METHODS: We searched databases including Embase, PubMed, Cochrane, and Clinical Trials.gov to identify relevant literature published in English up to September 2023. We used Stata to compare various parameters. This study is registered in PROSPERO (CRD42023471634). Nine comparative experiments were conducted, involving a total of 659 participants. RESULTS: The laser group showed significantly better results compared to the cold knife group in terms of postoperative 12-month maximum urinary flow rate (mean differences [MD] 2.131; 95% [1.015, 3.249], P < .0001), postoperative bleeding (RR 0.277, 95% [0.079, 0.977], P = .046), and 1-year recurrence rate (RR 0.667, 95% [0.456, 0.976], P = .037). However, there were no significant differences in postoperative 6-month and 3-month Qmax, surgical time, urethral leakage complications, overall complications, and Visual Analog Scale (VAS) scores. CONCLUSION: The current study results suggest that laser urethral incision has greater advantages in the long-term (12 months), 1-year recurrence rate, and bleeding complications compared to cold knife urethral incision in the treatment of urethral stricture (<2 cm). Therefore, laser urethral incision may be a better choice for patients with urethral stricture.


Assuntos
Terapia a Laser , Uretra , Estreitamento Uretral , Estreitamento Uretral/cirurgia , Humanos , Terapia a Laser/métodos , Terapia a Laser/efeitos adversos , Uretra/cirurgia , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Masculino , Recidiva , Duração da Cirurgia , Procedimentos Cirúrgicos Urológicos Masculinos/métodos
3.
Eur J Med Res ; 29(1): 271, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711117

RESUMO

Dexmedetomidine (Dex) has been used in surgery to improve patients' postoperative cognitive function. However, the role of Dex in stress-induced anxiety-like behaviors and cognitive impairment is still unclear. In this study, we tested the role of Dex in anxiety-like behavior and cognitive impairment induced by acute restrictive stress and analyzed the alterations of the intestinal flora to explore the possible mechanism. Behavioral and cognitive tests, including open field test, elevated plus-maze test, novel object recognition test, and Barnes maze test, were performed. Intestinal gut Microbe 16S rRNA sequencing was analyzed. We found that intraperitoneal injection of Dex significantly improved acute restrictive stress-induced anxiety-like behavior, recognition, and memory impairment. After habituation in the environment, mice (male, 8 weeks, 18-23 g) were randomly divided into a control group (control, N = 10), dexmedetomidine group (Dex, N = 10), AS with normal saline group (AS + NS, N = 10) and AS with dexmedetomidine group (AS + Dex, N = 10). By the analysis of intestinal flora, we found that acute stress caused intestinal flora disorder in mice. Dex intervention changed the composition of the intestinal flora of acute stress mice, stabilized the ecology of the intestinal flora, and significantly increased the levels of Blautia (A genus of anaerobic bacteria) and Coprobacillus. These findings suggest that Dex attenuates acute stress-impaired learning and memory in mice by maintaining the homeostasis of intestinal flora.


Assuntos
Dexmedetomidina , Microbioma Gastrointestinal , Homeostase , Estresse Psicológico , Animais , Dexmedetomidina/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Masculino , Homeostase/efeitos dos fármacos , Estresse Psicológico/complicações , Estresse Psicológico/tratamento farmacológico , Memória/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Aprendizagem em Labirinto/efeitos dos fármacos , Ansiedade/tratamento farmacológico
4.
J Hum Genet ; 69(8): 401-409, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38769386

