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1.
Zhongguo Zhen Jiu ; 42(4): 385-9, 2022 Apr 12.
Artigo em Chinês | MEDLINE | ID: mdl-35403396

RESUMO

OBJECTIVE: To assess the efficacy on relieving pain and improving the range of motion of shoulder joint in post-stroke shoulder-hand syndrome of phlegm-stasis obstruction in treatment of the combined therapy of eye acupuncture, Tengliao (Chinese herbal warm dressing technique) and rehabilitation training (eye acupuncture + Tengliao + rehabilitation) as compared with the combined treatment of Tengliao and rehabilitation training (Tengliao + rehabilitation) and the simple rehabilitation training (rehabilitation). METHODS: A total of 356 patients with post-stroke shoulder-hand syndrome of phlegm-stasis obstruction were randomized into an eye acupuncture + Tengliao + rehabilitation group (group A, 122 cases, 2 cases dropped off), a Tengliao + rehabilitation group (group B, 120 cases, 3 cases dropped off) and a rehabilitation group (group C, 114 cases, 1 case dropped off). In the group C, the basic treatment was combined with routine rehabilitation training. In the group B, on the base of the treatment as the group C, Tengliao was exerted. A medical bag composed of over 20 Chinese herbal materials was heated and dressed at the affected area, 30 min each time, 5 times weekly. In the group A, besides the treatment as the group B, eye acupuncture was applied to heart region, kidney region, upper jiao region and lower jiao region, 30 min each time, 5 times weekly. The treatment lasted 28 days in all of three groups. Separately, before treatment, in 7, 14, 21 and 28 days of treatment, as well as in 14 days after treatment of follow-up, the score of visual analogue scale (VAS) for pain, the score of guides to evaluation of permanent impairment (GEPI) and the score of National Institutes of Health stroke scale (NIHSS) were observed in each group. RESULTS: The scores of VAS, GEPI and NIHSS were all improved with the treatment lasting in the three groups (P<0.000 1). In 7, 14, 21 and 28 days of treatment and in follow-up as well, VAS scores in the group A were all lower than the group C (P<0.05). After 14 days of treatment, GEPI score showed increasing trend, while NIHSS score showed decreasing trend in the group A compared with the group B. Before treatment, GEPI score was lower and NIHSS score was higher in the group A compared with the group C (P<0.05). It was suggested that the illness was slightly serious in the group A. After propensity score matching, in 14, 21 and 28 days as well as in follow-up, GEPI scores in the group A were higher than the group C respectively (P<0.05). Regarding NIHSS score at each time point, the difference had no statistical significance between the group A and the group C (P>0.05). CONCLUSION: The combined therapy of eye acupuncture, Tengliao and rehabilitation training obtains a better efficacy on post-stroke shoulder-hand syndrome of phlegm-stasis obstruction as compared with rehabilitation training.


Assuntos
Terapia por Acupuntura , Distrofia Simpática Reflexa , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Pontos de Acupuntura , Terapia por Acupuntura/métodos , Humanos , Dor , Distrofia Simpática Reflexa/terapia , Acidente Vascular Cerebral/complicações , Resultado do Tratamento
2.
New Phytol ; 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35342951

RESUMO

Green algae can accumulate high levels of triacylglycerol (TAG), yet knowledge remains fragmented on the regulation of lipid metabolic pathways by transcription factors (TFs). Here, via bioinformatics and in vitro and in vivo analyses, we revealed the roles of a myeloblastosis (MYB) TF in regulating TAG accumulation in green algae. CzMYB1, an R2R3-MYB from Chromochloris zofingiensis, was transcriptionally upregulated upon TAG-inducing conditions and correlated well with many genes involved in the de novo fatty acid synthesis, fatty acid activation and desaturation, membrane lipid turnover, and TAG assembly. Most promoters of these genes were transactivated by CzMYB1 in the yeast one-hybrid assay and contained the binding elements CNGTTA that were recognized by CzMYB1 through the electrophoretic mobility shift assay. CrMYB1, a close homologue of CzMYB1 from Chlamydomonas reinhardtii that recognized similar elements for binding, also transcriptionally correlated with many lipid metabolic genes. Insertional disruption of CrMYB1 severely suppressed the transcriptional expression of CrMYB1, as well as of key lipogenic genes, and impaired TAG level considerably under stress conditions. Our results reveal that this MYB, conserved in green algae, is involved in regulating global lipid metabolic pathways for TAG biosynthesis and accumulation.

