Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 44
Filtrar
1.
Comput Math Methods Med ; 2021: 2725799, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790251

RESUMO

Type 1 regulatory T (Tr1) cells play a fundamental role in maintaining and inducing immune tolerance. Our preliminary study demonstrated that an interleukin- (IL-) 10-mediated pathway is a possible regulatory mechanism underlying the xenoantigen-specific human Treg enhanced suppressive capacity. Here, we developed a feasible protocol for expanding IL-10-induced xenoantigen-specific human Tr1 cells in vitro which would be more efficient in transplantation immunotherapy efficiency. In this study, xenoantigen-specific Tr1 cells are generated from human naive CD4+ T cells expanded for two subsequent xenoantigen-stimulation cycles with recombinant human IL-10. The phenotype and suppressive capacity of xenoantigen-stimulated Tr1 cells are assessed, and the mechanism of their suppression is studied. Tr1 cells can be induced by porcine xenoantigen stimulation combined with IL-10, IL-2, and IL-15, displaying an increased expression of CD49b, CTLA-4, and LAG-3 without expressing Foxp3 which also showed an effector memory Treg phenotype and expressed high levels of CD39. After xenoantigen stimulation, the IL-10 and IL-5 gene expression in Tr1 cells increased, secreting more IL-10, and xenoantigen-stimulated Tr1 cells changed their T cell receptor (TCR) Vß repertoire, increasing the expression of TCR Vß2, TCR Vß9, and TCR Vß13. In a pig to human mixed lymphocyte reaction (MLR), xenoantigen-stimulated Tr1 cells displayed enhanced suppressive capacity via CD39 in a dose-dependent manner. Moreover, IL-5 could affect the proliferation of xenoantigen-specific Tr1 cells, but not their phenotypes' expression. This study provides a theory and feasible method for immune tolerance induction in clinical xenotransplantation.

2.
Front Immunol ; 12: 729382, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675921

RESUMO

Calcium oxalate (CaOx) stones are the most common type of kidney stones and are associated with high recurrence, short chain fatty acids (SCFAs), and inflammation. However, it remains uncertain whether SCFAs affect the formation of CaOx stones through immunomodulation. We first performed mass cytometry (CyTOF) and RNA sequencing on kidney immune cells with glyoxylate-induced CaOx crystals (to elucidate the landscape of the associated immune cell population) and explored the role of SCFAs in renal CaOx stone formation through immunomodulation. We identified 29 distinct immune cell subtypes in kidneys with CaOx crystals, where CX3CR1+CD24- macrophages significantly decreased and GR1+ neutrophils significantly increased. In accordance with the CyTOF data, RNA sequencing showed that most genes involved were related to monocytes and neutrophils. SCFAs reduced kidney CaOx crystals by increasing the frequency of CX3CR1+CD24- macrophages and decreasing GR1+ neutrophil infiltration in kidneys with CaOx crystals, which was dependent on the gut microbiota. GPR43 knockdown by transduction with adeno-associated virus inhibited the alleviation of crystal formation and immunomodulatory effects in the kidney, due to SCFAs. Moreover, CX3CR1+CD24- macrophages regulated GR1+ neutrophils via GPR43. Our results demonstrated a unique trilateral relationship among SCFAs, immune cells, and the kidneys during CaOx formation. These findings suggest that future immunotherapies may be used to prevent kidney stones using SCFAs.

3.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(8): 831-837, 2021 Aug 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34565726

