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1.
J Am Chem Soc ; 146(21): 14685-14696, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38717074

RESUMO

The exploration of new polymer materials required the development of efficient, economic, robust, and scalable synthetic routes, taking energy consumption, environmental benefit, and sustainability into overall consideration. Herein, through retro-polymerization analysis of functional aromatic polythioureas, a multicomponent reaction of elemental sulfur, CH2Cl2, and aromatic amines was designed with the assistance of fluoride, and efficient, economic, and robust multicomponent polymerizations (MCPs) of these three abundantly available cheap monomers, elemental sulfur, CH2Cl2, and aromatic diamines, were developed to realize scalable conversion directly from sulfur to a series of functional aromatic polythioureas with high molecular weights (Mn up to 50,800 g/mol) in excellent yields (up to 98%). The synergistic cooperation of the strong and selective coordination of thiourea with gold ions and the redox property of aromatic polythiourea enable in situ reduction of Au3+ to elemental gold under a normal bench condition. Furthermore, the functional aromatic polythiourea could be chemically recycled through aminolysis with NH3·H2O to afford a diamine monomer in 83% isolated yield. The development of elemental sulfur-based MCP has brought the opportunity to access cost-effective and sustainable sulfur-containing functional polymer materials, which is anticipated to provide a solution for the utilization of sulfur waste and making profitable polymer materials.

2.
Langenbecks Arch Surg ; 408(1): 305, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37566144

RESUMO

BACKGROUND AND AIMS: The use of sutures to strengthen the anastomosis after rectal cancer surgery to reduce the possibility of anastomotic leakage has been debated. The aim of this systematic review and meta-analysis was to investigate the influence of intraoperative anastomotic reinforcing sutures on anastomotic leakage of double-stapling anastomosis for laparoscopic rectal cancer surgery. METHODS: A systematic search of PubMed, Embase, Web of Science, and Cochrane databases was performed to identify literature examining anastomotic leak as the primary outcome to compare studies of laparoscopic surgery for rectal cancer using the double-stapling anastomosis technique with or without intraoperative anastomotic reinforcement with sutures. RESULTS: A total of 1122 rectal cancer patients from 5 nonrandomized studies were included in the research. In the combined trial, intraoperative anastomotic reinforcement sutures significantly reduced the incidence of anastomotic leakage in patients who underwent laparoscopic rectal cancer surgery (OR, 0.32; 95% CI, 0.19-0.55; p < 0.0001). With or without intraoperative anastomotic reinforcing sutures, the incidence of postoperative reoperation for anastomotic leak did not differ substantially (OR, 0.32; 95% CI, 0.08-1.21, p = 0.09). Moreover, the surgery was prolonged due to anastomotic reinforcement with sutures (OR, 6.64; 95% CI, - 6.18 to 19.47, p = 0.31). CONCLUSIONS: Intraoperative anastomotic reinforcement with sutures may be associated with a lower incidence of anastomotic leakage. The amount of research evidence is limited because most of the studies analyzed did not include patients with factors such as neoadjuvant therapy or prophylactic stomas. Therefore, additional multicenter randomized controlled studies with larger size samples are needed to support the validity of the approach.


Assuntos
Laparoscopia , Neoplasias Retais , Humanos , Fístula Anastomótica/etiologia , Fatores de Risco , Anastomose Cirúrgica/métodos , Laparoscopia/métodos , Neoplasias Retais/cirurgia , Suturas/efeitos adversos , Estudos Multicêntricos como Assunto
3.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(2): 136-140, 2020 Feb.
Artigo em Zh | MEDLINE | ID: mdl-32051080

