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1.
Andrologia ; : e13627, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32352595

RESUMO

The aim of our study was to investigate whether low androgen level inhibits the erectile function of rats by regulating the expression of P2X receptors. Thirty-six 8-week-old male SD rats were randomly divided into six groups: sham-operated groups (4w-sham, 8w-sham), castration groups (4w-cast, 8w-cast) and androgen replacement after castration groups (4w-cast + T, 8w-cast + T). The maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP), the levels of serum testosterone (T) and nitric oxide (NO), and the expression of P2X1, P2X2, P2X3, eNOS, p-eNOS, ROCK1 and ROCK2 in the cavernous tissue of rats were determined. The serum T, ICPmax/MAP and NO levels in penile corpus cavernosum in the castration groups were significantly lower than those in other groups (p < .01). The protein expression of P2X1, P2X2, P2X3, ROCK1 and ROCK2 in the castration groups was significantly higher than those in other groups (p < .01). P-eNOS/eNOS of the castration groups were significantly lower than those of other groups (p < .01). The serum T level was negatively correlated with the expression of P2X1, P2X2 and P2X3 in the corpus cavernosum. Low androgen level inhibits erectile function by up-regulating the expression of P2X1, P2X2, P2X3 and RhoA/Rho-kinase resulting in reducing the ratio of p-eNOS/eNOS and the level of NO in corpus cavernosum of rats.

2.
J Phys Chem Lett ; : 3962-3968, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32354216

RESUMO

The production of ammonia from nitrogen reduction reaction (NRR) under mild conditions is one of the most challenging issues in modern chemistry. The linear scaling relationship between the adsorption energies of -N2H and -NH2 on a single active site is a well-established bottleneck. By investigating a series of densely monodispersed Mo-N-C sites embedded in graphene using first-principles calculations, we found that previously underappreciated neighboring effects between adjacent active sites may help break the limit: they not only improve the energetics of potential determining steps of NRR but also promote an alternative associative mechanism based on a cooperative bridge-on adsorption of N2 by two Mo-N-C sites of ∼6 Šapart. Further, a barrier of 0.71 eV for N-N bond dissociation is achieved by proper ratio of coordinated C/N atoms of Mo. Our work suggests the cooperation of two adjacent active sites may offer an alternative strategy of nitrogen fixation.

3.
J Diabetes Complications ; : 107612, 2020 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-32402842

RESUMO

BACKGROUND: Primary liver cancer (PLC) is a commonly diagnosed malignancy, especially in developing countries. Diabetes is one of the well-determined risk factors for PLC. We aimed to describe the temporal trends of PLC mortality among diabetic patients. METHODS: We retrieved the PLC mortality data among diabetic patients from the Global Burden of Disease (GBD) study 2017 online database. Estimated average percentage change (EAPC) was used to quantify the PLC age-standardized mortality rate (ASMR) trends, by sex and country, between 1990 and 2017. RESULTS: Globally, the number of PLC related deaths increased from 3732.1 in 1990 to 9506.4 in 2017, with the ASMR increased from 0.09/100,000 to 0.12/100,000 (EAPC = 0.98, 95% CI 0.82, 1.14) among diabetic patients. Both the ASMR of PLC and its temporal trend were highly heterogeneous across the world. Between 1990 and 2017, a total of 135, 19, and 41 countries or territories experienced a significant increase, remained stable, and experienced a significant decrease in PLC ASMR, respectively. The greatest increase was mainly detected in developed countries, such as the USA, the UK, and Australia. By contrast, the most pronounced decrease was majorly found in developing regions. CONCLUSIONS: In diabetic patients, the PLC mortality was significantly increased at the global level and in approximately 70% of countries or territories over the last three decades. The increasing trend indicated that diabetes is an increasingly important risk factor for PLC and suggested that more tailored prevention strategies are needed for each country.

