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1.
Proc Natl Acad Sci U S A ; 121(28): e2407077121, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38954553

RESUMO

An array of motor proteins consumes chemical energy in setting up the architectures of chromosomes. Here, we explore how the structure of ideal polymer chains is influenced by two classes of motors. The first class which we call "swimming motors" acts to propel the chromatin fiber through three-dimensional space. They represent a caricature of motors such as RNA polymerases. Previously, they have often been described by adding a persistent flow onto Brownian diffusion of the chain. The second class of motors, which we call "grappling motors" caricatures the loop extrusion processes in which segments of chromatin fibers some distance apart are brought together. We analyze these models using a self-consistent variational phonon approximation to a many-body Master equation incorporating motor activities. We show that whether the swimming motors lead to contraction or expansion depends on the susceptibility of the motors, that is, how their activity depends on the forces they must exert. Grappling motors in contrast to swimming motors lead to long-ranged correlations that resemble those first suggested for fractal globules and that are consistent with the effective interactions inferred by energy landscape analyses of Hi-C data on the interphase chromosome.


Assuntos
Cromossomos , Cromatina/química , Cromatina/metabolismo , Proteínas Motores Moleculares/metabolismo , Proteínas Motores Moleculares/química
2.
Nat Cell Biol ; 26(6): 878-891, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38783142

RESUMO

When cells are stressed, DNA from energy-producing mitochondria can leak out and drive inflammatory immune responses if not cleared. Cells employ a quality control system called autophagy to specifically degrade damaged components. We discovered that mitochondrial transcription factor A (TFAM)-a protein that binds mitochondrial DNA (mtDNA)-helps to eliminate leaked mtDNA by interacting with the autophagy protein LC3 through an autolysosomal pathway (we term this nucleoid-phagy). TFAM contains a molecular zip code called the LC3 interacting region (LIR) motif that enables this binding. Although mutating TFAM's LIR motif did not affect its normal mitochondrial functions, more mtDNA accumulated in the cell cytoplasm, activating inflammatory signalling pathways. Thus, TFAM mediates autophagic removal of leaked mtDNA to restrict inflammation. Identifying this mechanism advances understanding of how cells exploit autophagy machinery to selectively target and degrade inflammatory mtDNA. These findings could inform research on diseases involving mitochondrial damage and inflammation.


Assuntos
Autofagia , DNA Mitocondrial , Proteínas de Ligação a DNA , Inflamação , Mitocôndrias , Proteínas Mitocondriais , Fatores de Transcrição , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Inflamação/metabolismo , Inflamação/patologia , Inflamação/genética , Animais , Humanos , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Mitocôndrias/metabolismo , Mitocôndrias/genética , Camundongos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Ligação Proteica , Citoplasma/metabolismo , Lisossomos/metabolismo , Transdução de Sinais , Células HEK293 , Camundongos Endogâmicos C57BL , Proteínas de Grupo de Alta Mobilidade
3.
Neural Regen Res ; 19(10): 2281-2289, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38488562

RESUMO

JOURNAL/nrgr/04.03/01300535-202410000-00029/figure1/v/2024-02-06T055622Z/r/image-tiff Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer's disease. Magnesium-L-threonate has recently been found to have protective effects on learning and memory in aged and Alzheimer's disease model mice. However, the effects of magnesium-L-threonate on the gut microbiota in Alzheimer's disease remain unknown. Previously, we reported that magnesium-L-threonate treatment improved cognition and reduced oxidative stress and inflammation in a double-transgenic line of Alzheimer's disease model mice expressing the amyloid-ß precursor protein and mutant human presenilin 1 (APP/PS1). Here, we performed 16S rRNA amplicon sequencing and liquid chromatography-mass spectrometry to analyze changes in the microbiome and serum metabolome following magnesium-L-threonate exposure in a similar mouse model. Magnesium-L-threonate modulated the abundance of three genera in the gut microbiota, decreasing Allobaculum and increasing Bifidobacterium and Turicibacter. We also found that differential metabolites in the magnesium-L-threonate-regulated serum were enriched in various pathways associated with neurodegenerative diseases. The western blotting detection on intestinal tight junction proteins (zona occludens 1, occludin, and claudin-5) showed that magnesium-L-threonate repaired the intestinal barrier dysfunction of APP/PS1 mice. These findings suggest that magnesium-L-threonate may reduce the clinical manifestations of Alzheimer's disease through the microbiota-gut-brain axis in model mice, providing an experimental basis for the clinical treatment of Alzheimer's disease.

