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1.
iScience ; 27(5): 109705, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38660399

RESUMO

The incidence of type 2 diabetes mellitus (T2DM) induced by obesity is rapidly increasing. Although there are many synthetic drugs for treating T2DM, they have various side effects. Here, we report that miR8175, a plant miRNA from burdock root, has effective antidiabetic activity. After administration of burdock decoction or synthetic miR8175 by gavage, both burdock decoction and miR8175 can significantly improve the impaired glucose metabolism of diabetic mice induced by a high-fat diet (HFD). Our results demonstrate that burdock decoction and miR8175 enhance the insulin sensitivity of the hepatic insulin signaling pathway by targeting Ptprf and Ptp1b, which may be the reason for the improvement in metabolism. This study provides a theoretical basis for the main active component and molecular mechanism of burdock to improve insulin resistance. And the study also suggests that plant miRNA may be an indispensable nutrient for maintaining human health.

2.
BMC Cancer ; 24(1): 72, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38218811

RESUMO

BACKGROUND: Radiotherapy (RT) is an effective and available local treatment for patients with refractory or relapsed (R/R) aggressive B-cell lymphomas. However, the value of hypofractionated RT in this setting has not been confirmed. METHODS: We retrospectively analyzed patients with R/R aggressive B-cell lymphoma who received hypofractionated RT between January 2020 and August 2022 at a single institution. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and acute side effects were analyzed. RESULTS: A total of 30 patients were included. The median dose for residual disease was 36 Gy, at a dose per fraction of 2.3-5 Gy. After RT, the ORR and complete response (CR) rates were 90% and 80%, respectively. With a median follow-up of 10 months (range, 2-27 months), 10 patients (33.3%) experienced disease progression and three died. The 1-year OS and PFS rates for all patients were 81.8% and 66.3%, respectively. The majority (8/10) of post-RT progressions involved out-of-field relapses. Patients with relapsed diseases, no response to systemic therapy, multiple lesions at the time of RT, and no response to RT were associated with out-of-field relapses. PFS was associated with response to RT (P = 0.001) and numbers of residual sites (P < 0.001). No serious non-hematological adverse effects (≥ grade 3) associated with RT were reported. CONCLUSION: These data suggest that hypofractionated RT was effective and tolerable for patients with R/R aggressive B-cell lymphoma, especially for those that exhibited localized residual disease.


Assuntos
Linfoma de Células B , Linfoma Difuso de Grandes Células B , Humanos , Rituximab/uso terapêutico , Estudos Retrospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/radioterapia , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/radioterapia , Recidiva , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento
3.
J Affect Disord ; 347: 269-277, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-37940057

RESUMO

BACKGROUND: Depression is one of the most common types of mental disorders. Guided by the theory of social determinants of health (SDH), the study aimed to assess the prevalence of depressive symptoms and to identify factors related to depressive symptoms in the general population of China. METHODS: A cross-sectional, online survey was conducted among 101,392 residents from 31 provinces of mainland China from January to March 2019, and 97,126 survey responses were included in the final analysis. Multilevel linear regression models were used to identify SDH associated with depressive symptoms. RESULTS: The prevalence of depressive symptoms (PHQ-9 scores ≥10) in Chinese residents was 15.81 %. The results of the multilevel analysis demonstrated that depressive symptoms were affected by various factors on five levels, including individual characteristics, behavioral lifestyle, community support network, social structural factors, and macro social factors. LIMITATIONS: The cross-sectional design of the study makes it difficult to establish causality between variables. CONCLUSIONS: The prevalence of depressive symptoms is high among general population in China. According to the theory of SDH, the study shows that the depressive symptoms are complex and involves all areas of social life. Therefore, adopting a multi-level, cross-sectoral intervention approach will be instrumental to improving the mental health of residents in China.