RESUMO

Human infertility affects 10-15% of couples. Asthenozoospermia accounts for 18% of men with infertility and is a common male infertility phenotype. The nexin-dynein regulatory complex (N-DRC) is a large protein complex in the sperm flagellum that connects adjacent doublets of microtubules. Defects in the N-DRC can disrupt cilia/flagellum movement, resulting in primary ciliary dyskinesia and male infertility. Using whole-exome sequencing, we identified a pathological homozygous variant of the dynein regulatory complex subunit 3 (DRC3) gene, which expresses leucine-rich repeat-containing protein 48, a component of the N-DRC, in a patient with asthenozoospermia. The variant ENST00000313838.12: c.644dup (p. Glu216GlyfsTer36) causes premature translational arrest of DRC3, resulting in a dysfunctional DRC3 protein. The patient's semen count, color, and pH were normal according to the reference values of the World Health Organization guidelines; however, sperm motility and progressive motility were reduced. DRC3 protein was not detected in the patient's sperm and the ultrastructure of the patient's sperm flagella was destroyed. More importantly, the DRC3 variant reduced its interaction with other components of the N-DRC, including dynein regulatory complex subunits 1, 2, 4, 5, 7, and 8. Our data not only revealed the essential biological functions of DRC3 in sperm flagellum movement and structure but also provided a new basis for the clinical genetic diagnosis of male infertility.


Assuntos
Astenozoospermia , Homozigoto , Infertilidade Masculina , Humanos , Masculino , Astenozoospermia/genética , Astenozoospermia/patologia , Infertilidade Masculina/genética , Infertilidade Masculina/patologia , Motilidade dos Espermatozoides/genética , Adulto , Espermatozoides/metabolismo , Espermatozoides/patologia , Sequenciamento do Exoma , Cauda do Espermatozoide/metabolismo , Cauda do Espermatozoide/patologia , Dineínas/genética , Dineínas/metabolismo , Mutação
5.
Phytomedicine ; 129: 155598, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38608596

RESUMO

BACKGROUND: Over years, there has been a widespread quest for effective dietary patterns and natural extracts to mitigate prostate cancer risk. However, despite numerous experimental studies conducted on various natural extracts, the evidence substantiating their efficacy remains largely insufficient. This dearth of compelling evidence presents a significant challenge in advocating for their widespread use as preventive measures against prostate cancer. OBJECTIVE: Our study endeavors to undertake a network meta-analysis to evaluate the influence of natural extracts on prostate cancer. METHODS: Researchers systematically searched through Embase, PubMed, Cochrane Library, and Web of Science databases until December 2023. The main focus was on assessing primary outcomes comprising prostate-specific antigen (PSA), insulin-like growth factor-binding protein-3 (IGFBP-3), insulin-like growth factor-1 (IGF-1). We conducted data analysis utilizing StataMP 15.0 software. Therapeutic effects were ranked based on the probability values derived from Surface Under the Cumulative Ranking curve (SUCRA). Additionally, cluster analysis was employed to assess the impacts of natural extracts on three distinct outcomes. RESULTS: Following screening procedures, the 28 eligible studies were incorporated, the selected studies encompassed 1,566 prostate cancer patients and evaluated 16 different natural extract treatments. Specifically, 24 trials included PSA indicators, 10 included IGF-1 indicators, and 8 included IGFBP-3 indicators. The findings revealed that, based on the SUCRA values, the combined therapy of silybin with selenium (74%) appears to be the most effective approach for reducing serum PSA levels. Simultaneously, silybin alone (84.6%) stands out as the most promising option for decreasing serum IGF-1 levels. Lastly, concerning IGFBP-3, silybin alone (67.7%) emerges as the optimal choice. Twelve studies provided comprehensive information on adverse drug reactions/events (ADR/ADE), whereas five articles did not report any significant ADR/ADE. CONCLUSION: The NMA suggests that, compared to placebo, utilizing silybin either alone or in combination with selenium has been shown to enhance therapeutic effects, offering potential benefits to patients with prostate cancer. This study can offer valuable insights for prostate patients considering natural extract treatments. Further evidence is required to confirm the safety profile of these treatments.