4.
Small ; : e1907663, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32406193

RESUMO

It is a big challenge to reveal the intrinsic cause of a nanotoxic effect due to diverse branches of signaling pathways induced by engineered nanomaterials (ENMs). Biotransformation of toxic ENMs involving biochemical reactions between nanoparticles (NPs) and biological systems has recently attracted substantial attention as it is regarded as the upstream signal in nanotoxicology pathways, the molecular initiating event (MIE). Considering that different exposure routes of ENMs may lead to different interfaces for the arising of biotransformation, this work summarizes the nano-bio interfaces and dose calculation in inhalation, dermal, ingestion, and injection exposures to humans. Then, five types of biotransformation are shown, including aggregation and agglomeration, corona formation, decomposition, recrystallization, and redox reactions. Besides, the characterization methods for investigation of biotransformation as well as the safe design of ENMs to improve the sustainable development of nanotechnology are also discussed. Finally, future perspectives on the implications of biotransformation in clinical translation of nanomedicine and commercialization of nanoproducts are provided.

5.
J Cell Mol Med ; 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32406586

RESUMO

Interleukin (IL)-15 is a recently identified cytokine, which belongs to the interleukin-2(IL-2) family, and plays an important role in innate and adaptive immunoreaction. Given the fact that the structure of IL-15 is partially similar to IL-2, they share some common biological effects, including immunoregulation. IL-2 was proven to protect cardiac function in mouse myocardial infarction models. Cardiovascular diseases (CVDs) dominate the cause of mortality worldwide. Besides atherosclerosis, inflammation is also widely involved in the pathogenesis of many CVDs including hypertension, heart failure (HF) and aneurysm. IL-15, as a pro-inflammatory cytokine, is up-regulated in some cardiovascular diseases, such as myocardial infarction and atherosclerosis. The current understanding of IL-15, including its signal pathway and cellular function, was described. Furthermore, IL-15 has a protective effect in myocardial infarction and myocarditis by decreasing cardiomyocyte death and improving heart function. The inhibited effect of IL-15 in ductus arteriosus (DA) should be focused on. IL-15 promoted atherogenesis. IL-15 may be a good target in treatment of cardiovascular diabetology. Finally, future research direction of IL-15 deserves attention. Since IL-15 plays several roles in CVDs, understanding the role of the IL-15/IL-15R system may provide a scientific basis for the development of new approaches that use IL-15 for the treatment of CVDs.

6.
Anal Chem ; 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32366094

RESUMO

Electrochemical (EC) sensors have been widely developed for DNA detection, but they are seldom used in a simple, economic, and efficient manner. In this work, for the first time, EC cloth-based DNA sensors (ECDSs) are developed as a new class of EC DNA sensors, without the need for cumbersome chip fabrication and high-cost peripheral facilities. Carbon ink- and solid wax-based screen printing were used to produce ultracheap sensing devices (the cost of one sensor is estimated to be $0.045). Also, a CdTe QDs/MWCNTs nanocomposite (CdTe-MWCNTs) was applied to modify the sensing interface to obtain a stronger EC signal. Specifically, the newly developed double linear hybridization chain reaction (DL-HCR) greatly amplified the EC signal, relative to the conventional linear HCR. Under optimized conditions, target DNA (TD) samples (75-bp DNA fragments prepared via PCR amplification) were determined in a range from 20 fM to 5 nM, with a detection limit of 8.74 fM and relative standard deviations of 2.04% and 4.75% for intra- and inter-assays at 50 pM TD, respectively. Additionally, the ECDSs had an acceptable storage stability and high selectivity. Importantly, the ECDSs, coupled with simple enzyme digestion, could detect genomic DNA from Listeria monocytogenes (L. monocytogenes), and a detection limit of 0.039 ng/µL was obtained. When coupled with enzyme digestion and PCR amplification, the ECDSs could determine L. monocytogenes in milk samples, with detection limits of approximately 1.64 × 104 and 11 CFU/mL. These results demonstrate that the method offers a broad prospect for cost-effective, reliable, and highly sensitive gene-sensing applications.