RESUMO

OBJECTIVE: To study the effect of low-dose dopamine adjuvant therapy on inflammatory factors and prognosis in preterm infants with necrotizing enterocolitis (NEC). METHODS: A total of 100 preterm infants with NEC from June 2017 to June 2019 were enrolled and divided into a dopamine treatment group and a conventional treatment group using a random number table, with 50 infants in each group. The infants in the conventional treatment group were given symptomatic treatment, and those in the dopamine treatment group were given low-dose dopamine adjuvant therapy in addition to the conventional treatment. ELISA was used to measure the levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-8 (IL-8). The two groups were compared in terms of time to relief of clinical symptoms, fasting time, treatment outcome, prognosis, and adverse reactions. RESULTS: Both groups had significant reductions in the levels of CRP, TNF-α, and IL-8 after treatment, and the dopamine treatment group had significantly lower levels of these markers than the conventional treatment group after treatment (P<0.05). Compared with the conventional treatment group, the dopamine treatment group had significantly shorter time to defecation improvement, time to relief of abdominal distension and diarrhea, and fasting time (P<0.05), a significantly higher response rate (P<0.05), and a significantly lower surgery rate (P<0.05). There were no significant differences in the mortality rate and incidence of adverse events between the two groups (P>0.05). CONCLUSIONS: Low-dose dopamine adjuvant therapy can effectively improve the levels of inflammatory factors and clinical symptoms in preterm infants with NEC and has good safety, and therefore, it holds promise for clinical application.


Assuntos
Enterocolite Necrosante , Doenças do Recém-Nascido , Dopamina , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Prognóstico
4.
World J Urol ; 37(6): 1197-1204, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30251051

RESUMO

PURPOSE: Our study aimed to investigate the clinical significance of urinary neutrophil gelatinase-associated lipocalin (NGAL) as an effective real-time monitoring biomarker of renal function in patients with obstructive ureteral calculi presenting renal colic. METHODS: A cohort of 89 first-visit patients with renal colic caused by unilateral ureteral calculi were retrospectively reviewed. 46 of which received double-J ureteral stent placement (group 1) and the remaining 43 treated conservatively with analgesics and hydration (group 2) when diagnosed. Urinary NGAL (uNGAL) values in the baseline, 2 h and 1 day after treatments were recorded. The variation of this parameter over time and the association with patients' characteristics were analyzed. RESULTS: uNGAL levels decreased as time went by for patients receiving double-J ureteral stent placement (47.23 ± 28.32 ng/mL for baseline, 40.73 ± 21.86 ng/mL for 2 h and 34.67 ± 18.00 ng/mL for 1 day after operation; p = 0.0363). Nevertheless, for those treating conservatively, the levels emerged a mild increase (50.63 ± 32.30 ng/mL, 56.00 ± 32.01 ng/mL and 60.63 ± 34.08 ng/mL, correspondingly; p = 0.3708). By analyzing the association between uNGAL variation and patients' characteristics of group 1, operation duration showed the best correlation coefficient (Pearson r = 0.6106, r2 = 0.3728, p < 0.0001). CONCLUSIONS: uNGAL can be used as a biomarker to monitor the renal function effectively when serum creatinine (sCr) was within normal limits. And double-J ureteral stent can be considered as a protective factor to renal function in patients with obstructive ureteral calculi presenting renal colic.


Assuntos
Lipocalina-2/urina , Cálculos Ureterais/urina , Obstrução Ureteral/urina , Biomarcadores/urina , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Cólica Renal/etiologia , Cólica Renal/urina , Estudos Retrospectivos , Cálculos Ureterais/complicações , Obstrução Ureteral/complicações , Obstrução Ureteral/etiologia
5.
Aging Male ; 21(4): 231-237, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29316842

RESUMO

BACKGROUND: Enzalutamide, a novel androgen receptor (AR) signaling inhibitor, has been widely used to increase survival in patients with castration-resistant prostate cancer. However, resistance to enzalutamide invariably develops. METHODS: To understand the underlying mechanisms of resistance to enzalutamide, we performed integrative analysis on multiple transcriptome datasets to identify those genes constantly up- or down-regulated in response to enzalutamide treatment. RESULTS: There were 703 and 581 differentially expressed genes derived from enzalutamide-sensitive and -resistant cell lines, respectively. Functional enrichment analysis on these genes demonstrated that biological processes of cell proliferation and ubiquitin mediated proteolysis pathway are specifically disturbed in sensitive cell lines but not resistant ones. Such divergence explained why enzalutamide ineffective for resistant prostate cancer. CONCLUSIONS: Taken together, the present study revealed a set of critical genes, which can provide etiologic clues as to enzalutamide-resistant prostate cancer and guide novel therapeutic approaches.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Perfilação da Expressão Gênica , Expressão Gênica/efeitos dos fármacos , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Antineoplásicos/uso terapêutico , Benzamidas , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Masculino , Nitrilas , Feniltioidantoína/farmacologia , Feniltioidantoína/uso terapêutico , Transdução de Sinais/genética , Falha de Tratamento
6.
Phys Chem Chem Phys ; 20(42): 26995-27002, 2018 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-30328434