3.
Nature ; 603(7903): 835-840, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35355001

RESUMO

The quality of crystalline two-dimensional (2D) polymers1-6 is intimately related to the elusive polymerization and crystallization processes. Understanding the mechanism of such processes at the (sub)molecular level is crucial to improve predictive synthesis and to tailor material properties for applications in catalysis7-10 and (opto)electronics11,12, among others13-18. We characterize a model boroxine 2D dynamic covalent polymer, by using in situ scanning tunnelling microscopy, to unveil both qualitative and quantitative details of the nucleation-elongation processes in real time and under ambient conditions. Sequential data analysis enables observation of the amorphous-to-crystalline transition, the time-dependent evolution of nuclei, the existence of 'non-classical' crystallization pathways and, importantly, the experimental determination of essential crystallization parameters with excellent accuracy, including critical nucleus size, nucleation rate and growth rate. The experimental data have been further rationalized by atomistic computer models, which, taken together, provide a detailed picture of the dynamic on-surface polymerization process. Furthermore, we show how 2D crystal growth can be affected by abnormal grain growth. This finding provides support for the use of abnormal grain growth (a typical phenomenon in metallic and ceramic systems) to convert a polycrystalline structure into a single crystal in organic and 2D material systems.

4.
Quant Imaging Med Surg ; 12(2): 1257-1269, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35111621

RESUMO

BACKGROUND: We aimed to optimize the diagnostic strategy for dynamic computed tomography myocardial perfusion imaging (CT-MPI) and CT fractional flow reserve (CT-FFR) in the evaluation of coronary artery disease (CAD). METHODS: Patients who had undergone coronary CT angiography (CCTA) + dynamic CT-MPI and invasive coronary angiography (ICA)/FFR within a 4-week period were retrospectively included. Lesion-specific characteristics were recorded, and multivariate logistic regression was performed to determine the predictors of mismatched CT findings with ICA results. An optimized diagnostic strategy was proposed based on the diagnostic performance of dynamic CT-MPI and CT-FFR compared with ICA/FFR. A net reclassification index (NRI) was calculated to determine the incremental discriminatory power of optimized CT-FFR + dynamic CT-MPI strategy compared to CT-FFR alone. RESULTS: The study included 180 patients with 229 diseased vessels. For CT-FFR, a calcified lesion with a calcium arc >180° was the only independent predictor for misdiagnosis of ischemic coronary stenosis (odds ratio =2.367; P=0.002). For noncalcified lesions and calcified lesions with a calcium arc ≤180°, the sensitivity and negative predictive value (NPV) of CT-FFR were similar to those of CT-MPI (all P values >0.05), whereas the specificity and positive predictive value (PPV) of CT-FFR were significantly lower (all P values <0.05). For calcified lesions with a calcium arc >180°, the specificity, NPV, and PPV of CT-FFR were inferior to those of CT-MPI (21.2% vs. 100%, 58.3% vs. 86.8%, and 62.9% vs. 100%, respectively; all P values <0.05). As guided by lesion-specific calcium morphology, an optimized CT-FFR + dynamic CT-MPI strategy (NRI =0.2; P=0.004) would have resulted in a 27.0% and 33.9% reduction of radiation dose and contrast medium consumption, respectively, and 25.3% of patients would have avoided unnecessary invasive tests. CONCLUSIONS: The diagnostic performance of CT-FFR was significantly inferior in lesions with a calcium arc >180°. Lesion-specific calcium morphology is the preferred parameter to guide the appropriate use of CT-based functional assessment.

5.
Artigo em Inglês | MEDLINE | ID: mdl-35140051

RESUMO

BACKGROUND: Pericoronary adipose tissue (PCAT) attenuation is an indicator of active inflammation of perivascular adipose tissue, which is supposed to increase in diabetic patients. We aimed to investigate the PCAT attenuation values and high-risk plaque (HRP) features in diabetic and non-diabetic subjects with different stenotic extents. METHODS: Consecutive type 2 diabetes patients and non-diabetic patients with chest pain and intermediate pre-test probability of coronary artery disease (CAD) were prospectively enrolled and underwent coronary computed tomography angiography (CCTA). At per-patient level, PCAT attenuation values of three major epicardial coronary vessels, as well as HRP features were measured. PCAT attenuation values and HRP features were compared between diabetic and non-diabetic subjects according to the presence or absence of obstructive stenosis. RESULTS: 1700 patients (mean age: 65.5 â€‹± â€‹11.7, 940 males) were divided into two groups according to presence of obstructive stenosis on CCTA. Propensity score matching was performed in further analysis. RCAPCAT was significantly higher in diabetic subjects than that in non-diabetic subjects, regardless of the presence of obstructive stenosis (-83.60 â€‹± â€‹9.51 HU vs. -88.58 â€‹± â€‹9.37 HU, p â€‹< â€‹0.001) or absence of obstructive stenosis (-83.70 â€‹± â€‹10.32 HU vs. -88.76 â€‹± â€‹8.28 HU, p â€‹< â€‹0.001). In contrast, HRP features were more commonly presented in diabetic patients with obstructive stenosis than in those without obstructive stenosis. According to subgroup analysis based on acquisition tube voltage, RCAPCAT was the only parameter showing consistent difference between diabetic and non-diabetic patients. CONCLUSIONS: RCAPCAT was significantly higher in diabetic patients than that in non-diabetic patients regardless of stenotic severity and plaque vulnerability.