Assuntos
Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Fator de Crescimento Insulin-Like I , Metanálise em Rede , Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Neoplasias da Próstata/tratamento farmacológico , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Antígeno Prostático Específico/sangue , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Produtos Biológicos/farmacologia
6.
Kidney Blood Press Res ; 49(1): 211-217, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38447536

RESUMO

INTRODUCTION: Cyanotic nephropathy, a rare disease characterized by proteinuria, decreased estimated glomerular filtration rate, thrombocytopenia, polycythemia, and hyperuricemia, may occasionally be secondary to cyanotic congenital heart disease (CHD). There are currently no detailed diagnostic criteria or treatments for cyanotic nephropathy, owing to its extremely low incidence. Eisenmenger syndrome (ES) was initially defined by Paul Wood in pathophysiologic terms as "pulmonary hypertension (PH) at the systemic level, caused by a high pulmonary vascular resistance, with a reversed or bidirectional shunt at the aorto-pulmonary, ventricular, or atrial level." It typically develops in the presence of large, unrepaired atrial or ventricular septal defects, arterial shunts, or complex forms of CHD and is the most severe hemodynamic phenotype of pulmonary arterial hypertension associated with CHD. This study aimed to outline the case of an ES patient who developed cyanotic nephropathy and successfully achieved clinical remission through primary disease treatment and symptomatic management. Overall, this case expands our understanding of cyanotic nephropathy and lays a theoretical reference for the treatment of ES. CASE PRESENTATION: A 33-year-old Chinese female attended the outpatient department with abnormal urine test results over the past two and a half years. Following a comprehensive medical history collection, she underwent the necessary tests. Cardiac color ultrasound displayed a significant widening of the pulmonary artery and PH (severe), as well as mild tricuspid regurgitation and patent ductus arteriosus. The results of the kidney biopsy, combined with clinical findings, suggested a high risk of polycythemia-related kidney disease. She was eventually diagnosed with cyanotic nephropathy and ES. Her symptoms were relieved following symptomatic treatment, such as the administration of ambrisentan, febuxostat, and home oxygen therapy. Her follow-up visit at 6 months demonstrated improvements in hyperuricemia and a significant increase in physical strength. CONCLUSION: Cyanotic nephropathy is a rare condition in adults. Kidney biopsy remains the gold standard of diagnosis for various nephropathies. Active treatment of CHD and alleviating hypoxia may be pivotal for the treatment of cyanotic nephropathy.


Assuntos
Complexo de Eisenmenger , Humanos , Feminino , Adulto , Complexo de Eisenmenger/complicações , Complexo de Eisenmenger/terapia , Nefropatias/etiologia , Cianose/etiologia , Policitemia/complicações , Policitemia/terapia
7.
Eur J Clin Microbiol Infect Dis ; 43(6): 1061-1072, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38536523

RESUMO

INTENTION: Immunosuppressive therapy is the major treatment approach for patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Due to impaired cellular immunological function and the use of glucocorticoids and immunosuppressants, AAV patients are predisposed to opportunistic infections, including tuberculosis (TB). This retrospective study aims to analyze the clinical characteristics of patients with AAV and TB and explore suitable glucocorticoid regimens for them. So as to provide a basis for future clinical guidelines and have important value for guiding clinical treatment. METHODS: This study retrospectively reviewed 58 AAV patients (18-80 years old) with TB admitted to Changsha Central Hospital Affiliated with the University of South China from 2016.1 to 2023.4 Patients were divided into standard-dose and reduced-dose glucocorticoid groups before retrospectively analyzing their medical records. RESULTS: A total of 58 AAV patients with TB were enrolled, with 15 dying throughout the monitoring period. Through analysis data, compared with the standard-dose group, the reduced group had less proteinuria and hematuria. In survival analysis, the reduced-dose glucocorticoid group had lower mortality than the standard-dose group (P = 0.03); however, no significant difference was noted in the use of immunoglobulin (P = 0.39), tuberculosis activity (P = 0.64), and age stratification (P = 0.40). The BVAS score before treatment and 6 months post-treatment suggest that the two regimens cause the same risk of ESKD (P > 0.05). CONCLUSION: In conclusion, the reduced glucocorticoid dose group can achieve the same curative effect as the standard dose group and has less damage to the kidney in hematuria and proteinuria. Therefore, the reduced glucocorticoid dose treatment regimen may be more suitable for AAV patients with TB.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Glucocorticoides , Tuberculose , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Masculino , Feminino , Idoso , Adulto , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Adulto Jovem , Idoso de 80 Anos ou mais , Adolescente , Tuberculose/tratamento farmacológico , Tuberculose/complicações , China , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico
8.
BMC Public Health ; 24(1): 831, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493080

