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1.
Food Chem Toxicol ; 144: 111537, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32649969

RESUMO

Ursolic acid (UA) is a pentacyclic triterpenoid and has the characteristics to serve as a potential therapeutic agent for a range of disorders. However, detailed studies of the toxicity of UA, especially developmental toxicity of UA, are non-existing. The objective of this study was to determine the potential effects of UA on fetal development, adult reproductive system, and major organs. UA was dissolved in a 0.5% hydroxypropyl methylcellulose, 0.1% Tween 80 in Milli-Q Water solution. A 100, 300 or 1000 mg/kg/day dose of UA or a control vehicle was administered orally for 15 days to adults (Han Wistar) and pregnant females (Sprague-Dawley). The administration of UA in adults did not cause deaths or resulted in abnormal (reproductive) organ or body weights at the dose up to 1000 mg/kg/day. The administration of UA resulted in no significant toxicological changes in either maternal nor fetal subjects in terms of body weight, organ weights, food consumption, gross pathology, sex organs, maternal performances, and fetal performances. Together, this study indicates that oral dosing with UA is safe for adult rats and their offspring and the no observed adverse effect level for UA is likely higher than 1000 mg/kg/day.

2.
Food Chem ; 332: 127387, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32629331

RESUMO

The simultaneous formation of acrylamide; ß-carboline heterocyclic amines (HAs): harmane and norharmane; and advanced glycation end products (AGEs) (Nε-(carboxymethyl)lysine (CML) and Nε-(carboxyethyl)lysine (CEL)) was analyzed based on an aqueous model system. The model systems included lysine-glucose (Lys/Glu), asparagine-glucose (Asn/Glu), tryptophan-glucose (Trp/Glu), and a mixture of these amino acids (Mix/Glu). Only AGEs were generated when heated at 100 °C, Asn and Trp competed with Lys for glucose and methylglyoxal (MGO), and glyoxal (GO) decreased AGE content. The k value of CML, CEL, and acrylamide decreased when heated at 130 °C, whereas that of harmane increased in the Mix/Glu, owing to the competition between Lys and Asn for glucose, GO, and MGO. Harmane preferably formed via the Pictet-Spengler condensation between Trp and acetaldehyde, which further reduced acrylamide formation via the acrolein pathway.

3.
J Cell Mol Med ; 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32627970

RESUMO

Calpains are calcium-dependent proteases and play critical roles in neuronal autophagy induced by inflammation. Propofol has been reported to exert anti-inflammatory effects in neurons. We aimed to identify whether and how propofol-modulated calpain activity and neuron autophagy in response to tumour necrosis factor-α (TNF-α). Mouse hippocampal neurons were pre-treated with propofol and exposed to TNF-α. Autophagy was evaluated by fluorescent autophagy assay and by measuring LC3I and LC3II expression. Intracellular calcium concentration was measured by fluorescent assay. Calpain activation was measured by calpain activity assay. The protein expression of intracellular signalling molecules was detected by Western blot analysis. Compared with untreated control neurons, 40 ng/mL TNF-α treatment for 2 hours induced neuron autophagy, which was attenuated by 25 µmol/L propofol. TNF-α induced intracellular calcium accumulation, the phosphorylation of calcium/calmodulin-dependent protein kinase II (CAMK II) and calpain-2, calpain activation and lysosomal cathepsin B release as well as tyrosine kinase receptor B (TrkB) truncation. These effects were alleviated by propofol, calcium chelator, CAMK II inhibitor, calpain-2 inhibitor, calpain-2 siRNA transfection and N-Methyl-d-aspartic acid (NMDA) receptor antagonist. Propofol, via NMDA receptor, inhibited TNF-α-mediated hippocampal neuron autophagy. The mechanism may involve calcium and calcium-dependent signalling pathway, especially CAMK II and calpain-2.

