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1.
J Colloid Interface Sci ; 605: 451-462, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34340032

RESUMO

Currently, it is critical but a tricky point to develop economical, high-efficiency, and durable non-precious metal electrocatalysts towards oxygen reduction and oxygen evolution reaction (ORR/OER) in rechargeable Zn-air batteries. Herein, N, Mn-codoped three-dimensional (3D) fluffy porous carbon nanostructures encapsulating FeCo/FeCoP alloyed nanoparticles (FeCo/FeCoP@NMn-CNS) are prepared by one-step pyrolysis of the metal precursors and polyinosinic acid. The optimized hybrid nanocomposite (obtained at 800 °C, named as FeCo/FeCoP@NMn-CNS-800) exhibits outstanding catalytic performance in the alkaline electrolyte with a half-wave potential (E1/2) of 0.84 V for the ORR and an overpotential of 325 mV towards the OER at 10 mA cm-2. Impressively, the FeCo/FeCoP@NMn-CNS-800-assembled rechargeable Zn-air battery presents an open-circuit voltage of 1.522 V (vs. RHE), a peak power density of 135.0 mW cm-2, and long-term durability by charge-discharge cycling for 200 h, surpassing commercial Pt/C + RuO2 based counterpart. This work affords valuable guidelines for exploring advanced bifunctional ORR and OER catalysts in rational construction of high-quality Zn-air batteries.

2.
Ann Transl Med ; 9(20): 1516, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34790722

RESUMO

Background: Few studies have exclusively investigated the value of pathological complete response (pCR), in esophageal squamous cell carcinoma (ESCC) patients, although it is a clinically significant parameter to evaluate the impact of neoadjuvant chemoradiotherapy (nCRT) on treatment outcome after surgery. The aim of our study was to explore the relationship between pCR after nCRT and survival among patients with local ESCC. Methods: All patients receiving nCRT followed by surgery in NEOCRTEC5010-trial (NCT01216527) were included. Non-pCR patients were classified into three subgroups: ypTanyN0M0, ypT0NanyM0 and ypTanyNanyM0. The Kaplan-Meier method with log-rank test was employed to evaluate disease-free survival (DFS) and overall survival (OS). Multivariate regression analysis was performed using a Cox proportional hazards model to identify clinicopathological parameters associated with pCR. Results: Among the 185 patients included, 80 (43.2%) achieved pCR after nCRT. The mean survival time of the pCR group was significantly longer than that of the non-pCR group (92.6 vs. 69.2 months; HR, 2.70; 95% CI: 1.48-4.92; P=0.001). The 5-year OS and DFS of the pCR group were 79.3% and 77% respectively, compared to 54.8% and 51.2%, respectively, in the non-pCR group. The results showed that the OS and DFS of the ypTanyN0M0 group were better than those of the ypT0NanyM0 group and the ypTanyNanyM0 group. We also found that the number of dissected lymph nodes and pCR were independent risk factors for DFS and OS rates. Conclusions: pCR after nCRT is an important prognostic indicator of OS and DFS in patients with ESCC. In addition, lymph-node status could represent an important parameter in the prognostic evaluation of esophageal cancer patients.

3.
J Mater Chem B ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34806096

RESUMO

Although silk proteins are considered promising in building a scaffold for tissue engineering, one of the silk proteins, Bombyx mori silk sericin (BS), has limited processability in producing nanofibrous scaffolds because its surface charge anisotropy promotes gelation instead. To overcome this daunting challenge, we developed a mild and simple procedure for assembling BS into nanofibers and nanofibrous scaffolds. Briefly, arginine was added to the aqueous BS solution to reduce the negative charge of BS, thereby inducing BS to self-assemble into nanofibers in the solution. Circular dichroism (CD) and Fourier transform infrared (FT-IR) spectra showed that arginine promoted the formation of ß-sheet conformation in BS and increased its thermal stability. Furthermore, the arginine-induced BS nanofiber solution could be casted into scaffolds made of abundant network-like nanofibrous structures. The BS scaffolds promoted cell adhesion and growth and stimulated osteogenic differentiation of the bone marrow mesenchymal stem cells (BMSCs) in the absence of differentiation inducers in culture media. Our study presents a new strategy for assembling proteins into osteogenic nanofibrous scaffolds for inducing stem cell differentiation in regenerative medicine.