6.
BMC Health Serv Res ; 22(1): 229, 2022 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-35183172

RESUMO

BACKGROUND: Pediatric leukemia is the most prevalent childhood cancer in China and incurs heavy economic burden to patients without sufficient insurance protection. Although all Chinese children are obliged to enroll in the national insurance scheme, "Resident Basic Medical Insurance (RBMI)", the protection may vary among patient subgroups. This study is designed to measure the disparities in economic burden for patients with leukemia under RBMI protection and explore the influencing factors. METHODS: The included patients were aged ≤ 15 and diagnosed with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML, with/without transplantation). They all completed treatment course consecutively in Nanfang Hospital and Zhujiang Hospital from Jan.1, 2015, to Dec.30, 2019, in Guangzhou, China. Their inpatient treatment and insurance settlement data were drawn from the Hospital Information System (HIS) and Insurance Settlement System (ISS). A total of 765 consecutive patients and 14,477 inpatient medical records were included and analyzed. Their insurance status (6 subtypes), economic burden [total cost, out-of-pocket cost (OOP), reimbursement, reimbursement rate (RR)], and cost structures (operation/procedure, blood products, drug, simple treatment) were calculated respectively. Non-normally distributed costs were reported as the median and interquartile range (IQR). Wilcoxon test was used for univariate tests and generalized linear model with log link was used to explore the influencing factors. RESULTS: The insured patients who were treated in the location of insurance with instant reimbursement reported the highest total cost and reimbursement, while those who seek medical care cross-province with no instant reimbursement reported the lowest total cost and highest OOP payment. In terms of annual change, the total cost of children with leukemia decreased from 2015-2019 with stably increasing reimbursement rate. Blood products and drugs were the major components of total cost, but they decreased annually. Patients who received transplantation and treated across provinces were with a higher economic burden. CONCLUSION: The economic burden for children with leukemia decreased overtime under the protection of RBMI, but disparities exist among subtypes. The payer-provider contract on instant reimbursement and drug cost control are effective measures for insurance administrators to curb the economic burdens of pediatric leukemia treatment.


Assuntos
Seguro , Leucemia , Idoso , Criança , China/epidemiologia , Estresse Financeiro , Gastos em Saúde , Humanos , Seguro Saúde , Leucemia/terapia
7.
BMC Cancer ; 22(1): 185, 2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35180841

RESUMO

BACKGROUND: The number of young patients with hepatocellular carcinoma (HCC) is increasing, but whether patients of different ages have a survival advantage is unclear. This study was conducted to investigate whether age differences in the Barcelona Clinic Liver Cancer (BCLC) classification system contribute to the long-term survival outcomes of patients with HCC. METHODS: A total of 1602 patients with HCC admitted to the Beijing Ditan Hospital was included in this study. Patients were divided into younger (≤45 years) and older (> 45 years) groups. Factors determining overall survival and progression-free survival were analyzed using univariate and multivariate analyses with the Kaplan-Meier method and Cox proportional hazard regression model. We calculated the cumulative incidence function using the Fine-Gray model. The effect of mortality on age was also estimated using a restricted cubic spline. RESULTS: After matching, overall survival and progression-free survival were significantly better in younger patients than in older patients with BCLC stage 0-B (p = 0.015 and p = 0.017, respectively). In BCLC stage 0-B, all-cause mortality increased with age and increased rapidly around the age of 40 years (non-linear, p < 0.05). In BCLC stages 0-B, HCC-related and non-HCC-related deaths significantly differed between younger and older individuals (p = 0.0019). CONCLUSION: In stage BCLC 0-B, age affects the long-term prognosis of patients.