RESUMO

A series of Ce3+/Tb3+ doped Li3Sc2(PO4)3 phosphors has been obtained using high temperature solid state reactions. Density functional theory (DFT) calculations using the CASTEP module have given an insight into the bandgap and electronic structures of the hosts. The phase formation and the crystal structure of the prepared samples were verified using X-ray diffraction and Rietveld structure refinement analysis. Samples singly doped with Ce3+ ions had an intense emission centered at 350 nm under UV light irradiation, while samples singly doped with Tb3+ ions exhibited a typical green emission under 230 nm irradiation. Efficient Ce3+→Tb3+ energy transfer can cause the Li3Sc2(PO4)3:Ce3+,Tb3+ samples to have an intense green emission at very low Tb3+ concentrations under 285 nm excitation, making Li3Sc2(PO4)3:Ce3+,Tb3+ an efficient UV-excited green phosphor. The mechanism and critical distance for Ce3+→Tb3+ energy transfer in the phosphor were determined by detailed luminescence decay curve analysis utilizing the I-H model. Moreover, a WLED device was fabricated using our prepared green phosphor.

7.
Kidney Blood Press Res ; 43(1): 152-161, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29444515

RESUMO

BACKGROUND/AIMS: Mesenchymal stromal cells (MSCs) participate in the tissue-specific repair of many different organs, especially the kidney. Their effects are primarily mediated by the paracrine release of factors including extracellular vesicles (EVs), which are composed of micro-vesicles and exosomes. The corresponding microRNAs (miRNAs) of EVs are considered important for their biological functions. METHODS: MSCs were cultured from the human umbilical cord, and EVs were isolated from the medium. The expression levels of miRNAs in MSCs and EVs were determined by microarray analysis, and gene ontology (GO) was used to analyze the functions of their target genes. RESULTS: MSCs and EVs had similar miRNA expression profiles, with the exception of a small number of selectively enriched miRNAs. GO analysis indicated that, unlike MSCs, the target genes of EV-enriched miRNAs were associated with calcium channel regulation and cell junction activities, which may indicate that MSC and EVs have different regulatory properties. Angiogenesis, oxidative stress, and inflammatory signaling pathways related to the repair of renal injury were also analyzed, and EV-enriched miRNAs targeted genes associated with oxidative stress, T cell activation, and Toll-like receptor signaling. The miRNAs enriched in both MSCs and EVs targeted different genes in signaling pathways regulating angiogenesis and chemokine release. CONCLUSION: MSCs and their EVs shared similar miRNA component, and some selectively enriched miRNAs observed in MSCs and EVs may affect different target genes through some specific signaling pathways.


Assuntos
Vesículas Extracelulares/metabolismo , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/análise , Ontologia Genética , Humanos , Transdução de Sinais , Análise Serial de Tecidos , Cordão Umbilical/citologia
8.
BMC Urol ; 18(1): 64, 2018 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-30041630