4.
Nat Commun ; 12(1): 6653, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34789768

RESUMO

BRCA1-BARD1 heterodimers act in multiple steps during homologous recombination (HR) to ensure the prompt repair of DNA double strand breaks. Dysfunction of the BRCA1 pathway enhances the therapeutic efficiency of poly-(ADP-ribose) polymerase inhibitors (PARPi) in cancers, but the molecular mechanisms underlying this sensitization to PARPi are not fully understood. Here, we show that cancer cell sensitivity to PARPi is promoted by the ring between ring fingers (RBR) protein RNF19A. We demonstrate that RNF19A suppresses HR by ubiquitinating BARD1, which leads to dissociation of BRCA1-BARD1 complex and exposure of a nuclear export sequence in BARD1 that is otherwise masked by BRCA1, resulting in the export of BARD1 to the cytoplasm. We provide evidence that high RNF19A expression in breast cancer compromises HR and increases sensitivity to PARPi. We propose that RNF19A modulates the cancer cell response to PARPi by negatively regulating the BRCA1-BARD1 complex and inhibiting HR-mediated DNA repair.

5.
Ann Med ; 53(1): 1914-1923, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34726101

RESUMO

OBJECTIVE: To identify risk factors of disease severity and between mild and severe colon ischaemia (CI) patients and to improve clinical outcomes, this study aimed to explore a novel scoring model. METHODS: Retrospective analyses of hospital records between January 2009 and December 2019 were included. Clinical manifestations, mortality, Oakland score, laboratory tests, colonoscopy, and histopathology were collected. Risk factors of severe CI were determined by univariate and multivariate logistic regression and used for the predicting model. RESULTS: A total of 203 patients with CI were included. Serum C-reactive protein (CRP) and albumin ratio (CAR) were much higher in the severe CI group compared with that of the mild CI group (3.33 ± 1.78 versus 0.68 ± 0.97, p < .001). The Oakland score was much higher in the severe CI group (12.00 ± 3.02 versus 8.77 ± 1.63, p < .001). The histopathological finding of fibrin thrombi was an independent risk factor that predicted poor outcomes (20.00% versus. 1.09%, p < .001). Patients present with CAR ≥3.33, Oakland score ≥12, and histopathological fibrin thrombi were independent risk factors. In addition, the final scoring model was 0.042 × Oakland score + 1.040 × CAR + 3.412 × fibrin thrombi, the area under the curve (AUC) was 0.960 (95% confidence interval:0.930-0.990), and the sensitivity and specificity of the novel scoring model were 95% and 92%, respectively. CONCLUSIONS: The novel prognostic model was established to predict CI severity and clinical outcomes efficiently.Key messagesIn this article, we discuss the scoring model for clinical outcomes of colon ischaemia patients.In our study, the sensitivity and specificity of a novel scoring model are very high.Thus, laboratory tests (CRP albumin ratio), Oakland score, and histopathological findings (fibrin thrombi) can be assessed efficiently for colon ischaemia outcomes.

6.
Opt Lett ; 46(21): 5505-5508, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34724512

RESUMO

The erbium-doped lithium niobate on insulator (LNOI) laser plays an important role in the complete photonic integrated circuits (PICs). Here, we demonstrate an integrated tunable whispering gallery single-mode laser (WGSML) by making use of a coupled microdisk and microring on LNOI. A 974 nm single-mode pump light can have an excellent resonance in the designed microdisk, which is beneficial to the whispering gallery mode (WGM) laser generation. The WGSML at 1560.40 nm with a maximum 31.4 dB side mode suppression ratio (SMSR) has been achieved. By regulating the temperature, the output power of the WGSML increases, and the central wavelength can be changed from 1560.30 to 1560.40 nm. Furthermore, 1560.60 and 1565.00 nm WGSMLs have been achieved by changing the coupling gap width between the microdisk and microring. We can also use the electro-optic effect of LNOI to obtain more accurate adjustable WGSMLs in further research.