RESUMO

OBJECTIVES: Diabetes can accelerate cognitive decline and hence affect the prognosis of patients with Type 2 diabetes mellitus (T2DM). Olfactory assessment can facilitate the early identification of cognitive impairment among T2DM patients. This study aims to evaluate the effects of olfactory function on mild cognitive impairment (MCI) in patients with T2DM. METHODS: A total of 472 T2DM patients who were hospitalized in a first-class hospital in Changsha City from June 2018 to June 2019 were enrolled for this study. Olfactory function and cognitive function were assessed by the alcohol sniff test and the Montreal Cognitive Assessment (MoCA) scale, respectively. Participants were categorized into a comorbidity of MCI and T2DM group and a T2DM group. General information was collected and some biochemical indices were tested. Difference in the alcohol sniff test score between the 2 groups was assessed by 2-sample t-test. Difference in the presence of olfactory dysfunction between the 2 groups was assessed by χ2 test, and multivariable logistic regression was used to determine the relevant factors contributing to the comorbidity of MCI and T2DM. RESULTS: Of the 472 participants, 162 were identified with MCI, making the comorbidity rate at 34.3%. Values of isopropyl alcohol sniff test were significantly different between the 2 groups [(9.15±3.22) cm vs (21.03±4.36) cm, P<0.05]. The number of patients with olfactory dysfunction also differed significantly between the 2 groups (120 vs 50). After adjustment for age, educational level, T2DM duration, fasting insulin, and glycosylated hemoglobin (HbA1c), multivariate logistic regression analysis showed older age (OR=1.14, 95% CI 1.09 to 1.20), longer course of diabetes (OR=1.21, 95% CI 1.12 to 1.31), and olfactory-impaired (OR=4.61, 95% CI 3.04 to 6.18) were independent risk factors for T2DM combined with MCI, and the high education level (OR=0.26, 95% CI 0.15 to 0.38) was an independent protective factor for T2DM combined with MCI. CONCLUSIONS: Olfactory dysfunction is an independent risk factor for the comorbidity of MCI and T2DM. Special attention should be paid to those with olfactory dysfunction when carrying out cognitive interventions in T2DM patients.


Assuntos
Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Transtornos do Olfato , Idoso , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Comorbidade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/etiologia , Fatores de Risco
4.
Iran J Public Health ; 50(7): 1398-1404, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34568178

RESUMO

Background: To explore the effects of predictive nursing intervention among patients with acute stroke. Methods: One hundred and sixty participants were included. They were hospitalized in the Department of Neurology of a third-level first-class hospital in Changsha, Hunan Province, from January to August 2019. They were categorized into control group and intervention group by random number table, with 80 patients in each group. General nursing for patients in Neurology Department was offered to the control group. On the basis of general nursing, predictive nursing intervention was offered to the intervention group. The effectiveness of predictive nursing intervention were evaluated by disparity in neurologic function, movement function, daily life ability and sleep quality before intervention and 2 weeks after intervention. The neurologic function, movement function, daily life ability and sleep quality were evaluated by National Institute of Health acute stroke scale (NIHSS), Fugl-Meyer scale, Barthel indicator, and Pittsburgh sleep quality indicator (PSQI), respectively. Results: There was no significant difference in gender, age, complications and treatment methods between two groups. There was no significant difference in the scores of NIHSS, Fugl-Meyer scale, Barthel indicator, and PSQI before intervention. The scores of NIHSS and PSQI were significantly lower in the intervention group than those in the control group, and the scores of Fugl-Meyer scale and Barthel indicator were significantly higher in the intervention group than those in the control group (P <0.05). Conclusion: Predictive nursing intervention could help improve not only neurologic function, movement function, and daily life ability, but also sleep quality among patients with acute stroke.

5.
Front Cardiovasc Med ; 8: 663346, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568440

RESUMO

Background: Adrenal myelolipoma (AML) is a nonfunctional benign neoplasm from the adrenal cortex, composed of mature fat and hematopoietic tissue. Usually, patients have no symptoms. However, some patients with hypertension and blood pressure normalize after AML surgery, indicating some connections between AML and hypertension. Materials and Methods: This was a retrospective cohort study of 369 patients diagnosed with AML from September 2008 to December 2018 collected in the Urology Department of West China Hospital, Chengdu, Sichuan, China. We collected clinical records of patients before surgery. Postoperative follow-up was also carried out for those with hypertension and whether patients needed to take antihypertensive drugs and postoperative blood pressure were recorded. We aim to explore the characteristics of both patients with AML having hypertension and having remission of hypertension in 1 year after surgery. Results: There were 369 patients with AML included in the study, 156 men and 213 women, aged 49.86 ± 11.61 years old. Among them, 121 (32.8%) patients presented with hypertension. Body mass index was significantly higher in the hypertension group than that in the nonhypertension group, even after adjusting other variables (26.26 ± 3.43 vs. 24.28 ± 3.38 kg/m2, P < 0.001 for both univariate and multivariate analyses). Sixty patients were followed up for 1-9 years, with a median follow-up of 52 months. The duration of hypertension in the remission group was shorter than that in the non-remission group (P = 0.020), and the tumor lateralization was significantly different between the two groups (P = 0.005). Conclusions: Nearly one-third of patients with AML suffered from hypertension in our study, and there existed some potential links between AML and hypertension. To be more specific, AML-related hypertension was more likely to result from obesity and renal compression by perirenal fat than from endocrine disorders or blood vessels compression. Patients with AML and with more than 3 years of hypertension might have less possibility to recover.