Assuntos
Depressão , Fatores Sociais , Humanos , Depressão/epidemiologia , Depressão/diagnóstico , Prevalência , Estudos Transversais , Determinantes Sociais da Saúde , China/epidemiologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-37667120

RESUMO

Water, energy and food security are at the heart of the UN 2030 Agenda for Sustainable Development. Maintaining water-energy-food (WEF) system security is critical to sustainable socio-economic development. To clarify the trends in China's WEF system stress, this paper analyses the spatial and temporal heterogeneity of WEF system stress using panel data for 30 Chinese provinces from 2002 to 2020. Using an extended STIRPAT model, we discuss the influencing factors of WEF system stress and forecast the WEF system stress index (WEF_SI) for 2021-2030. We find that China's WEF_SI has a significant positive spatial autocorrelation, with energy stress being the dominant stress in China's WEF system. Second, GDP per capita, urban population density, education level per capita, technology level and effective irrigated area have spatial and temporal heterogeneity in their effects on WEF system stress. Third, the prediction results show that China's WEF system stress will decrease in 2021-2030 but to a lesser extent. The government should coordinate the relationship between water, energy and food based on the evolutionary characteristics and projected trends of each element and formulate differentiated policies according to the resource endowment of each region to promote the coordinated development of the WEF system.

5.
Polymers (Basel) ; 15(10)2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37242892

RESUMO

Hyaluronic acid (HA), a main component of the extracellular matrix, is widely utilized to deliver anticancer drugs due to its biocompatibility, biodegradability, non-toxicity, non-immunogenicity and numerous modification sites, such as carboxyl and hydroxyl groups. Moreover, HA serves as a natural ligand for tumor-targeted drug delivery systems, as it contains the endocytic HA receptor, CD44, which is overexpressed in many cancer cells. Therefore, HA-based nanocarriers have been developed to improve drug delivery efficiency and distinguish between healthy and cancerous tissues, resulting in reduced residual toxicity and off-target accumulation. This article comprehensively reviews the fabrication of anticancer drug nanocarriers based on HA in the context of prodrugs, organic carrier materials (micelles, liposomes, nanoparticles, microbubbles and hydrogels) and inorganic composite nanocarriers (gold nanoparticles, quantum dots, carbon nanotubes and silicon dioxide). Additionally, the progress achieved in the design and optimization of these nanocarriers and their effects on cancer therapy are discussed. Finally, the review provides a summary of the perspectives, the lessons learned so far and the outlook towards further developments in this field.

6.
Cancer Med ; 12(10): 11438-11450, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37014817

RESUMO

PURPOSE: Distant metastasis (DM) and neoadjuvant treatment response prediction remain critical challenges in the management of locally advanced rectal cancer (LARC). The aim of this study was to investigate the clinical relevance of viable circulating tumor cells (CTCs) for DM or response in patients with LARC in a neoadjuvant setting. METHODS: The detection of viable CTCs at different stages of treatment was planned for consecutive patients from a prospective trial. The Kaplan-Meier method, Cox proportional hazards model, and logistic regression model were utilized to analyze factors associated with DM or pathological complete response (pCR) and clinical complete response (cCR). RESULTS: Between December 2016 and July 2018, peripheral blood samples from 83 patients were collected before any treatment (median follow-up time, 49.3 months). CTCs were present in 76 of 83 patients (91.6%) at baseline, and more than three CTCs detected in the blood sample was considered high risk. Only the CTC risk group was significantly associated with 3-year metastasis-free survival (MFS) (high risk vs. low risk, 57.1% (95% CI, 41.6-72.6) vs. 78.3% (95% CI, 65.8-90.8), p = 0.018, log-rank test). When all the important variables were entered into the Cox model, the CTC risk group remained the only significant independent factor for DM (hazard ratio (HR), 2.74; 95% CI, 1.17-6.45, p = 0.021). The pCR and continuous cCR rates were higher in patients with a decreased number of CTCs of more than one after radiotherapy (HR, 4.00; 95% CI, 1.09-14.71, P = 0.037). CONCLUSIONS: The dynamic detection of viable CTCs may strengthen pretreatment risk assessment and postradiotherapy decision making for LARC. This observation requires further validation in a prospective study.


