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1.
Eur Radiol ; 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35505116

RESUMO

OBJECTIVES: To determine patients with de novo metastatic nasopharyngeal carcinoma (mNPC) who would benefit from receiving definitive radiation therapy (DRT) along with their pre-existing palliative chemotherapy (PCT) by evaluating their post-PCT Deauville scores and EBV DNA. METHODS: A total of 570 mNPC patients, treated with PCT or PCT+DRT, were studied. EBV DNA levels, along with post-PCT Deauville scores, were used to stratify risk based on the recursive partitioning analysis (RPA). RESULTS: Significant differences were observed in the survival rates of patients with Deauville scores of 1-3 and 4-5 (2-year progression-free survival (PFS): 23.4% versus 8.5%, p < 0.001; 2-year overall survival (OS): 56.8% versus 18.8%, p < 0.001). RPA yielded three distinct groups in the increasing order of risk (Deauville scores of all RPA I-II were within the range of 1-3): (1) RPA I: EBV DNA levels at a pretreatment concentration ≤ 4000 copies/mL and undetectable post-PCT; (2) RPA II: EBV DNA levels either at a pretreatment concentration > 4000 copies/mL or at a pretreatment concentration ≤ 4000 copies/mL and detectable post-PCT; (3) RPA III: Deauville scores 4-5. While patients in RPA I and RPA II had significantly PFS rates when treated with PCT+DRT than when treated with PCT alone (RPA I: 72.7% versus 13.4%, RPA II: 37.8% versus 6.3%), those in RPA III did not experience such PFS benefits (6.5% versus 9.7%). CONCLUSION: PCT+DRT might improve the survival rates in mNPC patients in the low- and mid-risk strata but not those of patients in the high-risk strata. KEY POINTS: We use the Deauville scores and the concentrations of the Epstein-Barr virus (EBV) DNA to determine those patients with de novo metastatic NPC who would benefit from radiation therapy.

2.
Nano Lett ; 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35533100

RESUMO

As the size of magnetic devices continuously decreases, the creation of three-dimensional nanomagnets and the understanding of their magnetic configurations become increasingly important for modern applications. Here, by progressive nucleation during epitaxial nanoelectrodeposition, we synthesize single-crystal iron nanocuboids with sizes ranging 10 to 200 nm on one sample. The size-dependent magnetic configurations of these nanocuboids are studied by quantitative magnetic force microscopy and electron holography. In conjunction, a "magnetic configuration versus size" phase diagram is established via micromagnetic simulations. Both experiment and theory reveal a sequential transition from Landau pattern to vortex and finally single domain when decreasing the sizes of the nanocuboids. The combinatorial-like approach leads to a quantitative understanding of the magnetic configurations of the nanomagnets in a broad size range. It can be transferred to other materials and shapes and thereby presents an advanced route to enrich the material library for future nanodevice design.

3.
Polymers (Basel) ; 14(9)2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35566833

RESUMO

In order to study the mechanical behavior and energy dissipation of architectural membrane materials under multistage cyclic loading, the deformation behavior, energy dissipation, and damage characteristics of four kinds of warp-knitted and woven polyvinyl chloride (PVC) membrane materials were analyzed using multistage cyclic loading experiments. The results show that, compared with the uniaxial tensile strength, the peak values of the cyclic loading and unloading of the four material samples are lower in the warp direction but higher in the fill (weft) direction. Under multistage cyclic loading, the loading and unloading moduli of the warp knitting membrane increase with the increase in fabric density. At the same fabric density, the loading modulus and the unloading modulus are smaller than those of the warp knitting material. The total absorbed strain energy, elastic strain energy, and dissipation energy of the fill samples are higher than those of the warp samples at a low load level but lower than those at a high load level. PVC membrane materials' use strength should be controlled below a 15% stress level under long-term external force loading. In the cyclic loading process, the four PVC membrane materials are viscoelastic-plastic, so it is reasonable to define the damage variable based on the accumulation of plastic deformation.

