RESUMO
The ratio of red light to far-red light (R:FR) is perceived by light receptors and consequently regulates plant architecture. Regulation of shoot branching by R:FR ratio involves plant hormones. However, the roles of strigolactone (SL), the key shoot branching hormone and the interplay of different hormones in the light regulation of shoot branching in tomato (Solanum lycopersicum) are elusive. Here, we found that defects in SL synthesis genes CAROTENOID CLEAVAGE DIOXYGENASE 7 (CCD7) and CCD8 in tomato resulted in more lateral bud growth but failed to reverse the FR inhibition of lateral bud growth, which was associated with increased auxin synthesis and decreased synthesis of cytokinin (CK) and brassinosteroid (BR). Treatment of auxin also inhibited shoot branching in ccd mutants. However, CK released the FR inhibition of lateral bud growth in ccd mutants, concomitant with the upregulation of BR synthesis genes. Furthermore, plants that overexpressed BR synthesis gene showed more lateral bud growth and the shoot branching was less sensitive to the low R:FR ratio. The results indicate that SL synthesis is dispensable for light regulation of shoot branching in tomato. Auxin mediates the response to R:FR ratio to regulate shoot branching by suppressing CK and BR synthesis.
Assuntos
Solanum lycopersicum , Solanum lycopersicum/genética , Luz Vermelha , Brotos de Planta/metabolismo , Citocininas , Lactonas , Ácidos Indolacéticos , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
The control of apical dominance involves auxin, strigolactones (SLs), cytokinins (CKs), and sugars, but the mechanistic controls of this regulatory network are not fully understood. Here, we show that brassinosteroid (BR) promotes bud outgrowth in tomato through the direct transcriptional regulation of BRANCHED1 (BRC1) by the BR signaling component BRASSINAZOLE-RESISTANT1 (BZR1). Attenuated responses to the removal of the apical bud, the inhibition of auxin, SLs or gibberellin synthesis, or treatment with CK and sucrose, were observed in bud outgrowth and the levels of BRC1 transcripts in the BR-deficient or bzr1 mutants. Furthermore, the accumulation of BR and the dephosphorylated form of BZR1 were increased by apical bud removal, inhibition of auxin, and SLs synthesis or treatment with CK and sucrose. These responses were decreased in the DELLA-deficient mutant. In addition, CK accumulation was inhibited by auxin and SLs, and decreased in the DELLA-deficient mutant, but it was increased in response to sucrose treatment. CK promoted BR synthesis in axillary buds through the action of the type-B response regulator, RR10. Our results demonstrate that BR signaling integrates multiple pathways that control shoot branching. Local BR signaling in axillary buds is therefore a potential target for shaping plant architecture.
Assuntos
Brassinosteroides/metabolismo , Transdução de Sinais , Solanum lycopersicum/metabolismo , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: The combination therapy of hydrocortisone, vitamin C, and thiamine has been proposed as a potential treatment in patients with sepsis and septic shock. However, subsequent trials have reported conflicting results in relation to survival outcomes. Hence, we performed this randomized controlled trial (RCT) to evaluate the efficacy and safety of early combination therapy among adult patients with septic shock. METHODS: This single-center, double-blind RCT enrolled adult patients with diagnosis of septic shock within 12 h from Northern Jiangsu People's Hospital between February 2019 and June 2021. Recruited patients were randomized 1:1 to receive intervention (hydrocortisone 200 mg daily, vitamin C 2 g every 6 h, and thiamine 200 mg every 12 h) or placebo (0.9% saline) for 5 days or until ICU discharge. The primary endpoint was 90-day mortality. The secondary endpoints included mortality at day 28, ICU discharge, and hospital discharge; shock reversal; 72-h Delta SOFA score; ICU-free days, vasopressor-free days, and ventilator support -free days up to day 28; ICU length of stay (LOS) and hospital LOS. RESULTS: Among 426 patients randomized, a total of 408 patients with septic shock were included in the per-protocol (PP) analysis, of which 203 were assigned to the intervention group and 205 to the placebo group. In the PP population, the primary outcome of 90-day mortality was 39.9% (81/203) and 39.0% (80/205) in the intervention and the placebo groups, respectively, and was not significantly different (P = 0.86). There was no significant difference between two groups in 28-day mortality (36.5% vs. 36.1%, P = 0.94) or the ICU mortality (31.5% vs. 28.8%, P = 0.55) and hospital mortality (34.5% vs. 33.2%, P = 0.78). No other secondary outcomes showed significant differences between two groups, including shock reversal, vasopressor-free days, and ICU LOS. Intention-to-treat analysis included all the 426 patients and confirmed these results (all P > 0.05). CONCLUSION: Among adult patients with septic shock, early use of hydrocortisone, vitamin C, and thiamine combination therapy compared with placebo did not confer survival benefits. Trial registration ClinicalTrials.gov: NCT03872011 , registration date: March 12, 2019.