Assuntos
Células Neoplásicas Circulantes , Neoplasias Retais , Humanos , Células Neoplásicas Circulantes/patologia , Terapia Neoadjuvante , Estudos Prospectivos , Prognóstico , Neoplasias Retais/patologia
7.
J Colloid Interface Sci ; 642: 820-828, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37060648

RESUMO

Boosting the energy density and safety issue of lithium-ion batteries has become ever more important to satisfy the diverse applications such as energy storage and mobile electronic devices. Herein, we present a new high voltage polyether-based electrolyte (HVPEE) by solvation structure design that can endure high-voltage operations and also possess non-flammable features. Especially, HVPEEs show better compatibility and stability with electrode than conventional electrolyte. We find that the solvent separated ion pair (SSIP) and contact ion pair (CIP) dominate the ion-solvent structure of HVPEEs, rather than the free solvent and ions. In this way, the oxidative decomposition of HVPEE on the cathode interface can be suppressed significantly due to the reduced highest occupied molecular orbital of SSIP complex structure than that of free TFSI-. As a result, the oxidation voltage can achieve as high as 5.35 V when the ether group/Li is optimized at 10/1 in the HVPEE, enabling the LiFePO4//Li full cells deliver a capacity of 165 mA h g-1 with a capacity retention of 98 % after 200 cycles. Moreover, when the cut-off voltage is 4.5 V, the discharge capacity of the LiNi0.6Mn0.2Co0.2O2//Li full cell can reach 170 mA h g-1.

8.
J Colloid Interface Sci ; 638: 595-605, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36774873

RESUMO

Solid-state polymer electrolytes are outstanding candidates for next-generation lithium metal batteries in the realm of high specific energy densities, high safeties and tight contact with electrodes. However, their applications are still hindered by the limitations that no single polymer is electrochemically stable with the oxidizing high-voltage cathode and the highly reductive Li anode, simultaneously. Herein, a bilayer asymmetric polymer electrolyte (SL-SPE) without accessional interface resistance that using poly (ethylene glycol) diacrylate (PEGDA) as a "bridge" to connect the sulfonyl (OS = O)-contained oxidation-tolerated layer and polyether-derived reduction-tolerated layer (SPE), is proposed and synthesized by sequential two-step UV polymerizations. SL-SPE can provide widened electrochemical stability window up to 5 V, while simultaneously deploying a stable Janus interface property. Eventually, the superior high-voltage (4.4 V) cycling durability can be displayed in LiNi0.6Co0.2Mn0.2O2|SL-SPE|Li batteries. This finding provides a bran-new idea for designing multifunctional polymer electrolytes in the application of solid-state batteries.

9.
Angew Chem Int Ed Engl ; 62(6): e202215963, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36428247

RESUMO

Earth-abundant transition metal catalysis has emerged as an important alternative to noble transition metal catalysis in hydrogenation reactions. However, there has been no Earth-abundant transition metal catalyzed hydrogenation of thioamides reported so far, presumably due to the poisoning of catalysts by sulfur-containing molecules. Herein, we described the first manganese-catalyzed hydrogenative desulfurization of thioamides to amines or imines. The key to success is the use of MnBr(CO)5 instead of commonly-employed pincer-manganese catalysts, together with simple NEt3 and CuBr. This protocol features excellent selectivity on sole cleavage of the C=S bond of thioamides, in contrast to the only known Ru-catalyzed hydrogenation of thioamides, and unprecedented chemo-selectivity tolerating vulnerable functional groups such as nitrile, ketone, aldehyde, ester, sulfone, nitro, olefin, alkyne and heterocycle, which are usually susceptible to common hydride-type reductive protocols.

10.
Mol Biol Rep ; 50(2): 1545-1552, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36513867

RESUMO

BACKGROUND: Melaleuca alternifolia is a commercially important medicinal tea tree native to Australia. Tea tree oil, the essential oil distilled from its branches and leaves, has broad-spectrum germicidal activity and is highly valued in the pharmaceutical and cosmetic industries. Thus, the study of genome, which can provide reference for the investigation of genes involved in terpinen-4-ol biosynthesis, is quite crucial for improving the productivity of Tea tree oil. METHODS AND RESULTS: In our study, the next-generation sequencing was used to investigate the whole genome of Melaleuca alternifolia. About 114 Gb high quality sequence data were obtained and assembled into 1,838,159 scafolds with an N50 length of 1021 bp. The assembled genome size is about 595 Mb, twice of that predicted by flow cytometer (300 Mb) and k-mer analysis (345 Mb). Benchmarking Universal Single-Copy Orthologs analyses indicated that only 11.3% of the conserved single-copy genes were miss. Repetitive regions cover over 40.43% of the genome. A total of 44,369 protein-coding genes were predicted and annotated against Nr, Swissprot, Refseq, COG, KOG, and KEGG database. Among these genes, 32,909 and 16,241 genes were functionally annotated in Nr and KEGG, respectively. Moreover, 29,411 and 14,435 genes were functionally annotated in COG and KOG. Additionally, 457,661 simple sequence repeats and 1109 transcription factors (TFs) form 67 TF families were identified in the assembled genome. CONCLUSION: Our findings provide a draft genome sequencing of M. alternifolia which can act as a reference for the deep sequencing strategies, and are useful for future functional and comparative genomics analyses.