4.
Comput Intell Neurosci ; 2022: 7487452, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432505

RESUMO

Background: Chloasma is a common skin pigment disorder. Treatment of chloasma has been challenging, often unsatisfactory, and difficult to avoid recurrence. PRP is a new treatment for chloasma, but there is no consensus on its use. Lingyun Zhao's team recently reported a systematic evaluation and meta-analysis of the efficacy and safety of PRP in the treatment of chloasma, which is consistent with our ideas, but we will elaborate on the application of PRP in chloasma from a deeper and more comprehensive perspective. Before we started this study, we had registered with Prospero as CRD42021233721. Methods: The authors searched the public medical network, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ScienceDirect, Scopus, and Science Network. The clinical trials registry ClinicalTrials.gov databases were searched for relevant publications to June 2021. The results showed the area and severity of chloasma (MASI) or revised MASI (mMASI) score. Results: Three RCTs, one nonrandomized controlled study, and four were prospective before and after self-controlled studies met the inclusive criteria. Intradermal PRP injections significantly improved chloasma as indicated by the significant decrease MASI (average balance -6.71, 95% CI -8.99 to -4.33) and mMASI scores (average balance -2.94, 95% CI -4.81 to -1.07). The adverse reactions were mild, and there were no significant long-term adverse events. Conclusive. The data can reflect the effectiveness and safety of PRP therapy for chloasma. RCTs are needed to determine effective treatment parameters, and long-term follow-up should be included to better clarify the efficacy and side effects of PRP in treating chloasma.


Assuntos
Melanose , Plasma Rico em Plaquetas , Humanos , Estudos Prospectivos , Resultado do Tratamento
5.
EMBO J ; : e110324, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35451091

RESUMO

The mechanisms underlying cancer metastasis remain poorly understood. Here, we report that TFAM deficiency rapidly and stably induced spontaneous lung metastasis in mice with liver cancer. Interestingly, unexpected polymerization of nuclear actin was observed in TFAM-knockdown HCC cells when cytoskeleton was examined. Polymerization of nuclear actin is causally linked to the high-metastatic ability of HCC cells by modulating chromatin accessibility and coordinating the expression of genes associated with extracellular matrix remodeling, angiogenesis, and cell migration. Mechanistically, TFAM deficiency blocked the TCA cycle and increased the intracellular malonyl-CoA levels. Malonylation of mDia2, which drives actin assembly, promotes its nuclear translocation. Importantly, inhibition of malonyl-CoA production or nuclear actin polymerization significantly impeded the spread of HCC cells in mice. Moreover, TFAM was significantly downregulated in metastatic HCC tissues and was associated with overall survival and time to tumor recurrence of HCC patients. Taken together, our study connects mitochondria to the metastasis of human cancer via uncovered mitochondria-to-nucleus retrograde signaling, indicating that TFAM may serve as an effective target to block HCC metastasis.

6.
RSC Adv ; 12(18): 11413-11419, 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35425064

RESUMO

A single feature set is often unable to effectively classify complex biological samples due to their similar morphology and sizes. This paper proposes a protocol for the fast identification of seed medicinal materials based on micro-structural and infrared spectroscopic characteristics. Three different feature datasets, namely micro-CT, FTIR, and mixed datasets, were established via principal component analysis (PCA) and competitive adaptive reweighted sampling (CARS) and then used to train a back-propagation neural network. The mixed dataset consists of 34-dimensional micro-CT eigenvalues and 13-dimensional FTIR eigenvalues, optimized by PCA and CARS processing and then used to train a BP neural network. The results showed that the classification accuracy reached 89.5% for the micro-CT dataset and 93.3% for the FTIR dataset, and the classification accuracy of the mixed dataset achieved 99.2%, much higher than those of the traditional single feature datasets. This study provides a new protocol for multi-dimensional characteristic architecture with excellent performance for the classification and identification of Chinese medicinal materials.