4.
Oncologist ; 2020 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-32533785

RESUMO

LESSONS LEARNED: The efficacy of second-line treatment for advanced non-small cell lung carcinoma (NSCLC) without a sensitizing driver gene mutation is still unsatisfactory. The combination of apatinib and chemotherapy improved progression-free survival in the second-line therapy of advanced NSCLC without a sensitizing mutation. This study offers a new treatment strategy for second-line treatment of such patients but requires confirmation in a larger multi-institutional trial. BACKGROUND: This study explored the efficacy and safety of apatinib combined with single-agent chemotherapy versus single-agent chemotherapy in the second-line treatment of advanced non-small-cell lung carcinoma (NSCLC) without driver mutations. METHODS: In this double-arm, open label, exploratory clinical study, we enrolled patients with unresectable locally advanced or advanced NSCLC without driver mutations that had progressed following first-line chemotherapy. The subjects were allocated into an experimental group and a control group by 2:1. The experimental group received apatinib combined with four cycles of docetaxel or pemetrexed until disease progression, intolerable toxicity, or discontinuation at the patient' request. The control group only received four cycles of docetaxel or pemetrexed. The primary endpoints were progression-free survival (PFS), and the secondary endpoints were overall survival (OS), disease control rate (DCR), and safety. RESULTS: Thirty-seven patients were enrolled. The efficacy of 33 patients was evaluated. The median PFS was 5.47 versus 2.97 months, the DCR was 95% versus 73%, and the objective response rate (ORR) was 27% versus 9% in the experimental versus control group. The OS was still under follow-up. The most common adverse effects included hypertension, hand-foot skin reaction (HFSR), and fatigue. CONCLUSION: Apatinib combined with single-agent chemotherapy may be a novel option for second-line treatment of advanced NSCLC.

5.
Meat Sci ; 169: 108203, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32485562

RESUMO

The aim of this study was to investigate the inhibitory effect of non-precursors amino acids (histidine, leucine, proline and methionine) which have advantages of safety, inexpensiveness and high standardization on the formation of ß-carbolines in roast beef patties and glucose/creatine/creatinine/tryptophan model system, and the possible pathway of inhibition by monitoring the scavenging of free radicals by electron paramagnetic resonance (EPR) spectroscopy and the consumption of tryptophan by HPLC in a glucose/tryptophan model system. Almost all amino acids can inhibit ß-carbolines in roast beef patties (up to 80.62%) and model system (up to 67.01%). Histidine showed an excellent alkyl radical scavenging ability (up to 82.59%) and a highly competitive inhibition ability (up to 65.60%) against ß-carbolines generation. The corresponding abilities of leucine and methionine were less remarkable. Proline could only suppress ß-carbolines through competitive inhibition. The results could shed light on the reduction of ß-carbolines during meat processing.

6.
Food Res Int ; 135: 109299, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32527489

RESUMO

Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), principal component analysis (PCA) and orthogonal projection to latent structure-discriminant analysis (OPLS-DA) were used to explore the effects of the amide components (capsaicin, sanshoamide, piperine) of pungent spices widely consumed in China (chili pepper, Sichuan pepper and black pepper) on the profiles of 17 heterocyclic amines (HAs) from seven categories in roast beef patties. Four groups of HAs were detected and quantified in both free and protein-bound states: imidazopyridines (DMIP, 1,5,6-TMIP), imidazoquinolines (MeIQ), imidazoquinoxalines (IQx, 4,8-MeIQx) and ß-carbolines (norharman, harman). Notably, different amounts of added capsaicin, sanshoamide and piperine had significant inhibitory effects on free DMIP, MeIQx, 4,8-DiMeIQx and harman formation in roast beef patties. Additionally, all three amide components significantly inhibited the formation of protein-bound MeIQ, 4,8-DiMeIQx, harman, norharman and MeAαC. In general, amide ingredients inhibited the formation of ß-carbolines and total HAs by approximately 70%. Furthermore, the addition of 0.005% and 0.010% capsaicin suppressed imidazopyridine formation by 44% and 35%, respectively, and 0.015% capsaicin inhibited imdazoquinoxaline formation by 33%. These findings shed light on the effects of amide ingredients on the formation of free and protein-bound HAs.