Assuntos
Melaleuca , Óleos Voláteis , Óleo de Melaleuca , Humanos , Melaleuca/genética , Árvores , Chás Medicinais
11.
Sci Bull (Beijing) ; 67(20): 2085-2095, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36546108

RESUMO

As a star representative of transition metal sulfides, SnS is viewed as a promising anode-material candidate for sodium ion batteries due to its high theoretical capacity and unique layered structure. However, the extremely poor electrical conductivity and severe volume expansion strongly hinder its practical application while achieving a high reversible capacity with long-cyclic stability still remains a grand challenge. Herein, different from the conventional enhancement method of elemental doping, we report a rational strategy to introduce PO43- into the SnS layers using phytic acid as the special phosphorus source. Intriguingly, the presence of PO43- in the form of Sn-O-P covalent bonds can act as a conductive pillar to buffer the volume expansion of SnS while expanding its interlay spacing to allow more Na+ storage, supported by both experimental and theoretical evidences. Profiting from this effect combined with microstructural metrics by loading on high pyridine N-doped reduced graphene oxide, the as-prepared material presented an unprecedented ultra-long cyclic stability even after 10,000 cycles along with high reversible capacity and excellent full-cell performances. The findings herein open up new opportunities for elevating electrochemical performances of metal sulfides and provide inspirations for the fabrication of advanced electrode materials for broad energy use.

12.
J Control Release ; 350: 829-840, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36100192

RESUMO

Hypoxia at the solid tumor site is generally related to the unrestricted proliferation and metabolism of cancerous cells, which can cause tumor metastasis and aggravate tumor progression. Besides, hypoxia plays a substantial role in tumor treatment, and it is one of the main reasons that malignant tumors are difficult to cure and have a poor prognosis. On account of the tumor specific hypoxic environment, many hypoxia-associative nanomedicine have been proposed for tumor treatment. Considering the enhanced targeting effect, designing hypoxia-associative nanomedicine can not only minimize the adverse effects of drugs on normal tissues, but also achieve targeted therapy at the lesion site. Mostly, there can be three strategies for the treatment of hypoxic tumor, including improvement of hypoxic environment, hypoxia responsive drug release and hypoxia activated prodrug. The review describes the design principle and applications of tumor hypoxia-associative nanomedicine in recent years, and also explores its development trends in solid tumor treatment. Moreover, this review presents the current limitations of tumor hypoxia-associative nanomedicine in chemotherapy, radiotherapy, photodynamic therapy, sonodynamic therapy and immunotherapy, which may provide a reference for clinic translation of tumor hypoxia-associative nanomedicine.


Assuntos
Neoplasias , Pró-Fármacos , Humanos , Hipóxia , Nanomedicina , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Pró-Fármacos/farmacologia , Hipóxia Tumoral
13.
Plant Sci ; 319: 111222, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35487672

RESUMO

Almost all genomes have orphan genes, the majority of which are not functionally annotated. There is growing evidence showed that orphan genes may play important roles in the environmental stress response of Physcomitrium patens. We identified PpARDT (ABA-responsive drought tolerance) as a moss-specific and ABA-responsive orphan gene in P. patens. PpARDT is mainly expressed during the gametophytic stage of the life cycle, and the expression was induced by different abiotic stresses. A PpARDT knockout (Ppardt) mutant showed reduced dehydration-rehydration tolerance, and the phenotype could be rescued by exogenous ABA. Meanwhile, transgenic Arabidopsis lines exhibiting heterologous expression of PpARDT were more sensitive to exogenous ABA than wild-type (Col-0) plants and showed enhanced drought tolerance. These indicate that PpARDT confers drought tolerance among land plants potentially by enhancing ABA response. Further, we identified genes encoding abscisic acid receptor PYR/PYL family proteins, and ADP-ribosylation factors (Arf) as hub genes associated with the Ppardt phenotype. Given the lineage-specific characteristics of PpARDT, our results provide insights into the roles of orphan gene in shaping lineage-specific adaptation possibly by recruiting common pre-existed pathway components.