7.
Oral Oncol ; 128: 105851, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35430526

RESUMO

BACKGROUND: To evaluate the cost-effectiveness of stage-based post-radiotherapy (PRT) nasopharyngeal carcinoma (NPC) surveillance strategies. METHODS: Four post-radiotherapy surveillance strategies were established by a Markov model based on data from 1664 patients: 1) clinical follow-up (CFP) with biannual Epstein-Barr virus (EBV) DNA (EBV DNA strategy); 2) CFP with biannual EBV DNA, annual head and neck magnetic resonance imaging (HNMRI), chest X-ray, abdominal ultrasonography, bone scan (only for the first two years) for five years (MCWU strategy); 3) CFP with biannual EBV DNA, annual HNMRI, chest, abdomen, pelvic computerized tomography (CT) and bone scan for the first two years, followed by annual MCWU strategy (without bone scans) for the last three years (CT strategy); 4) CFP with biannual EBV DNA, annual whole-body positron emission/computerized tomography (PET/CT) for the first two years and biannual EBV DNA for the last three years (PET/CT strategy). RESULTS: Compared with the EBV DNA strategy, the MCWU, CT, and PET/CT strategies gained 0.017, 0.047, and 0.082 quality-adjusted life years (QALY) for stage I-II patients. For stage III and IVa patients, the PET/CT strategy had a favorable incremental effectiveness (ICERs) of 0.277 and 0.385 QALY, respectively. The ICERs for the MCWU, CT, and PET/CT strategies were $74,037, $34,882, and $34,696 for stage III and $62,364, $27,981, and $28,340 for stage IVa, respectively. CONCLUSION: EBV DNA strategy was cost-effective for the long-term surveillance of stage I-II NPC patients with CR. PET/CT strategy was recommeded for patients having IVa NPC. As for stage III NPC, PET/CT strategy was still acceptable with the development of economy in China.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Análise Custo-Benefício , DNA , DNA Viral/genética , Infecções por Vírus Epstein-Barr/epidemiologia , Herpesvirus Humano 4/genética , Humanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
8.
Front Psychiatry ; 13: 854698, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432040

RESUMO

Background: The novel coronavirus disease 2019 (COVID-19) outbreak has seriously threatened the mental health of college students. This study intended to invest whether perceived threat avoidability of COVID-19 relates to psychic anxiety among college students during the early stage of the COVID-19 pandemic, as well as the mediating roles of COVID-19-specific wishful thinking and COVID-19-specific protective behaviors in this relationship. Methods: A cross-sectional study was conducted in China, using a random sampling method (February 6-25, 2020). Self-reported questionnaires were conducted online included the Perceived Threat Avoidability of COVID-19 Scale, COVID-19-specific Wishful Thinking Scale, COVID-19-specific Protective Behaviors Scale, and the Hamilton Psychogenic Anxiety Scale. The data were analyzed using Structural equation modeling and Bootstrapping procedure. Results: A total of 2922 samples were collected in this study. Perceived threat avoidability of COVID-19 is negatively related to psychic anxiety (ß = -0.158, p< 0.001), and both COVID-19-specific wishful thinking (ß = -0.006, p = 0.029, 95% CI: [-0.012, -0.001]) and protective behaviors (ß = -0.029, p< 0.001, 95% CI: [-0.043, -0.018]) mediate this relationship. Also, COVID-19-specific wishful thinking is found to correlate with COVID-19-specific protective behaviors negatively (ß = -0.112, p < 0.001). Conclusion: Perceived threat avoidability of COVID-19 contributes to psychic anxiety among college students. COVID-19-specific wishful thinking strategy plays a negative mediating role and increases the level of anxiety; COVID-19-specific protective behaviors strategy plays a positive mediating role and reduces the level of anxiety; meanwhile, wishful thinking also suppresses college students from adopting protective behaviors.