RESUMO

BACKGROUND: The Guangxi government initiated two rounds of the Guangxi AIDS Conquering Project (GACP) in 2010 (Phase I) and 2015 (Phase II) to control human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemics. However, the effectiveness of GACP in HIV prevention and treatment has rarely been reported. This study aimed to assess the effectiveness of the GACP implemented in Guangxi, China and provide data for strategy and praxis improvements to achieve Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95 targets. METHODS: We used spatial approaches to trace the spatiotemporal distribution properties, epidemic trends, and correlation between macroscopic factors and HIV incidence using data from the Chinese HIV/AIDS case reporting system to explore the effects of the GACP. RESULTS: During the GACP era, the HIV epidemic stabilized in urban centers, showing a downward trend in the Hengzhou and Binyang Counties in the eastern region, whereas it continued to increase in rural areas of the northwest region, such as the Long'an, Mashan, Shanglin, and Wuming Districts. The linear directional mean (LDM) of HIV infection reported cases displayed a southeast-northwest direction, with an LDM value of 12.52°. Compared with that in Phase I, Hengzhou withdrew from the high-high clustering area, and the west-north suburban counties pulled out the low-low clustering area during Phase II. Significant HIV clusters were identified in the eastern region during Phase I, whereas these clusters emerged in the northwestern areas during Phase II. Regarding HIV, socioeconomic status, population mobility, and medical care levels were the key social drivers of heterogeneous spatial distribution. CONCLUSIONS: The GACP assisted in effectively managing the HIV epidemic in urban and eastern areas of Nanning City. However, prevention and control efforts in rural regions, particularly those located in the northwest, may not have yielded comparable outcomes. To address this disparity, allocating additional resources and implementing tailored intervention measures for these rural areas are imperative.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Humanos , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Síndrome da Imunodeficiência Adquirida/epidemiologia , HIV , Prevalência , China/epidemiologia
9.
Mol Cell ; 84(3): 570-583.e7, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38215752

RESUMO

Adhesion G protein-coupled receptors (aGPCRs) are evolutionarily ancient receptors involved in a variety of physiological and pathophysiological processes. Modulators of aGPCR, particularly antagonists, hold therapeutic promise for diseases like cancer and immune and neurological disorders. Hindered by the inactive state structural information, our understanding of antagonist development and aGPCR activation faces challenges. Here, we report the cryo-electron microscopy structures of human CD97, a prototypical aGPCR that plays crucial roles in immune system, in its inactive apo and G13-bound fully active states. Compared with other family GPCRs, CD97 adopts a compact inactive conformation with a constrained ligand pocket. Activation induces significant conformational changes for both extracellular and intracellular sides, creating larger cavities for Stachel sequence binding and G13 engagement. Integrated with functional and metadynamics analyses, our study provides significant mechanistic insights into the activation and signaling of aGPCRs, paving the way for future drug discovery efforts.


Assuntos
Antígenos CD , Receptores Acoplados a Proteínas G , Transdução de Sinais , Humanos , Adesão Celular , Microscopia Crioeletrônica , Complexo Glicoproteico GPIb-IX de Plaquetas , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismo , Antígenos CD/química , Antígenos CD/metabolismo
10.
PeerJ ; 11: e16060, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37790613