7.
Nucleic Acids Res ; 49(19): 11224-11240, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34606619

RESUMO

The human RecQ helicase BLM is involved in the DNA damage response, DNA metabolism, and genetic stability. Loss of function mutations in BLM cause the genetic instability/cancer predisposition syndrome Bloom syndrome. However, the molecular mechanism underlying the regulation of BLM in cancers remains largely elusive. Here, we demonstrate that the deubiquitinating enzyme USP37 interacts with BLM and that USP37 deubiquitinates and stabilizes BLM, thereby sustaining the DNA damage response (DDR). Mechanistically, DNA double-strand breaks (DSB) promotes ATM phosphorylation of USP37 and enhances the binding between USP37 and BLM. Moreover, knockdown of USP37 increases BLM polyubiquitination, accelerates its proteolysis, and impairs its function in DNA damage response. This leads to enhanced DNA damage and sensitizes breast cancer cells to DNA-damaging agents in both cell culture and in vivo mouse models. Collectively, our results establish a novel molecular mechanism for the USP37-BLM axis in regulating DSB repair with an important role in chemotherapy and radiotherapy response in human cancers.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34497657

RESUMO

Background: Male reproductive damage, as a common complication of diabetes mellitus (DM), is getting more attention lately. We aimed to explore the protective effects and mechanism of cornuside (Cor) modulating gut microbiota to alleviate diabetes mellitus- (DM-) induced testicular damage. Methods: KK-Ay mice with reproductive damage were randomly divided into the model and Cor treatment groups, and the C57BL/6J mice were used as the normal group. These mice were orally administered Cor for 8 weeks. Results: Cor administration ameliorated the diabetes-related symptoms of polydipsia and polyphagia and lowered the fasting blood glucose (FBG) level. The results of pathological injury showed that Cor improved testicular lesions (the rupture of seminiferous tubules, degeneration of germ cells, and structural shrinkage and separation from each other) in DM model mice. Cor significantly increased the testis/body weight ratio, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels in KK-Ay mice. Cor also protected from reproductive damage by inhibiting apoptosis in the testes of KK-Ay mice. Moreover, Cor significantly increased the sperm count and sperm motility. Additionally, 16S rDNA sequencing analysis showed that Cor could notably reverse the changes in the distribution of gut microbiota and decrease the abundance of Weissella confusa (Weissella), Clostridium sp. ND2 (Clostridium sensu stricto 1), uncultured bacterium (Roseburia), Anaerotruncus colihominis DSM 17241 (Anaerotruncus), [Clostridium] leptum (Anaerotruncus), unidentified (Ruminococcus 1), and uncultured bacterium (Bilophila), which may be a potential biomarker for diagnosing the testicular injury caused by DM. Meanwhile, the heat map of phylum level suggested that the testicular injury caused by DM is closely related to gut microbiota. Conclusions: Cor could alleviate DM-induced testicular damage, probably by modulating the gut microbiota.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34554611

RESUMO

AIM: This study assessed the diagnostic performance of liver stiffness measurement (LSM) in detecting liver fibrosis in paediatric patients with non-alcoholic fatty liver disease (NAFLD) through meta-analysis. METHODS: Online database searches of PubMed, EMBASE, the Cochrane Library and the Web of Science were conducted for studies that evaluated the performance of LSM for diagnosing liver fibrosis in paediatric patients with NAFLD until 1 January 2021. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to assess the quality of the included studies. Three measures were used to assess the performance of LSM for detecting liver fibrosis in paediatric patients with NAFLD, including the summary sensitivities and specificities, the summary area under the receiver operating characteristic curves and the summary diagnostic odds ratios. RESULTS: Our final data included seven studies with a total of 436 paediatric patients with NAFLD for meta-analysis. The overall prevalence of mild fibrosis, significant fibrosis, advanced fibrosis and cirrhosis was 66.3, 31.5, 14.9 and 1.2%, respectively. The summary sensitivity, specificity and area under the receiver operating characteristic values of LSM were 80, 92 and 0.94 for the prediction of mild fibrosis; 91, 97 and 0.98 for the prediction of significant fibrosis; and 89, 93 and 0.96 for the prediction of advanced fibrosis, respectively. CONCLUSION: Liver stiffness measurement exhibited good diagnostic performance in predicting liver fibrosis and can be used as a non-invasive tool in the management of paediatric patients with non-alcoholic fatty liver disease.

