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1.
Infect Dis Ther ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33826105

RESUMO

INTRODUCTION: Levornidazole is a novel nitroimidazole antimicrobial agent active against anaerobes. We aimed to investigate the pharmacokinetic (PK) profile of levornidazole after single and multiple oral doses of levornidazole tablets in healthy Chinese subjects and propose the dosing regimen based on pharmacokinetic/pharmacodynamic (PK/PD) analysis. METHODS: A single-center, randomized, double-blind, placebo-controlled study was conducted with a single ascending dose (250, 500, 1000, and 1500 mg) and multiple doses of 500 mg levornidazole q12h for 7 days. Food effect on PK and absolute bioavailability were investigated at the 500 mg dose level. Blood and urine samples were collected to determine the PK parameters of levornidazole. The probability of target attainment (PTA) and cumulative fraction of response (CFR) were calculated by Monte Carlo simulation to predict the clinical efficacy of levornidazole tablets. RESULTS: Plasma concentration reached peak about 0.5 h after single dose (250-1500 mg) of levornidazole tablets. The maximal concentration (Cmax) and exposure (AUC0-∞) of levornidazole increased linearly with dose. High-fat diet did not affect the absorption extent of levornidazole tablets. The absolute oral bioavailability of levornidazole tablets was 98.3% ± 7.6%, associated with large apparent volume of distribution (48.68 ± 4.92 l) and long half-life (11.93 ± 1.28 h). The urinary excretion of levornidazole was 7.99%. Levornidazole, administered at either 500 mg q12h or 750 mg q24h, achieved a CFR > 95.4% and PTA > 99% for B. fragilis (minimum inhibitory concentration ≤ 1.0 mg/l) infections. CONCLUSION: Levornidazole tablets are absorbed rapidly and completely and distributed extensively with a long half-life and low urinary excretion after a single dose or multiple doses in healthy Chinese subjects. Levornidazole tablets can be taken with or without food. Levornidazole tablets 500 mg q12h and 750 mg q24h are expected to achieve the desired efficacy in B. fragilis infections. CLINICAL TRAIL REGISTRATION: Trial registration number CTR20160786 at http://www.chinadrugtrials.org.cn/ .

2.
Foods ; 10(3)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807644

RESUMO

The defatted seeds of Oenothera biennis (DSOB) are a by-product of evening primrose oil production that are currently not effectively used. In this study, α-glucosidase inhibition, aldose reductase inhibition, antioxidant capacity, polyphenol composition, and nutritional value (carbohydrates, proteins, minerals, fat, organic acid, and tocopherols) of DSOB were evaluated using the seeds of Oenothera biennis (SOB) as a reference. DSOB was an excellent inhibitor of α-glucosidase (IC50 = 3.31 µg/mL) and aldose reductase (IC50 = 2.56 µg/mL). DSOB also showed considerable antioxidant capacities (scavenging of 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid, nitric oxide, peroxynitrite, and hydroxyl radicals). DSOB was a reservoir of polyphenols, and 25 compounds in DSOB were temporarily identified by liquid chromatography coupled with electrospray ionization-quadrupole time of flight-mass spectrometry analysis. Moreover, the carbohydrate, protein, and mineral content of DSOB were increased compared to that of SOB. DSOB contained large amounts of fiber and low levels of sugars, and was rich in calcium and iron. These results imply that DSOB may be a potential functional food ingredient for diabetes, providing excellent economic and environmental benefits.

3.
Oncogene ; 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824471

RESUMO

Chronic myeloid leukemia (CML) is an age-dependent blood malignancy. Like many other age-dependent human diseases, laboratory animal research of CML uses young mice that do not factor in the influence of aging. To understand how aging may impact animal modeling of human age-dependent diseases, we established the first aging mouse model of human CML in BALB/c mice in the advanced age defined by 75% survival. This model was developed by noncytotoxic depletion of bone marrow lineage-positive cells followed by BCR-ABL retroviral transduction and transplantation. CML developed in aging mice shared many similarities to that in young mice, but had increased incidence of anemia that is often seen in human CML. Importantly, we showed that aging of both donor hematopoietic stem cells and recipient bone marrow niche impacted BCR-ABL mediated leukemogenesis and leukemia spectrum. Optimal CML induction relied on age-matching for donors and recipients, and cross-transplantation between young and old mice produced a mixture of different leukemia. Therefore, our model provides initial evidence of the feasibility and merit of CML modeling in aging mice and offers a new tool for future studies of CML stem cell drug resistance and therapeutic intervention in which aging would be taken into consideration as an influencing factor.