Assuntos
Choque Séptico , Adulto , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Quimioterapia Combinada , Humanos , Hidrocortisona , Solução Salina/uso terapêutico , Tiamina/farmacologia , Tiamina/uso terapêutico , Vasoconstritores/uso terapêutico , Vitaminas/uso terapêuticoRESUMO
BACKGROUND: The purpose of this study was to compare the outcome between percutaneous pedicle screw fixation (PPSF) and the mini-open Wiltse approach with pedicle screw fixation (MWPSF) for neurologically intact thoracolumbar fractures. METHODS: From January 2017 to January 2019, ninety-four patients with neurologically intact thoracolumbar fractures were included in this study. In this retrospective study, forty-nine patients were operated with the PPSF and forty-five patients received MWPSF. The clinical information, surgery-related results and radiographic outcome were collected and compared between the two groups. RESULTS: There was no significant difference between the two groups in total length of incisions, blood loss, post-operative hospitalization time, visual analog scale (VAS) score and Oswestry disability index (ODI) score. There was also no significant difference in the accuracy rate of pedicle screw placement between two groups; however, the facet joint violation (FJV) was significantly higher in the PPSF group. The atrophic area of multifidus muscle in the PPSF group is significantly larger than that in the MWPSF group and the operative time of MWPSF group was shorter than that in the PPSF group. Meanwhile, the PPSF group obtaining significantly more cumulative exposure to radiation (p < 0.001). The result of vertebral body angle (VBA), Cobb's angle and AVH rate in the MWPSF group were significantly better than those in the PPSF group at the last post-operative follow-up. CONCLUSIONS: Both minimally invasive treatment techniques (PPSF and MWPSF) are safe and effective in treatment of neurologically intact thoracolumbar fractures. Nevertheless, our results indicate that MWPSF may be a better choice for neurologically intact thoracolumbar fractures, since it protects multifidus muscle, and decreases facet joint violation, operation time, as well as radiation exposure. In addition, MWPSF was associated with better reduction of kyphosis.
Assuntos
Fraturas Ósseas , Parafusos Pediculares , Fraturas da Coluna Vertebral , Fixação Interna de Fraturas/métodos , Humanos , Vértebras Lombares/lesões , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/lesões , Vértebras Torácicas/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: The efficacy of low-dose hydrocortisone therapy in the management of septic shock remains controversial in critical care for many years. Hence, we performed this meta-analysis of randomized controlled trials (RCTs) with trial sequential analysis (TSA) to evaluate its effect on clinical outcome among adult patients with septic shock. METHODS: We identified relevant RCTs published from inception to March 7, 2018 comparing low-dose hydrocortisone with placebo or no intervention in adults admitted to the intensive care unit (ICU) for septic shock. Meta-analyses were performed for the primary and secondary outcomes. The risk of bias was assessed using the Cochrane Collaboration's instrument. Trial sequential analysis was used to pool the results from the included studies for the primary outcomes. RESULTS: Thirteen studies were retrieved by our literature search strategy. There were no significant differences in 28-day mortality (odds ratio [OR] = 0.90, 95% confidence interval [CI] = 0.81-1.00; P = .05) and hospital mortality (OR = 0.91, 95% CI = 0.82-1.02; P = .09) between the 2 groups, which were confirmed by TSA. However, there was a significant improvement in shock reversal in the hydrocortisone group (OR = 1.33, 95% CI = 1.02-1.72; P = .03). Furthermore, subgroup analyses revealed that hydrocortisone plus fludrocortisone statistically reduced the rate of 28-day mortality (OR = 0.79, 95% CI = 0.64-0.97; P = .03), ICU mortality (OR = 0.77, 95% CI = 0.63-0.95; P = .02), and hospital mortality (OR = 0.77, 95% CI = 0.63-0.95; P = .01) in comparison with the placebo, the results were also confirmed by TSA. CONCLUSION: Among adult patients with septic shock, the use of low-dose hydrocortisone compared with control did not confer overall survival benefits, albeit improving shock reversal rate. The benefit of reducing 28-day mortality, ICU mortality, and hospital mortality was observed in combination use of hydrocortisone and fludrocortisone.