6.
Front Pharmacol ; 12: 559368, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33762931

RESUMO

Background: Few studies have investigated the association between regulatory emotional self-efficacy (RESE) and immunosuppressive medication adherence or the mechanisms underlying this relationship. Considering that previous evidence of immunosuppressive medication adherence depended on the level of immunosuppressive medication beliefs, a model of multiple mediation was tested in which immunosuppressive medication beliefs acted as mediators of the relationship between RESE and immunosuppressive medication adherence. Methods: A retrospective cross-sectional study was performed in 293 renal transplant patients during outpatient follow-ups from November 2019 to February 2020 in China. All participants completed a general demographic questionnaire, the Chinese version of the RESE, the Beliefs about Medication Questionnaire, and the Basel Assessment of Adherence with Immunosuppressive Medication Scale (BAASIS). Spearson correlation analysis was carried out to identify the correlation between RESE and immunosuppressive medication adherence. Binary logistic regression analysis was performed to confirm factors associated with immunosuppressive medication adherence in renal transplant recipients. Mediating effect analysis was used to explore the internal interaction between RESE and immunosuppressive medication adherence. Results: A total of 293 renal transplant patients were recruited, including 111 women and 182 men with a mean age of 42.5 years (SD = 10.0). A total of 23.21% of patients exhibited immunosuppressive medication none-adherence behavior, and 12.97% reported altering the prescribed amount of immunosuppressive medication without physician permission, which was most popular behavior among patients. The mean RESE score was 45.78 ± 6.12; the positive (POS) score was the highest, and the anger-irritation (ANG) score was the lowest. The correlation analysis results showed that RESE (r = -0.642, p < 0.01) and immunosuppressive medication beliefs (r = -0.534, p < 0.01) were significantly associated with immunosuppressive medication adherence. Binary logistic regression analysis indicated that marital status, fertility status, rejection, immunosuppressive medication beliefs, and RESE were found to be independent predictors of immunosuppressive medication adherence [R 2 = 0.803, p < 0.05]. The results of the mediating effect analysis showed that immunosuppressive medication necessity had a partial mediating effect, RESE directly and indirectly affected immunosuppressive medication adherence via immunosuppressive medication necessity, and immunosuppressive medication concerns were not a mediator between RESE and immunosuppressive medication adherence. Conclusion: The levels of immunosuppressive medication adherence in renal transplant patients need to be improved in China. Marital status, fertility status, rejection, immunosuppressive medication beliefs, and RESE were major factors affecting immunosuppressive medication adherence. RESE could affect immunosuppressive medication adherence indirectly through immunosuppressive medication necessity.

7.
Prostate ; 81(6): 347-356, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33710645

RESUMO

BACKGROUND: Prostate cancer (PCa) is a leading cause of death in men, and effective treatment of PCa requires further development. Our study aimed to investigate the potential role of vinculin (VCL) in PCa progression in vitro and in vivo. METHODS: We investigated the methylation level of the VCL promoter based on the TCGA database. The knockdown efficacy of VCL gene expression was confirmed by quantitative polymerase chain reaction, Western blot analysis, and immunofluorescence. Furthermore, morphological changes in PCa cells were detected using phalloidin staining. The mobility of PCa cells was measured using transwell assays and high-content analysis. Moreover, cell growth and viability were determined using the colony formation and cell counting kit-8 assays. The role of VCL in tumor growth in vivo was investigated using a subcutaneous xenograft model generated by injecting tumor cells into the right flank of BALB/c nude mice. RESULTS: The methylation level of the VCL promoter in PCa was significantly downregulated concomitant with age and the progression of nodal metastasis. VCL expression was markedly decreased by shRNA. Importantly, VCL knockdown significantly changed the cell morphology; inhibited the migration, invasion, and movement; and repressed colony formation and viability of PCa cells in vitro. Furthermore, downregulation of VCL suppressed tumor growth in vivo. CONCLUSIONS: Our study comprehensively evaluated the role of VCL in PCa progression in vivo and in vitro. The findings of the present study suggest that VCL can be a potential target for PCa prognosis and treatment.