7.
J Orthop Surg Res ; 15(1): 169, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393353

RESUMO

BACKGROUND: Developmental dysplasia of the hip (DDH) is a common disease in infants and children, and the treatment of bilateral DDH remains controversial. This study aimed to evaluate the stability of one-stage bilateral Salter pelvic osteotomy for bilateral DDH in patients of walking age. METHODS: In total, nine child cadavers aged 2-6 years were included. A universal mechanical testing machine was used for stability test. We performed two different surgical procedures on the specimens: nine child cadavers underwent unilateral Salter pelvic osteotomy, and six child cadavers were randomly selected to undergo Salter pelvic osteotomy again to simulate one-stage bilateral Salter pelvic osteotomy. The stability of the bilateral sacroiliac joints, local stability of the operation area, ultimate load test, and axial stiffness were evaluated. RESULTS: Both unilateral and bilateral Salter osteotomy could destroy the integrity of the pelvic ring and increase the risk of pelvic instability. In this study, compared with unilateral Salter osteotomy, bilateral Salter osteotomy had similar pelvic stability, and there was no significant difference between unilateral and bilateral Salter osteotomy in sacroiliac joint stability (p > 0.05), local stability (p = 0.763), ultimate load (p = 0.328), and axial stiffness (p = 0.480). CONCLUSIONS: One-stage bilateral Salter pelvic osteotomy as a potential surgical method is viable and stable for children with bilateral DDH.

8.
Phys Chem Chem Phys ; 22(18): 10343-10350, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32364215

RESUMO

Cr3+ in the Ca3Sc2Si3O12 garnet (CSSG) has the ability to convert blue light to broadband near-infrared (NIR) emissions, which is a promising strategy for next-generation smart NIR light sources based on blue LEDs. The Cr3+ luminescence strongly depends on temperature due to electron-phonon coupling (EPC). We reveal the EPC mechanism of Cr3+ in CSSG for the first time by temperature-dependent photoluminescence measurement from 77 to 573 K and cathodoluminescence using a scanning electron microscope. Cr3+ occupies the Sc3+ site and experiences a weak crystal field in CSSG, manifesting a broad NIR emission in the 700-900 nm range that originates from the 4T2g→4A2g transition. The zero phonon line (ZPL) of the 4T2 state is observed at ∼713 nm with a vibrational energy of ∼310 cm-1. A strong EPC leads to a large Stokes shift (∼2900 cm-1). The Huang-Rhys parameter (S = 4), crystal field strength (Dq/B), and Racah parameters (B and C) are estimated.

9.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(2): 147-151, 2020 Feb 29.
Artigo em Chinês | MEDLINE | ID: mdl-32376532

RESUMO

The SARS-CoV-2 epidemic starting in Wuhan in December, 2019 has spread rapidly throughout the nation. The control measures to contain the epidemic also produced influences on the transport and treatment process of patients with acute myocardial infarction (AMI), and adjustments in the management of the patients need to be made at this particular time. AMI is characterized by an acute onset with potentially fatal consequence, a short optimal treatment window, and frequent complications including respiratory infections and respiratory and circulatory failure, for which active on-site treatment is essential. To standardize the management and facilitate the diagnosis and treatment, we formulated the guidelines for the procedures and strategies for the diagnosis and treatment of AMI, which highlight 5 Key Principles, namely Nearby treatment, Safety protection, Priority of thrombolysis, Transport to designated hospitals, and Remote consultation. For AMI patients, different treatment strategies are selected based on the screening results of SARS-CoV-2, the time window of STEMI onset, and the vital signs of the patients. During this special period, the cardiologists, including the interventional physicians, should be fully aware of the indications and contraindications of thrombolysis. In the transport and treatment of AMI patients, the physicians should strictly observe the indications for patient transport with appropriate protective measurements of the medical staff.