Assuntos
Anti-Inflamatórios/administração & dosagem , Cuidados Críticos/métodos , Hidrocortisona/administração & dosagem , Choque Séptico/tratamento farmacológico , Choque Séptico/mortalidade , Adulto , Idoso , Resultados de Cuidados Críticos , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The objective of this study was to assess cost and effectiveness of osimertinib in treating newly diagnosed advanced non-small cell lung cancer with an epidermal growth factor receptor (EGFR) mutation from a public payer's perspective in the U.S. and China. MATERIALS AND METHODS: Markov models were developed to compare three treatment strategies: first-line use of osimertinib, first-line use of the standard first-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) followed by the second-line use of osimertinib, and the standard first-generation EGFR-TKI therapy (standard care [SOC]). Clinical data, cost, and utility data were mainly derived from published literatures. Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the incremental cost per quality-adjusted life year (QALY) between the treatments. RESULTS: The resultant incremental cost per QALY gained for the first-line osimertinib versus SOC was $312,903 in the U.S. and $41,512 in China. The incremental cost per QALY for the second-line osimertinib versus SOC was $284,532 in the U.S. and $38,860 in China. The probability of the SOC strategy being cost-effective is 1.0 if the willingness to pay threshold is below $150,000/QALY in the U.S. and below $30,000/QALY in China. CONCLUSION: Osimertinib as first-line treatment could gain more health benefits in comparison with standard EGFR-TKIs or second-line use of osimertinib. However, because of the high cost of treatment, the cost-effectiveness analyses were not in favor of the first-line use of osimertinib from a public payer's perspective in the U.S. and China. IMPLICATIONS FOR PRACTICE: Osimertinib as first-line treatment yielded the greatest health outcomes but is not a cost-effective strategy for lung cancer in the U.S. and China. The price of osimertinib has a substantial impact on economic outcomes.
Assuntos
Acrilamidas/uso terapêutico , Compostos de Anilina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/economia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/economia , Acrilamidas/farmacologia , Compostos de Anilina/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Análise Custo-Benefício , Humanos , Neoplasias Pulmonares/patologia , MutaçãoRESUMO
While chemotherapy is an important and widely used therapeutic for cancer, it may facilitate cancer metastasis. Herein, we report that human lung cancer cells exert higher invasion and metastasis after chemotherapy. In a human lung cancer xenograft model, chemotherapy promotes the cancer invasion and metastasis in HMGB1-dependent manner. Further studies identify HMGB1-containing nucleosome from chemotherapy-induced apoptotic cancer cells as an effective factor. Such nucleosome functions through TLR4 and TLR9 to drive cancer invasion and metastasis. In lung cancer patients, circulating HMGB1-containing nucleosome is higher in those under chemotherapy, predicting poorly cancer cell differentiation state, enhanced cancer invasion and advanced TNM stages. These findings provide a novel mechanism by which the tumor metastasis is propagated in lung cancer patients, especially in those under chemotherapy, and a clue for developing therapeutic strategies against chemotherapy-induced metastasis.