Assuntos
Fatores Etários , Carcinoma Hepatocelular/mortalidade , Hepatectomia/mortalidade , Neoplasias Hepáticas/mortalidade , Medição de Risco/estatística & dados numéricos , Adulto , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
8.
Ann Hepatol ; 27(2): 100672, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35065261

RESUMO

INTRODUCTION: Among all immune cells, natural killer (NK) cells play an important role as the first line of defense against tumor. The purpose of our study is to observe whether the NK cell counts can predict the overall survival of patients with hepatocellular carcinoma (HCC). METHODS: To develop a novel model, from January 2010 to June 2015, HCC patients enrolled in Beijing Ditan hospital were divided into training and validation cohort. Cox multiple regression analysis was used to analyze the independent risk factors for 1-year, 3-year and 5-year overall survival (OS) of patients with HCC, and the nomogram was used to establish the prediction model. In addition, the decision tree was established to verify the contribution of NK cell counts to the survival of patients with HCC. RESULTS: The model used in predicting overall survival of HCC included six variables (namely, NK cell counts, albumin (ALB) level, alpha-fetoprotein (AFP) level, portal vein tumor thrombus (PVTT), tumor number and treatment). The C-index of nomogram model in HCC patients predicting 1-year, 3-year and 5-year overall survival was 0.858, 0.788 and 0.782 respectively, which was higher than tumor-lymph node-metastasis (TNM) staging system, Okuda, model for end-stage liver disease (MELD), MELD-Na, the Chinese University Prognostic Index (CUPI) and Japan Integrated Staging (JIS) scores (p < 0.001). The decision tree showed the specific 5-year OS probability of HCC patients under different risk factors, and found that NK cell counts were the third in the column contribution. CONCLUSIONS: Our study emphasizes the utility of NK cell counts for exploring interactions between long-term survival of HCC patients and predictor variables.


Assuntos
Carcinoma Hepatocelular , Doença Hepática Terminal , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Contagem de Células , Humanos , Neoplasias Hepáticas/patologia , Estadiamento de Neoplasias , Nomogramas , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença
9.
Brachytherapy ; 21(2): 193-201, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34980568

RESUMO

PURPOSE: Intracavitary and/or interstitial brachytherapy is an integral component of the management of patients with central pelvic-recurrent cervical cancer after primary hysterectomy, and is typically delivered using conventional applicators. We investigated the efficacy and safety of three-dimensional (3D)-printed, customizable applicators for those patients. METHODS AND MATERIALS: Twenty-six patients were treated with combination external beam radiotherapy and brachytherapy. Patients with lesions ≤1 and >1 cm before brachytherapy were treated with intracavitary and interstitial brachytherapy, respectively. Dosimetric plans were compared between the vaginal cylinder and 3D-printed applicator for the first 9 patients. Outcomes and treatment-related complications were also investigated. RESULTS: The median tumor size before brachytherapy was 0.81 cm. Intracavitary, interstitial, and combined interstitial-intracavitary brachytherapy were performed in 22 (85%), 3 (11%), and 1 (4%) of the patients, respectively. The clinical target volume (CTV) coverage goal was achieved with all 3D-printed plans but failed with three single-channel cylinder plans (33.3%). Owing to 3D-printed transvaginal applicator guidance, there was no need to adjust the needle position after implantation. The mean CTV dose for all patients was 71 ± 8.2 Gy; all met the dose constraints to the organs at risk, but 1 (4%) had a rectal D2cc overdose. The 2-year local control, progression-free survival, and overall survival rates were 87.8%, 71.0%, and 91.6%, respectively. Four patients (21%) developed early grade 3-4 hematological toxicities and 1 (4%) developed a late grade 3 adverse event. CONCLUSIONS: High-quality intracavitary and/or interstitial brachytherapy can be achieved using a 3D-printed applicator and yields favorable outcomes with acceptable toxicity.


Assuntos
Braquiterapia , Neoplasias do Colo do Útero , Braquiterapia/métodos , Feminino , Humanos , Histerectomia , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/radioterapia , Impressão Tridimensional , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/radioterapia
10.
Diabetes Res Clin Pract ; 184: 109193, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35032561

RESUMO

AIMS: To examine the predictive factors associated with the progression of different prediabetic status to diabetes. METHODS: A two-year retrospective cohort study was conducted on 5741 participants aged 40 years or older. Finally, 1685 participants with prediabetes defined by IFG (impaired fasting glucose), IGT (impaired glucose tolerance) and CGI (combined IFG and IGT) were included. Logistic regression model was used to evaluate the risk of prediabetes progression to diabetes. RESULTS: Of the 1685 subjects with prediabetes at baseline, 212 (12.6%) subjects progressed to diabetes and 1473 (87.4%) subjects did not. Logistic regression analysis demonstrated that people with CGI were associated with an increased risk of progressing to diabetes compared to those with IFG (OR, 95% CI: 3.127, 2.047-4.776). Moreover, males, obese people, people with increased BMI and WHR (Waist/ Hip ratio), and hypertension were positively associated with the progression to diabetes, while HOMA-ß was negatively associated with the progression to diabetes. CONCLUSIONS: Subjects with CGI are prone to progressed to diabetes compared to those with IFG or IGT in middle-aged and older person in China. More attention should be paid to male and obese prediabetic subjects, and measures should be taken to control the increase in their BMI and WHR.