10.
ACS Appl Mater Interfaces ; 13(40): 47371-47381, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34582680

RESUMO

Silk fibroin (SF) is a biomacromolecule that can be assembled into nanostructures and induce biomimetic nucleation of inorganic materials. Zeolitic imidazolate framework-8 (ZIF-8), a metal-organic framework (MOF), can be dissolved selectively under acidic pH. Here, we integrated SF and ZIF-8 to develop novel drug carriers that selectively release drug in the acidic intracellular environment of cancer cells. Specifically, SF was assembled into nanoparticles (SF-NPs), which were then loaded with an antitumor drug, doxorubicin (DOX), to form DSF-NPs. Due to the SF-mediated organization of ZIF-8 precursors such as zinc ions, the DSF-NPs further templated the nucleation of ZIF-8 onto their surface to generate core-shell-structured NPs (termed DSF@Z-NPs) with ZIF-8 as a shell and DSF-NP as a core. We found that the DSF@Z-NPs, highly stable under neutral conditions, could be uptaken by breast cancer cells, release DOX selectively owing to dissolution of ZIF-8 shells in the acidic intracellular environment in a controlled manner, and induce cell apoptosis. We also confirmed that the DSF@Z-NPs could inhibit tumor growth more efficiently to reach a higher survival rate than their controls by inducing cell apoptosis in vivo. Our study suggests that SF and MOF could be combined to design a new type of cancer therapeutics.

11.
Front Psychiatry ; 12: 699778, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34393860

RESUMO

Many epidemiological studies have demonstrated the therapeutic benefits of exercise (EX) that can be used for adjunctive treatment in mental disorders. Despite several clinical experiments using exercise interventions, controlled studies are sparse in most disorder groups. Square dance is a popular aerobic exercise for older women in China. This study aimed to explore the effect of Chinese square dance exercise on mild mental disorders in older women. Participants included 109 older women with mild cognitive impairment from four large nursing homes. Participants were assigned either to the intervention group (n = 62) or the control group (n = 47), according to their residential nursing home. The intervention group underwent an 18-week square dance exercise, while the control group maintained their usual lifestyle. The outcomes were tested at baseline and weeks 9 and 18. The results showed that square dance exercise positively affected the results of all evaluations, especially on the participants' depressive symptoms and quality-of-life-related mental health. This study demonstrates that square dance exercise is a safe and effective approach for older women with mild cognitive impairment that benefits their long-term health.

12.
Nat Commun ; 12(1): 4947, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34400648

RESUMO

Phase separation at the molecular scale affects many biological processes. The theoretical requirements for phase separation are fairly minimal, and there is growing evidence that analogous phenomena occur at other scales in biology. Here we examine colony formation in the nematode C. elegans as a possible example of phase separation by a population of organisms. The population density of worms determines whether a colony will form in a thresholded fashion, and a simple two-compartment ordinary differential equation model correctly predicts the threshold. Furthermore, small, round colonies sometimes fuse to form larger, round colonies, and a phenomenon akin to Ostwald ripening - a coarsening process seen in many systems that undergo phase separation - also occurs. These findings support the emerging view that the principles of microscopic phase separation can also apply to collective behaviors of living organisms.


Assuntos
Fenômenos Biológicos , Caenorhabditis elegans/fisiologia , Animais , Bactérias , Comportamento Animal , Quimiotaxia , Modelos Biológicos , Comportamento Social
13.
Nat Cell Biol ; 23(8): 894-904, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34354233

RESUMO

The shieldin complex functions as the downstream effector of 53BP1-RIF1 to promote DNA double-strand break end-joining by restricting end resection. The SHLD2 subunit binds to single-stranded DNA ends and blocks end resection through OB-fold domains. Besides blocking end resection, it is unclear how the shieldin complex processes SHLD2-bound single-stranded DNA and promotes non-homologous end-joining. Here, we identify a downstream effector of the shieldin complex, ASTE1, as a structure-specific DNA endonuclease that specifically cleaves single-stranded DNA and 3' overhang DNA. ASTE1 localizes to DNA damage sites in a shieldin-dependent manner. Loss of ASTE1 impairs non-homologous end-joining, leads to hyper-resection and causes defective immunoglobulin class switch recombination. ASTE1 deficiency also causes resistance to poly(ADP-ribose) polymerase inhibitors in BRCA1-deficient cells owing to restoration of homologous recombination. These findings suggest that ASTE1-mediated 3' single-stranded DNA end cleavage contributes to the control of DSB repair choice by 53BP1, RIF1 and shieldin.