4.
CNS Neurosci Ther ; 30(4): e14492, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-37864441

RESUMO

BACKGROUND: Medial temporal lobe atrophy (MTA) is a diagnostic marker for mild cognitive impairment (MCI) and Alzheimer's disease (AD), but the accuracy of quantitative MTA (QMTA) in diagnosing early AD is unclear. This study aimed to investigate the accuracy of QMTA and its related components (inferior lateral ventricle [ILV] and hippocampus) with MTA in the early diagnosis of MCI and AD. METHODS: This study included four groups: normal (NC), MCI stable (MCIs), MCI converted to AD (MCIs), and mild AD (M-AD) groups. Magnetic resonance image analysis software was used to quantify the hippocampus, ILV, and QMTA. MTA was rated by two experienced neurologists. Receiver operating characteristic area under the curve (AUC) analysis was performed to compare their capability in differentiating AD from NC and MCI, and optimal thresholds were determined using the Youden index. RESULTS: QMTA distinguished M-AD from NC and MCI with higher diagnostic accuracy than MTA, hippocampus, and ILV (AUCNC = 0.976, AUCMCI = 0.836, AUCMCIs = 0.894, AUCMCIc = 0.730). The diagnostic accuracy of QMTA was superior to that of MTA, the hippocampus, and ILV in differentiating MCI from AD. The diagnostic accuracy of QMTA was found to remain the best across age, sex, and pathological subgroups analyzed. The sensitivity (92.45%) and specificity (90.64%) were higher in this study when a cutoff value of 0.635 was chosen for QMTA. CONCLUSIONS: QMTA may be a better choice than the MTA scale or the associated quantitative components alone in identifying AD patients and MCI individuals with higher progression risk.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Diagnóstico Diferencial , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Hipocampo/patologia , Imageamento por Ressonância Magnética/métodos , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Diagnóstico Precoce , Atrofia/diagnóstico por imagem , Atrofia/patologia
5.
Chaos ; 33(6)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37276569

RESUMO

Recent developments in nonequilibrium thermodynamics, known as thermodynamic uncertainty relations, limit the system's accuracy by the amount of free-energy consumption. A transport efficiency, which can be used to characterize the capacity to control the fluctuation by means of energy cost, is a direct result of the thermodynamic uncertainty relation. According to our previous research, biochemical systems consume much lower energy cost by noise-induced oscillations to keep almost equal efficiency to maintain precise processes than that by normal oscillations. Here, we demonstrate that the performance of noise-induced oscillations propagating can be further improved through a cascade reaction mechanism. It has been discovered that it is possible to considerably enhance the transport efficiency of the biochemical reactions attained at the terminal cell, allowing the cell to use the cascade reaction mechanism to operate more precisely and efficiently. Moreover, an optimal reaction coupling strength has been predicted to maximize the transport efficiency of the terminal cell, uncovering a concrete design strategy for biochemical systems. By using the local mean field approximation, we have presented an analytical framework by extending the stochastic normal form equation to the system perturbed by external signals, providing an explanation of the optimal coupling strength.

6.
J Phys Chem Lett ; 14(1): 66-72, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36566388

RESUMO

Mandal and Jarzynski have proposed a fully autonomous information heat engine, consisting of a demon, a mass, and a memory register interacting with a thermal reservoir. This device converts thermal energy into mechanical work by writing information to a memory register or, conversely, erasing information by consuming mechanical work. Here, we derive a speed limit inequality between the relaxation time of state transformation and the distance between the initial and final distributions, where the combination of the dynamical activity and entropy production plays an important role. Such inequality provides a hint that a speed-performance trade-off relation exists between the relaxation time to a functional state and the average production. To obtain fast functionalization while maintaining the performance, we show that the relaxation dynamics of the information heat engine can be accelerated significantly by devising an optimal initial state of the demon. Our design principle is inspired by the so-called Mpemba effect, where water freezes faster when initially heated.