RESUMO

Objectives: Liver fibrosis is a key stage in the progression of various chronic liver diseases to cirrhosis and liver cancer, but at present, there is no effective treatment. This study investigated the therapeutic effect of the new antifibrotic drug fluorofenidone (AKF-PD) on liver fibrosis and its related mechanism, providing implications for liver cancer. Materials and Methods: The effects of AKF-PD on hepatic stellate cell (HSC) autophagy and extracellular matrix (ECM) expression were assessed in a carbon tetrachloride (CCl4)-induced rat liver fibrosis model. In vitro, HSC-T6 cells were transfected with Smad2 and Smad3 overexpression plasmids and treated with AKF-PD. The viability and number of autophagosomes in HSC-T6 cells were examined. The protein expression levels of Beclin-1, LC3 and P62 were examined by Western blotting. The Cancer Genome Atlas (TCGA) database was used for comprehensively analyzing the prognostic values of SMAD2 and SMAD3 in liver cancer. The correlation between SMAD2, SMAD3, and autophagy-related scores in liver cancer was explored. The drug prediction of autophagy-related scores in liver cancer was explored. Results: AKF-PD attenuated liver injury and ECM deposition in the CCl4-induced liver fibrosis model. In vitro, the viability and number of autophagosomes in HSCs were reduced significantly by AKF-PD treatment. Meanwhile, the protein expression of FN, α-SMA, collagen III, Beclin-1 and LC3 was increased, and P62 was reduced by the overexpression of Smad2 and Smad3; however, AKF-PD reversed these effects. SMAD2 and SMAD3 were hazardous factors in liver cancer. SMAD2 and SMAD3 correlated with autophagy-related scores in liver cancer. Autophagy-related scores could predict drug response in liver cancer. Conclusions: AKF-PD alleviates liver fibrosis by inhibiting HSC autophagy via the transforming growth factor (TGF)-ß1/Smadpathway. Our study provided some implications about how liver fibrosis was connected with liver cancer by SMAD2/SMAD3 and autophagy.


Assuntos
Células Estreladas do Fígado , Neoplasias Hepáticas , Ratos , Animais , Fator de Crescimento Transformador beta1/genética , Proteína Beclina-1/metabolismo , Transdução de Sinais , Cirrose Hepática/tratamento farmacológico , Fibrose , Autofagia , Neoplasias Hepáticas/tratamento farmacológico
11.
Front Oncol ; 13: 1161544, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37091146

RESUMO

Background: The nerve-sparing (NS) effect of robot-assisted radical prostatectomy (RARP) on patients with a high-risk prostate cancer remains unclear. The objective of this study was to compare the urinary continence, erectile function and oncology outcomes of the nerve-sparing and non-nerve-sparing (NNS) group during RARP surgeries. Methods: We systematically searched databases including PubMed, Embase, Cochrane Library and Web of Science to identify relevant studies published in English up to December 2022. Newcastle-Ottawa Scale (NOS) was used as a quality evaluation tool to evaluate the quality of the literature parameters involved, including urinary continence, erectile function and oncologic outcomes, which were compared using the Stata 15.1 software (StataSE, USA). Results: A total of 8 cohort studies involving 2499 patients were included. A meta-analysis of results showed that the NS group was beneficial to the recovery of urinary continence (RR 0.46, 95%CI 0.22, 0.96; p=0.045<0.05) and erectile function (RR 0.32, 95%CI 0.16, 0.63; p=0.001<0.05) 12 months after surgeries, which showed a better oncological outcome (RR 1.31, 95%CI 1.01, 1.69; p=0.01<0.05). Conclusions: The current study results indicate that intraoperative NS during RARP is beneficial to long-term postoperative functional recovery and tumor prognosis of patients with high-risk prostate cancers. Due to interstudy interferences, the results should be interpreted with caution. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022384647.

12.
J Robot Surg ; 17(4): 1271-1285, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36929480

RESUMO

The influence of robot-assisted radical prostatectomy (RARP) on patients who have previously undergone transurethral resection of the prostate (TURP) versus TURP-naive patients is still debatable. The present study aimed to compare perioperative, functional, and oncologic outcomes of RARP between TURP and Non-TURP groups. We systematically searched the databases such as Science, PubMed, Embase, Web of Science, and the Cochrane Library database to identify relevant studies published in English up to August 2022. Review Manager was used to compare various parameters. The study was registered with PROSPERO (CRD42022378126). Eight comparative trials with a total of 4186 participants were conducted. The TURP group had a longer operative time (WMD 22.22 min, 95% CI 8.48, 35.95; p = 0.002), a longer catheterization time (WMD 1.32 day, 95% CI 0.37, 2.26; p = 0.006), a higher estimated blood loss (WMD 23.86 mL, 95% CI 2.81, 44.90; p = 0.03), and higher bladder neck reconstruction rate (OR 8.02, 95% CI 3.07, 20.93; p < 0.0001). Moreover, the positive surgical margin (PSM) was higher in the TURP group (OR 1.49, 95% CI 1.12, 1.98 p = 0.007). However, there was no difference between the two groups regarding the length of hospital stay, transfusion rates, nerve-sparing status, complication rates, long-term continence, potency rates and biochemical recurrence (BCR). Performing RARP on patients who have previously undergone TURP is a safe procedure. Furthermore, the current findings demonstrated that the TURP group had comparable oncologic and long-term functional outcomes to the Non-TURP group.