Assuntos
Diabetes Mellitus Tipo 2 , Intolerância à Glucose , Resistência à Insulina , Estado Pré-Diabético , Adulto , Idoso , Glicemia , Estudos de Coortes , Jejum , Intolerância à Glucose/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/epidemiologia , Estudos Retrospectivos
11.
New Phytol ; 233(2): 823-837, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34665469

RESUMO

Long-chain acyl-CoA synthetases (LACSs) play many roles in mammals, yeasts and plants, but knowledge on their functions in microalgae remains fragmented. Here via genetic, biochemical and physiological analyses, we unraveled the function and roles of LACSs in the model microalga Chlamydomonas reinhardtii. In vitro assays on purified recombinant proteins revealed that CrLACS1, CrLACS2 and CrLACS3 all exhibited bona fide LACS activities toward a broad range of free fatty acids. The Chlamydomonas mutants compromised in CrLACS1, CrLACS2 or CrLACS3 did not show any obvious phenotypes in lipid content or growth under nitrogen (N)-replete condition. But under N-deprivation, CrLACS1 or CrLACS2 suppression resulted in c. 50% less oil, yet with a higher amount of chloroplast lipids. By contrast, CrLACS3 suppression impaired oil remobilization and cell growth severely during N-recovery, supporting its role in fatty acid ß-oxidation to provide energy and carbon sources for regrowth. Transcriptomics analysis suggested that the observed lipid phenotypes are likely not due to transcriptional reprogramming but rather a shift in metabolic adjustment. Taken together, this study provided solid experimental evidence for essential roles of the three Chlamydomonas LACS enzymes in lipid synthesis, remodeling and catabolism, and highlighted the importance of lipid homeostasis in cell growth under nutrient fluctuations.


Assuntos
Chlamydomonas reinhardtii , Chlamydomonas , Chlamydomonas reinhardtii/genética , Chlamydomonas reinhardtii/metabolismo , Coenzima A/metabolismo , Ácidos Graxos/metabolismo , Ligases/metabolismo
12.
Crit Rev Microbiol ; 48(3): 270-282, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34403642

RESUMO

Membrane contact sites (MCSs) refer to the areas of close proximity between heterologous membranes. A growing body of evidence indicates that MCSs are involved in important cellular functions, such as cellular material transfer, organelle biogenesis, and cell growth. Importantly, the study of MCSs at the bacteria-host interface is an emerging popular research topic. Intracellular bacterial pathogens have evolved a variety of fascinating strategies to interfere with MCSs by injecting effectors into infected host cells. Bacteria-containing vacuoles establish direct physical contact with organelles within the host, ensuring vacuolar membrane integrity and energy supply from host organelles and protecting the vacuoles from the host endocytic pathway and lysosomal degradation. An increasing number of bacterial effectors from various bacterial pathogens hijack components of host MCSs to form the vacuole-organelle MCSs for material exchange. MCS-related events have been identified as new mechanisms of microbial pathogenesis to greatly improve bacterial survival and replication within host cells. In this review, we will discuss the recent advances in MCSs at the bacteria-host interface, focussing on the roles of MCSs mediated by bacterial effectors in microbial pathogenesis.


Assuntos
Bactérias , Vacúolos , Bactérias/genética , Vacúolos/metabolismo , Vacúolos/microbiologia
13.
Life Sci ; 289: 120231, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34921867

RESUMO

AIMS: To investigate the role of Skp2 and JunB on acute promyelocytic leukemia (APL) progression and the related mechanism. MATERIALS AND METHODS: The expression of Skp2 in NB4 cell line was depleted to explore its effect on proliferation and differentiation both in vitro and in vivo assays. Western blot and quantitative RT-PCR analysis were performed to explore Skp2-regulated downstream target genes. Luciferase and co-immunoprecipitation analysis indicated that PML-RARα inhibited the transactivation of JunB by interacting with the PU.1 protein. The western blot analysis confirmed that Skp2 could maintain the stability of PML-RARα. KEY FINDINGS: We report that the progression of APL and the attenuation of APL sensitivity to ATRA are positively associated with Skp2. Elevated Skp2 expression promotes APL progression by decreasing the expression of lncRNA HOTAIRM1 and inactivation of GSK3ß, causing autophagy inhibition followed by the suppression of PML-RARα ubiquitylation and degradation, which represses JunB transcriptional activation through PU.1/PML-RARα transcriptional complex to block cell differentiation. Coupled with ATRA or GSK3ß inhibitor treatment, genetic or pharmacological inhibition of Skp2 strikingly induces JunB expression by accelerating the degradation of PML-RARα, which contributes to the eradication of APL. Additionally, the expressions of Skp2 and JunB are negatively correlated in mice subcutaneous leukemia xenograft tumors. SIGNIFICANCE: Collectively, this study uncovers the roles of Skp2 in PML-RARα stabilization and in APL oncogenic functions. We reveal a novel mechanism of PML-RARα degradation and JunB regulation that constitute an important signaling network of Skp2-GSK3ß-PML/RARα-JunB.