RESUMO

BACKGROUND: The current research aims to evaluate the risk factors of urethrocutaneous fistula after hypospadias surgery among the youth in China. METHODS: One hundred twenty hypospadias patients were enrolled in our study. All of them were defined as Tanner 4 or 5. The information collected from the participants include age, urethral operation history, urinary comorbidities before operation, urine test before operation, body temperature before and after operation, type of surgical repair, chordee degree, urethral defect length and whether received vesicostomy after surgery or not. Independent t test, chi-square test and multivariate logistic regression were performed to evaluate the risk factor of urethrocutaneous fistula. RESULTS: Among the enrolled patients, 39 patients (32.5%) developed urethrocutaneous fistula after hypospadias repair. Our result showed significant association between the group with urethrocutaneous fistula and the group without urethrocutaneous fistula with respect to age, pyuria before operation, urethral defect length and the urethral operation history. The following logistic regression showed that urethral defect length and the urethral operation history were the risk factors of urethrocutaneous fistula. CONCLUSIONS: Urethral defect length and urethral operation history should be taken into consideration before undergoing hypospadias surgery since our study discovered that the risk of developing urethrocutaneous fistula after hypospadias repair is associated with urethral defect length and urethral operation history. Age, surgical procedure, type of surgical repair, chordee degree and other factors were not obviously related to the development of urethrocutaneous fistula.


Assuntos
Fístula Cutânea/epidemiologia , Hipospadia/cirurgia , Complicações Pós-Operatórias/epidemiologia , Doenças Uretrais/epidemiologia , Fístula Urinária/epidemiologia , Procedimentos Cirúrgicos Urológicos Masculinos/efeitos adversos , Adolescente , Adulto , Criança , China/epidemiologia , Fístula Cutânea/etiologia , Humanos , Incidência , Masculino , Estudos Retrospectivos , Fatores de Risco , Doenças Uretrais/etiologia , Fístula Urinária/etiologia , Adulto Jovem
9.
Aging Male ; 20(4): 250-256, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28787260

RESUMO

BACKGROUND: The etiology of benign prostatic hyperplasia (BPH) has not been well established. The preferred medical treatment for many men with symptomatic benign prostatic hyperplasia is either an α-adrenergic receptor antagonist (α-blocker), or a 5α-reductase inhibitor. Single nucleotide polymorphism (SNP) is a powerful tool for successful implementation of individualized treatment. METHODS: Eighteen SNPs associated with drug efficacy in a Chinese population were genotyped in 790 BPH cases (330 aggressive and 460 non-aggressive BPH cases) and 1008 controls. All BPH patients were treated with α-adrenergic blockers for at least 9 months. We tested the associations between tagging single nucleotide polymorphism and BPH risk/aggressiveness, clinical characteristics at baseline, including the International Prostate Symptom Score (IPSS) and total prostate volume, and changes in clinical characteristics after treatment. RESULTS: There were nine SNPs associated with BPH risk, clinical progression and therapeutic effect. (1) There were nine tSNPs been chosen in CYP3A4, CYP3A5 and RANBP3L genes. (2) The SNP, rs16902947 in RANBP3L at 5p13.2 (p = .01), was significantly associated with BPH. (3) We found two SNPs, rs16902947 in RANBP3L at 5p13.2 (p = .0388) and rs4646437 in CYP3A4 at 7q21.1 (p = .0325), associated with drug effect. (4) Allele "G" for rs16902947 was found to be risk alleles for BPH risk (OR= 2.357, 95%CI 1.01-1.48). The "A" allele of rs4646437 was associated with lower IPSS at baseline (ß= -0.4232, p= .03255). CONCLUSIONS: rs16902947, rs16902947 and rs4646437 single nucleotide polymorphisms are significantly associated with the clinical characteristics of benign prostatic hyperplasia and the efficacy of benign prostatic hyperplasia treatment.


Assuntos
Inibidores de 5-alfa Redutase/uso terapêutico , Antagonistas Adrenérgicos alfa/uso terapêutico , Próstata/efeitos dos fármacos , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/genética , Idoso , Estudos de Casos e Controles , Progressão da Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Próstata/patologia
10.
World J Urol ; 32(2): 329-33, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22885658

RESUMO

PURPOSE: To evaluate elastography using a bi-plane transducer for localizing prostate cancer (PCa) in patients scheduled for radical prostatectomy (RP), in comparison with step section pathological analysis. METHODS: Fifty-six consecutive PCa patients underwent real-time elastography examination with a bi-plane transducer before RP. Transverse elastographic images were obtained from the apex to the base by slightly compressing and releasing the prostate tissue using the probe. The diagnostic performance of elastography was evaluated in correlation with step section RP histopathology. RESULTS: In 56 PCa patients, gray-scale ultrasonography detected at least one lesion in 36 patients, whereas elastography detected at least one lesion in 53 patients (P = 0.001). The overall sensitivity, specificity and accuracy of elastography in depicting tumor lesions were 67.6, 89.5 and 82.7 %, respectively. The detection rate of a PCa lesion with elastography was best in the left posterior region, followed by the right posterior region. Elastography was more sensitive in detecting PCa lesions with higher Gleason scores, diameter >5 mm and extracapsular extension. CONCLUSIONS: The additional use of elastography with the bi-plane transducer can improve PCa detection rate by providing more information about tissue stiffness within the prostate gland.