Assuntos
Neoplasias da Próstata/genética , Vinculina/genética , Animais , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Progressão da Doença , Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Invasividade Neoplásica , Metástase Neoplásica , Transplante de Neoplasias , Processos Neoplásicos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/fisiopatologia , Neoplasias da Próstata/secundário
8.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(6): 733-738, 2020 Jun 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32879132

RESUMO

Coping style is a cognitive or behavioral strategy taken by individuals in the face of stress. Positive coping style is of great significance for improving the physical and mental outcomes of elderly patients with urinary incontinence. Accurate assessment of coping styles for the elderly patients with urinary incontinence can provide reference for the subsequent development of intervention measures. The existing coping style assessment tools for elderly incontinence at home and abroad include specific scale of incontinence, relevant psychological assessment scale, and universal scale. In a word, the progress in the studies on relevant assessment tools is slow, and it mainly focuses on the assessment of female population. The assessment content is relatively single and lacks of pertinence and systematization. In the future, a comprehensive scale with strong adaptability should be developed based on the characteristics of elderly incontinence patients in China.


Assuntos
Adaptação Psicológica , Incontinência Urinária , Idoso , China , Feminino , Humanos
9.
Biomaterials ; 256: 120217, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32736172

RESUMO

The high potential for cancer relapse has emerged as a crucial challenge of human bladder cancer treatment. To date, those stem-like bladder cancer cells (BCSCs) have been considered as seeds that induce frequent tumor recurrence. However, the cell origin of cancer stem cells (CSCs) is still a controversial issue, due in part to the findings that CSCs not only origin from normal stem cells but also converted from differentiated tumor cells. Here, we describe a biomaterial 3D collagen I gel culture system, where non-tumorigenic cells can obtain tumorigenic potential and revert back into CSCs through the integrin α2ß1/PI3K/AKT/NF-κB cascade, resulting in the tumorigenesis in bladder tissues. Furthermore, inhibiting this integrin α2ß1/PI3K/AKT/NF-κB signal pathways can significantly impair the tumorigenic capacity of CSCs. Simultaneously, in vivo studies demonstrate that IFN-γ secreted by T cells can trigger those CSCs into dormancy through the IDO/Kyn/AHR/P27 cascade, which elicit chemotherapy resistance and cancer relapse. To address the challenges of suppressing bladder tumor growth and preventing tumor reoccurrence, we use IDO and integrin α2ß1 signal pathway inhibitors combine with chemotherapeutic agents to awaken dormant bladder CSCs and inhibit their tumorigenic ability as well as effectively eliminate CSCs. The therapeutic approaches we propose provide new insights for eradicating tumors and reducing bladder cancer relapse after therapy.


Assuntos
Microambiente Tumoral , Neoplasias da Bexiga Urinária , Materiais Biocompatíveis , Carcinogênese , Linhagem Celular Tumoral , Colágeno , Humanos , Recidiva Local de Neoplasia , Células-Tronco Neoplásicas , Fosfatidilinositol 3-Quinases
10.
Am J Transl Res ; 12(6): 2769-2780, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32655808

RESUMO

BACKGROUND: Epilepsy (EP) is a very dangerous neurological disease. MiR-181b was reported to play a regulatory role during the progression of EP. However, the mechanism by which miR-181b regulates the process of EP remains unclear. METHODS: Hippocampal neurons were extracted from rats, which were treated with magnesium-free to mimic EP in vitro. CCK-8 assay was performed to test the cell viability. Gene and protein expressions in hippocampal neurons were detected by qRT-PCR, immunofluorescence and western blot, respectively. In addition, TUNEL staining was performed to test the cell apoptosis. Finally, dual luciferase report assay was used to verify the relation between miR-181b, ZNF883 and RASSF1A. RESULTS: Magnesium-free significantly inhibited the proliferation of hippocampal neurons, which was reversed by miR-181b mimics. In consistent, magnesium-free induced apoptosis of cells was notably inhibited by miR-181b mimics. In addition, miR-181b suppressed the progression of EP via directly targeting RASSF1A and activating PI3K/Akt signaling. Finally, upregulation of miR-181b notably suppressed the progression of EP via regulation of ZNF883. CONCLUSION: MiR-181b suppressed the progression of epilepsy via regulation of RASSF1A and lncRNA ZNF883. Thus, miR-181b might serve as a new target for treatment of EP.