Assuntos
Reparo do DNA por Junção de Extremidades , Desoxirribonuclease I/fisiologia , Proteínas/fisiologia , Animais , Proteínas de Ciclo Celular/fisiologia , DNA/metabolismo , Proteínas de Ligação a DNA/fisiologia , Feminino , Instabilidade Genômica , Células HEK293 , Humanos , Switching de Imunoglobulina/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Recombinantes de Fusão
14.
Chem Biol Interact ; 348: 109625, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34416245

RESUMO

Catalpol is an iridoid glycoside compound isolated from the root of Rehmannia glutinosa, which has been reported to be a promising candidate for the treatment of diabetic diseases. The present study aimed at investigating the effects and potential mechanism of catalpol on endothelial dysfunction and inflammation in diabetic nephropathy (DN). We constructed DN mice and advanced glycation end products (AGEs)-induced mouse glomerular endothelial cells (mGECs) injury model. The results demonstrated that catalpol effectively improved renal pathology and decreased levels of urine protein, serum creatinine, and blood urea nitrogen in DN mice. Catalpol significantly reduced endothelial dysfunction and inflammatory infiltration of macrophages in DN mice and AGEs-induced mGECs. To further study the protective mechanism of catalpol, we transfected DN mice with recombinant adeno-associated virus expressing receptor of AGEs (RAGE) and intervened AGEs-induced mGECs with inhibitors. Catalpol reversed endothelial dysfunction and inflammation aggravated by RAGE overexpression in DN mice. Meanwhile, catalpol significantly inhibited the RAGE/Ras homolog gene family member A (RhoA)/Rho-associated kinase (ROCK) pathway in DN mice with RAGE overexpression. Moreover, the combination of catalpol with inhibitors of RAGE, RhoA and ROCK exerted stronger anti-endothelial dysfunction and anti-macrophage infiltration effects on AGEs-induced mGECs compared with catalpol alone. In short, this study indicated that catalpol could ameliorate endothelial dysfunction and inflammation via suppression of RAGE/RhoA/ROCK pathway, hereby delaying the progression of DN.


Assuntos
Nefropatias Diabéticas/patologia , Endotélio/efeitos dos fármacos , Glucosídeos Iridoides/farmacologia , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Transdução de Sinais/efeitos dos fármacos , Quinases Associadas a rho/metabolismo , Animais , Nefropatias Diabéticas/tratamento farmacológico , Endotélio/patologia , Inflamação/complicações , Glucosídeos Iridoides/uso terapêutico , Macrófagos/efeitos dos fármacos , Camundongos , Proteína rhoA de Ligação ao GTP/metabolismo
15.
Front Pharmacol ; 12: 678300, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262451

RESUMO

Radix Rehmanniae and Cornus Officinalis (RR-CO) have been widely used as "nourishing Yin and tonifying kidney" herb pairs for the treatment of diabetes mellitus (DM) and its complications in traditional Chinese medicine (TCM). Based on the theory of "kidney governing reproduction" in TCM, the aim of this study was to investigate the therapeutic effects of RR-CO on DM-induced reproduction damage through regulating testicular glycolysis. Moreover, the regulation of AGEs/RAGE/HIF-1α axis on the testicular glycolysis process has also been studied. Spontaneous DM model KK-Ay mice were used to investigate the protective effect of RR, CO, RR-CO on DM-induced reproductive disturbances. RR, CO, RR-CO improved DM-induced renal and testicular morphology damages. Moreover, the impaired spermatogenesis, germ cell apoptosis and motility in testis induced upon DM were also attenuated by RR, CO or RR-CO, accompanied by an increased level of glycolysis metabolomics such as l-lactate, d-Fructose 1,6-bisphosphate, etc. Meanwhile, glucose membrane transporters (GLUT1, GLUT3), monocarboxylate transporter 4 (MCT4) expression, lactate dehydrogenase (LDH) activity, HIF-1α were upregulated by RR, CO and RR-CO treatment compared with the model group, whereas AGE level and RAGE expression were decreased with the drug administration. The RR-CO group was associated with superior protective effects in comparison to RR, CO use only. Aminoguanidine (Ami) and FPS-ZM1, the AGEs and RAGE inhibitors, were used as a tool drug to study the mechanism, showing different degrees of protection against DM-induced reproductive damage. This work preliminarily sheds light on the herb pair RR-CO exhibited favorable effects against DM-induced reproductive disturbances through enhancing testicular glycolysis, which might be mediated by AGEs/RAGE/HIF-1α axis.