9.
Immunobiology ; 227(3): 152205, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35279479

RESUMO

BACKGROUND: Early biomarkers allowing effective treatment stratification in adult T-cell acute lymphoblastic leukemia (T-ALL) patients remain elusive. MATERIALS AND METHODS: The mutation spectrum of 116T-ALL adult patients enrolled in the Shanghai Institute of Hematology (SIH)-based hospital network or Multicenter Hematology-Oncology Protocols Evaluation System (M-HOPES) in China were studied by using RNA-sequencing or targeted next generation sequencing. A comprehensive survival analysis based on clinical characteristics, immunophenotype and oncogenetic classifier was performed. RESULTS: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) has higher mutation rates of N/K-RAS and lower mutation rates of FBXW7 compared to non-ETP ALL, but the survival probability of ETP-ALL patients is similar to that of non-ETP ALL patients. T-ALLs with a NOTCH1/FBXW7 (N/F) mutation in the absence of RAS or PTEN abnormalities (NFRP class I) show a more favorable outcome compared to T-ALLs with no N/F mutation and/or with the presence of RAS/PTEN alterations (NFRP class II). A survival analysis of T-ALL, taking into account both the ETP-ALL/non-ETP T-ALL groups and the NFRP oncogenetic classifier, demonstrates that, within the non-ETP T-ALL subtype, NFRP class II identifies a group with poor prognosis and significant decreases of both OS (14.8% versus 50.9%, P = 0.019) and EFS (11.4% versus 42.4%, P = 0.001). In contrast, no survival difference is observed within ETP-ALL between the NFRP class I or class II (OS: 37.9% versus 33%, P = 0.876; EFS: 39.8% versus 33.7%, P = 0.969). CONCLUSION: In summary, the oncogenetic classifier based on the NFRP classes is particularly useful to improve the stratification of non-ETP ALL.

10.
Artigo em Inglês | MEDLINE | ID: mdl-35154341

RESUMO

BACKGROUND: According to Chinese constitutional theory, people can be divided into nine constitutions, which represent distinctive vulnerability to different diseases such as metabolic syndrome, atherosclerosis, and immunity-related disease, and so forth in modern medicine, phlegm-dampness constitution (PDC) is one of the nine constitutions, which is susceptible to metabolic syndrome (MS) and atherosclerosis that associate with lipid metabolism and immunity dysregulation closely. OBJECTIVES: In this study, we aimed to investigate the metabolic and immunity profiles of phlegm-damp constitution (PDC), including metabolites, lymphocytes distribution, and inflammatory cytokines. METHODS: A total of 74 patients with PDC and 66 individuals with gentle constitution (GC) were enrolled in this study. We utilized biochemical methods to detect metabolic parameters, flow cytometry to survey T/B/NK/NKT lymphocyte subgroups distribution, and ELISA to assay inflammatory cytokines. RESULTS: The subjects with PDC had higher GLU, AI TC, TG, and LDL-C and lower HDL-C levels. The immunity profile indicated that PDC subjects had higher percentage of WBCs, neutrophils, lymphocytes, B cells, and natural killer T cells compared with subjects with GC (P < 0.05). Serum levels of IL-10 decreased significantly in the subjects with phlegm-damp constitution, whereas IL-12 levels increased dramatically in the PDC group compared with the GC group (both P < 0.05). Additionally, logistic regression identified four independent variables (GLU, TG, LDL-C, and lymphocytes) that were highly correlated with PDC (P < 0.05). The area under the curve of the receiver operating characteristic curve was 0.878, which indicated the data were reliable to distinguish the subjects with PDC from the ones with GC. CONCLUSION: Phlegm-damp constitution was prone to hyperglycemia and hyperlipidemia syndrome, promoting the occurrence and progression of metabolic-related diseases. Interestingly, proinflammatory cells and cytokines were activated in the PDC group as well. Our findings could offer a profile of early screening indicators to identify high-risk patients of metabolic- and immunity-related diseases from Chinese constitution.