7.
J Nanobiotechnology ; 20(1): 322, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35836190

RESUMO

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disorder without effective therapy and lack diagnosis strategy for preclinical AD patients. There is an urgent need for development of both early diagnosis and therapeutic intervention of AD. RESULTS: Herein, we developed a nanotheranostics platform consisting of Curcumin (Cur), an anti-inflammatory molecule, and superparamagnetic iron oxide (SPIO) nanoparticles encapsulated by diblock 1,2-dio-leoyl-sn-glycero-3-phosphoethanolamine-n-[poly(ethylene glycol)] (DSPE-PEG) that are modified with CRT and QSH peptides on its surface. Furthermore, we demonstrated that this multifunctional nanomaterial efficiently reduced ß-amyloid plaque burden specifically in APP/PS1 transgenic mice, with the process noninvasively detected by magnetic resonance imaging (MRI) and the two-dimensional MRI images were computed into three-dimension (3D) plot. Our data demonstrated highly sensitive in vivo detection of ß-amyloid plaques which more closely revealed real deposition of Aß than previously reported and we quantified the volumes of plaques for the first time based on 3D plot. In addition, memory deficits of the mice were significantly rescued, probably related to inhibition of NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasomes. CONCLUSIONS: Gathered data demonstrated that this theranostic platform may have both early diagnostic and therapeutic potential in AD.


Assuntos
Doença de Alzheimer , Curcumina , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/química , Animais , Cognição , Curcumina/química , Curcumina/farmacologia , Curcumina/uso terapêutico , Modelos Animais de Doenças , Imageamento por Ressonância Magnética , Camundongos , Camundongos Transgênicos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Placa Amiloide/diagnóstico por imagem , Placa Amiloide/tratamento farmacológico , Nanomedicina Teranóstica
8.
Front Hum Neurosci ; 16: 760360, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35774484

RESUMO

Background: White matter hyperintensities (WMHs) and regional brain lobe atrophy coexist in the brain of patients with Alzheimer's disease (AD), but the association between them in patients with AD still lacks comprehensive investigation and solid imaging data support. Objective: We explored whether WMHs can promote the pathological process of AD by aggravating atrophy in specific brain regions and tried to explain the regional specificity of these relationships. Methods: A sample of 240 adults including 180 normal controls (NCs) and 80 cases with AD were drawn from the ADNI database. T1-weighted magnetic resonance imaging (MRI) and T2-weighted fluid-attenuated MRI of the participants were downloaded and were analyzed using AccuBrain® to generate the quantitative ratio of WMHs (WMHr, WMH volumes corrected by intracranial volume) and regional brain atrophy. We also divided WMHr into periventricular WMHr (PVWMHr) and deep WMHr (DWMHr) for the purpose of this study. The Cholinergic Pathways Hyperintensities Scale (CHIPS) scores were conducted by two evaluators. Independent t-test, Mann-Whitney U test, or χ2 test were used to compare the demographic characteristics, and Spearman correlation coefficient values were used to determine the association between WMHs and different regions of brain atrophy. Results: Positive association between WMHr and quantitative medial temporal lobe atrophy (QMTA) (r s = 0.281, p = 0.011), temporal lobe atrophy (r s = 0.285, p = 0.011), and insular atrophy (r s = 0.406, p < 0.001) was found in the AD group before Bonferroni correction. PVWMHr contributed to these correlations. By separately analyzing the relationship between PVWMHr and brain atrophy, we found that there were still positive correlations after correction in QMTA (r s = 0.325, p = 0.003), temporal lobe atrophy (r s = 0.298, p = 0.007), and insular atrophy (r s = 0.429, p < 0.001) in AD group. Conclusion: WMH severity tends to be associated with regional brain atrophy in patients with AD, especially with medial temporal lobe, temporal lobe, and insular lobe atrophy. PVWMHs were devoted to these correlations.