Assuntos
Infecções por Coronavirus , Infarto do Miocárdio , Pandemias , Pneumonia Viral , Betacoronavirus , Consenso , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Humanos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/terapia , Pandemias/prevenção & controle , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Guias de Prática Clínica como Assunto , Consulta Remota , Terapia Trombolítica , Transporte de Pacientes
10.
Nanoscale ; 12(19): 10842-10853, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32396585

RESUMO

Under coordination driving force of tungsten and rare-earth (RE) bridges, we synthesized a novel giant multi-tungsten-and-RE-bridging octameric tellurotungstate (TT) [H2N(CH3)2]16K8Na6H10[Pr8(H2O)20W16O48][B-α-TeW9O33]8·70H2O (1) in CH3CN-H2O mixed solvent. The cluster anion {[Pr8(H2O)20W16O48][B-α-TeW9O33]8}40- features sixteen WVI bridges, eight PrIII bridges and eight trivacant Keggin [B-α-TeW9O33]8- fragments, which the square {W4O12} cluster can be imagined as a seed to induce the aggregation of eight [B-α-TeW9O33]8- fragments by coordination driving force of additional twelve WVI bridges and eight PrIII ions. Furthermore, the 2D 1@DODA (dimethyldioctadecyl ammonium bromide = DODA·Br) honeycomb composite material was prepared. The honeycomb morphology of the 1@DODA composite material provides rich binding sites for electrodepositing Au nanoparticles to make Au/1@DODA electrodes. The aptamer of 17ß-estradiol (E2) hormone can be grafted to the Au/1@DODA electrodes via Au-S bonding interaction to construct the Au/1@DODA aptamer biosensors. By virtue of the specific recognition interaction of aptamer and the electrochemical signal amplification function of methylene blue and cDNA, the Au/1@DODA aptamer biosensors can realize the electrochemical detection of E2. This finding not only offers an electrochemical biosensing platform for detecting E2, but also expands POM-based composite materials in the applications of clinical detection and biological analysis.

11.
J Environ Sci (China) ; 92: 141-150, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32430117

RESUMO

Bauxite residue, a byproduct of alumina manufacture, is a serious environmental pollutant due to its high leaching contents of metals and caustic compounds. Four typical anions of CO32-, HCO3-, Al(OH)4- and OH- (represented caustic compounds) and metal ions (As, B, Mo and V) were selected to assess their leaching behavior under dealkalization process with different conditions including liquid/solid ratio (L/S ratio), temperature and leaching time. The results revealed that washing process could remove the soluble composition in bauxite residue effectively. The leaching concentrations of typical anions in bauxite residue decreased as follows: c(CO32-) > c(HCO3-) > c[Al(OH)4-] > c(OH-). L/S ratio had a more significant effect on leaching behavior of OH-, whilst the leaching concentration of Al(OH)4- varied larger underleaching temperature and time treatment. Under the optimal leaching, the total alkaline, soluble Na concentrations, exchangeable Ca concentrations were 79.52, 68.93, and 136.0 mmol/L, respectively, whilst the soluble and exchangeable content of As, B, Mo and V in bauxite residue changed slightly. However, it should be noted that water leaching has released metal ions such as As, B, Mo and V in bauxite residue to the surrounding environment. The semiquantitative analysis of XRD revealed that water leaching increased the content of gismondine from 2.4% to 6.4%. The SEM images demonstrated the dissolution of caustic compounds on bauxite residue surface. The correlation analysis indicated that CO32- and HCO3- could effectively reflect the alkalinity of bauxite residue, and may be regarded as critical dealkalization indicators to evaluate alkalinity removal in bauxite residue.

12.
Fish Physiol Biochem ; 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32440967

RESUMO

The present study evaluated the effect of cinnamaldehyde (CIN) on the growth performance and digestion and absorption capacity of grass carp (Ctenopharyngodon idella). Fish were fed five diets including graded levels of CIN for 60 days. The results indicated that (1) appropriate CIN supplementation increased the growth performance and promoted the intestine growth of grass carp; (2) dietary appropriate CIN supplementation increased the digestion and absorption capacity by increasing the activities of intestinal and hepatopancreas digestive enzymes (lipase, chymotrypsin, trypsin, and amylase) and intestinal brush border enzymes (creatine kinase (CK), Na+/K+-ATPase, γ-glutamyl transpeptidase (γ-GT), and alkaline phosphatase (AKP)); (3) dietary CIN increased the absorption capacity which may be associated with the upregulated messenger RNA (mRNA) abundances of their amino acid transporters (AATs) in the intestine, which might be associated with activating the target of rapamycin (TOR) signaling pathway. The best CIN supplementation in the diets of grass carp was estimated to be 76.40 mg kg-1 diet based on the best percent weight gain (PWG). In general, CIN increased the digestion and absorption capacity of grass carp and raised the mRNA abundances of AATs which may be partly related to activation of the TOR signaling pathway.