11.
Head Neck ; 44(5): 1057-1068, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35146832

RESUMO

BACKGROUND: We aimed to evaluate patients suitable for definitive radiation therapy (DRT) and liver local therapy (LLT) in addition to palliative chemotherapy (PCT) among those with de novo liver metastatic nasopharyngeal carcinoma (lmNPC). METHODS: The overall survival (OS) and progression-free survival (PFS) rates were calculated and compared in 610 patients with lmNPC. RESULTS: Both the PCT+DRT and PCT+DRT+LLT groups had better survival outcomes than the PCT group. Among patients with complete response/partial response (CR/PR) after PCT, no significant differences in survival rates were observed between those treated with PCT+DRT and PCT+DRT+LLT (2-year PFS: 27.0% vs. 32.9%, p = 0.263). Among patients with progressive disease/stable disease (PD/SD) after PCT, significantly better survival rates were observed in patients treated with PCT+DRT+LLT. CONCLUSIONS: DRT might benefit patients with lmNPC regardless of the tumor response after PCT. For patients with CR/PR, LLT might not be needed. For patients with PD/SD, LLT might improve survival outcomes.


Assuntos
Neoplasias Nasofaríngeas , Estudos de Coortes , Humanos , Fígado/patologia , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Estudos Retrospectivos
12.
Cell Death Differ ; 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35105963

RESUMO

Epstein-Barr virus (EBV) was the first oncogenic virus identified in humans. It is primarily associated with multiple lymphoid and epithelial cancers, including nasopharyngeal carcinoma (NPC). However, its association with ferroptosis and its role in cancer therapy resistance have not been fully elucidated. Here, we show that EBV infection reduces the sensitivity of NPC cells to ferroptosis by activating the p62-Keap1-NRF2 signaling pathway in conjunction with upregulation of SLC7A11 and GPX4 expression. Knockdown of endogenous GPX4 or blockade of GPX4 using a specific inhibitor enhanced the chemosensitivity of EBV-infected NPC cells. Functional studies revealed that GPX4 knockdown suppresses the proliferation and colony formation of NPC cells. Mechanistically, GPX4 interacts with the TAK1-TAB1/TAB3 complex, regulates TAK1 kinase activity, and further activates downstream MAPK-JNK and NFκB pathways. High GPX4 expression is correlated with poor clinical outcomes in patients with NPC and other cancer types. Taken together, our findings suggest that EBV infection has important effects on redox homeostasis, revealing a previously unappreciated role for GPX4 in tumor progression. This novel mechanism provides a potential new target for the treatment of EBV-related tumors.

13.
Water Res ; 212: 118120, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35114530

RESUMO

The distribution and fate of contaminants of emerging concern (CECs) was studied in relation to hydrological conditions, land use characteristics, and spatial contiguity in Houxi River. Thirty-four CECs were detected in the surface water during a three-year sampling campaign. Caffeine was most prevalent (99% frequency), while bisphenol A had the highest median concentration (78.2 ng/L) among the detected CECs. Caffeine and the other prevalent CECs lincomycin and bisphenol A, with median concentrations of 3.89 ng/L, 0.26 ng/L, and 78.2 ng/L, respectively, were positively correlated with land use types related to anthropogenic activities (grass, barren, built up, and cropland areas and landscape indexes for human activities). The analysis of similarities revealed significant annual variations, with increasing trends in both the concentrations and detection frequencies of CECs. Spatial variations were demonstrated by higher concentrations and detection frequencies downstream compared to upstream. The singular value decomposition analysis revealed that the downstream sites were the major contributors (55.6%-100%) to the spatial variability of most CECs. Moran's I analysis based on downstream contiguity indicated strong spatial autocorrelation among the connected sites for most CECs. This was further supported by longer correlation lengths for 18 CECs than the average distance between the sampling sites. The spatial autocorrelation can be attributed to the physicochemical properties of CECs and local hydrological dynamics, including temperature, wind speed, and sunshine hours. For most CECs, local contribution predominated over neighbor influence with an average value of 75.5%. The results of this study provide new insight to evaluate CEC distributions, which will be beneficial to policymakers for the management and prioritization of CEC contaminants in the Houxi watershed.