Assuntos
Adenocarcinoma/diagnóstico , Técnicas de Imagem por Elasticidade/métodos , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Idoso , Estudos de Coortes , Técnicas de Imagem por Elasticidade/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Próstata/patologia , Prostatectomia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Transdutores
11.
iScience ; 27(1): 108737, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38269099

RESUMO

Lead (Pb(II)) contamination is common in liquid foods and can result from Pb(II) being present in the raw materials or during handling processes. However, due to the complexity of food matrices, there is limited data available concerning Pb(II) ion removal from food sources. This study focused on fabricating a PVA/PAA/DMTD electrospun nanofibrous membrane (ENFM) to efficiently and selectively remove Pb(II) ions from liquid foods. The PVA/PAA/DMTD ENFM had a maximum adsorption capacity of 138.3 mg/g for Pb(II) ions and demonstrated high selectivity toward the removal of Pb(II) ions. Negative values of the Gibbs free energy (ΔG°) showed that the spontaneous nature of the adsorption process was feasible at different temperatures. Moreover, it successfully removed Pb(II) ions from selected samples of commercially available drinks. Therefore, this adsorbent exhibits significant potential for removing Pb(II) ions from liquid food products, thereby reducing daily dietary exposure to Pb(II).

12.
PLoS One ; 19(3): e0300931, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38512874

RESUMO

A uniaxial compression test was conducted on sandstone specimens at various inclination angles to determine the energy evolution characteristics during deformation and damage. Based on the principle of minimum energy dissipation, an intrinsic model incorporating the damage threshold was developed to investigate the mechanical properties of sandstone at different inclination angles, and the energy damage evolution during deformation and damage. This study indicated that when the inclination angle of the structural surface remained below 40°, sandstone exhibited varying mechanical properties based on different inclination angles. The peak strain was positively correlated with the inclination angle, whereas the compressive strength and modulus of elasticity showed negative correlations. From an energy perspective, the deformation and damage of sandstone under external loading entail processes of energy input, accumulation, and dissipation. Moreover, higher inclination angles of the structural surface resulted in a smaller absorbed peak strain and a reduced proportion of dissipated energy relative to the energy input, thereby affecting the evolution of energy damage throughout the process. As the inclination angle of the structural surface increased, the absorbed total strain at the peak value decreased, whereas the proportion of the dissipated energy increased. Additionally, the damage threshold and critical value of the rock specimens increased with the inclination angle. The critical value, a composite index comprising the peak strain, compressive strength, and elastic modulus, also increased accordingly. These findings can offer a novel perspective for analyzing geological disasters triggered by fissure zones within underground rock formations.


Assuntos
Desastres , Salicilatos , Força Compressiva , Módulo de Elasticidade , Elasticidade
13.
World J Gastrointest Surg ; 16(2): 438-450, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38463372