Assuntos
Proteína HMGB1/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Nucleossomos/metabolismo , Linhagem Celular Tumoral , Progressão da Doença , Humanos , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Receptores Toll-Like/metabolismoRESUMO
OBJECTIVE: The aim of this study was to validate the reliability of the Chinese version of Addenbrooke's Cognitive Examination III (ACE-III) for detecting dementia. Furthermore, the present study compares the diagnostic accuracy of ACE-III with that of mini-mental state examination (MMSE). METHODS: One hundred seventy-seven patients with dementia and 180 healthy controls were included in the study. RESULTS: The reliability of ACE-III was very good (α-coefficient = 0.888). There was a significant negative correlation between Clinical Dementia Rating Scale score and total ACE-III score. Further, there was a positive correlation between MMSE score and total ACE-III score. Age exerted a significant effect on total ACE-III score, memory score, and language score. In the present study, the cutoff score of 83 showed a sensitivity of 91.1% and a specificity of 83.1%. CONCLUSIONS: The present findings support that the Chinese version of ACE-III is a reliable assessment tool for dementia. Copyright © 2017 John Wiley & Sons, Ltd.
Assuntos
Transtornos Cognitivos/diagnóstico , Demência/diagnóstico , Testes Neuropsicológicos/normas , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Transtornos Cognitivos/psicologia , Demência/psicologia , Feminino , Humanos , Idioma , Masculino , Pessoa de Meia-Idade , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Physiologic dose hydrocortisone is part of the suggested adjuvant therapies for patients with septic shock. However, the association between the corticosteroid therapy and mortality in patients with septic shock is still not clear. Some authors considered that the mortality is related to the time frame between development of septic shock and start of low dose hydrocortisone. Thus we designed a placebo-controlled, randomized clinical trial to assess the importance of early initiation of low dose hydrocortisone for the final outcome. METHODS: A total of 118 patients with septic shock were recruited in the study. All eligible patients were randomized to receive hydrocortisone (n=58) or normal saline (n=60). The study medication (hydrocortisone and normal saline) was initiated simultaneously with vasopressors. The primary end-point was 28-day mortality. The secondary end-points were the reversal of shock, in-hospital mortality and the duration of ICU and hospital stay. RESULTS: The proportion of patients with reversal of shock was similar in the two groups (P=0.602); There were no significant differences in 28-day or hospital all-cause mortality; length of stay in the ICU or hospital between patients treated with hydrocortisone or normal saline. CONCLUSION: The early initiation of low-dose of hydrocortisone did not decrease the risk of mortality, and the length of stay in the ICU or hospital in adults with septic shock. TRIAL REGISTRATION: www.clinicaltrials.govNCT02580240.
Assuntos
Anti-Inflamatórios/administração & dosagem , Hidratação/métodos , Hidrocortisona/administração & dosagem , Tempo de Internação/estatística & dados numéricos , Choque Séptico/tratamento farmacológico , Vasoconstritores/administração & dosagem , Idoso , China/epidemiologia , Esquema de Medicação , Feminino , Mortalidade Hospitalar , Humanos , Infusões Intravenosas , Unidades de Terapia Intensiva , Masculino , Choque Séptico/mortalidade , Choque Séptico/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
This study aimed to explore the different pathogeneses of combined pulmonary fibrosis and emphysema (CPFE) from emphysema and pulmonary fibrosis. The levels of transforming growth factor-ß1 (TGF-ß1), vascular endothelial growth factor (VEGF), Krebs Von Den Lungen-6 (KL-6), matrix metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinases-1 (TIMP-1), cytokeratin 19 fragment (CYFRA21-1), squamous cell carcinoma antigen (SCC), and the telomerase activity in peripheral blood were measured in 38 CPFE patients, 50 pulmonary emphysema patients, and 34 idiopathic pulmonary fibrosis (IPF) patients. The results demonstrated that the levels of VEGF and TGF-ß1 in IPF patients were significantly higher than those in emphysema patients (p < 0.05), and no significant differences were detected between CPFE patients and other two groups (p > 0.05). The levels of KL-6 and CYFRA21-1 in IPF patients were significantly higher than those in emphysema and CPFE patients (p < 0.05), and the latter had the similar levels (p > 0.05). Among the three groups, the levels of SCC, MMP-9, TIMP-1, MMP-9/TIMP-1 ratio, and telomerase activity were not different (p > 0.05). Our study showed that VEGF, TGF-ß1, KL-6, and CYFRA21-1 may play a role in the pathogenesis of pulmonary fibrosis. The lower levels of KL-6 and CYFRA21-1 in CPFE patients may be one of the reasons why these patients develop emphysema on the basis of fibrosis.