Assuntos
Monitoramento Ambiental , Poluentes Químicos da Água , Humanos , Rios , Análise Espacial , Águas Residuárias , Poluentes Químicos da Água/análise
14.
Molecules ; 27(4)2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-35208943

RESUMO

Sanghuangporus vaninii (Ljub.) L.W. Zhou & Y.C. Dai (SV) is a major cultivar of Sanghuang, which is well known as an excellent anti-tumour drug and reaches the mainstream market in China. Water, 60% ethanol and 95% ethanol were used to extract the drug, and three kinds of polar extracts were obtained separately. Compared with water extracts and 95% ethanol extracts, the 60% ethanol extract had the highest flavonoid content, and its polysaccharide content was greater than that in the 95% ethanol extract and lower than that in the water extract. Its essential components were phenolics whose majority were phenolic acids, flavonoids and phenylpropanoids. This extract has better inhibition effects on the proliferation of SW480 human colon cancer cells, inducing cell apoptosis and blocking G2/M period cells. It can significantly inhibit gene expression and reduce the activation of the AKT/mTOR signalling pathway. The anti-cancer activity of the 60% ethanol extract is satisfactory and may be a result of the combined effects of polysaccharides and flavonoids. The data suggest that the 60% ethanol extract can be used as an adjuvant for chemotherapy and as a potential anti-cancer agent with broad development prospects.


Assuntos
Antineoplásicos/farmacologia , Basidiomycota/química , Neoplasias do Colo , Misturas Complexas/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Misturas Complexas/química , Humanos
15.
J Contam Hydrol ; 245: 103958, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35065315

RESUMO

This study presents an interval multi-objective fuzzy-interval credibility-constrained nonlinear programming (IMFICNP) model combined with spatial water requirement of ecological vegetation (SEWR) estimation for solving the problem of allocation of agricultural and ecological water in irrigation districts under uncertainties. Through techniques of remote sensing (RS) and geographic information system (GIS), the ecological vegetation is subdivided into three types including forest land, grassland and shrubland and the water requirement of ecological vegetation is extended from site-specific sample to spatial decision-making unit (DMU), which provides a set of spatial data for input parameters of constraints. The IMFICNP model can be formulated through combination of interval parameter programming, multi-objective programming and fuzzy-interval credibility-constrained programming, which can handle the conflicts of multiple objectives under uncertainties such as single uncertainty (interval and fuzzy parameters) and dual-uncertainties (fuzzy-interval sets), and finally generate optimal water allocation schemes for crop and ecological vegetation under different credibility levels. The interval quadratic crop water production functions (IQCWPFs) are introduced to express the nonlinear relationships between crop yield and irrigation amount. Then, this model is applied to a case study of Huangyang Irrigation District (HID) in Shiyang River Basin to demonstrate its applicability. The results indicate that a higher credibility level is accompanied by less amount of water allocation and lower system benefit. The amount of water allocation at the DMU is dominated by planting area of crops and ecological vegetation, but there are few exceptions that optimal solutions are determined by the economic value. In addition, SEWR enables to reflect spatial heterogeneity of the DMU at a larger scale. IMFICNP model can coordinate conflicts among multiple objectives and it can tackle the violation of system constraints with fuzzy-interval sets. Therefore, these results can effectively balance the agricultural and ecological water management in irrigation districts, and provide valuable basis for the sustainable development of arid and semi-arid areas.


Assuntos
Modelos Teóricos , Água , Incerteza , Recursos Hídricos , Abastecimento de Água
16.
J Clin Oncol ; 40(11): 1163-1173, 2022 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-34990291