17.
J Chromatogr Sci ; 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059885

RESUMO

A sensitive and selective gas chromatography-tandem mass spectrometry method was developed for the identification and quantification of five potential genotoxic impurities (PGIs), i.e., chloromethane, 2-chloropropane, 2-bromopropane, 4-chloro-1-butanol and diethyl sulfate, in abiraterone acetate. The method was validated according to the International Council for Harmonisation (ICH) guidelines. The linearity was established for the concentration range of 30-480 ng/mL (2-chloropropane, 2-bromopropane, 4-chloro-1-butanol and diethyl sulfate) and 90-1440 ng/mL (chloromethane). The correlation coefficient of each PGIs was >0.995. The extraction recoveries ranged from 90.49 to 106.79% for the five PGIs. The quantitation limit, detection limit, accuracy, precision, repeatability and stability of the method demonstrated that the method was an adequate quality control tool for quantitation and identification of chloromethane, 2-chloropropane, 2-bromopropane, 4-chloro-1-butanol and diethyl sulfate at trace levels in drug substances and drug products.

18.
JAMA Surg ; 156(8): 721-729, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34160577

RESUMO

Importance: The prognosis of patients with locally advanced esophageal squamous cell carcinoma (ESCC) remains poor after surgery. Neoadjuvant chemoradiotherapy (NCRT) has been shown to potentially improve survival. Objective: To compare the treatment efficacy of NCRT plus surgery with surgery alone for long-term survival among patients with locally advanced ESCC. Design, Setting, and Participants: The Neoadjuvant Chemoradiotherapy for Esophageal Cancer 5010 study was a multicenter open-label randomized phase 3 clinical trial that enrolled patients between June 1, 2007, and December 31, 2014. Follow-up ended on December 31, 2019. The study was conducted at 8 centers in China. A total of 451 patients aged 18 to 70 years with thoracic ESCC stage T1-4N1M0/T4N0M0 were enrolled and randomized. Data were analyzed from December 1, 2019, to June 30, 2020. Interventions: Patients randomized to receive NCRT plus surgery (NCRT group) received preoperative chemotherapy (25 mg/m2 of vinorelbine on days 1 and 8 and 75 mg/m2 of cisplatin on day 1 or 25 mg/m2 of cisplatin on days 1 to 4) every 3 weeks for 2 cycles and concurrent radiotherapy (40.0 Gy, administered in 20 fractions of 2.0 Gy for 5 days per week) followed by surgery. Patients randomized to receive surgery alone (surgery group) underwent surgery after randomization. Main Outcomes and Measures: The primary end point was overall survival in the intention-to-treat population. The secondary end point was disease-free survival. Results: A total of 451 patients (mean [SD] age, 56.5 [7.0] years; 367 men [81.4%]) were randomized to the NCRT (n = 224) and surgery (n = 227) groups and were eligible for the intention-to-treat analysis. By December 31, 2019, 224 deaths had occurred. The median follow-up was 53.5 months (interquartile range, 18.2-87.4 months). Patients receiving NCRT plus surgery had prolonged overall survival compared with those receiving surgery alone (hazard ratio, 0.74; 95% CI, 0.57-0.97; P = .03), with a 5-year survival rate of 59.9% (95% CI, 52.9%-66.1%) vs 49.1% (95% CI, 42.3%-55.6%), respectively. Patients in the NCRT group compared with the surgery group also had prolonged disease-free survival (hazard ratio, 0.60; 95% CI, 0.45-0.80; P < .001), with a 5-year survival rate of 63.6% (95% CI, 56.0%-70.2%) vs 43.0% (95% CI, 36.0%-49.7%), respectively. Conclusions and Relevance: In this randomized clinical trial, treatment with NCRT plus surgery significantly improved long-term overall survival and disease-free survival and therefore may be considered a standard of care for patients with locally advanced ESCC. Trial Registration: ClinicalTrials.gov Identifier: NCT01216527.