13.
J Phys Chem Lett ; 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32419469

RESUMO

Molecular junctions hold great potential for future micro-electronics, while the practical utilization has long been limited by the problem of conformational deformation during charge transport. Here we present a first-principles theoretical study on the surface-enhanced Raman spectroscopy (SERS) characterization of the p-terphenyl-4,4"-dithiol molecule and its 2,2',5',2"-tetramethylated analogue in gold junctions, to investigate the molecular deformation mechanism. The effects of charge injection and external electric field were examined, both of which could change π-conjugation by varying the dihedral angle between the central and ending rings (DIPT). The induced significant structural deformations then change SERS responses. While only the SERS responses under external electric field can account for the experimentally observed Raman spectra, and those of charge injections cannot. Moreover, applying a strong electric field could enlarge the conductivities of the two molecular junctions, agreeing well with experiments. These information not only elaborate that the electric field effect constitutes one important mechanism for molecular deformation, but also provide useful insights for the control of charge transport in molecular junctions.

14.
J Clin Oncol ; : JCO1902474, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32275467

RESUMO

PURPOSE: Standard adjuvant chemotherapy for triple-negative breast cancer (TNBC) includes a taxane and an anthracycline. Concomitant capecitabine may be beneficial, but robust data to support this are lacking. The efficacy and safety of the addition of capecitabine into the TNBC adjuvant treatment regimen was evaluated. PATIENTS AND METHODS: This randomized, open-label, phase III trial was conducted in China. Eligible female patients with early TNBC after definitive surgery were randomly assigned (1:1) to either capecitabine (3 cycles of capecitabine and docetaxel followed by 3 cycles of capecitabine, epirubicin, and cyclophosphamide) or control treatment (3 cycles of docetaxel followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide). Randomization was centralized without stratification. The primary end point was disease-free survival (DFS). RESULTS: Between June 2012 and December 2013, 636 patients with TNBC were screened, and 585 were randomly assigned to treatment (control, 288; capecitabine, 297). Median follow-up was 67 months. The 5-year DFS rate was higher for capecitabine than for control treatment (86.3% v 80.4%; hazard ratio, 0.66; 95% CI, 0.44 to 0.99; P = .044). Five-year overall survival rates were numerically higher but not significantly improved (capecitabine, 93.3%; control, 90.7%). Overall, 39.1% of patients had capecitabine dose reductions, and 8.4% reported grade ≥ 3 hand-foot syndrome. The most common grade ≥ 3 hematologic toxicities were neutropenia (capecitabine, 136 [45.8%]; control, 118 [41.0%]) and febrile neutropenia (capecitabine, 50 [16.8%]; control, 46 [16.0%]). Safety data were similar to the known capecitabine safety profile and generally comparable between arms. CONCLUSION: Capecitabine when added to 3 cycles of docetaxel followed by 3 cycles of a 3-drug anthracycline combination containing capecitabine instead of fluorouracil significantly improved DFS in TNBC without new safety concerns.