4.
JAMA Netw Open ; 4(4): e215250, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33835174

RESUMO

Importance: The prevention of chemotherapy-induced nausea and vomiting has an important role in the overall management of cancer treatment. Objective: To evaluate whether adding aprepitant to palonosetron and dexamethasone can further prevent the incidence and severity of nausea and vomiting caused by FOLFIRI (fluorouracil, leucovorin, and irinotecan) or FOLFOX (fluorouracil, leucovorin, and oxaliplatin) chemotherapy regimens among women with gastrointestinal cancer at higher risk. Design, Setting, and Participants: This phase 3, double-blind, placebo-controlled randomized clinical trial recruited young women (age ≤50 years) who drank little or no alcohol and had gastrointestinal cancer for which they received FOLFOX or FOLFIRI chemotherapy. A total of 248 women were enrolled and assigned in the ratio 1:1 to intervention and control groups from August 4, 2015, to March 31, 2020. Intention-to-treat analysis was used to evaluate patient baseline characteristics and efficacy. The analysis was conducted on October 30, 2020. Interventions: Patients were randomly assigned to the aprepitant group (aprepitant, 125 mg, orally 60 minutes before initiation of chemotherapy on day 1 and 80 mg orally each morning of days 2 and 3; palonosetron, 0.25 mg, intravenously; and dexamethasone, 6 mg, orally 30 minutes before chemotherapy initiation on day 1) or the placebo group (placebo, 125 mg, orally 60 minutes before initiation of chemotherapy on day 1 and 80 mg orally on each morning of days 2 and 3; palonosetron, 0.25 mg, intravenously; and dexamethasone, 12 mg, orally 30 minutes before chemotherapy initiation on day 1). Main Outcomes and Measures: The primary end point was the complete response (CR) rate, defined as the proportion of patients without emesis episodes or rescue medication use during the overall phase of the first cycle. Other efficacy indicators, such as no vomiting and no nausea, were measured as the secondary and exploratory end points. Results: A total of 248 women from 4 clinical centers in China entered this study, and 243 patients (aprepitant regimen, 125 patients [51.4%]; placebo regimen, 118 patients [48.5%]) were evaluable for efficacy and safety; mean (SD) age of the total population was 40.1 (7.3) years. The CR rate was significantly higher in the aprepitant group vs the control group overall (107 [87.0%] vs 80 [66.7%]; P < .001) and in the acute (114 [92.7%] vs 91 [75.8%]; P = .001) and delayed (109 [88.6%] vs 84 [70.0%]; P = .001) phases of the trial. The incidence of adverse events was similar between the 2 groups (100 [80.0%] vs 96 [81.3%]; P = .79), and no grade 3 or 4 aprepitant treatment-related adverse events were observed. Multivariable analysis revealed that aprepitant use was the only independent factor associated with CR during the overall phase. Conclusions and Relevance: The combination of aprepitant with palonosetron and dexamethasone provided increased antiemetic efficacy in the FOLFOX or FOLFIRI chemotherapy regimen and was well tolerated by younger women with gastrointestinal cancer who have a history of little or no alcohol consumption. Trial Registration: ClinicalTrials.gov Identifier: NCT03674294.