RESUMO

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), a composite inflammatory biomarker, is associated with the prognosis in patients with colorectal tumors. However, whether the NLR can be used as a predictor of symptomatic postoperative anastomotic leakage (AL) in elderly patients with colon cancer is unclear. AIM: To assess the role of the NLR in predicting the occurrence of symptomatic AL after surgery in elderly patients with colon cancer. METHODS: Data from elderly colon cancer patients who underwent elective radical colectomy with anastomosis at three centers between 2018 and 2022 were retrospectively analyzed. Receiver operating characteristic curve analysis was performed to determine the best predictive cutoff value for the NLR. Twenty-two covariates were matched using a 1:1 propensity score matching method, and univariate and multivariate logistic regression analyses were used to determine risk factors for the development of postoperative AL. RESULTS: Of the 577 patients included, 36 (6.2%) had symptomatic AL. The optimal cutoff value of the NLR for predicting AL was 2.66. After propensity score matching, the incidence of AL was significantly greater in the ≥ 2.66 NLR subgroup than in the < 2.66 NLR subgroup (11.5% vs 2.5%; P = 0.012). Univariate logistic regression analysis revealed statistically significant correlations between blood transfusion intraoperatively and within 2 d postoperatively, preoperative albumin concentration, preoperative prognostic nutritional index, and preoperative NLR and AL occurrence (P < 0.05); multivariate logistic regression analysis revealed that an NLR ≥ 2.66 [odds ratio (OR) = 5.51; 95% confidence interval (CI): 1.50-20.26; P = 0.010] and blood transfusion intraoperatively and within 2 d postoperatively (OR = 2.52; 95%CI: 0.88-7.25; P = 0.049) were risk factors for the occurrence of symptomatic AL. CONCLUSION: A preoperative NLR ≥ 2.66 and blood transfusion intraoperatively and within 2 d postoperatively are associated with a higher incidence of postoperative symptomatic AL in elderly patients with colon cancer. The preoperative NLR has predictive value for postoperative symptomatic AL after elective surgery in elderly patients with colon cancer.

14.
Biomed Pharmacother ; 176: 116807, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38795644

RESUMO

Metabolic syndrome (MetS) is a widespread and multifactorial disorder, and the study of its pathogenesis and treatment remains challenging. Autophagy, an intracellular degradation system that maintains cellular renewal and homeostasis, is essential for maintaining antimicrobial defense, preserving epithelial barrier integrity, promoting mucosal immune response, maintaining intestinal homeostasis, and regulating gut microbiota and microbial metabolites. Dysfunctional autophagy is implicated in the pathological mechanisms of MetS, involving insulin resistance (IR), chronic inflammation, oxidative stress, and endoplasmic reticulum (ER) stress, with IR being a predominant feature. The study of autophagy represents a valuable field of research with significant clinical implications for identifying autophagy-related signals, pathways, mechanisms, and treatment options for MetS. Given the multifactorial etiology and various potential risk factors, it is imperative to explore the interplay between autophagy and gut microbiota in MetS more thoroughly. This will facilitate the elucidation of new mechanisms underlying the crosstalk among autophagy, gut microbiota, and MetS, thereby providing new insights into the diagnosis and treatment of MetS.


Assuntos
Autofagia , Microbioma Gastrointestinal , Resistência à Insulina , Síndrome Metabólica , Autofagia/fisiologia , Microbioma Gastrointestinal/fisiologia , Síndrome Metabólica/microbiologia , Síndrome Metabólica/metabolismo , Humanos , Resistência à Insulina/fisiologia , Animais , Transdução de Sinais
15.
Cancer Lett ; 597: 217070, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38880227

RESUMO

The androgen receptor signaling inhibitor (ARSI) enzalutamide (Enz) has shown critical efficacy in the treatment of advanced prostate cancer (PCa). However, the development of drug resistance is a significant factor contributing to mortality in PCa patients. We aimed to explore the key mechanisms of Enz-resistance. Through analysis of GEO databases, we identified SLC4A4 as a novel driver in Enz resistance. Long-term Enz treatment leads to the up-regulation of SLC4A4, which in turn mediates P53 lactylation via the NF-κB/STAT3/SLC4A4 axis, ultimately leading to the development of Enz resistance and progression of PCa. SLC4A4 knockdown overcomes Enz resistance both in vitro and in vivo. Hence, our results suggest that targeting SLC4A4 could be a promising therapeutic strategy for Enz resistance. STATEMENT OF SIGNIFICANCE: SLC4A4 is a novel driver of enzalutamide resistance.