RESUMO

PURPOSE: Cumulative doses of 200 mg/m2 for concurrent cisplatin (DDP) were indicated by retrospective studies as sufficient in conferring survival benefit for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We performed an open-label, phase II, randomized, controlled trial to test the noninferiority of a two-cycle 100 mg/m2 concurrent DDP regimen over three-cycle in patients with low-risk LA-NPC with pretreatment Epstein-Barr virus DNA levels < 4,000 copies/mL. PATIENTS AND METHODS: Eligible patients were randomly assigned 1:1 to receive two cycles or three cycles concurrent DDP-based chemoradiotherapy. The primary end point was 3-year progression-free survival (PFS). The secondary end points included overall survival, distant metastasis-free survival, locoregional relapse-free survival, etc. RESULTS: Between September 2016 and October 2018, 332 patients were enrolled, with 166 in each arm. After a median follow-up of 37.7 months, the estimated 3-year PFS rates were 88.0% in the two-cycle group and 90.4% in the three-cycle group, with a difference of 2.4% (95% CI, -4.3 to 9.1, Pnoninferiority = .014). No differences were observed between groups in terms of PFS, overall survival, and the cumulative incidences of locoregional relapse and distant metastasis. Patients in the three-cycle group developed significantly more grade 3-4 mucositis (41 [24.8%] v 25 [15.1%]), hyponatremia (26 [15.8%] v 14 [8.4%]), and dermatitis (9 [5.5%] v 2 [1.2%]). The overall all-grade and grade 3-4 toxicity burdens were heavier in three-cycle group (T-scores, 12.33 v 10.57, P < .001 for all grades; 1.76 v 1.44, P = .05 for grade 3-4). Patients in the three-cycle group also showed more all-grade hearing impairment, dry mouth and skin fibrosis, and impaired long-term quality of life. CONCLUSION: Intensity-modulated radiotherapy plus two cycles of concurrent 100 mg/m2 DDP could be an alternative treatment option for patients with low-risk LA-NPC.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/efeitos adversos , Cisplatino , DNA/uso terapêutico , Herpesvirus Humano 4/genética , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Qualidade de Vida , Estudos Retrospectivos
17.
Clin Chem ; 68(4): 561-573, 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-34993545

RESUMO

BACKGROUND: Many studies have demonstrated the high efficacy of cell-free nuclear DNA in cancer diagnostics. Compared to nuclear DNA, mitochondrial DNA (mtDNA) exhibits distinct characteristics, including multiple copies per cell and higher mutation frequency. However, the potential applicability of cell-free mtDNA (cf-mtDNA) in plasma and urine remains poorly investigated. METHODS: Here, we comprehensively analyzed the fragmentomic and mutational characteristics of cf-mtDNA in urine and plasma samples from controls and cancer patients using next-generation sequencing. RESULTS: Compared to plasma cf-mtDNA, urine cf-mtDNA exhibited increased copy numbers and wider spread in fragment size distributions. Based on 2 independent animal models, urine cf-mtDNA originated predominantly from local shedding and transrenal excretion. Further analysis indicated an enhanced fragmentation of urine cf-mtDNA in renal cell carcinoma (RCC) and colorectal cancer (CRC) patients. Using the mtDNA sequence of peripheral blood mononuclear cells for reference, the mutant fragments were shorter than wild-type fragments in urine cf-mtDNA. Size selection of short urine cf-mtDNA fragments (<150 bp) significantly enhanced the somatic mutation detection. Our data revealed remarkably different base proportions of fragment ends between urine and plasma cf-mtDNA that also were associated with fragment size. Moreover, both RCC and CRC patients exhibited significantly higher T-end and lower A-end proportions in urine cf-mtDNA than controls. By integrating the fragmentomic and mutational features of urine cf-mtDNA, our nomogram model exhibited a robust efficacy for cancer diagnosis. CONCLUSIONS: Our proof-of-concept findings revealed aberrant fragmentation and mutation profiles of urine cf-mtDNA in cancer patients that have diagnostic potential.


Assuntos
DNA Mitocondrial , Neoplasias , Animais , DNA Mitocondrial/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Leucócitos Mononucleares , Mutação
18.
Int J Cancer ; 150(10): 1677-1689, 2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35001369