5.
Platelets ; : 1-8, 2021 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-33813995

RESUMO

It remains unclear whether low-dose ticagrelor offers better safety and similar efficacy for Asian patients with acute coronary syndromes (ACS). We aimed to compare the safety and effectiveness of low-dose ticagrelor vs standard-dose ticagrelor in Chinese patients with ACS undergoing percutaneous coronary intervention (PCI). In this observational cohort study, a total of 2110 ACS patients who were event-free at 3 months after the index PCI were divided into standard-dose ticagrelor (90 mg twice daily) (n = 1830) or low-dose ticagrelor (45 mg twice daily) (n = 280) on a background of aspirin 100 mg once daily for at least another 9 months. The primary end point was type 2, 3, or 5 bleeding according to the Bleeding Academic Research Consortium (BARC) criteria over a 1-year follow-up period post-PCI. Predictors of the primary end point were identified. Both Cox regression and propensity score matching analyses were used. The cumulative incidence of BARC type 2, 3, or 5 bleeding was lower in the low-dose ticagrelor group vs the standard-dose group either before (adjusted HR 0.24; 95% CI 0.07-0.77; p = .016) or after matching (HR 0.25; 95% CI 0.08-0.85; p = .026). A composite of cardiac death, myocardial infarction, or stroke was not significantly different between the two groups (0.4% vs 0.9%, respectively). By multivariate analysis, only low-dose ticagrelor was a protected predictor of BARC type 2, 3, or 5 bleeding either before (HR 0.28, 95% CI 0.09-0.89) or after matching (HR 0.24, 95% CI 0.07-0.82). A low-dose regimen of ticagrelor might provide better safety than standard-dose ticagrelor in Chinese patients with ACS undergoing PCI.

6.
Pharmaceutics ; 13(4)2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33804947

RESUMO

The emergence and prevalence of multidrug-resistant (MDR) bacteria have posed a serious threat to public health. Of particular concern are methicillin-resistant Staphylococcus aureus (MRSA) and blaNDM, mcr-1 and tet(X)-positive Gram-negative pathogens. The fact that few new antibiotics have been approved in recent years exacerbates this global crisis, thus, new alternatives are urgently needed. Antimicrobial peptides (AMPs) originated from host defense peptides with a wide range of sources and multiple functions, are less prone to achieve resistance. All these characteristics laid the foundation for AMPs to become potential antibiotic candidates. In this study, we revealed that peptide WW307 displayed potent antibacterial and bactericidal activity against MDR bacteria, including MRSA and Gram-negative bacteria carrying blaNDM-5, mcr-1 or tet(X4). In addition, WW307 exhibited great biofilm inhibition and eradication activity. Safety and stability experiments showed that WW307 had a strong resistance against various physiological conditions and displayed relatively low toxicity. Mechanistic experiments showed that WW307 resulted in membrane damage by selectively targeting bacterial membrane-specific components, including lipopolysaccharide (LPS), phosphatidylglycerol (PG), and cardiolipin (CL). Moreover, WW307 dissipated membrane potential and triggered the production of reactive oxygen species (ROS). Collectively, these results demonstrated that WW307 represents a promising candidate for combating MDR pathogens.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33786954

RESUMO

Surface vacancies can exert positive impact on CO2 photoreduction activity, yet difficultly maintaining long-term stability. Herein, we first design a fast low-pressure ultraviolet light irradiation strategy for easily regenerating the nearly equivalent surface vacancies, thus concurrently optimizing CO2 photoreduction activity and stability. Taking the defective Bi2O2CO3 nanosheets as an example, nearly equal amount of oxygen vacancies can be regenerated under UV light irradiation. Synchrotron-radiation quasi in-situ X-ray photoelectron spectra disclose the Bi sites in the O-defective Bi2O2CO3 nanosheets can act as the highly active sites, which not only help to activate CO2 molecules, but also contribute to stabilizing the rate-limiting COOH* intermediate. Also, in-situ Fourier transform infrared spectroscopy and in-situ mass spectrometry unravel the UV light irradiation contributes to accelerating CO desorption process. As a result, the O-defective Bi2O2CO3 nanosheets achieve a stability up to 2640 h over 110 cycling tests and a high evolution rate of 275 µmol g-1 h-1 for visible-light-driven CO2 reduction to CO. This study offers a new way for developing sustainable CO2 reduction photocatalysts.