Assuntos
Biomarcadores Tumorais/sangue , Enfisema Pulmonar/sangue , Fibrose Pulmonar/sangue , Idoso , Antígenos de Neoplasias/sangue , Feminino , Humanos , Fibrose Pulmonar Idiopática/sangue , Queratina-19/sangue , Masculino , Metaloproteinase 9 da Matriz/sangue , Mucina-1/sangue , Enfisema Pulmonar/complicações , Fibrose Pulmonar/complicações , Serpinas/sangue , Telomerase/sangue , Inibidor Tecidual de Metaloproteinase-1/sangue , Fator de Crescimento Transformador beta1/sangue , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
This study aims to investigate CNE1 and CNE2 cell proliferation and apoptosis of nasopharyngeal cancer (NPC) and X-linked inhibitor of apoptosis protein (XIAP) expression in NPC patients after radiotherapy. Quantitative real-time quantitative polymerase chain reaction (qRT-PCR) and Western Blot detected XIAP and XIAP-associated factor1 (XAF1) messenger RNA (mRNA) and protein expression of CNE1 and CNE2 in NPC cells irradiated by γ-ray; MTT and flow cytometry assays detected CNE2 cells proliferation and apoptotic rate, respectively. With a retrospective analysis of 109 NPC patients in Xinxiang Central Hospital, immunohistochemistry (IHC) method detected XIAP expression, followed by a 5-year clinical analysis of the prognosis relevance after radiotherapy. In vitro, the inhibition and apoptotic rates of cells increased with the growth of radiation dose. qRT-PCR and Western blot detection declared that XIAP mRNA and protein expression increased, whereas XAF1 mRNA and protein expression decreased with the growth of radiation dose and exposure time. And XIAP mRNA and protein expression were negatively correlated with proliferation and apoptotic rates of the cells. In vivo, positive XIAP expression rate was negatively correlated with pathological tumor-node-metastasis (p-TNM) staging and tumor differentiation. Further, high XIAP expression, high p-TNM staging, and lower degree of differentiation were significantly correlated with the decrease of NPC patients' survival rate. Additionally, XIAP expression, p-TNM staging, and degrees of differentiation were independent risk factors for the survival of the NPC patients after radiotherapy. Increased XIAP expression and decreased XAF1 expression may be one reason for the apoptosis delays of CNE1 and CNE2 cells after irradiation, and the XIAP expression or the p-TNM staging and degree of differentiation are independent risk factors for NPC patients' survival after radiotherapy, providing a molecular rationale for radiotherapy and prognosis of NPC.
Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/radioterapia , Proteínas de Neoplasias/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Proteínas Adaptadoras de Transdução de Sinal , Apoptose/genética , Apoptose/efeitos da radiação , Proteínas Reguladoras de Apoptose , Western Blotting , Proliferação de Células/genética , Proliferação de Células/efeitos da radiação , Relação Dose-Resposta à Radiação , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/metabolismo , Proteínas de Neoplasias/metabolismo , Prognóstico , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismoRESUMO
Stanniocalcin 1 (STC1) is reported to functionally participate in the development of several cancers. However, the role of STC1 in the tumorigenesis and progression of lung adenocarcinoma remains to be fully elucidated. Here, we found that the average levels of serum STC1 were 5.47, 5.53, and 6.94 ng/mL (P = 0.0045) in the healthy subjects and patients with lung adenocarcinoma at tumor stages I-II and III-IV according to Union for International Cancer Control (UICC), respectively. Subsequently, the positive correlation between the STC1 expression level in lung adenocarcinoma tissues and tumor stages was confirmed by immunohistochemical staining assay. Additionally, studies in the STC1-overexpressing or STC1-silenced stable cell lines showed that STC1 increased cell proliferation by promoting G1/S transition in cell cycle progression via up-regulating cyclin B1 and cyclin E. Moreover, studies in the STC1-overexpressing or STC1-silenced stable cell lines also showed that STC1 inhibited cell apoptosis by up-regulating the expression of anti-apoptosis proteins Bcl-2 and Bcl-xl and down-regulating the expression of pro-apoptosis proteins Bax, Bak, and Bid via the activation of the ERK and JNK signaling pathway. In addition, neutralization of STC1 with monoclonal antibody significantly increased the apoptosis of A549 cells. Taken together, our findings strongly suggest that elevated expression of STC1 protein at the III-IV stage of lung adenocarcinoma promotes tumorigenesis of lung adenocarcinoma and positively associates with the cancer progression, which may be of potential value as tumor marker in clinical tracking lung adenocarcinoma progression.
Assuntos
Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , Glicoproteínas/sangue , Neoplasias Pulmonares/sangue , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Adulto , Idoso , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
OBJECTIVE: To identify potential mutation of the colony stimulating factor 1 receptor gene (CSF1R) in a large Chinese family affected with hereditary diffuse leukoencephalopathy with spheroids (HDLS) and analyze the genotype-phenotype correlation. METHODS: The proband was evaluated physically and radiologically to ascertain the HDLS phenotype. Genomic DNA was extracted from peripheral blood samples from family members. The coding region of the CSF1R gene was amplified with PCR and subjected to direct DNA sequencing. RESULTS: There were 9 affected members (5 alive) in this five-generation family (1 member had died during the follow-up). A missense mutation c.2563C>A (p.P855T) of the CSF1R gene has been identified in the proband. The same mutation was identified in 3 affected and 1 unaffected members of the family. CONCLUSION: The family was consistent with autosomal dominant inheritance. CSF1R gene mutation is also a disease-causing mutation in Chinese patients.
Assuntos
Povo Asiático/genética , Leucoencefalopatias/genética , Mutação de Sentido Incorreto , Receptor de Fator Estimulador de Colônias de Macrófagos/genética , Adulto , Sequência de Bases , Criança , Feminino , Genes Dominantes , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , LinhagemRESUMO
OBJECTIVE: To explore the characteristics of cognitive impairment and correlation analysis in patients with chronic renal failure (CRF). METHODS: The Addenbrooke's cognitive examination revised (ACE-R) scale was used to evaluate the cognitive function for 101 cases of chronic renal failure patients (group CRF) receiving outpatient and inpatient treatments and selected 30 individuals with normal renal function as normal controls (group NC) for cross-sectional analysis. T test, receiver operating characteristic (ROC) curve and other statistical methods were adopted for comparing differences. RESULTS: (1) Compared with group NC (83.4 ± 6.5), group CRF (71.9 ± 17.6) showed significantly statistical difference on Addenbrooke's cognitive examination revised (ACE-R) scale scores (P < 0.01); (2)compared with normal controls, the patients with CRF had significantly statistical difference on the scores of visual spatial ability (11.5 ± 3.2, 14.0 ± 3.0 respectively), language fluency (7.0 ± 2.6, 8.7 ± 1.9) (P < 0.01) and memory (18.1 ± 7.0, 21.5 ± 3.6 respectively) (P < 0.05); (3) the cognitive function of patients with CRF were significantly positive correlated with glomerular filtration rate (GFR) (r = 0.614, P < 0.01) and negatively correlated with the duration of illness (r = -0.492, P < 0.01); (4) From ROC curve and the area under curve (AUC), ACE-R scale (AUC = 0.680) showed a higher sensitivity than mini-mental state examination scale (AUC = 0.576) in assessing cognitive function in patients with CRF (P < 0.01). CONCLUSION: (1) Under similar basic conditions of age, level of education and background, CRF patients showed significant damage overall cognitive function, cognitive impairment in visual spatial ability, executive function, long-term memory and logical judgment ability was particularly impaired. Immediate and delayed memory, attention, orientation and language ability also manifested different degrees of decline; (2) the severity of cognitive impairment in patients with CFR was closely related with the level of GFR; (3) the ACE-R scale showed a higher sensitivity than mini-mental state examination scale in assessing cognitive function in patients with CRF.