9.
J Chem Phys ; 157(2): 025102, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35840371

RESUMO

Biochemical oscillations, regulating the timing of life processes, need to consume energy to achieve good performance on crucial functions, such as high accuracy of the phase period and high sensitivity to external signals. However, it is a great challenge to precisely estimate the energy dissipation in such systems. Here, based on the stochastic normal form theory, we calculate the Pearson correlation coefficient between the oscillatory amplitude and phase, and a trade-off relation between transport efficiency and phase sensitivity can then be derived, which serves as a tighter form than the estimator resulting from the conventional thermodynamic uncertainty relation. Our findings demonstrate that a more precise energy dissipation estimation can be obtained by enhancing the sensitivity of the biochemical oscillations. Moreover, the internal noise and amplitude power effects have also been discovered.


Assuntos
Modelos Biológicos , Termodinâmica , Incerteza
10.
Front Aging Neurosci ; 14: 859492, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572149

RESUMO

Background and Objective: Early identification is important for timely Alzheimer's disease (AD) treatment. Apolipoprotein E ε4 allele (APOE-ε4) is an important genetic risk factor for sporadic AD. The AD-Resemblance Atrophy Index (RAI)-a structural magnetic resonance imaging-derived composite index-was found to predict the risk of progression from mild cognitive impairment (MCI) to AD. Therefore, we investigated whether the AD-RAI can predict cognitive decline and progression to AD in patients with MCI carrying APOE ε4. Methods: We included 733 participants with MCI from the Alzheimer's Disease Neuroimaging Initiative Database (ADNI). Their APOE genotypes, cognitive performance, and levels of AD-RAI were assessed at baseline and follow-up. Linear regression models were used to test the correlations between the AD-RAI and baseline cognitive measures, and linear mixed models with random intercepts and slopes were applied to investigate whether AD-RAI and APOE-ε4 can predict the level of cognitive decline. Cox proportional risk regression models were used to test the association of AD-RAI and APOE status with the progression from MCI to AD. Results: The baseline AD-RAI was higher in the MCI converted to AD group than in the MCI stable group (P < 0.001). The AD-RAI was significantly correlated with cognition, and had a synergistic effect with APOE-ε4 to predict the rate of cognitive decline. The AD-RAI predicted the risk and timing of MCI progression to AD. Based on the MCI population carrying APOE-ε4, the median time to progression from MCI to AD was 24 months if the AD-RAI > 0.5, while the median time to progression from MCI to AD was 96 months for patients with an AD-RAI ≤ 0.5. Conclusion: The AD-RAI can predict the risk of progression to AD in people with MCI carrying APOE ε4, is strongly correlated with cognition, and can predict cognitive decline.

11.
World J Psychiatry ; 12(3): 410-424, 2022 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-35433327

RESUMO

BACKGROUND: Oxidative stress results in the production of excess reactive oxygen species (ROS) and triggers hippocampal neuronal damage as well as occupies a key role in the pathological mechanisms of neurodegenerative disorders such as Alzheimer's disease (AD). A recent study confirmed that magnesium had an inhibitory effect against oxidative stress-related malondialdehyde in vitro. However, whether Magnesium-L-threonate (MgT) is capable of suppressing oxidative stress damage in amyloid ß (Aß)25-35-treated HT22 cells and the AD mouse model still remains to be investigated. AIM: To explore the neuroprotective effect of MgT against oxidative stress injury in vitro and in vivo, and investigate the mechanism. METHODS: Aß25-35-induced HT22 cells were preconditioned with MgT for 12 h. APPswe/PS1dE9 (APP/PS1) mice were orally administered with MgT daily for 3 mo. After MgT treatment, the viability of Aß25-35-treated HT22 cells was determined via conducting cell counting kit-8 test and the cognition of APP/PS1 mice was measured through the Morris Water Maze. Flow cytometry experiments were applied to assess the ROS levels of HT22 cells and measure the apoptosis rate of HT22 cells or hippocampal neurons. Expression of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax), hypoxia-inducible factor (HIF)-1α, NADPH oxidase (NOX) 4, Aß1-42 and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway proteins was quantified by Western blot. RESULTS: In vitro data confirmed that Aß25-35-induced HT22 cells had a significantly lower cell viability, higher ROS level and higher apoptosis rates compared with those of control cells (all P < 0.001). MgT prevented the Aß25-35-triggered oxidative stress damage by elevating viability and decreasing ROS formation and apoptosis of HT22 cells (all P < 0.001). APP/PS1 mice exhibited worse cognitive performance and higher apoptosis rate of hippocampal neurons than wild-type (WT) mice (all P < 0.01). Meanwhile, significant higher expression of Aß1-42 and NOX4 proteins was detected in APP/PS1 mice than those of WT mice (both P < 0.01). MgT also ameliorated the cognitive deficit, suppressed the apoptosis of hippocampal neuron and downregulated the expression of Aß1-42 and NOX4 proteins in APP/PS1 mouse (all P < 0.05). Moreover, MgT intervention significantly downregulated HIF-1α and Bax, upregulated Bcl-2 and activated the PI3K/Akt pathway both in vitro and in vivo (all P < 0.05). CONCLUSION: MgT exhibits neuroprotective effects against oxidative stress and hippocampal neuronal apoptosis in Aß25-35-treated HT22 cells and APP/PS1 mice.