Assuntos
Arabidopsis , Bryopsida , Ácido Abscísico/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Bryopsida/genética , Secas , Estresse Fisiológico/genética
14.
Histol Histopathol ; 37(8): 723-737, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35417038

RESUMO

Direct reprogramming, whether in vitro or in vivo, has attracted great attention because of its advantages of convenience, short-term conversion, direct targets, no immune rejection, and potential clinical applications. In addition, due to its independence from the pluripotent state, direct programming minimizes some safety concerns associated with the use of human pluripotent stem cells. However, the significant limitations of reprogrammed cells, such as poor proliferative ability, low efficiency, and immature function, need to be addressed before the clinical application potential can be expanded. Here, we review the recent achievements of direct reprogramming in 2D and 3D systems in vitro and in vivo, covering cells derived from the three germ layers from stem/progenitor cells to terminal cells, such as hepatocytes, pancreatic ß cells, cardiomyocytes, endothelial cells, osteoblasts, chondrocytes, neurons, and melanocytes. Combining our lab experiences with current work, we summarize the practical and potential issues that need to be solved and the prospects of strategies for addressing the current dilemmas. Through comprehensive analyses, it is concluded that the directions for dealing with efficiency and functionality issues could be the optimization of transcription factors, the upgradation for delivery systems, the regulation of epigenetic factors and pathways, and the improvement of cellular maintenance conditions. Besides, converting cells into the progenitor state firstly and then differentiating them into the desired cell types with chemical compounds may provide an approach to obtaining functional and safe converted cells in batches with a better proliferative ability. With the emergence of more and more direct reprogramming techniques and approaches with both safety and effectiveness, it is bound to bring a new dawn for mechanism research and therapeutic applications for relevant diseases in the future.


Assuntos
Reprogramação Celular , Células-Tronco Pluripotentes Induzidas , Células Endoteliais , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Miócitos Cardíacos/metabolismo , Fatores de Transcrição/metabolismo
15.
EBioMedicine ; 78: 103945, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35306340

RESUMO

BACKGROUND: Multiple approaches based on cell-free DNA (cfDNA) have been applied to detect minimal residual disease (MRD) and to predict prognosis or recurrence. However, a comparison of the approaches used in different cohorts and studies is difficult. We aimed to compare multiple approaches for MRD analysis after neoadjuvant therapy (NAT) in patients with locally advanced rectal cancer (LARC). METHODS: Sixty patients with LARC from a multicentre, phase II/III randomized trial were included, with tissue and blood samples collected. For each cfDNA sample, we profiled MRD using 3 approaches: personalized assay targeting tumour-informed mutations, universal panel of genes frequently mutated in colorectal cancer (CRC), and low depth sequencing for copy number alterations (CNAs). FINDINGS: Positive MRD based on post-NAT personalized assay was significantly associated with an increased risk of recurrence (HR = 27.38; log-rank P < 0.0001). MRD analysis based on universal panel (HR = 5.18; log-rank P = 0.00086) and CNAs analysis (HR = 9.24; log-rank P = 0.00017) showed a compromised performance in predicting recurrence. Both the personalized assay and universal panel showed complementary pattern to CNAs analysis in detecting cases with recurrence and the combination of the two types of biomarkers may lead to better performance. INTERPRETATION: The combination of mutation profiling and CNA profiling can improve the detection of MRD, which may help optimize the treatment strategies for patients with LARC. FUNDING: The Beijing Municipal Science & Technology Commission, National Natural Science Foundation of China, and CAMS Innovation Fund for Medical Sciences.