Assuntos
Transtornos Cognitivos , Falência Renal Crônica , Testes Neuropsicológicos , Área Sob a Curva , Atenção , Estudos Transversais , Humanos , Memória , Curva ROCRESUMO
Disruption of the epithelial-mesenchymal transition (EMT) of activated lung cells is an important strategy to inhibit the progression of idiopathic pulmonary fibrosis (IPF). The present study investigated the role of exosomes derived from airway basal cells on EMT of lung cells and elucidate the underlying mechanism. Exosomes were characterized by nanoparticle tracking analysis, transmission electron microscopy imaging and markers detection. The role of exosome on the EMT of lung epithelial cells and lung fibroblasts induced by TGF-ß1 was detected. RNA sequencing screened dysregulated genes in exosome-treated group, followed by the bioinformatical analysis. One of the candidates, anoctamin-1 (ANO1), was selected for further gain-and-loss phenotype assays. A bleomycin-induced pulmonary fibrosis model was used to evaluate the treatment effect of exosomes. Exosomes were round-like and positively expressed CD63 and tumor susceptibility gene 101 protein. Treatment with exosomes inhibited the EMT of lung cells activated by TGF-ß1. 4158 dysregulated genes were identified in exosome-treated group under the threshold of |log2 fold-change| value >1 and they were involved in the metabolism of various molecules, as well as motility-related biological processes. A key gene, ANO1, was verified by reverse transcription-quantitative PCR, whose overexpression induced the EMT of lung cells. By contrast, ANO1 knockdown reversed the EMT induced by TGF-ß1. In vivo assay indicated that exosome treatment ameliorated pulmonary fibrosis and inhibited the upregulation of ANO1 induced by bleomycin. In conclusion, airway basal cell-derived exosomes suppressed the EMT of lung cells via the downregulation of ANO1. These exosomes represent a potential therapeutic option for patients with IPF.
RESUMO
In this paper, a new type of recycled polyurethane material is used as a new type of wall insulation material, and the new building insulation wall made of this paper has high efficiency thermal insulation and energy-saving characteristics and also has certain environmental significance. The thermal conductivity of the new building cold insulation recycled polyurethane material is 0.023 W/(m·K), and the thermal conductivity of the new building insulation wall prepared is 0.297 W/(m·K). Compared with traditional double-sided plastered porous wall tiles, it can save 85.4% of energy consumption per square meter, with higher thermal insulation characteristics and economic benefits. The preparation of a new type of building insulation wall proposed in this paper provides a new and green way for wall insulation.
RESUMO
In this study, a liquid regenerated polyether polyol was obtained after the degradation of waste PU foam by the two-component decrosslinker agents ethylene glycol and ethanolamine. The regenerated polyol-based polyurethane foam was modified by adding different ratios of SiO2 aerogel through the self-preparation of silica aerogel (SiO2 aerogel) to prepare aerogel/regenerated polyurethane foam nanocomposites of SiO2 aerogel-modified regenerated polyurethane composites. A series of analytical tests on self-prepared silica aerogel and aerogel-modified recycled polyurethane foam composites were performed. The analysis of the test results shows that the regenerated rigid PU foam obtained with SiO2 aerogel addition of 0.3% in the polyurethane degradation material has a small density, low thermal conductivity, and higher compressive strength; hence, the prepared silica aerogel-regenerated polyol-based polyurethane nanocomposite has good thermal insulation and strength support properties. The clean, low-carbon, and high-value utilization of recycled waste polyurethane was achieved.