15.
Platelets ; : 1-9, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32326796

RESUMO

Introduction: This prospective, multicenter, randomized study was designed to analyze the benefits of ticagrelor over clopidogrel in reducing subclinical stent thrombosis (ST) in patients with coronary artery disease who underwent implantation of a second-generation drug-eluting stent (DES).Methods: About 352 patients with single de novo coronary stenosis were randomly assigne`d to either clopidogrel group (aspirin plus clopidogrel) or ticagrelor group (aspirin plus ticagrelor) after DES implantation for 1 year. Baseline clinical characteristics, blood chemistry markers, coronary artery angiography (CAG), and optical coherence tomography (OCT) were obtained during the index procedure. Data about clinic, CAG and OCT were also collected after 1 year follow-up. Intention-to-treat (ITT), per protocol set (PPS), and sensitivity analysis of subclinical ST were performed. Major factors associated with subclinical ST were analyzed by multivariable and univariable logistic regression models.Results: The incidence of subclinical ST in ticagrelor group was significantly low as compared to clopidogrel group (P < .05) at 1-year follow-up. Ticagrelor use was an independent factor in reducing subclinical ST (P < .05). The percentage of endothelial coverage, neointimal hyperplasia, malapposition, and edge dissection about stents were not different between the two groups (P > .05). Bleeding ratio was not markedly altered after ticagrelor treatment (P > .05). Not any significant differences were detected with regard to baseline clinical characteristics, CAG results, and DES between ticagrelor and clopidogrel groups (P > .05).Conclusion: In patients who underwent a second-generation DES implantation, using aspirin plus ticagrelor was associated with a significant reduction in subclinical ST. (ClinicalTrials.gov. Number: NCT02140801).

16.
Adv Mater ; 32(19): e1907888, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32227397

RESUMO

Y3 Al5 O12 :Ce3+ (YAG:Ce3+ ) transparent ceramic phosphors (TCPs) are regarded as the most promising luminescent converter for laser-driven (LD) lighting. High-quality YAG:Ce3+ TCPs are still urgent for high efficiency LD lighting devices. YAG:Ce3+ TCPs in a vacuum ambience by using nano-sized raw materials are prepared. Controlling defects by adding nano-sized MgO and SiO2 simultaneously enables a high transmittance nearly 80%. After annealing in air furthermore, the luminous efficiency is enhanced greatly from 106 to 223 lm W-1 , which is the best result reported now for LD lighting. These results demonstrate that the optimizing YAG:Ce3+ TCPs in a fitting strategy will brighten once again in the next-generation LD lighting. Based on scanning electron microscopy (SEM) coupled with a cathodoluminescence system, defects and Ce3+ distributions in grains are identified directly for the first time.

17.
Adv Ther ; 37(5): 2493-2506, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32319040

RESUMO

INTRODUCTION: This study characterized the multidose pharmacokinetic (PK) characteristics of posaconazole tablets used as prophylactic antifungal therapy in Chinese patients with acute myelogenous leukemia (AML) at risk for invasive fungal infection (IFI). METHODS: Participants in this open-label, single-arm, phase 1b study received posaconazole 300 mg twice daily on day 1 and then once daily for up to 28 days. In the intensive PK sampling subgroup, posaconazole was administered under fasting conditions on days 1 and 8, and blood samples were regularly collected over 24 h. Trough PK sampling was conducted in all participants on days 1, 2, 3, 8, 14, 21, and 28 without regard for food intake. Population PK characteristics were predicted using PK modeling. Primary endpoints were steady-state average concentration (Cavg) and percentage of participants with steady-state Cavg (predicted and observed) > 500 ng/ml. Treatment safety and efficacy were secondary endpoints. RESULTS: Sixty-five adult Chinese participants were enrolled. On day 8, steady-state arithmetic mean Cavg was 1610 ng/ml (% coefficient of variation [%CV] 42.8%) in the intensive PK subgroup (n = 20). All participants achieved a steady-state Cavg > 500 ng/ml. Predicted Cavg (pCavg) was 1770 ng/ml (%CV 33.7%) in the total population (n = 64); 92.2% of participants had pCavg values ≥ 500 ng/ml (n = 59). The posaconazole tablet safety profile was consistent with that of the oral formulation, and the IFI rate was 3%. CONCLUSION: In Chinese AML patients, the posaconazole 300-mg tablet provided PK data comparable with those of previous studies and was generally well tolerated and efficacious. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02387983.