Assuntos
Ácidos Nucleicos Livres , DNA Tumoral Circulante , Neoplasias Retais , Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/genética , DNA Tumoral Circulante/genética , Humanos , Terapia Neoadjuvante , Neoplasia Residual/genética , Neoplasias Retais/diagnóstico , Neoplasias Retais/genética , Neoplasias Retais/terapia , Medição de Risco
16.
J Clin Oncol ; 40(15): 1681-1692, 2022 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-35263150

RESUMO

PURPOSE: To ascertain if preoperative short-term radiotherapy followed by chemotherapy is not inferior to a standard schedule of long-term chemoradiotherapy in patients with locally advanced rectal cancer. MATERIALS AND METHODS: Patients with distal or middle-third, clinical primary tumor stage 3-4 and/or regional lymph node-positive rectal cancer were randomly assigned (1:1) to short-term radiotherapy (25 Gy in five fractions over 1 week) followed by four cycles of chemotherapy (total neoadjuvant therapy [TNT]) or chemoradiotherapy (50 Gy in 25 fractions over 5 weeks, concurrently with capecitabine [chemoradiotherapy; CRT]). Total mesorectal excision was undertaken 6-8 weeks after preoperative treatment, with two additional cycles of CAPOX (intravenous oxaliplatin [130 mg/m2, once a day] on day 1 and capecitabine [1,000 mg/m2, twice a day] from days 1 to 14) in the TNT group and six cycles of CAPOX in the CRT group. The primary end point was 3-year disease-free survival (DFS). RESULTS: Between August 2015 and August 2018, a total of 599 patients were randomly assigned to receive TNT (n = 302) or CRT (n = 297). At a median follow-up of 35.0 months, 3-year DFS was 64.5% and 62.3% in TNT and CRT groups, respectively (hazard ratio, 0.883; one-sided 95% CI, not applicable to 1.11; P < .001 for noninferiority). There was no significant difference in metastasis-free survival or locoregional recurrence, but the TNT group had better 3-year overall survival than the CRT group (86.5% v 75.1%; P = .033). Treatment effects on DFS and overall survival were similar regardless of prognostic factors. The prevalence of acute grade III-V toxicities during preoperative treatment was 26.5% in the TNT group versus 12.6% in the CRT group (P < .001). CONCLUSION: Short-term radiotherapy with preoperative chemotherapy followed by surgery was efficacious with acceptable toxicity and could be used as an alternative to CRT for locally advanced rectal cancer.


Assuntos
Segunda Neoplasia Primária , Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/uso terapêutico , Quimiorradioterapia/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Terapia Neoadjuvante/efeitos adversos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Segunda Neoplasia Primária/patologia , Neoplasias Retais/patologia
17.
Front Oncol ; 11: 784156, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869040

RESUMO

OBJECTIVES: To develop a prognostic prediction MRI-based nomogram model for locally advanced rectal cancer (LARC) treated with neoadjuvant therapy. METHODS: This was a retrospective analysis of 233 LARC (MRI-T stage 3-4 (mrT) and/or MRI-N stage 1-2 (mrN), M0) patients who had undergone neoadjuvant radiotherapy and total mesorectal excision (TME) surgery with baseline MRI and operative pathology assessments at our institution from March 2015 to March 2018. The patients were sequentially allocated to training and validation cohorts at a ratio of 4:3 based on the image examination date. A nomogram model was developed based on the univariate logistic regression analysis and multivariable Cox regression analysis results of the training cohort for disease-free survival (DFS). To evaluate the clinical usefulness of the nomogram, Harrell's concordance index (C-index), calibration plot, receiver operating characteristic (ROC) curve analysis, and decision curve analysis (DCA) were conducted in both cohorts. RESULTS: The median follow-up times were 43.2 months (13.3-61.3 months) and 32.0 months (12.3-39.5 months) in the training and validation cohorts. Multivariate Cox regression analysis identified MRI-detected extramural vascular invasion (mrEMVI), pathological T stage (ypT) and perineural invasion (PNI) as independent predictors. Lymphovascular invasion (LVI) (which almost reached statistical significance in multivariate regression analysis) and three other independent predictors were included in the nomogram model. The nomogram showed the best predictive ability for DFS (C-index: 0.769 (training cohort) and 0.776 (validation cohort)). It had a good 3-year DFS predictive capacity [area under the curve, AUC=0.843 (training cohort) and 0.771 (validation cohort)]. DCA revealed that the use of the nomogram model was associated with benefits for the prediction of 3-year DFS in both cohorts. CONCLUSION: We developed and validated a novel nomogram model based on MRI factors and pathological factors for predicting DFS in LARC treated with neoadjuvant therapy. This model has good predictive value for prognosis, which could improve the risk stratification and individual treatment of LARC patients.