Assuntos
Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Robótica , Ressecção Transuretral da Próstata , Masculino , Humanos , Ressecção Transuretral da Próstata/efeitos adversos , Ressecção Transuretral da Próstata/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias da Próstata/cirurgia , Resultado do Tratamento , Prostatectomia/efeitos adversos , Prostatectomia/métodos
14.
Rapid Commun Mass Spectrom ; 36(12): e9302, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35344234

RESUMO

RATIONALE: Rankinidine belongs to the humantenine-type alkaloids isolated from Gelsemium. Currently, the mechanism behind the toxicity differences of rankinidine has not been explained. In this study, our purpose was to elucidate the major in vitro metabolic pathways of rankinidine and to compare the formation of metabolites of rankinidine in human (HLMs), rat (RLMs), goat (GLMs) and pig (PLMs) liver microsomes. METHODS: This is the first study to compare the in vitro metabolism of rankinidine with high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (LC/QTOF). The MS/MS data and LC/MS peak area acquired in positive ion mode were used to analyze metabolite structures and compare metabolism. RESULTS: We identified 11 metabolites (M1-M11) in total and found five main metabolic pathways, consisting of demethylation (M1), reduction (M2), oxidation at different positions (M3-M5), oxidation and reduction (M6-M10) and demethylation and oxidation (M11). The metabolism of rankinidine has qualitative and quantitative species-specific differences in vitro. In PLMs and GLMs, the main metabolic pathway of rankinidine was oxidation. Notably, among the four species, the oxidation ability of rankinidine was highest in pigs and goats, and the demethylation and reduction abilities of rankinidine were highest in humans and rats. CONCLUSIONS: The interspecific metabolic differences of rankinidine in HLMs, PLMs, GLMs and RLMs were compared and studied for the first time using LC/QTOF. These findings will certainly support future studies of rankinidine metabolism in vivo and will contribute to elucidating the cause of species-specific differences behind Gelsemium toxicity.


Assuntos
Alcaloides , Antineoplásicos , Gelsemium , Alcaloides/metabolismo , Animais , Cromatografia Líquida de Alta Pressão/métodos , Indóis , Microssomos Hepáticos/metabolismo , Ratos , Suínos , Espectrometria de Massas em Tandem/métodos
15.
Biosens Bioelectron ; 206: 114139, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35272213

RESUMO

Sensitive and accurate miRNAs assay is critical for early diagnosis of non-small-cell lung carcinomas (NSCLC). Herein, we demonstrate a photothermal and electrochemical dual-readout assay method for miRNA detection based on a novel biocatalysis-mediated MOF-to-prussian blue (PB) transformation (BMMPT) strategy and the catalytic hairpin assembly (CHA) amplification strategy. It is found that the Fe2+-based MOF (MOF-Fe2+) can act as the Fe2+ source to react with K3[Fe(CN)6], leading to the in-situ formation of prussian blue (PB) on MOF-Fe2+. Due the inherent near-infrared (NIR) photothermal conversion ability and electrochemical signal of PB, the resulting PB@MOF-Fe2+ is employed to arouse temperature readout or electrochemical signal. The presence of target miRNA-21 triggers the CHA reaction on magnetic beads (MBs), resulting the capture of numerous glucose oxidase (GOx) tags on MBs. The GOx tags then catalyze the generation of H2O2 using glucose as substrate. The H2O2 is used to inhibit the MOF-to-PB transformation process by oxidizing Fe2+ into Fe3+, leading to the decrease in temperature and electrochemical readout aroused by PB@MOF-Fe2+. By this means, a signal-off assay mode with dual readout is established for miRNA-21. Under the optimal conditions, using temperature readout or electrochemical readout, miRNA-21 can be detected at concentrations as low as 0.3 fM and 0.32 fM, respectively. Moreover, the developed method is successfully applied to evaluate the expression level of miRNA-21 in serum of NSCLC patients. This work not only provides a practical tool for NSCLC diagnosis but also presents the new features of MOF materials as signal transduction tags.