7.
J Int Med Res ; 48(6): 300060520930168, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32579483

RESUMO

OBJECTIVES: This prospective, randomized, controlled study aimed to explore the efficacy of dexmedetomidine combined with epidural blockade on postoperative recovery of elderly patients after radical resection for colorectal cancer. METHODS: Ninety-six elderly patients who underwent radical resection for colorectal cancer were randomly divided into the following four groups: dexmedetomidine, epidural blockade (ropivacaine), combined (dexmedetomidine + epidural blockade), and control (0.9% saline). The Mini-Mental State Examination (MMSE), Visual Analog Scale (VAS), and Ramsay scores at 48 hours, and time to first activity, length of hospital stay, and postoperative complication rates at 3 months were assessed. RESULTS: Twelve hours after surgery, Ramsay scores were higher in the combined compared with the control and epidural blockade groups. Twenty-four hours after surgery, MMSE scores were higher in the combined compared with the other groups. The combined group showed the lowest VAS scores except at 48 hours. Time to first activity and length of hospital stay were significantly shorter in the combined compared with the other groups. There was no difference in total postoperative complication rates among the groups. CONCLUSIONS: A combination of intraoperative dexmedetomidine infusion and epidural blockade could mitigate pain after surgery, improve cognitive dysfunction in early surgery, and facilitate recovery.

8.
Food Funct ; 11(5): 3867-3878, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32426776

RESUMO

The interaction and antioxidant capacity between epigallocatechin gallate (EGCG) and ß-lactoglobulin (ß-Lg) under thermal treatments at 25-121 °C were investigated in this study. Fluorescence spectroscopy analysis showed that EGCG complexed with ß-Lg mainly via non-covalent interactions and the binding affinity of EGCG to ß-Lg was enhanced with heat treatment. EGCG showed a strong binding affinity to ß-Lg after 85 °C heat treatment was applied, with a Ka of 30.69 (±0.87) × 105 M-1 (pH 6.8, 298 K). Circular dichroism (CD) results showed that heat treatment did not result in greatly affected changes in the ß-Lg secondary structure induced by ß-Lg-EGCG interactions. MALDI-TOF/TOF-MS analysis showed that ß-Lg-EGCG covalent conjugates initially formed after heat was applied at 60 °C, and their proportions increased under heat treatment ranging from 85 to 121 °C. The amino group of a lysine residue was further confirmed as the covalent binding site of EGCG to ß-Lg. The ß-Lg-EGCG interaction showed little effect on the antioxidant capacity (ABTS and ferric reducing antioxidant power (FRAP) values) of EGCG after heat treatment at 25-60 °C, but did induce an obvious reduction at temperatures above 85 °C. This study will provide the foundation for the use of EGCG in processing dairy products (such as milk tea beverages) with desirable nutrition and physiological functions.

9.
Food Chem ; 326: 127016, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32428855

RESUMO

The effects of sodium tripolyphosphate (TPP), sodium pyrophosphate (PP), and NaCl at different ionic strengths on the formation of heterocyclic amines (HAs) were investigated in roasted beef patties. Six HAs (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine [PhIP], 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline [MeIQx], 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline [4,8-DiMeIQx], 2-amino-3-methylimidazo[4,5-f]quinoline [IQ], 1-methyl-9H-pyrido[3,4-b] indole [harman], and 9H-pyrido[3,4-b] indole [norharman]) were identified and quantified. The presence of 0.3% and 0.45% PP significantly increased the formation of PhIP (P < 0.05). Different levels of TPP/PP had no effect on MeIQx, 4,8-DiMeIQx, IQ, norharman, or harman (P > 0.05), but these products increased in the presence of NaCl at three ionic strengths and NaCl + 0.3% and 0.45% TPP/PP (P < 0.05). High hardness and surface temperatures were observed after treatments with NaCl and NaCl + TPP/PP. The increase in these six HAs in beef patties with the addition of polyphosphates and NaCl did not involve changes in pH, but mainly stemmed from higher surface temperatures during roasting.