16.
Cancer Lett ; 587: 216725, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38364963

RESUMO

Next-generation androgen receptor signaling inhibitors (ARSIs), such as enzalutamide (Enza) and darolutamide (Daro), are initially effective for the treatment of advanced prostate cancer (PCa) and castration-resistant prostate cancer (CRPC). However, patients often relapse and develop cross-resistance, which consequently makes drug resistance an inevitable cause of CRPC-related mortality. By conducting a comprehensive analysis of GEO datasets, CRISPR genome-wide screening results, ATAC-seq data, and RNA-seq data, we systemically identified PAK1 as a significant contributor to ARSI cross-resistance due to the activation of the PAK1/RELA/hnRNPA1/AR-V7 axis. Inhibition of PAK1 followed by suppression of NF-κB pathways and AR-V7 expression effectively overcomes ARSI cross-resistance. Our findings indicate that PAK1 represents a promising therapeutic target gene for the treatment of ARSI cross-resistant PCa patients in the clinic. STATEMENT OF SIGNIFICANCE: PAK1 drives ARSI cross-resistance in prostate cancer progression.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/metabolismo , Receptores Androgênicos/metabolismo , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Detecção Precoce de Câncer , Recidiva Local de Neoplasia/genética , Nitrilas/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Quinases Ativadas por p21/genética , Quinases Ativadas por p21/metabolismo
17.
World J Surg Oncol ; 11: 216, 2013 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-23987305

RESUMO

BACKGROUND: Although nephron-sparing surgery has been reported not to affect total renal function, it is a non-negligible fact that functional damage of the operated kidney usually results, for various reasons. This study aimed to explore the effects of preoperative baseline characteristics, tumor characteristics, and function protection methods on postoperative renal damage. METHODS: This study was a retrospective review of 51 patients who underwent open nephron-sparing surgery. The mean age of the patients (39 men, 12 women) was 54.2 ± 13.9 years, range 32 to 71 years. The glomerular filtration rate (GFR) was measured preoperatively and 6th months after the operation. Univariate analysis was used to screen indicators with significant differences in different levels of renal function damage. All variables found to be significant on univariate analysis were entered into a multiple logistic regression model to predict risk factors for renal function damage. RESULTS: Univariate analysis showed that there was a significant difference in age, GFR of operated kidney, tumor diameter, tumor depth, and ischemic protection type between patients with little damage and those with heavy damage (P < 0.05). Forward stepwise logistic regression analysis suggested that age (odds ratio, 3.08; 95% confidence interval 1.78 to 7.04; P = 0.037), preoperative GFR of operated kidney (odds ratio, 0.51; 95% confidence interval 0.11 to 0.73; P = 0.033), and tumor diameter (odds ratio, 5.49; 95% confidence interval 2.14 to 7.88; P = 0.012) and depth (odds ratio, 5.82; 95% confidence interval 2.66 to 8.06; P = 0.010) were independent risk factors for postoperative renal function damage. CONCLUSIONS: Patients with older age, poor renal function, and large tumor diameter and depth might be at higher risk of renal function damage after nephron-sparing surgery.


Assuntos
Nefropatias/diagnóstico , Neoplasias Renais/cirurgia , Rim/fisiopatologia , Nefrectomia/efeitos adversos , Néfrons/cirurgia , Complicações Pós-Operatórias , Adulto , Idoso , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Nefropatias/etiologia , Nefropatias/fisiopatologia , Testes de Função Renal , Neoplasias Renais/complicações , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tratamentos com Preservação do Órgão , Prognóstico , Estudos Retrospectivos
18.
Medicine (Baltimore) ; 102(16): e33597, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37083782