11.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 37(2): 207-210, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32329270

RESUMO

Three dimensional (3D) bioprinting is a new biological tissue engineering technology in recent years. The development of 3D bioprinting is conducive to solving the current problems of clinical tissue and organ repairing. This article provides a review about the clinical and research status of 3D bioprinting and urinary system reconstruction. Furthermore, the feasibility and clinical value of 3D bioprinting in urinary system reconstruction will be also discussed.


Assuntos
Bioimpressão/tendências , Impressão Tridimensional , Engenharia Tecidual/tendências , Sistema Urinário , Humanos
12.
J Cell Mol Med ; 24(9): 5082-5096, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32191396

RESUMO

Benign prostatic hyperplasia (BPH) occurs most commonly among older men, often accompanied by chronic tissue inflammation. Although its aetiology remains unclear, autoimmune dysregulation may contribute to BPH. Regulatory T cells (Tregs) prevent autoimmune responses and maintain immune homeostasis. In this study, we aimed to investigate Tregs frequency, phenotype, and function in BPH patients and to evaluate adoptive transfer Tregs for immunotherapy in mice with BPH via CD39. Prostate specimens and peripheral blood from BPH patients were used to investigate Treg subsets, phenotype and Treg-associated cytokine production. Sorted CD39+/- Tregs from healthy mice were adoptively transferred into mice before or after testosterone propionate administration. The Tregs percentage in peripheral blood from BPH patients was attenuated, exhibiting low Foxp3 and CD39 expression with low levels of serum IL-10, IL-35 and TGF-ß. Immunohistochemistry revealed Foxp3+ cells were significantly diminished in BPH prostate with severe inflammatory. Although the Tregs subset was comprised of more effector/memory Tregs, CD39 was still down-regulated on effector/memory Tregs in BPH patients. Before or after testosterone propionate administration, no alterations of BPH symptoms were observed due to CD39- Tregs in mice, however, CD39+ Tregs existed more potency than Tregs to regulate prostatic hyperplasia and inhibit inflammation by decreasing IL-1ß and PSA secretion, and increasing IL-10 and TGF-ß secretion. Furthermore, adoptive transfer with functional Tregs not only improved prostate hyperplasia but also regulated muscle cell proliferation in bladder. Adoptive transfer with Tregs may provide a novel method for the prevention and treatment of BPH clinically.


Assuntos
Apirase/metabolismo , Inflamação/metabolismo , Hiperplasia Prostática/terapia , Linfócitos T Reguladores/metabolismo , Transferência Adotiva , Adulto , Animais , Autoimunidade , Citocinas/metabolismo , Progressão da Doença , Regulação da Expressão Gênica , Humanos , Imunoterapia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fenótipo , Próstata/metabolismo , Hiperplasia Prostática/metabolismo , Propionato de Testosterona/administração & dosagem , Adulto Jovem
13.
J Cell Biochem ; 121(11): 4496-4504, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32065420