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This work proposes an efficient catalytic recovery and utilization method for waste polyurethane foam. This method uses ethylene glycol (EG) and propylene glycol (PPG) as two-component alcohololytic agents for the alcoholysis of waste polyurethane foams. For the preparation of recycled polyethers, the conditions of different catalytic degradation systems were catalyzed by duplex metal catalysts (DMC) and alkali metal catalysts, and a synergy with both was also used. The experimental method was adopted with the blank control group and was set up for comparative analysis. The effect of the catalysts on the recycling of waste polyurethane foam was investigated. The catalytic degradation of DMC and the alkali metal catalysts alone, as well as the synergistic effect of the two catalysts, was explored. The findings revealed that the NaOH and DMC synergistic catalytic system was the best, and that the system activity was high under a two-component catalyst synergistic degradation. When the amount of NaOH added in the degradation system was 0.25%, the amount of DMC added was 0.04%, the reaction time was 2.5 h, and the reaction temperature was 160 °C, the waste polyurethane foam was completely alcoholized, and the prepared regenerated polyurethane foam had high compressive strength and good thermal stability. The efficient catalytic recycling method of waste polyurethane foam proposed in this paper has certain guiding and reference values for the practical production of solid-waste-recycled polyurethane.
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This paper presents an in-depth comparative study of the effects of different molten salt systems, catalyst additions, preparation temperatures, temperature rise rates, and holding times on the properties of mullite whiskers during their preparation process, as well as exploring the enhancement of the toughening effect of mullite whiskers on ceramics. The morphology, crystal structure, and composition of the whiskers were analyzed via SEM, XRD, TG, strength tests, etc. The results show that the best-performing mullite whisker was prepared with an aluminum sulfate molten salt system, with the addition of aluminum fluoride catalyst at 4%, a temperature increase rate of 5 °C, a temperature increase up to 850 °C, and a holding time of 5 h, and its aspect ratio reached 20.64. By adding different contents of mullite whiskers and comparing the toughness strengths and wear rates of the silicon carbide ceramics, it was found that the toughness strength of the ceramics was improved by more than 16.5% and the wear rate was lower than 0.4% when the addition of mullite whisker was more than 3%.
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PURPOSE: Considering the high susceptibility of patients with advanced non-small cell lung cancer (NSCLC) to COVID-19, we explored the susceptible cell types and potential routes of SARS-CoV-2 infection in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) by analyzing the expression patterns of the entry receptor angiotensin converting enzyme 2 (ACE2) and the spike (S) protein priming proteases transmembrane serine protease 2 (TMPRSS2) and FURIN. METHODS: Single-cell transcriptomic analysis of 14 LUSC and 12 LUAD samples was utilized to exhibit the heterogeneous expression of ACE2, TMPRSS2 and FURIN across different cell subsets and individuals. RESULTS: 12 cell types and 33 cell clusters were identified from 26 cancer samples. ACE2, TMPRSS2 and FURIN were heterogeneously expressed across different patients. Among all cell types, ACE2, TMPRSS2 and FURIN were predominately expressed in cancer cells and alveolar cells, and lowly uncovered in other cells. Compared to LUSC, the protein priming proteases (TMPRSS2 and FURIN) were highly found in LUAD samples. However, ACE2 was not differentially expressed in cancer cells between the two cancer types. Moreover, ACE2, TMPRSS2, and FURIN expressions were not higher in any cell type of smokers than non-smokers. CONCLUSION: Our research first revealed the heterogeneous expression of ACE2, TMPRSS2, and FURIN in different cell subsets of NSCLC and also across different individuals. These results provide insight into the specific cells targeted by SARS-CoV-2 (i.e., cancer cells and alveolar cells) in patients with advanced NSCLC, and indicate that smoking may be not an independent risk factor for NSCLC combined with COVID-19.