Assuntos
Regulação Leucêmica da Expressão Gênica , Leucemia Promielocítica Aguda/metabolismo , Proteínas de Fusão Oncogênica/metabolismo , Proteínas Quinases Associadas a Fase S/metabolismo , Fatores de Transcrição/biossíntese , Ativação Transcricional , Animais , Células HEK293 , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/patologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Proteínas de Fusão Oncogênica/genética , Estabilidade Proteica , Proteínas Quinases Associadas a Fase S/genética , Fatores de Transcrição/genética , Células U937 , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Neurosci Lett ; 769: 136424, 2022 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-34958911

RESUMO

Cognitive impairment in Parkinson disease (PD) leads to substantial disability. Unlike external manifestations such as tremor, the decay of cognitive function is often an underlying process, and its neuroanatomic substrates are not yet fully elucidated. Knowledge regarding cognitive-related alterations in white matter (WM) pathways helps us understand the mechanisms of cognitive decline in patients with PD. Previous voxel-based analyses with Diffusion tensor imaging (DTI) metrics, such as fractional anisotropy (FA) and mean diffusivity (MD) have uncovered white matter differences in groupwise, but the conclusions were inconsistent. That was partially due to white matter fibers that are known to affect cognition, such as the corpus callosum (CC) and superior longitudinal fasciculus that cross in voxel, and are hard to interpreted by the abovementioned metrics. Furthermore, cognitive decay is a continuous process, it is difficult to reflect the continuous changes of white matter fibers between groups comparison. In the present work, we chose the constrained spherical deconvolution (CSD) and the fixel model, which avoided the effect of crossing fibers. To compare the white matter fiber in different cognitive stages of patients with PD, the results found that the CC, the cingulum bundle (CB), and the corticospinal tract (CST) showed the same trend in the decline of cognitive function, and this change may lead to the impairment of cognitive function. Our findings can help physicians determine the cognitive stage of PD from the perspective of white matter fiber and provide a reference for clinical trials and predictions.


Assuntos
Cognição , Doença de Parkinson/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Idoso , Imagem de Tensor de Difusão/métodos , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/patologia , Substância Branca/patologia
15.
Front Cell Neurosci ; 15: 764141, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899191

RESUMO

Trigeminal neuralgia (TN) is a severe chronic neuropathic pain. Despite numerous available medical interventions, the therapeutic effects are not ideal. To control the pain attacks, the need for more contemporary drugs continues to be a real challenge. Our previous study reported that Ca2+-activated K+ channels (BK Ca ) channels modulated by mitogen-activated protein kinases (MAPKs) in the trigeminal ganglia (TG) neurons play crucial roles in regulating TN, and some research studies demonstrated that inflammatory cytokine tumor necrosis factor alpha (TNF-α) could promote neuropathic pain. Meanwhile, the trigeminal nucleus caudalis (TNC), the first central site of the trigeminal nociceptive pathway, is responsible for processing sensory and pain signals from the peripheral orofacial area. Thus, this study is aimed to further investigate whether TNF-α and MAPKs phosphorylation in the TNC could mediate the pathogenesis of TN by modulating BK Ca channels. The results showed that TNF-α of the TNC region is upregulated significantly in the chronic constriction injury of infraorbital nerve (ION-CCI) rats model, which displayed persistent facial mechanical allodynia. The normal rats with target injection of exogenous TNF-α to the fourth brain ventricle behaved just like the ION-CCI model rats, the orofacial mechanical pain threshold decreased clearly. Meanwhile, the exogenous TNF-α increased the action potential frequency and reduced the BK Ca currents of TNC neurons significantly, which could be reversed by U0126 and SB203580, the inhibitors of MAPK. In addition, U0126, SB203580, and another MAPK inhibitor SP600125 could relieve the facial mechanical allodynia by being injected into the fourth brain ventricle of ION-CCI model rats, respectively. Taken together, our work suggests that the upregulation of TNF-α in the TNC region would cause the increase of MAPKs phosphorylation and then the negative regulation of BK Ca channels, resulting in the TN.