19.
Int J Neuropsychopharmacol ; 24(10): 798-807, 2021 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-34153098

RESUMO

OBJECTIVE: Although metabolic disorders and smoking are common in schizophrenia, few studies have investigated the effects of smoking on metabolic disorders or metabolic syndrome (MetS) in schizophrenia patients, especially in first-episode drug-naïve (FEDN) patients. We sought to investigate the differences in metabolic disorders and MetS between smoking and nonsmoking FEDN schizophrenia patients. METHODS: A total of 428 FEDN schizophrenia patients and 435 controls were recruited. Blood pressure, waist circumference, body mass index (BMI), lipid profiles, and glucose metabolism were measured. The psychopathology was evaluated by Positive and Negative Syndrome Scale. RESULTS: FEDN schizophrenia patients had a higher smoking rate than controls (23.8% vs 14.0%, P < .001). After adjusting for confounding variables, the prevalence of MetS, overweight, hypertension, hypertriglyceridemia, elevated insulin, and insulin resistance in smoking patients was higher than those in nonsmoking patients, while overweight and hypertension were higher in the smoking controls than in nonsmoking controls (all P < .05). In smoking patients, triglyceridemia, high-density lipoprotein cholesterol, and fasting blood glucose were the main contributing components to MetS, while in nonsmoking patients, waist circumference, systolic blood pressure, triglyceridemia, high-density lipoprotein cholesterol, and fasting blood glucose were the main contributing components to MetS. In smoking patients, BMI and homeostatic model assessment for insulin resistance were associated factors of MetS (both P < .05). In nonsmoking patients, sex, BMI, insulin, and homeostatic model assessment for insulin resistance were associated factors of MetS (all P < .05). CONCLUSIONS: Our study indicates that smoking schizophrenia patients have a higher prevalence of MetS and metabolic disorders than nonsmoking patients. Moreover, smoking and nonsmoking patients have different contributing components and associated factors for MetS.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33982301

RESUMO

BACKGROUND AND AIM: An accurate assessment of liver fibrosis is critical for the management of chronic hepatitis B (CHB) patients. Two-dimensional shear wave elastography (2D-SWE) and magnetic resonance elastography (MRE) have recently been proposed to diagnose liver fibrosis. To determine the optimal noninvasive method for diagnosing fibrosis in CHB, we conducted a meta-analysis to compare the performance of 2D-SWE and MRE for diagnosing fibrosis in patients with CHB. METHODS: Literature databases were searched until January 1st 2021. Three measures, the summary area under the receiver operating characteristic curve (AUSROC), the summary diagnostic odds ratios, and the summary sensitivities and specificities, were used to assess the performance of 2D-SWE and MRE for detecting liver fibrosis. RESULTS: Twenty-four studies with 5126 CHB patients were included. The summary sensitivities and specificities of 2D-SWE and MRE were 82% and 81%, 91% and 94%, respectively, for detecting significant fibrosis, 88% and 85%, 93% and 93%, respectively, for detecting advanced fibrosis, and 89% and 87%, 92% and 92%, respectively, for detecting cirrhosis. The AUSROC value of MRE (0.97) in predicting significant fibrosis was significantly higher than those of 2D-SWE (0.88, P < 0.001). The AUSROC values of 2D-SWE and MRE were 0.93 and 0.98, respectively, for the diagnosis of advanced fibrosis, and 0.94 and 0.97, respectively, for the diagnosis of cirrhosis. CONCLUSIONS: MRE and 2D-SWE are excellent tools for staging fibrosis in patients with CHB. MRE probably exhibit the better diagnostic accuracy in detecting significant fibrosis as compared to 2D-SWE.

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