18.
Plant Sci ; 313: 111070, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34763863

RESUMO

R-loops, consisting of a DNA:RNA hybrid and a single-stranded DNA (ssDNA), form naturally as functional chromosome structures and are crucial in many vital biological processes. However, disrupted R-loop homeostasis will threat to the integrity and stability of genome. As the endonuclease, RNase H1 can efficiently recognize and remove excess R-loops to protect organisms from DNA damage induced by R-loop over-accumulation. Here, we investigated the function of RNase H1 in Physcomitrium (Physcomitrella) patens to illustrate its important role in the evolution of plants. We found that PpRNH1A dysfunction seriously affected shoot growth and branch formation in P. patens, revealing a noticeable functional difference between PpRNH1A and AtRNH1A of Arabidopsis. Furthermore, auxin signaling was significantly affected at the transcriptional level in PpRNH1A mutant plants, as a result of the accumulation of R-loops at several auxin-related genes. This study provides evidence that PpRNH1A regulates the development of P. patens by controlling R-loop formation at specific loci to modulate the transcription of auxin-related genes. It also highlights the interspecific functional differences between early land plants and vascular plants, despite crucial and conserved role of RNase H1 played in maintaining R-loop homeostasis.


Assuntos
Bryopsida/crescimento & desenvolvimento , Bryopsida/genética , Diferenciação Celular/genética , Ácidos Indolacéticos/metabolismo , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/genética , Ribonuclease H/genética , Diferenciação Celular/fisiologia
19.
World J Gastrointest Surg ; 13(9): 904-922, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34621469

RESUMO

With the continuous development of digital medicine, minimally invasive precision and safety have become the primary development trends in hepatobiliary surgery. Due to the specificity and complexity of hepatobiliary surgery, traditional preoperative imaging techniques such as computed tomography and magnetic resonance imaging cannot meet the need for identification of fine anatomical regions. Imaging-based three-dimensional (3D) reconstruction, virtual simulation of surgery and 3D printing optimize the surgical plan through preoperative assessment, improving the controllability and safety of intraoperative operations, and in difficult-to-reach areas of the posterior and superior liver, assistive robots reproduce the surgeon's natural movements with stable cameras, reducing natural vibrations. Electromagnetic navigation in abdominal surgery solves the problem of conventional surgery still relying on direct visual observation or preoperative image assessment. We summarize and compare these recent trends in digital medical solutions for the future development and refinement of digital medicine in hepatobiliary surgery.

20.
Front Oncol ; 11: 710649, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604050

RESUMO

PURPOSE: To create a prognostic prediction radiomics model for soft tissue sarcoma (STS) of the extremities and trunk treated with neoadjuvant radiotherapy. METHODS: This study included 62 patients with STS of the extremities and trunk who underwent magnetic resonance imaging (MRI) before neoadjuvant radiotherapy. After tumour segmentation and preprocessing, 851 radiomics features were extracted. The radiomics score was constructed according to the least absolute shrinkage and selection operator (LASSO) method. Survival analysis (disease-free survival; DFS) was performed using the log-rank test and Cox's proportional hazards regression model. The nomogram model was established based on the log-rank test and Cox regression model. Harrell's concordance index (C-index), calibration curve and receiver operating characteristic (ROC) curve analysis were used to evaluate the prognostic factors. The clinical utility of the model was assessed by decision curve analysis (DCA). RESULTS: The univariate survival analysis showed that tumour location (p = 0.032), clinical stage (p = 0.022), tumour size (p = 0.005) and the radiomics score were correlated with DFS (p < 0.05). The multivariate analysis showed that tumour location, tumour size, and the radiomics score were independent prognostic factors for DFS (p < 0.05). The combined clinical-radiomics model based on the multivariate analysis showed the best predictive ability for DFS (C-index: 0.781; Area Under Curve: 0.791). DCA revealed that the use of the radiomics score-based nomogram was associated with better benefit gains relative to the prediction of 2-year DFS events than other models in the threshold probability range between 0.12 and 0.38. CONCLUSION: The radiomics score from pretreatment MRI is an independent prognostic factor for DFS in patients with STS of the extremities and trunk. The radiomics score-based nomogram could improve prognostic stratification ability and thus contribute to individualized therapy for STS patients.

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