16.
Artigo em Inglês | MEDLINE | ID: mdl-34724115

RESUMO

PURPOSE: This study aimed to evaluate the safety and efficacy of chimeric antigen receptor (CAR) disialoganglioside 2 (GD2)-specific (4SCAR-GD2) T cells for treatment of refractory and/or recurrent neuroblastoma (NB) in pediatric patients. EXPERIMENTAL DESIGN: A phase I clinical study using 4SCAR-GD2 T cells for the treatment of NB in pediatric patients was conducted. This study was registered at www.clinicaltrials.gov (NCT02765243). A lentiviral CAR with the signaling domains of CD28/4-1BB/CD3ζ-iCasp9 was transduced into activated T cells. The response to 4SCAR-GD2 T-cell treatment, and 4SCAR-GD2 T-cell expansion and persistence in patients were evaluated. Toxicities were determined based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.03. RESULTS: Twelve patients were enrolled and finally ten patients were included in this clinical trial which started from January 1, 2016, to August 1, 2017. These patients had progressive disease (PD) before CAR T-cell infusion. After 4SCAR-GD2 T-cell treatment, 6 (6/10) had stable disease (SD) at 6 months, and 4 (4/10) remained SD at 1 year and alive after 3-4 years of follow-up. Six patients died due to disease progression by the end of July 1, 2020. The median overall survival (OS) time was 25 months (95% CI, 0.00-59.43), and the median progression-free survival (PFS) time was 8 months (95% CI, 0.25-15.75). Grade 3 or 4 hematological toxicities were the common adverse events frequently occurred after fludarabine and cyclophosphamide (Flu/cy) chemotherapy. Grade 1-2 toxicities such as cytokine release syndrome (CRS) and neuropathic pain were common, but were transient and mild. CONCLUSIONS: The 4SCAR-GD2 T-cell therapy demonstrated antitumor effect and manageable toxicities, indicating its potential to benefit children with refractory and/or recurrent NB.

17.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(11): 987-995, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34809738

RESUMO

Objective To investigate the effect of lncRNA CRNDE on proliferation, apoptosis, and cell cycle of U937 cells and its mechanism. Methods The expression level of CRNDE in bone marrow cells of AML patients was analyzed by GEPIA database; the mRNA expression levels of miR-136-5p, CRNDE, and minichromosome maintenance 5(MCM5) in AML cell lines were detected by quantitative real-time PCR (qRT-PCR). The lentiviral vector with CRNDE knocked down was constructed and transfected into U937 cells which were randomized into CRNDE knockdown group (sh-CRNDE group) and negative control group (sh-NC group); miR-136-5p mimic and miR-136-5p inhibitor were transfected respectively to overexpress and knock down miR-136-5p in U937 cells which were randomized into miR-136-5p-mimic group, NC-mimic group, miR-136-5p-inhibitor group, and NC-inhibitor group. The effect of CRNDE and miR-136-5p on proliferation was detected by CCK-8 assay and cell counting assay, and the effect of them on cell cycle and apoptosis was detected by flow cytometry. The mRNA expressions of miR-136-5p, CRNDE, and MCM5 were detected by qRT-PCR, and the protein expressions of MCM5, Bcl2, cyclin D1, and cyclin A2 were detected by Western blotting. Results CRNDE was highly expressed in the bone marrow and cell lines of AML patients. Knockdown of CRNDE upregulated miR-136-5p, inhibited the MCM5 mRNA and protein expressions and the cell proliferation, promoted the cell apoptosis, and blocked the cell cycle in G1 phase. Overexpression of miR-136-5p also inhibited the expression of MCM5 at both mRNA and protein levels, while knockdown of miR-136-5p reversed those effects. Conclusion CRNDE promotes the proliferation and inhibits the apoptosis of U937 cells by downregulating miR-136-5p and upregulating MCM5.


Assuntos
MicroRNAs , RNA Longo não Codificante , Apoptose/genética , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , MicroRNAs/genética , Células U937
18.
J Hepatocell Carcinoma ; 8: 1253-1267, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34708007

RESUMO

BACKGROUND AND AIMS: Although antiviral treatment has been shown to reduce mortality in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients with high HBV-DNA levels, it is still unclear whether it is useful in reducing mortality in patients with low HBV-DNA levels. METHODS: A retrospective analysis of 756 HBV-associated HCC patients at the Beijing Ditan Hospital with HBV-DNA levels < 500 IU/mL was conducted between January 2008 and June 2017. Patients were divided into antiviral and non-antiviral groups based on whether they received nucleos(t)ide analogue (NA) treatment when they were diagnosed with HCC in our hospital for the first time. We used 1:4 frequency matching by age, gender, tumor size, Barcelona Clinic Liver Cancer (BCLC) staging, anti-tumor therapy, cirrhosis, diabetes, and hyperlipoidemia to compare the antiviral (n = 366) and non-antiviral (n = 100) groups. A Cox multivariate regression analysis was employed to evaluate the effects of NA therapy on the hazard ratio (HR), and the Kaplan-Meier survival curve was used to determine the mortality risk in patients with HCC. A Log rank test was performed to analyze the effects of NA therapy on the survival rate of patients with HCC. RESULTS: After propensity score matching, the 1-, 3-, and 5-year overall survival (OS) rates for the antiviral and non-antiviral groups were 82.5%, 68.6%, and 52.2%, and 61.0%, 51.0%, and 38.0%, respectively. The l-year progression-free survival (PFS) rates for the two groups were 68.0% and 47.0%, respectively. The OS of the antiviral group was significantly higher than that of the control group (P < 0.001, P = 0.001, and P = 0.013, respectively). The 1-year PFS for the antiviral group was also significantly better than that for the non-antiviral groups (P = 0.005). After adjusting for confounding prognostic factors in the Cox model, the HR of 5-year death after antiviral treatment was 0.721 (95% confidence interval [CI], 0.530-0.980, P = 0.037). Antiviral therapy is an independent protective factor for 5-year mortality in patients with HCC and low-level viremia. CONCLUSION: Antiviral therapy significantly reduced mortality in HCC patients with low HBV-DNA levels.