8.
Angew Chem Int Ed Engl ; 60(16): 8813-8817, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33682269

RESUMO

High-efficiency organic solar cells (OSCs) largely rely on polymer donors. Herein, we report a new building block BNT and a relevant polymer PBNT-BDD featuring B-N covalent bond for application in OSCs. The BNT unit is synthesized in only 3 steps, leading to the facile synthesis of PBNT-BDD. When blended with a nonfullerene acceptor Y6-BO, PBNT-BDD afforded a power conversion efficiency (PCE) of 16.1 % in an OSC, comparable to the benzo[1,2-b:4,5-b']dithiophene (BDT)-based counterpart. The nonradiative recombination energy loss of 0.19 eV was afforded by PBNT-BDD. PBNT-BDD also exhibited weak crystallinity and appropriate miscibility with Y6-BO, benefitting of morphological stability. The singlet-triplet gap (ΔEST ) of PBNT-BDD is as low as 0.15 eV, which is much lower than those of common organic semiconductors (≥0.6 eV). As a result, the triplet state of PBNT-BDD is higher than the charge transfer (CT) state, which would suppress the recombination via triplet state effectively.

9.
Theranostics ; 11(10): 4910-4928, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33754035

RESUMO

Antimicrobial resistance has been a global health challenge that threatens our ability to control and treat life-threatening bacterial infections. Despite ongoing efforts to identify new drugs or alternatives to antibiotics, no new classes of antibiotic or their alternatives have been clinically approved in the last three decades. A combination of antibiotics and non-antibiotic compounds that could inhibit bacterial resistance determinants or enhance antibiotic activity offers a sustainable and effective strategy to confront multidrug-resistant bacteria. In this review, we provide a brief overview of the co-evolution of antibiotic discovery and the development of bacterial resistance. We summarize drug-drug interactions and uncover the art of repurposing non-antibiotic drugs as potential antibiotic adjuvants, including discussing classification and mechanisms of action, as well as reporting novel screening platforms. A pathogen-by-pathogen approach is then proposed to highlight the critical value of drug repurposing and its therapeutic potential. Finally, general advantages, challenges and development trends of drug combination strategy are discussed.

11.
J Immunol ; 206(8): 1966-1975, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33722878

RESUMO

Inflammation has long been associated with cancer initiation and progression; however, how inflammation causes immune suppression in the tumor microenvironment and resistance to immunotherapy is not well understood. In this study, we show that both innate proinflammatory cytokine IL-1α and immunotherapy-induced IL-1α make melanoma resistant to immunotherapy. In a mouse melanoma model, we found that tumor size was inversely correlated with response to immunotherapy. Large tumors had higher levels of IL-1α, Th2 cytokines, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), and regulatory T cells but lower levels of IL-12, Th1 cytokines, and activated T cells. We found that therapy with adenovirus-encoded CD40L (rAd.CD40L) increased tumor levels of IL-1α and PMN-MDSCs. Blocking the IL-1 signaling pathway significantly decreased rAd.CD40L-induced PMN-MDSCs and their associated PD-L1 expression in the tumor microenvironment and enhanced tumor-specific immunity. Similarly, blocking the IL-1 signaling pathway improved the antimelanoma activity of anti-PD-L1 Ab therapy. Our study suggests that blocking the IL-1α signaling pathway may increase the efficacy of immunotherapies against melanoma.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33706518

RESUMO

Two-dimensional (2D) materials have attracted extensive attention for use in fiber lasers for pulse generation due to their unique nonlinear optical properties. While 2D materials with tunable band gaps hold promise as versatile saturable absorber materials, their L-band (long-band) pulse generation capability remains challenging. Metal phosphorus trichalcogenides (MPX3) have recently attracted the attention of researchers and shown potential for sub-band gap saturable absorption in the L-band due to their high diversity of chemical components and band structural complexity. Herein, high-quality MnPSe3 is synthesized and exhibits broad-band linear and nonlinear absorption with the modulation depth and saturation intensity of 5.4% and 0.295 MW/cm2, respectively. Moreover, a stable passive pulse generation in the L-band is demonstrated in a fiber laser. The wavelengths of the passively pulsed laser at different pump powers are recorded, featuring a fixed central wavelength located at around 1602 nm with a maximum output power of 19.54 mW. This research promotes the realization of L-band pulsed lasers based on 2D materials, inspiring further exploration of the unique properties of the MPX3 family.