RESUMO

Extracellular matrix (ECM) accumulation plays a key role in the progression of bladder outlet obstruction (BOO). Muscarinic receptors have been widely reported to serve as pivotal regulators in lung tissue remodeling. However, the influence of them on human bladder smooth muscle cells (HBSMCs) and the underlying molecular mechanisms have not yet been evaluated. The purposes of the present study are to investigate the effect of muscarinic receptors on the synthesis of ECM in HBSMCs and the involvement of intracellular signal transducers. The results indicated that M1 -M5 muscarinic receptors were all encoded in HBSMCs. The expression rank order was M2 > M1 > M5 > M3 > M4 . The gene and protein expression of collagen I (COL1), TIMP-1, and TIMP-2 was carbachol (CCH) concentration-dependently enhanced. The synthesis of COL1 in the supernatant of cell culture medium was significantly elevated by exposure to CCH. The CCH-induced protein expression of COL1, TIMP-1, and TIMP-2, however, was obviously reduced by the pretreatment of muscarinic receptor antagonists, atropine, and M3 -preferring antagonist (1,1-dimethyl-4-diphenyl-acetoxypiperidinium iodide [4-DAMP]). Furthermore, ERK1/2 was activated by 100 µM CCH when compared with the control group and the pretreatment of ERK1/2 inhibitor significantly suppressed the synthesis of COL1 induced by 100 µM CCH. Besides, CCH-induced phosphorylation of ERK1/2 was remarkably restrained by the pretreatment of 4-DAMP. All in all, these findings demonstrated that M3 receptor can modulate extracellular matrix synthesis via the ERK1/2 signaling pathway, which may provide potential novel therapeutic targets for BOO.


Assuntos
Matriz Extracelular/metabolismo , Regulação da Expressão Gênica , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Miócitos de Músculo Liso/metabolismo , Receptor Muscarínico M3/metabolismo , Bexiga Urinária/metabolismo , Proliferação de Células , Células Cultivadas , Matriz Extracelular/efeitos dos fármacos , Humanos , Antagonistas Muscarínicos/farmacologia , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Fosforilação , Receptor Muscarínico M3/química , Bexiga Urinária/citologia , Bexiga Urinária/efeitos dos fármacos
14.
Asian J Androl ; 22(2): 177-183, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31169138

RESUMO

This study aimed to further validate the prognostic role of fibrinogen in upper tract urothelial carcinoma (UTUC) in a large Chinese cohort. A total of 703 patients who underwent radical nephroureterectomy were retrospectively identified. Fibrinogen levels of ≥4.025 g l-1 were defined as elevated. Logistic regression analysis was performed to determine the association between fibrinogen and adverse pathological features. Kaplan-Meier analysis and Cox regression models were used to assess the associations of fibrinogen with cancer-specific survival (CSS), disease recurrence-free survival (RFS), and overall survival (OS). Harrell c-index and decision curve analysis were used to assess the clinical utility of multivariate models. The median follow-up duration was 42 (range: 1-168) months. Logistic regression analysis revealed that elevated fibrinogen was associated with higher tumor stage and grade, lymph node involvement, lymphovascular invasion, sessile carcinoma, concomitant variant histology, and positive surgical margins (all P < 0.05). Multivariate Cox regression analysis demonstrated that elevated fibrinogen was independently associated with decreased CSS (hazard ratio [HR]: 2.33; P < 0.001), RFS (HR: 2.09; P < 0.001), and OS (HR: 2.09; P < 0.001). The predictive accuracies of the multivariate models were improved by 3.2%, 2.0%, and 2.8% for CSS, RFS, and OS, respectively, when fibrinogen was added. Decision curve analysis showed an added benefit for CSS prediction when fibrinogen was added to the model. Preoperative fibrinogen may be a strong independent predictor of worse oncologic outcomes in UTUC; therefore, it may be valuable to apply this marker to the current risk stratification in UTUC.


Assuntos
Carcinoma de Células de Transição/sangue , Fibrinogênio/análise , Nefroureterectomia , Neoplasias Urológicas/sangue , Idoso , Biomarcadores Tumorais , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , China , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia , Neoplasias Urológicas/cirurgia
15.
Medicine (Baltimore) ; 98(35): e17060, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464967

RESUMO

BACKGROUND: To evaluate the effectiveness and safety of neoadjuvant chemotherapy (NAC) for locally advance prostate patients undergoing radical prostatectomy. METHODS: PubMed/Medline, EMBASE, Web of Science, Ovid, Web of Knowledge, and Cochrane Library will be searched for studies related to the topic. The identification, inclusion and exclusion flow charts will be conducted according to PRISMA guidelines. The identified reports will be critically appraised using GRADE approach. Bias and heterogeneity of included studies will be assessed, and outcome measurements from individual studies will be combined with 95% confidence interval using a fixed- or random-effects model if qualified. RESULTS: This study will provide evidence and data on the tolerance and efficacy of NAC followed by radical prostatectomy (RP). CONCLUSION: The application of taxanes-based chemotherapy has been widened to metastatic hormone sensitive prostate cancer in recent years. To be more vigorous, whether neoadjuvant administration of these cytotoxic agents can improve the outcome of RP in locally advance prostate cancer patients has been explored. This study aims to synthesis data regarding the adverse effect, response rate, recurrence, and survival from multiple trials, and to guide the healthcare practitioners using an evidence-based approach.