RESUMO

Next-generation sequencing (NGS) of mitochondrial DNA (mtDNA) has widespread applications in aging and cancer studies. However, cross-contamination of mtDNA constitutes a major concern. Previous methods for the detection of mtDNA contamination mainly focus on haplogroup-level phylogeny, but neglect haplotype-level differences, leading to limited sensitivity and accuracy. In our study, we present mitoDataclean, a random-forest-based machine learning package for accurate identification of cross-contamination, evaluation of contamination levels and detection of contamination-derived variants in mtDNA NGS data. Comprehensive optimization of mitoDataclean revealed that training simulation with mixtures of small haplogroup distance and low polymorphic difference was critical for optimal modeling. Compared to existing methods, mitoDataclean exhibited significantly improved sensitivity and accuracy for the detection of sample contamination in simulated data. In addition, mitoDataclean achieved area under the curve values of 0.91 and 0.97 for discerning genuine and contamination-derived mtDNA variants in a simulated Western dataset and private sequencing contamination data, respectively, suggesting that this tool may be applicable for different populations and samples with different sources of contamination. Finally, mitoDataclean was further evaluated in several private and public datasets and showed a robust ability for contamination detection. Altogether, our study demonstrates that mitoDataclean may be used for accurate detection of contaminated samples and contamination-derived variants in mtDNA NGS data.


Assuntos
DNA Mitocondrial , Neoplasias , DNA Mitocondrial/genética , DNA de Neoplasias , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Aprendizado de Máquina , Mutação , Neoplasias/genética , Análise de Sequência de DNA
19.
J Contam Hydrol ; 246: 103956, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35038637

RESUMO

Drought is one of the main factors negatively affecting crop growth. Optimizing irrigation time and irrigation amount are two effective ways to improve crop yield and water use efficiency. In order to achieve process-based optimization in shallow groundwater area, a comprehensive model is established by combining EPIC crop growth module, soil and groundwater water-salt balance models, and multi-objectives 0-1 programming. Multi-objectives are set to maximize crop biomass accumulated in drought period and improve water use efficiency for saving water. The irrigation amount and irrigation time of maize during drought periods are optimized by the day. The results indicate that soil salinization can aggravate the water stress to crops. The optimized schemes show the significant difference of total biomass and water use efficiency when irrigating at different time during drought conditions. Water sensitivity coefficients can be used to roughly guide the irrigation strategies that irrigation should be conducted as early as possible during water sensitive periods, so as to guarantee the high crop biomass and water use efficiency. The integrated model established in this study provides a reference approach for optimizing irrigation time and irrigation amount based on dynamic changes. The established model and obtained results in this study seek to potentially provide effective strategies combating agricultural droughts.


Assuntos
Secas , Água Subterrânea , Irrigação Agrícola , Agricultura , Solo
20.
Radiother Oncol ; 167: 252-260, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34998900

RESUMO

BACKGROUND: Salvage radiotherapy (RT) is a potentially curative approach for advanced locally recurrent nasopharyngeal carcinoma (NPC), but it is associated with severe toxicities. We aimed to develop a model to predict which patients would benefit from salvage RT. METHODS: A total of 809 patients who were diagnosed with advanced locally recurrent NPC and treated with salvage RT or palliative chemotherapy (CT) at a high-volume cancer center were included. Patients were randomly split into a training and validation set and matched using inverse probability of treatment weighting. The primary outcome was overall survival (OS). Candidate variables associated with heterogeneous treatment effects were identified with interaction terms in Cox model and incorporated into Salvage Radiotherapy Outcome Score (SARTOS). RESULTS: The final model included five interaction terms indicating that female sex, presence of prior RT-induced grade ≥ 3 late toxicities and suboptimal performance status were associated with less benefit from salvage RT. SARTOS from the model significantly predicted treatment effects of salvage RT in matched training (Pinteration < 0.001) and validation cohorts (Pinteration = 0.027). Of patients in high SARTOS subgroup, salvage RT significantly improved survival versus palliative CT in matched training (3-year OS 67.3% vs. 42.0%, HR 0.51, 95% CI 0.32-0.82, P = 0.005) and validation cohorts (3-year OS 71.8% vs. 22.8%, HR 0.40, 95% CI 0.17-0.97, P = 0.042); in low SARTOS subgroup, salvage RT failed to induce survival benefit. CONCLUSIONS: We found that the SARTOS model could identify a subgroup of patients who benefit from salvage RT versus palliative CT, which helps personalize treatment recommendations for patients with recurrent NPC.


Assuntos
Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Feminino , Humanos , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/patologia , Radioterapia de Intensidade Modulada/efeitos adversos , Terapia de Salvação
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