10.
Food Chem ; 320: 126655, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32224423

RESUMO

The effects of ß-cyclodextrin (ß-CD), whey protein (WP), and soy protein (SP) on the color loss and degradation of anthocyanins in purple-fleshed sweet potato anthocyanin extracts (PFSPAEs) during thermal treatment and shelf-life storage in model beverage systems by performing chromaticity, degradation kinetics, and principal component analysis. Results showed that WP and SP improved the thermal stability of the PFSPAE, but WP accelerated the color loss of the extract. However, the addition of 25 mg/L SP improved the color and thermal stability of the anthocyanins when heated at 100 °C for 30 min. With regard to the shelf-life storage, the addition of SP and WP showed non-significant effect on the storage stability of the PFSPAE. However, the addition of 2500 mg/L ß-CD significantly improved the storage stability of the PFSPAE. In summary, our findings provide useful information on improving the thermal and storage stability of PFSPAEs in beverage systems using food biopolymers.


Assuntos
Antocianinas/química , Ipomoea batatas/química , Proteínas de Soja/química , Proteínas do Soro do Leite/química , beta-Ciclodextrinas/química , Antocianinas/análise , Bebidas , Armazenamento de Alimentos , Temperatura Alta
12.
Materials (Basel) ; 13(6)2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32168797

RESUMO

A Ta coating has been successfully fabricated on the surface of zirconia polycrystals ceramic (3 mol% yttria, 3Y-TZP) by a plasma surface alloying technique. The X-ray diffraction (XRD) and scanning electron microscopy (SEM) results showed that a α-Ta coating with a continuous and compact surface morphology which consisted of a deposited layer with a thickness of 390 nm and a diffusion layer with a thickness of 200 nm covered the 3Y-TZP. Due to the effect of inhabitation the t→m transformation by the deposited Ta coating, the biaxial flexural strength caused by the phase transformation during hydrothermal aging is reduced e.g. p < 0.05 after 20 h and/or 100 h. In addition, the Ta coating shows non-cytotoxicity and improved proliferation ability of osteoblasts.

13.
Curr Med Imaging ; 16(3): 262-272, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32133956

RESUMO

BACKGROUND: This study is carried out targeting the problem of slow response time and performance degradation of imaging system caused by large data of medical ultrasonic imaging. In view of the advantages of CS, it is applied to medical ultrasonic imaging to solve the above problems. OBJECTIVES: Under the condition of satisfying the speed of ultrasound imaging, the quality of imaging can be further improved to provide the basis for accurate medical diagnosis. METHODS: According to CS theory and the characteristics of the array ultrasonic imaging system, block compressed sensing ultrasonic imaging algorithm is proposed based on wavelet sparse representation. RESULTS: Three kinds of observation matrices have been designed on the basis of the proposed algorithm, which can be selected to reduce the number of the linear array channels and the complexity of the ultrasonic imaging system to some extent. CONCLUSION: The corresponding simulation program is designed, and the result shows that this algorithm can greatly reduce the total data amount required by imaging and the number of data channels required for linear array transducer to receive data. The imaging effect has been greatly improved compared with that of the spatial frequency domain sparse algorithm.