13.
Orthop Surg ; 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33709496

RESUMO

OBJECTIVE: To compare the clinical efficacy of the direct anterior approach in lateral decubitus position (L-DAA) and supine position (S-DAA) for unilateral total hip arthroplasty. METHODS: A retrospective study was conducted on 89 patients who underwent primary unilateral total hip arthroplasty in our department between August 2016 and December 2017. There were 46 patients who underwent L-DAA and 43 patients who underwent S-DAA. The body mass index (BMI), operation time, blood loss, preoperative Hb, first day and third day postoperative Hb, incision length, hospital stay, preoperative and postoperative Harris score, preoperative and postoperative visual analogue scale (VAS) score, radiological evaluation, intraoperative and postoperative complication, postoperative absolute length difference of lower extremity were recorded and analyzed. P < 0.05 was set as the significant difference. RESULTS: All patients were followed up for 8-23 months, with an average of 15.6 months. No significant differences were found in preoperative and postoperative Harris scores, preoperative Hb, incision lengths, radiological evaluations, preoperative and postoperative VAS scores, and hospital stay (P > 0.05). However, significant differences were detected in BMI, blood loss, first day and third day postoperative Hb, and operation time (P < 0.05). There were no postoperative complications in the L-DAA and S-DAA groups. During the operation, two cases of proximal femoral fracture occurred in the L-DAA group, four in the S-DAA group, and the difference was statistically significant. There were significant differences found in the postoperative absolute length difference of lower extremity between the two groups. CONCLUSION: Compared with the S-DAA approach, the L-DAA approach had the advantages of shorter operation time and less blood loss. Compared with S-DAA, it was easier to expose the proximal femur, and lower BMI was required in L-DAA. However, it was more difficult to compare the length of both lower extremities in the L-DAA approach than in the S-DAA approach.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33758948

RESUMO

BACKGROUND: Tigecycline and carbapenems are regarded as vital antimicrobials to treat serious bacterial infections. Co-occurrence of resistance genes conferring resistance to both tigecycline and carbapenems in Pseudomonas spp. was not investigated. OBJECTIVES: To characterize a megaplasmid co-harbouring tmexCD1-toprJ1 and blaVIM-2 in Pseudomonas putida of migratory bird origin. METHODS: One tigecycline- and carbapenem-resistant strain was isolated and characterized by antimicrobial susceptibility testing, conjugation assay, WGS and bioinformatics analysis. RESULTS: The strain P. putida ZXPA-20 resistant to meropenem and tigecycline was positive for blaVIM-2 and tmexCD1-toprJ1 genes. The gene blaVIM-2 was inserted into the backbone of the megaplasmid pZXPA-20 within a Tn5090-like structure. The genetic context of tmexCD1-toprJ1 in the megaplasmid was identical to many chromosomal tmexCD1-toprJ1 of Pseudomonas species. Plasmid-mediated tmexCD1-toprJ1 gene cluster in Pseudomonas spp. was more common than that in Klebsiella pneumoniae. To the best of our knowledge, this is the first report of co-occurrence of blaVIM-2 and tmexCD1-toprJ1 in one plasmid. CONCLUSIONS: Emergence of plasmid-mediated carbapenem and tigecycline resistance genes in P. putida from migratory birds highlighted the importance of surveillance of novel mobile resistance genes in migratory birds, which may play a vital role in global transmission of novel resistance genes.