12.
J Chem Phys ; 155(23): 234901, 2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34937364

RESUMO

Various microswimmers move along circles rather than straight lines due to their swimming mechanisms, body shapes, or hydrodynamic effects. In this paper, we adopt the concepts of stochastic thermodynamics to analyze circle swimmers confined to a two-dimensional plane and study the trade-off relations between various physical quantities, such as precision, energy cost, and rotational speed. Based on these findings, we predict principles and strategies for designing microswimmers of special optimized functions under limited energy resource conditions, which will bring new experimental inspiration for designing smart motors.


Assuntos
Biomimética , Hidrodinâmica , Natação , Metabolismo Energético , Rotação
13.
J Alzheimers Dis ; 79(3): 1023-1032, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33459705

RESUMO

BACKGROUND: Magnetic resonance imaging (MRI) provides objective information about brain structural atrophy in patients with Alzheimer's disease (AD). This multi-structural atrophic information, when integrated as a single differential index, has the potential to further elevate the accuracy of AD identification from normal control (NC) compared to the conventional structure volumetric index. OBJECTIVE: We herein investigated the performance of such an MRI-derived AD index, AD-Resemblance Atrophy Index (AD-RAI), as a neuroimaging biomarker in clinical scenario. METHOD: Fifty AD patients (19 with the Amyloid, Tau, Neurodegeneration (ATN) results assessed in cerebrospinal fluid) and 50 age- and gender-matched NC (19 with ATN results assessed using positron emission tomography) were recruited in this study. MRI-based imaging biomarkers, i.e., AD-RAI, were quantified using AccuBrain®. The accuracy, sensitivity, specificity, and area under the ROC curve (AUC) of these MRI-based imaging biomarkers were evaluated with the diagnosis result according to clinical criteria for all subjects and ATN biological markers for the subgroup. RESULTS: In the whole groups of AD and NC subjects, the accuracy of AD-RAI was 91%, sensitivity and specificity were 88% and 96%, respectively, and the AUC was 92%. In the subgroup of 19 AD and 19 NC with ATN results, AD-RAI results matched completely with ATN classification. AD-RAI outperforms the volume of any single brain structure measured. CONCLUSION: The finding supports the hypothesis that MRI-derived composite AD-RAI is a more accurate imaging biomarker than individual brain structure volumetry in the identification of AD from NC in the clinical scenario.


Assuntos
Doença de Alzheimer/diagnóstico , Encéfalo/patologia , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Atrofia , Biomarcadores , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
14.
Alzheimers Res Ther ; 13(1): 23, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436059