14.
J Sci Food Agric ; 100(6): 2732-2741, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32003461

RESUMO

BACKGROUND: Recombinant plant-based whipping cream (RSWC) has been widely studied in recent years. The present study investigated the effects of soybean protein and its hydrolysates on the stability and physical properties of the RSWC. The RSWC was made with 28% soybean oil bodies and 4% additional soy proteins or its hydrolysates. The proteins used were soy protein isolate, 7S, 11S, oil body protein, soybean proteins isolate hydrolyzed by pepsin (SPHPe) and soybean protein isolate hydrolyzed by papain (SPHPa). RESULTS: RSWC made with SPHPa containing a large amount of small-molecule polypeptide had the lowest apparent viscosity, shortest whipping time, best overrun and worst whipping stability, whereas RSWC made with SPHPe containing the α, ß subunit and small-molecule polypeptides exhibited the second highest overrun and best whipping stability. The partial coalescence of fat and confocal micrographs of cream emulsions suggested that oil body protein was displaced by the small peptides from the interface, which led to partial destabilization and sufficient coalescence of fat globules after aging and whipping. CONCLUSION: Selectively hydrolyzed soy protein, such as SPHPe, can be used for the production of RSWC with sufficient overrun and whipping stability. This research is of great significance and opens a route to production of the recombinant plant-based cream in the future. © 2020 Society of Chemical Industry.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31900085

RESUMO

The recycling of municipal household solid waste (MHSW) is important for environmental preservation and wellbeing of the society. In recent decades, continuous efforts in research, policy-making and municipal administration have led to improvements towards more sustainable MHSW recycling. However, MHSW recycling remains a major challenge for China. This paper analyzes the current value and potential value of MHSW recycling in order to guide residents to recycle MHSW effectively and to reduce the amount of recycle-worthy materials missing recycling. A multivariate probit model is developed to ascertain the current value and potential value of MHSW recycling. Results from a case study of Shanghai reveal that waste glass has low current value and low potential value, and waste plastics has low current value but high potential value. The results also indicate that the waste metal has high current value and high potential value, whereas waste paper has high current value but low potential value. These findings provide policymakers with useful information and rationale for directing efforts to achieve a better or optimal MHSW recycling practice.

16.
Autophagy ; : 1-13, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31971848

RESUMO

How energy deprivation induces macroautophagy/autophagy is not fully understood. Here, we show that Atg11, a receptor protein for cargo recognition in selective autophagy, is required for the initiation of glucose starvation-induced autophagy. Upon glucose starvation, Atg11 facilitates the interaction between Snf1 and Atg1, thus is required for Snf1-dependent Atg1 activation. Phagophore assembly site (PAS) formation requires Atg11 via its control of the association of Atg17 with Atg29-Atg31. The binding of Atg11 with Atg9 is crucial for recruiting Atg9 vesicles to the PAS and, thus, glucose starvation-induced autophagy. We propose Atg11 as a key initiation factor controlling multiple key steps in energy deprivation-induced autophagy.Abbreviations: AMPK: AMP-activated protein kinase; Ams1: α-mannosidase; Ape1: aminopeptidase I; Cvt: cytoplasm-to-vacuole targeting; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; GFP: green fluorescent protein; MBP: myelin basic protein; MMS: methanesulfonate; PAS: phagophore assembly site; PNBM: p-nitrobenzyl mesylate; SD-G: glucose starvation medium; SD-N: nitrogen starvation medium; ULK1, unc-51 like autophagy activating kinase 1; WT: wild type.

17.
Food Chem ; 308: 125598, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31648096

RESUMO

An in vitro gastrointestinal digestion model was used to investigate the effects of milk matrix: skimmed milk (Sm), whole milk (Wm) and processing methods: pH adjustment, high pressure homogenization processing (HPHP), thermal treatment (TT) on the antioxidant capacity, phenolics bioaccessibility of coffee. Our findings showed that the antioxidant capacity of all the samples decreased or unchanged after in vitro digestion. The total phenolic bioaccessibility of coffee (C), coffee with whole milk (Cwm), and coffee with skimmed milk (Csm) decreased by 29.2%, 28.5%, 21.1% from the HPHP treatment and by 14.7%, 34.2%, and 33.8% from TT, respectively. pH adjustment had little effect on the total phenolic bioaccessibility of Cwm and Csm but significantly decreased that of C. Wm showed better protective effect on the phenolic bioaccessibility than Sm. These results may contribute to the optimization of formulations and processing methods in coffee beverage production, thereby increasing the health benefits of coffee.