Assuntos
Prostatectomia/métodos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia , Fatores Etários , Quimioterapia Adjuvante , Humanos , Masculino , Projetos de Pesquisa , Fatores Socioeconômicos
16.
Clin Genitourin Cancer ; 17(5): e968-e980, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31229458

RESUMO

BACKGROUND: Previous studies have revealed lymph node density (LND) to be an independent prognostic factor in cancer. However, data from 20 years ago failed to demonstrate the prognostic value of LND in node-positive renal-cell carcinoma (RCC). This study was undertaken to comprehensively investigate the prognostic value of LND in node-positive RCC. PATIENTS AND METHODS: Within the Surveillance, Epidemiology and End Results database, we accessed data on patients diagnosed with histologically confirmed node-positive RCC from 2004 to 2014. The cubic spline smoothing technique and Cox regression were used to evaluate the correlation between LND and cancer-specific mortality (CSM). The X-Tile program was used to identify the optimal cut point of LND in node-positive RCC. Robustness of the results in various subgroups was also explored. Univariable and multivariable analyses were performed to determine predictors of CSM. Sensitivity analyses were performed. RESULTS: A total of 1750 node-positive RCCs were identified. We found a nonlinear positive correlation between the likelihood of CSM and LND. X-Tile analysis identified best cut point of LND as 35% with a maximum chi-square of 18.58. Every 10% increase in LND increased CSM by 5% (hazard ratio = 1.05; 95% confidence interval, 1.02-1.07; P < .0001), and LND ≥ 35% was associated with 41% increase in CSM (hazard ratio = 1.41; 95% confidence interval, 1.20-1.65; P < .0001) in fully adjusted Cox regression. Results of sensitivity analyses were consistent with those of the primary analysis. CONCLUSION: LND is an independent prognostic factor in node-positive RCC and should be incorporated into the cancer staging system.


Assuntos
Carcinoma de Células Renais/mortalidade , Neoplasias Renais/mortalidade , Linfonodos/patologia , Idoso , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/patologia , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Medição de Risco , Programa de SEER
17.
Mol Genet Genomic Med ; 7(5): e619, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30829463

RESUMO

BACKGROUND: Osteogenesis imperfecta (OI), a genetically determined connective tissue disorder, is characterized by increased bone fragility and reduced bone mass. Clinical presentation severity ranges from very mild types with nearly no fractures to intrauterine fractures and perinatal lethality. It can be accompanied by blue sclerae, dentinogenesis imperfecta (DI), hearing loss, muscle weakness, ligament laxity, and skin fragility. This study sought to identify pathogenic gene variants in a four-generation Han Chinese family with OI type I. METHODS: In order to unveil the molecular genetic factors underlying the disease phenotype, whole exome sequencing in a member, with OI type I, of a Han Chinese family from Hunan, China was performed. The variant identified by whole exome sequencing was further tested by Sanger sequencing in the family members. RESULTS: A heterozygous missense variant (NM_000089.3: c.3197G>T; NP_000080.2: p.Gly1066Val) in the collagen type I alpha 2 chain gene (COL1A2) was identified in four patients. It co-segregated with the disease in the family. CONCLUSION: The sequence variant may be a disease-causing factor resulting in abnormal type I procollagen synthesis and leading to OI type I. This finding has significant implications for genetic counseling and clinical monitoring of high-risk families and may be helpful for understanding pathogenic mechanism of OI and developing therapies.