18.
Med Sci Monit ; 26: e922420, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32348295

RESUMO

BACKGROUND The prognostic role of axillary lymph node ratio (LNR) after neoadjuvant chemotherapy (NAC) in breast cancer has not been illuminated. This study was designed to investigate the prognostic role of LNR in breast cancer compared with traditional ypN stage. MATERIAL AND METHODS A total of 306 breast cancer patients diagnosed with positive axillary lymph nodes from January 2007 to December 2014 were eligible for this retrospective analysis. All enrolled patients were treated with a median of 4 cycles of NAC followed by mastectomy and level I, II, and III axillary lymph node dissection (ALND). RESULTS The median duration of follow-up was 78 months (range, 7-147 months). Univariate analysis indicated that both the LNR category (P<0.001) and ypN stage (P<0.001) were significant associated with event-free survival (EFS) and overall survival (OS). However, multivariate analysis indicated that the LNR category was independently associated with EFS (P<0.001) and OS (P<0.001), while the ypN stage showed no statistical effect on EFS (P=0.391) or OS (P=0.081). On additional analyses stratified by molecular subtypes, we found that the prognosis of triple negative breast cancer could be better discriminated when the cutoff value of LNR was set at 0.15. CONCLUSIONS LNR showed a superior predictive value in evaluating prognosis of breast cancer patients after NAC. In addition, the LNR cutoff point 0.15 can accurately discriminate survival outcomes for different triple negative breast cancer subtypes.

19.
Oncologist ; 25(5): e833-e842, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32250517

RESUMO

BACKGROUND: Because of rapid disease progression and lack of optimal treatment strategies beyond the second-line, the prognosis of patients with extensive-stage (ES) small cell lung cancer (SCLC) still remains depressing. Alternative treatment strategies are required to improve their prognosis. In this prospective clinical study, we aimed to evaluate the feasibility of single-agent apatinib, a vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, as a treatment option for patients with ES-SCLC after failure of at least two prior chemotherapy regimens. MATERIALS AND METHODS: Twenty-two patients with ES-SCLC treated with 500 mg single-agent apatinib as subsequent-line regimen in our institution from November 2016 to August 2018 were enrolled in the study. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). RESULTS: Clinical outcomes included partial response in 3 patients (13.6%), stable disease in 18 patients (81.8%), and disease progression in 1 patient (4.5%), with an ORR of 13.6% and DCR of 95.5%. The median PFS and OS were 5.4 and 10.0 months, respectively. Apatinib demonstrated a manageable toxicity profile, with grade I-III secondary hypertension and proteinuria as the most common AEs. No grade IV and V AEs were observed among the patients. Multivariate analysis revealed secondary hypertension as an independent predictor of OS (p = .047); however, the association became insignificant after Q correction (p = .455). CONCLUSIONS: Apatinib was safe and effective in the management of patients with ES-SCLC and can be considered as a treatment option after failure of at least two prior chemotherapy regimens. ClinicalTrials.gov identifier. NCT02995187 IMPLICATIONS FOR PRACTICE: This study indicated the acceptable toxicity profile and promising efficacy of apatinib in the management of patients with extensive-stage small cell lung cancer after failure from at least two prior chemotherapy regimens. Secondary hypertension can be a potential prognostic factor for apatinib treatment.

20.
Nature ; 580(7801): 93-99, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32238934

RESUMO

Prostate cancer is the second most common cancer in men worldwide1. Over the past decade, large-scale integrative genomics efforts have enhanced our understanding of this disease by characterizing its genetic and epigenetic landscape in thousands of patients2,3. However, most tumours profiled in these studies were obtained from patients from Western populations. Here we produced and analysed whole-genome, whole-transcriptome and DNA methylation data for 208 pairs of tumour tissue samples and matched healthy control tissue from Chinese patients with primary prostate cancer. Systematic comparison with published data from 2,554 prostate tumours revealed that the genomic alteration signatures in Chinese patients were markedly distinct from those of Western cohorts: specifically, 41% of tumours contained mutations in FOXA1 and 18% each had deletions in ZNF292 and CHD1. Alterations of the genome and epigenome were correlated and were predictive of disease phenotype and progression. Coding and noncoding mutations, as well as epimutations, converged on pathways that are important for prostate cancer, providing insights into this devastating disease. These discoveries underscore the importance of including population context in constructing comprehensive genomic maps for disease.

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