RESUMO

Marriage has been reported as a beneficial factor associated with improved survival among cancer patients, but conflicting results have been observed in cervical adenocarcinoma (AC). Thus, this study is aimed to examine the relationship between the prognosis of cervical AC and marital status. Eligible patients were selected from 2004 to 2015 using the surveillance, epidemiology and end results (SEER) database. Cancer-specific survival (CSS) and overall survival (OS) were compared between married and unmarried groups. A total of 3096 patients had been identified, with married ones accounting for 51.29% (n = 1588). Compared to unmarried groups, more patients in the married group were relatively younger (aged ≤ 45) and belonged to white race, with grade I/II, Federation of International of Gynecologists and Obstetricians (FIGO) stage I/II and tumor size ≤4 cm. Apart from that, more patients received surgery, whereas fewer patients received chemotherapy and radiotherapy (all P < 0.05). The 5-year CSS and OS rates were 80.16% and 78.26% in married patients, 68.58% and 64.62% in the unmarried group (P < .0001). Multivariate analysis showed that marital status was an independent prognostic factor, and the married group performed better CSS (hazard ratio [HR]: 0.770; 95% confidence interval [CI]: 0.663-0.895; P = .001) as well as OS (HR: 0.751; 95%CI: 0.653-0.863; P < .001). As demonstrated by the results of subgroup analysis, married patients had better CSS and OS survival than unmarried ones in nearly all the subgroups. Marital status was identified as an independent prognostic factor for improved survival in patients with cervical AC.


Assuntos
Adenocarcinoma , Casamento , Humanos , Prognóstico , Programa de SEER , Estado Civil , Adenocarcinoma/terapia
19.
Medicine (Baltimore) ; 102(48): e36453, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38050222

RESUMO

The aim was to construct and verify a nomogram-based assessment of cancer-specific survival (CSS) in patients with colorectal signet ring cell carcinoma after surgery. Patients were collected from Surveillance, Epidemiology, and End Results program between 2004 and 2015. Independent prognostic indicators were determined in the training cohort by Cox regression model. We identified 2217 eligible patients, who were further categorized into the training set (n = 1693) as well as the validation set (n = 524). Multivariate analysis revealed that age at diagnosis, gender, grade, tumor size, T stage, N stage, and M stage were independent predictive indicators. Then, the above 7 predictive factors were incorporated into a nomogram model to assess CSS, which showed good calibration and discrimination capacities in both sets. Both internal and external calibration plot diagrams revealed that the actual results were consistent with the predicted outcomes. The time-independent area under the curves for 3-year and 5-year CSS in the nomogram were larger than American Joint Committee on Cancer and Surveillance, Epidemiology, and End Results summary stage system. Moreover, decision curve analysis indicated the clinical utility of the nomogram. The nomogram demonstrated favorable predictive accuracy of survival in colorectal signet ring cell carcinoma patients after surgery, which should be further confirmed before clinical implementation.


Assuntos
Carcinoma de Células em Anel de Sinete , Neoplasias Colorretais , Humanos , Nomogramas , Pesquisa , Calibragem , Carcinoma de Células em Anel de Sinete/cirurgia , Neoplasias Colorretais/cirurgia , Programa de SEER
20.
Sci Rep ; 13(1): 18674, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37907624

RESUMO

The present aims to investigate the mechanical characteristics and energy evolution in rock masses containing weak structural planes under conventional triaxial loading conditions. Using a fluid-solid coupling test system of coal rock, numerous conventional triaxial compression tests were performed on rock masses at various dip angles of the structural plane. The obtained empirical outcomes revealed that the deviatoric stress-strain curve of the weak structural plane rock mass with an inclination angle greater than 20° rises step-by-step. On the macro level, slip-stability occurs on the upper and lower parts of the rock mass on the weak structural plane. Then mechanism of the slip-stability phenomenon is explored by analyzing the stress level in the rock mass with various inclination angles. It is found that the energy evolution during deformation and failure reflects the damaged state of the rock. Accordingly, the concept of 'slip dissipation energy' is proposed, and the values of each energy are calculated. The results have a good correspondence with the deviatoric stress-strain curve. Furthermore, it was found that the energy evolution of rock mass with a weak structural plane can be primarily classified into four stages, including storage of the initial energy, slip dissipation, abrupt increase in the pre-peak dissipation energy, and sudden drop in post-peak energy. Rock masses with various levels of dip angles exhibit similar elastic strain energy and dissipation energy at the peak point, demonstrating that energy evolution is dominated by energy storage and dissipation. At the same time, a negative correlation is observed between the structural plane dip angle and the occurrence of instantaneous impact instability failure in rock masses, indicating that a greater dip angle makes the rock mass less prone to experiencing instantaneous impact instability failure. This article provides a new idea for analyzing the geological disasters caused by external disturbances.

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