RESUMO

BACKGROUND: The differential diagnosis of frontotemporal dementia (FTD) and Alzheimer's disease (AD) is difficult due to the overlaps of clinical symptoms. Structural magnetic resonance imaging (sMRI) presents distinct brain atrophy and potentially helps in their differentiation. In this study, we aim at deriving a novel integrated index by leveraging the volumetric measures in brain regions with significant difference between AD and FTD and developing an MRI-based strategy for the differentiation of FTD and AD. METHODS: In this study, the data were acquired from three different databases, including 47 subjects with FTD, 47 subjects with AD, and 47 normal controls in the NACC database; 50 subjects with AD in the ADNI database; and 50 subjects with FTD in the FTLDNI database. The MR images of all subjects were automatically segmented, and the brain atrophy, including the AD resemblance atrophy index (AD-RAI), was quantified using AccuBrain®. A novel MRI index, named the frontotemporal dementia index (FTDI), was derived as the ratio between the weighted sum of the volumetric indexes in "FTD dominant" structures over that obtained from "AD dominant" structures. The weights and the identification of "FTD/AD dominant" structures were acquired from the statistical analysis of NACC data. The differentiation performance of FTDI was validated using independent data from ADNI and FTLDNI databases. RESULTS: AD-RAI is a proven imaging biomarker to identify AD and FTD from NC with significantly higher values (p < 0.001 and AUC = 0.88) as we reported before, while no significant difference was found between AD and FTD (p = 0.647). FTDI showed excellent accuracy in identifying FTD from AD (AUC = 0.90; SEN = 89%, SPE = 75% with threshold value = 1.08). The validation using independent data from ADNI and FTLDNI datasets also confirmed the efficacy of FTDI (AUC = 0.93; SEN = 96%, SPE = 70% with threshold value = 1.08). CONCLUSIONS: Brain atrophy in AD, FTD, and normal elderly shows distinct patterns. In addition to AD-RAI that is designed to detect abnormal brain atrophy in dementia, a novel index specific to FTD is proposed and validated. By combining AD-RAI and FTDI, an MRI-based decision strategy was further proposed as a promising solution for the differential diagnosis of AD and FTD in clinical practice.


Assuntos
Doença de Alzheimer , Demência Frontotemporal , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Atrofia/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Demência Frontotemporal/diagnóstico por imagem , Demência Frontotemporal/patologia , Humanos , Imageamento por Ressonância Magnética
15.
Med Sci Monit ; 24: 9073-9080, 2018 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-30550533

RESUMO

BACKGROUND Serum alkaline phosphatase (ALP) has been proved to be a negative prognostic factor for several malignancies, but its clinical significance in gastric cancer (GC) patients has not been sufficiently studied. In the present retrospective study, we investigated the effect of serum ALP on disease-free survival (DFS) after radical gastrectomy. MATERIAL AND METHODS We included 491 GC patients receiving radical gastrectomy at the Chinese People's Liberation Army 309th Hospital. Univariate and multivariate analyses were performed to determine factors influencing serum ALP and DFS. The changes in serum ALP and its clinical relevance were also analyzed using the log-rank test and Cox proportional hazards model. RESULTS There were 491 patients who met our inclusion and exclusion criteria. Pre-treatment serum ALP was elevated in 87 of these patients and was normal in the other 404 patients. Elevation of pre-treatment serum ALP was correlated with the tumor diameter (OR=2.642, P=0.017), TNM stage (OR=4.592, P=0.005), and T classification (OR=1.746, P=0.043). DFS was significantly different between patients with normal or elevated pre-treatment serum ALP (median 42.1 vs. 32.8 months, P=0.001) and multivariate analysis suggested pre-treatment serum ALP is an independent risk factor for poor DFS after radical gastrectomy (HR=2.035, P=0.021). In addition, removal of the primary tumor lesion led to an obvious decline in serum ALP activity (median 262 U/L vs. 152 U/L, P<0.001), and monitoring changes in serum ALP can help evaluate the risk of tumor relapse in GC patients (χ²=17.814, P<0.001). CONCLUSIONS Serum ALP is a good predictor of GC patient DFS after radical gastrectomy, and patients with elevated serum ALP have shorter relapse times.