19.
Neurooncol Adv ; 3(1): vdab134, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34693286

RESUMO

BACKGROUND: Medulloblastoma (MB) is the most common malignant central nervous system tumor of childhood. Management requires interdisciplinary care and is associated with unique challenges in developing regions. Here, we report the characteristics, clinical outcome and treatment barriers for Chinese children with MB based on a multi-institutional cohort from the Chinese Children's Cancer Group (CCCG). METHODS: Retrospective cohort study among 12 Chinese pediatric oncology units from the CCCG Brain Tumor Workgroup on patients aged <18 years diagnosed with MB from 2016 to 2019. RESULTS: 221 patients (male:female = 138:83) were included, 175 (79%) were ≥3 years of age, and 46 (21%) <3 years. 177 patients (80%) were completely staged, among which 50 (28%) had metastasis and 70 (40%) were considered to have high-risk (HR) disease. Gross/near-total resection was achieved in 203 patients (92%). In patients where molecular grouping could be assigned, 19 (16%), 35 (29%), and 65 (54%), respectively had WNT-activated, SHH-activated, and Group 3/4 MB. The median duration between resection and initiation of adjuvant therapy was 36 days. Respective 2-year PFS and OS rates were 76.0 ± 3.0% and 88.0 ± 2.3%. PFS was significantly associated with age, metastatic status and clinical risk grouping. Chemotherapy use during CSI or alkylator choice were not significant predictors for patient outcome. CONCLUSIONS: We reported the clinical profiles and outcome from the largest cohort of Chinese children with MB after multi-modal therapy. Strengths and limitations on the local provision of neuro-oncology service are identified.

20.
Biomed Res Int ; 2021: 9924549, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34651051

RESUMO

OBJECTIVE: To study the protective effect of trimetazidine on myocardial cells in rats with myocardial infarction and explore its effect on ERK signaling pathway. METHODS: 40 SD rats were randomly divided into the sham operation group, model group, low-dose group, and high-dose group (intra-abdominal injection of trimetazidine 5 mg/kg and 10 mg/kg, respectively), construction of rat myocardial infarction model by coronary artery left anterior descending artery ligation. 7 days after surgery, the survival rate and cardiac function of each group of rats were recorded. The myocardial infarct size was detected by TTC staining. The apoptosis level of rat cardiomyocytes was detected by TUNEL staining. The content of ROS in rat cardiomyocytes was detected by DCFH-DA. Western-blot was used to detection of Caspase-3, Bcl-2/Bax, and ERK signaling pathway-related proteins in myocardial tissue. RESULTS: Compared with the model group, the survival rate of the rats in the low-dose group and the high-dose group was significantly increased (P < 0.01), the cardiac function was significantly improved (P < 0.01), the myocardial infarct size was significantly decreased (P < 0.01), the level of apoptosis was significantly decreased (P < 0.01), the content of ROS in cardiomyocytes was significantly decreased (P < 0.01), the protein expression of Caspase-3 and NF-κB in cardiomyocytes was significantly decreased (P < 0.01), and the expression of Bcl-2/Bax and p-ERK were significantly increased (P < 0.01). CONCLUSION: Trimetazidine can activate ERK signaling pathway in cardiomyocytes of rats with myocardial infarction, increase the expression of p-ERK, decrease the content of ROS in cardiomyocytes, decrease the expression of apoptotic proteins, reduce myocardial infarct size, improve cardiac function, and increase myocardial function.


Assuntos
Cardiotônicos/farmacologia , Sistema de Sinalização das MAP Quinases , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/patologia , Miocárdio/patologia , Trimetazidina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Testes de Função Cardíaca , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Infarto do Miocárdio/fisiopatologia , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Análise de Sobrevida
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