Assuntos
Técnicas Biossensoriais , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Biocatálise , Técnicas Biossensoriais/métodos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Técnicas Eletroquímicas , Ferrocianetos , Humanos , Peróxido de Hidrogênio , Limite de Detecção , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , MicroRNAs/genética
16.
Genes Genomics ; 43(7): 807-814, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33893626

RESUMO

BACKGROUND: PTX is widely used in cancer treatments. OBJECTIVE: In this paper, we explored the role and potential molecular mechanism of propofol in regulating PTX sensitivity in PC cells. METHODS: Prostatic cancer cell line PC3 was treated using different concentrations of PTX (10 nM, 50 nM), propofol (150 µM, 300 µM) or transfected with overexpressed HOTAIR plasmid. HOTAIR expression was analyzed by RT-qPCR. Apoptosis of PC3 cells was observed by flow cytometry method while cell viability was evaluated by CCK-8. Moreover, apoptosis-related genes, Bcl-2 and Bax were detected by Western blot methods. E-cadherin, N-cadherin and Vimentin protein concentrations were monitored by ELISA. RESULTS: PTX significantly increased apoptosis of PC3 cells and reduced cell viability in a dose-dependent manner. Moreover, Protein expression of Bcl-2 was obviously inhibited while Bax protein expression level was provoked. Furthermore, E-cadherin protein concentration increased while N-cadherin and Vimentin decreased due to increasing PTX treatments. HOTAIR expression dropped due to PTX treatment while overexpression of HOTAIR induced cell viability, EMT and deterred apoptosis. Propofol ignited the PTX function while upregulation of HOTAIR partially reversed this. CONCLUSION: Propofol enhanced paclitaxel sensitivity in prostatic cancer cells through modulation of HOTAIR in vitro.


Assuntos
Sinergismo Farmacológico , Paclitaxel/farmacologia , Propofol/farmacologia , Neoplasias da Próstata/tratamento farmacológico , RNA Longo não Codificante/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Masculino
17.
Pestic Biochem Physiol ; 160: 181-186, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31519253

RESUMO

Fertility control is considered as the second-generation pest rodent management strategy. Most previous studies have focused on the dosage-dependent effects of quinestrol and levonorgestrel compounds (EP-1) at a ratio of 1:2, but the ratio-dependent effects of EP-1 have not been fully investigated, especially in male rodents. To test the ratio-dependent antifertility effects of EP-1 with different ratios (1:2, 1:1, and 2:1) on male Swiss outbred strain of laboratory mice, forty male mice were randomly assigned into four groups (n = 10). Mice in the three treatment groups were provided one of the three EP-1 mixture compounds for 3 successive days via gavage at a dosage of 50 mg/kg(body weight), and then all mice were sacrificed 15 days after the gavage treatment. Reproductive organ weights, sperm density and motility, levels of testosterone (T), estradiol (E2), luteinizing hormone (LH), and follicle stimulating hormone (FSH) in serum and/or testis, and androgen receptor (AR), estrogen receptor α (ERα), estrogen receptor ß (ERß), luteinizing hormone receptor (LHR), and aromatase in testis were determined. Each of the ratios of quinestrol and levonorgestrel significantly decreased the density and motility of sperm and induced atrophy of the epididymis and seminal vesicle. The combination of compounds also significantly reduced serum T and LH levels, increased testicular T levels and decreased testicular estradiol ERß and aromatase levels. EP-1 delivered at a ratio of 1:1 induced the most significant effects on the reproductive parameters assessed and shows the potential for use in fertility control of male rodents.