Assuntos
Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/análise , Fosfatase Alcalina/sangue , Povo Asiático/genética , Biomarcadores Tumorais/sangue , China , Intervalo Livre de Doença , Feminino , Gastrectomia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Fatores de Risco
16.
Chin Med J (Engl) ; 125(11): 1899-902, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22884050

RESUMO

BACKGROUND: Roux-en-Y gastric bypass (GBP) is the main surgical procedure used in type 2 diabetes. The objective of this study was to evaluate the different types of GBP in treatment of type 2 diabetes. METHODS: Patients with type 2 diabetes were randomly divided into two groups: those who underwent gastrojejunal loop anastomosis bypass and those who underwent gastrojejunal Roux-en-Y bypass. Blood glucose alterations, operation time, and operation complications were observed. RESULTS: Gastrojejunal loop anastomosis bypass and gastrojejunal Roux-en-Y bypass were both effective in the treatment of selected patients with type 2 diabetes. Compared with gastrojejunal Roux-en-Y bypass, gastrojejunal loop anastomosis bypass had the advantages of easier implementation, shorter operation time, and fewer operation complications. CONCLUSIONS: Gastrojejunal loop anastomosis is effective in treatment of type 2 diabetes. It is safe, easy to implement, and worthy of clinical popularization.


Assuntos
Diabetes Mellitus Tipo 2/cirurgia , Derivação Gástrica/métodos , Adulto , Anastomose em-Y de Roux , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
17.
Anal Chem ; 81(20): 8623-6, 2009 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-19743808

RESUMO

A newly developed high irradiance laser ionization orthogonal time-of-flight mass spectrometer (LI-O-TOFMS) was employed for the elemental analysis of residues, which were prepared by evaporating mixed salt solutions. The residues were first characterized in terms of shape and elemental distribution. In TOFMS detection, all of the metal elements in the residue can be observed in the spectra. Relative sensitivity coefficients for different elements were within 1 order of magnitude, which meets semiquantitative analysis criteria. By calculating the individual masses from the ablated area due to a single laser shot, the absolute detection limit reached 7 x 10(-15) g for most metal elements. The results indicate that LI-O-TOFMS is capable of performing ultratrace elemental qualification and quantification, with an absolute limit of detection and an absolute limit of quantitation at the femtogram level.

18.
Di Yi Jun Yi Da Xue Xue Bao ; 22(8): 734-5, 2002 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-12376265

RESUMO

OBJECTIVE: To investigate the effect of superselective intra-arterial infusion chemotherapy in the treatment of advanced recurrent cancer in the remnant stomach after previous partial gastrectomy. METHODS: Eighteen patients with advanced recurrent cancer in the remnant stomach that were non-resectable as confirmed in the operations were included in this study, who subsequently received superselective intra-arterial infusion chemotherapy. RESULTS: Improvement of the symptoms to various degrees were achieved in all patients after the therapy, with the total rate of tumor reduction of 77.8% and pathologically confirmed improvement rate of 83.3%. The 0.5-, 1.0-, 1.5- and 2.0-year survival rates were 94.4%, 66.7%, 50.0% and 27.8% respectively. CONCLUSION: Superselective catheterization is effective in treatment of advanced recurrent cancer in the remnant stomach, which can significantly prolong the tumor-bearing survival period of the patients.


Assuntos
Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Seguimentos , Coto Gástrico , Humanos , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida
19.
Zhonghua Zhong Liu Za Zhi ; 24(2): 167-9, 2002 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-12015040

RESUMO

OBJECTIVE: To evaluate the value of infusion chemotherapy by pump implantation via hepatic artery or portal vein or both (double-pump chemotherapy, DPC) for hepatic metastasis from colorectal cancer. METHODS: Thirty patients with hepatic metastasis from colorectal cancer were divided into three groups: 1. Group I-DPC (12 patients). 2. Group II-hepatic artery implantation chemotherapy (10 patients) and 3. Group III-portal vein implantation chemotherapy (8 patients). RESULTS: Response rate was 66.7% in group I, 60% in group II and 37.5% in group III. The 0.5-, 1-, 2-year survival rates were 100.0%, 75.0%, 41.7% in group I, 90.0%, 60.0%, 30.0% in group II and 87.5%, 50.0%, 25.0% in group III. CONCLUSION: Double pump implantation chemotherapy is effective in treating hepatic metastasis from colorectal cancer. It is better than hepatic artery or portal vein pump-implantation chemotherapy alone.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Bombas de Infusão Implantáveis , Neoplasias Hepáticas/tratamento farmacológico , Adulto , Idoso , Neoplasias Colorretais/patologia , Tratamento Farmacológico/métodos , Feminino , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Infusões Intravenosas , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Veia Porta , Terapêutica
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