15.
Sci Total Environ ; 776: 145596, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33652310

RESUMO

Hydrothermal liquefaction (HTL) is a promising thermochemical technology for the treatment of hazardous wastes such as penicillin residue (PR). For the treatment of aqueous waste produced by PR in the HTL process, aqueous phase circulation is an attractive solution, both environmentally and economically. The present study shows that aqueous phase circulation can promote the transfer of organic matter from the aqueous phase to bio-oil. The content of organic acids and alcohols in the aqueous phase decreased significantly, and the bio-oil yield and energy recovery efficiency also increased. Under non-catalytic conditions, the bio-oil yield increased from 26.09 wt% to 33.72 wt%. The use of Na2CO3 as a catalyst further improved the bio-oil yield. After a single aqueous phase circulation, the bio-oil yield increased to 34.63 wt%, and the energy recovery efficiency increased to 66.94%. Under catalytic hydrothermal conditions, the content of organic acids in the bio-oil was reduced using aqueous phase circulations, which improved the quality of the bio-oil. At the same time, the Na2CO3 catalyst promoted the hydrolysis of PR to form small molecule organic matter, inhibited the formation of coke, and reduced the content of carbon, hydrogen and oxygen in the solid residue. An increase of cycle times led to excessive accumulation of Na2CO3, which had a negative impact on the yield of bio-oil. Nitrogen-containing compounds in the bio-oil increased to a certain extent, which renders it necessary to consider denitrification treatments in the future. The work provides a useful reference for further research on the preparation of high quality bio-oil by PR hydrothermal liquefaction.

16.
Sci Total Environ ; 773: 145569, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33592471

RESUMO

Illegal addition of low-dose multi-component residue of hormone-like compounds have sprung up in human activities and production as a cunning strategy to escape from sanitation monitoring, sowing a horrible seed for accidents in food security. Hence, combined strategies with accuracy and efficiency are urgently needed to overcome current circumstance and practical hurdles. Herein, an integrated analysis that compromises recombinant gene yeast bioassay (V400E-YES) and high-performance liquid chromatography-mass spectrometry (HPLC-MS) determination was developed promptly with distinguishing advantage as optimized V400E-YES provides a sum of hormone-like compounds in sample, and subsequent HPLC-MS analysis can accurately quantify the concentration of compounds. In terms of V400E-YES, large-scale random mutagenesis was performed to obtain higher sensitivity hormone receptors. Excitingly, single mutation of estrogen receptor (ER) at V400E and amphimutation of androgen receptor (AR) at G581R/D831E conferred the highest detection sensitivity with a more than 10-fold increase. Subsequently, sensitive HPLC-MS methods for simultaneous detection of eleven estrogens and nine androgens, respectively, were well-constructed. Utilizing this integrated and validated methods, we successfully investigated the hormone residue in environmental samples from farms in Jiangsu, China. Collectively, with multiple estrogens and androgens residue are being widely detected in soil and sewage samples, the feasibility of this method is highlighted, as well as the increasing lurking peril of hormone-like substance residues in environment.


Assuntos
Bioensaio , Saccharomyces cerevisiae , China , Cromatografia Líquida de Alta Pressão , Estrogênios , Humanos , Saccharomyces cerevisiae/genética
17.
Cancer Med ; 10(5): 1535-1544, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33539664

RESUMO

PURPOSE: We aimed to construct a nomogram to predict personalized post-recurrence survival (PRS) among colorectal cancer liver metastasis (CRLM) patients with post-hepatectomy recurrence. METHODS: Colorectal cancer liver metastasis patients who received initial hepatectomy and had subsequent recurrence between 2001 and 2019 in Sun Yat-sen University Cancer Center from China were included in the study. Patients were randomly assigned to a training cohort and a validation cohort on a ratio of 2:1. Univariable analysis was first employed to select potential predictive factors for PRS. Then, the multivariable Cox regression model was applied to recognize independent prognostic factors. According to the model, a nomogram to predict PRS was established. The nomogram's predictive capacity was further assessed utilizing concordance index (C-index) values, calibration plots, and Kaplan-Meier curves. RESULTS: About 376 patients were finally enrolled, with a 3-year PRS rate of 37.3% and a 5-year PRS rate of 24.6%. The following five independent predictors for PRS were determined to construct the nomogram: the largest size of liver metastases at initial hepatectomy, relapse-free survival, CEA level at recurrence, recurrent sites, and treatment for recurrence. The nomogram displayed fairly good discrimination and calibration. The C-index value was 0.742 for the training cohort and 0.773 for the validation cohort. Patients were grouped into three risk groups very well by the nomogram, with 5-year PRS rates of 45.2%, 23.3%, and 9.0%, respectively (p < 0.001) in the training cohort and 36.0%, 9.2%, and 4.6%, respectively (p < 0.001) in the validation cohort. CONCLUSION: A novel nomogram was built and validated to enable the prediction of personal PRS in CRLM patients with post-hepatectomy recurrence. The nomogram may help physicians in decision making.