Assuntos
Antioxidantes/metabolismo , Café/metabolismo , Leite/metabolismo , Fenóis/metabolismo , Animais , Digestão , Trato Gastrointestinal/metabolismo
18.
J Food Biochem ; 43(10): e12817, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31608468

RESUMO

Interactions of the flavoring compounds hexyl acetate (HxAc), heptyl acetate (HpAc), linalyl formate (LiFo), linalyl acetate (LiAc), geraniol, linalool, limonene, and myrcene with soy protein isolate (SPI) were estimated in pH 3.0, 6.0, and 9.0 aqueous solutions using headspace solid-phase microextraction gas chromatography-mass spectrometry (SPME-GC-MS). The binding capacity of HxAc, HpAc, LiFo, LiAc, geraniol, and linalool increased in the pH of the medium from 3 to 9. For limonene and myrcene, an unexpected increase in headspace concentration or a "salting-out" effect was observed. Between pH 3 and 9, better accessibility to the primary hydrophobic sites as a result of a modification to the protein's flexibility was observed. PRACTICAL APPLICATIONS: SPME method is a technology of dynamic adsorption for flavors. The lowest level of lead be practicably detected in food as low as the practiced concentration of flavors (0.01-0.1 mM) in our study. At low concentrations of flavors, it is close to the actual flavor's concentration of food. In the previous studies, the technology, such as equilibrium dialysis, headspace-gas phase which need higher concentration of flavors (>0.2 mM). The interaction between flavors and protein has a different binding law at high and low concentrations. As we produced the acid fruit soy protein milk beverage, the off-flavors present in the beverage were due to the change in the interaction between denature SPI and flavors. The present work is aimed at paving the way for further research to elucidate flavor imbalances in acid fruit soy protein milk beverage.

19.
Chem Commun (Camb) ; 55(58): 8422-8425, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31257398

RESUMO

A tough double-network (DN) organohydrogel, obtained by simply soaking a poly(2-acrylamido-2-methylpropane sulfonic acid)/polyacrylamide (PAMPS/PAAm) hydrogel in an ethylene glycol solution of lithium chloride, retains high mechanical performance, flexibility (-80 to 120 °C) and conductivity (-20 to 120 °C), paving the way towards broad applications.

20.
BMC Palliat Care ; 18(1): 47, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31167668

RESUMO

BACKGROUND: Although palliative care has been accepted throughout the cancer trajectory, accurate survival prediction for advanced cancer patients is still a challenge. The aim of this study is to identify pre-palliative care predictors and develop a prognostic nomogram for overall survival (OS) in mixed advanced cancer patients. METHODS: A total of 378 consecutive advanced cancer patients were retrospectively recruited from July 2013 to October 2015 in one palliative care unit in China. Twenty-three clinical and laboratory characters were collected for analysis. Prognostic factors were identified to construct a nomogram in a training cohort (n = 247) and validated in a testing cohort (n = 131) from the setting. RESULTS: The median survival time was 48.0 (95% CI: 38.1-57.9) days for the training cohort and 52.0 (95% CI: 34.6-69.3) days for the validation cohort. Among pre-palliative care factors, sex, age, tumor stage, Karnofsky performance status, neutrophil count, hemoglobin, lactate dehydrogenase, albumin, uric acid, and cystatin-C were identified as independent prognostic factors for OS. Based on the 10 factors, an easily obtained nomogram predicting 90-day probability of mortality was developed. The predictive nomogram had good discrimination and calibration, with a high C-index of 0.76 (95% CI: 0.73-0.80) in the development set. The strong discriminative ability was externally conformed in the validation cohort with a C-index of 0.75. CONCLUSIONS: A validated prognostic nomogram has been developed to quantify the risk of mortality for advanced cancer patients undergoing palliative care. This tool may be useful in optimizing therapeutic approaches and preparing for clinical courses individually.


Assuntos
Neoplasias/mortalidade , Nomogramas , Cuidados Paliativos/normas , Idoso , Distribuição de Qui-Quadrado , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Cuidados Paliativos/métodos , Cuidados Paliativos/estatística & dados numéricos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo
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