Assuntos
Estrogênios/farmacologia , Levanogestrel/farmacologia , Quinestrol/farmacologia , Reprodução/efeitos dos fármacos , Animais , Aromatase/metabolismo , Hormônios Esteroides Gonadais/sangue , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/enzimologia , Testículo/metabolismo
18.
Urol Case Rep ; 23: 92-94, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30719410

RESUMO

Primary solitary fibrous tumors of kidney are rare in clinical practice. In literature, only eleven reported cases originated from renal pelvis. We report a case of a 45 year old middle-aged woman who was the first report that a small number of heterosexual cells have been found in urine. Definite diagnosis of this disease still depends on pathological examination, If preoperative puncture or other pathological examination supports the diagnosis of SFTs, the preferred treatment plan for it is surgical resection.

19.
Eur J Med Chem ; 157: 139-150, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30092368

RESUMO

A series of new 3-(1H-benzimidazol-2-yl)quinolin-2(1H)-one derivatives (5a1-5d6) were designed and synthesized as antitumor agents. In vitro antitumor assay results showed that some compounds exhibited moderate to high inhibitory activity against HepG2, SK-OV-3, NCI-H460 and BEL-7404 tumor cell lines, and most compounds exhibited much lower cytotoxicity against the HL-7702 normal cell line compared to 5-FU and cisplatin. In vivo antitumor assay results demonstrated that 5a3 exhibited effective inhibition on tumor growth in the NCI-H460 xenograft mouse model and that 5d3 displayed excellent antiproliferative activity in the BEL-7402 xenograft model. These results suggested that both 5a3 and 5d3 could be used as anticancer drug candidates. Mechanistic studies suggested that compounds 5a3 and 5d3 exerted their antitumor activity by up-regulation of Bax, intracellular Ca2+ release, ROS generation, downregulation of Bcl-2, activation of caspase-9 and caspase-3 and subsequent cleavage of PARP, inhibition of CDK activity and activation of the p53 protein.


Assuntos
Antineoplásicos/farmacologia , Benzimidazóis/farmacologia , Desenho de Fármacos , Quinolonas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Benzimidazóis/síntese química , Benzimidazóis/química , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Quinolonas/síntese química , Quinolonas/química , Relação Estrutura-Atividade , Proteína Supressora de Tumor p53/antagonistas & inibidores , Proteína Supressora de Tumor p53/biossíntese
20.
Pestic Biochem Physiol ; 143: 122-126, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29183580

RESUMO

The aim of this study was to assess the effects and reversibility of the synthetic estrogen compound, quinestrol, on the reproductive organs, steroid hormones, and drug-metabolizing enzymes CYP3A4 and CYP1A2 in liver and kidney over time after two quinestrol treatments in female Mongolian gerbils (Meriones unguiculatus). Female gerbils were treated with 4mg/kg quinestrol (9 gerbils/group, 3 treated group) (1 control group, 0mg/kg) for 3days and treated again after 25days. Animals were killed for collection of samples at 5, 10 and 15days after the second treatment ending. Two interval quinestrol treatments significantly increased uterine weight, with trend of increase over time, but no change could be detected in ovarian weights. Quinestrol treatment increased progesterone and estradiol levels, both with trend of decline over time. Quinestrol increased liver and kidney weights and total enzyme content of CYP3A4 and CYP1A2, with trend of decline over time. On the basis of reversible changes of detoxification enzymes or organs, interval quinestrol treatment effectively and reversibly influenced the reproductive hormone and organ to some extent.


Assuntos
Estrogênios/farmacologia , Quinestrol/farmacologia , Animais , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP3A/metabolismo , Estradiol/sangue , Feminino , Gerbillinae/sangue , Gerbillinae/metabolismo , Rim/efeitos dos fármacos , Rim/enzimologia , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Tamanho do Órgão/efeitos dos fármacos , Ovário/anatomia & histologia , Ovário/efeitos dos fármacos , Progesterona/sangue , Útero/efeitos dos fármacos , Útero/patologia
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