Assuntos
Colágeno Tipo I/genética , Mutação de Sentido Incorreto , Osteogênese Imperfeita/genética , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteogênese Imperfeita/patologia , Linhagem
18.
Genet Mol Biol ; 42(1): 48-51, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30816908

RESUMO

Autosomal recessive nonsyndromic hearing loss (ARNSHL) is a genetically heterogeneous neurosensory disorder, usually characterized by congenital or prelingual hearing loss. We report a Han Chinese male, born to consanguineous parents, presenting with nonsyndromic sensorineural hearing loss, whose clinical phenotype was also consistent with auditory neuropathy spectrum disorder (ANSD). After exome sequencing, a gap junction protein beta 2 gene (GJB2) c.235delC variant in the homozygous state was detected in the patient. Both parents were heterozygous for this variant, as documented by Sanger sequencing. The known pathogenic GJB2 c.235delC variant was not detected in 200 healthy controls. It is predicted to be a disease-causing alteration by generating a truncated protein p.(L79Cfs*3), disturbing the appropriate folding and/or oligomerization of connexins and leading to defective gap junction channels. This study shows that the association of homozygosity of the GJB2 c.235delC variant with ARNSHL and ANSD in a patient.

19.
Biochem Biophys Res Commun ; 511(3): 650-657, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30826058

RESUMO

Although vascular endothelial growth factor (VEGF) promotes vascular permeability and results in edema, studies have suggested it may protect the lung from inflammatory injury via poorly understood mechanisms. Using a mouse model of extracorporeal circulation (ECC), we found that levels of intravenous VEGF increased in lung tissue and inhibited inflammation, thereby attenuating lung injury. These effects could be obtained by intravenous injection or inhalation of VEGF, and they were abolished by treatment with anti-VEGF antibody. Detailed analyses using immunofluorescence and flow cytometry showed that VEGF increased the homing of CD133+ VEGFR1+ progenitors to lung tissue, and this homing could be mimicked in a dose-dependent manner by treatment with VEGF receptor 1 (VEGFR1) agonist and blocked by treatment with anti-VEGFR1 antibody. Interestingly, we found that exposing pulmonary monocytes in vitro to VEGF did not inhibit ECC-induced inflammation. Our results suggest that VEGF enters lung tissues from the circulation and that it attenuates lung injury not by directly inhibiting release of pro-inflammatory factors but by binding to VEGFR1 to recruit CD133+ progenitors. These progenitors then inhibit local inflammation.


Assuntos
Antígeno AC133/imunologia , Lesão Pulmonar/imunologia , Pneumonia/imunologia , Células-Tronco/imunologia , Fator A de Crescimento do Endotélio Vascular/imunologia , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/imunologia , Animais , Lesão Pulmonar/complicações , Lesão Pulmonar/patologia , Masculino , Camundongos Endogâmicos C57BL , Pneumonia/complicações , Pneumonia/patologia
20.
Medicine (Baltimore) ; 98(7): e14573, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30762807

RESUMO

BACKGROUND: To evaluate the diagnostic effectiveness and predictive value of fluorescence in situ hybridization (FISH) in the surveillance of non-muscle invasive bladder cancer (NMIBC). METHODS: PubMed/Medline, EMBASE, Web of Science, Ovid, Web of Knowledge, and Cochrane Library will be searched for studies related to the topic. The identification, inclusion, and exclusion flowcharts will be conducted according to preferred reporting items for systematic reviews and meta-analysis guidelines. The identified reports will be critically appraised according to the Newcastle-Ottawa scale, quality assessment of diagnostic accuracy studies-2 and standards for reporting of diagnostic accuracy 2015. Forest plots will be generated to display hazard ratios, sensitivities, and specificities. Pooled estimates with their 95% confidence intervals will be calculated using the bivariate model, the hierarchical summary receiver operating characteristic model and a fixed- or random-effects model. RESULTS: This study will provide evidence and data to form a comprehensive understanding of the value of FISH in the surveillance of NMIBC. CONCLUSION: The diagnostic efficacy of FISH will be affected by post-therapy factors. However, FISH still could facilitate the surveillance of NMIBC owing to its non-invasive feature. This study will improve the clinical decision-making and enlighten the future research of NMIBC.


Assuntos
Hibridização in Situ Fluorescente/métodos , Projetos de Pesquisa , Neoplasias da Bexiga Urinária/patologia , Progressão da Doença , Humanos , Invasividade Neoplásica , Recidiva Local de Neoplasia , Análise de Sobrevida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...