18.
Genomics ; 113(3): 983-991, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33640463

RESUMO

Skin appendages in vertebrates have individual morphological differences, but share the same evolutionary origin. In this study, we used Megalobrama amblycephala as a fish model to study the developmental regulation mechanism of a common skin appendage in fish: scales. By combining in-toto live imaging method and transcriptomic analysis during the scale development, we elucidated core features of scale patterning containing three distinct regions and experiencing four stages. Differentially expressed genes in skin tissues at the initial site before and after scale development were analyzed and some key regulatory genes (Wnt3, Wnt6, Fgf8, Fgf10, Fgf16, Fgfr1a, Ihhb and BMP6) which are crucial for scale morphogenesis were selected. This study provides a strong reference for further exploration of the function of genes related to the molecular regulation mechanism of scale development in M. amblycephala, as well as in other fishes.

19.
Oral Oncol ; 115: 105200, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33610003

RESUMO

INTRODUCTION: The current metastatic category (M) of nasopharyngeal carcinoma (NPC) is a "catch-all" category, we previously successfully established a M1 subdivision system based on prognostic metastatic characteristics in epidemic areas. We aimed to figure out metastatic characteristics associated with survival outcomes of NPC in non-epidemic areas. METHODS: A total of 428 newly diagnosed de novo metastatic NPC patients from 2010 to 2016 were analyzed from the population-based Surveillance, Epidemiology, and End Results program. Cox proportional hazard ratios (HRs) were used to identify independent prognostic factors for survival. RESULTS: The most frequently involved metastatic locations were the bones (53.04%), the lungs (36.68%), the livers (29.21%) and the distant lymph nodes (24.07%). Univariate analysis indicated that bone involvement (HR = 1.39, 95% CI = 1.09-1.77), liver involvement (HR = 1.44, 95% CI = 1.12-1.85) and multiple metastatic locations (HR = 1.32, 95% CI = 1.04-1.67) were negative prognostic factors of overall survival (OS) for patients with synchronous metastasis. We established a new M1 subdivision system based on metastatic characteristics: M1a, without bone and liver involvement; M1b, single bone or liver involvement; M1c, multiple metastatic locations including bone and/or liver. Multivariate analysis confirmed that our new subcategories were associated with significantly different OS (M1b vs M1a: HR = 1.54, 95% CI = 1.11-2.16; M1c vs M1a: HR = 2.03, 95% CI = 1.47-2.78). CONCLUSIONS: Synchronous metastatic NPC patients with multiple metastatic locations involved bone and/or liver were prone to suffer from dismal OS and might need more attentions for selection of treatment modality.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33528991

RESUMO

The conversion of CO2 into high value-added chemical products is the focus of current scientific research. We make use of the specific porous structure of nanosized metal-organic frameworks (MOFs) loading the highly active yet metastable nano Cu2O to catalyze the conversion of CO2 into a series of high value-added bioactive pyridone/pyrone-3-carboxylic acid products via heterocyclic 4-hydroxy-2-pyridones/pyrones, which exhibit high activity, selectivity, and reusability. Nano MOF sponge-covered metastable nanoparticles (NPs) converting CO2 into high value-added bioproducts provide a facile "dual-side surfactant" strategy, a highly efficient composite catalyst, and a practicable pathway not only for the sustainable use of CO2 but also for environment-friendly production of bioproducts.

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