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1.
Chin J Nat Med ; 18(6): 425-435, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32503734

RESUMO

Emodin (1, 3, 8-trihydroxy-6-methylanthraquinone) is a derived anthraquinone compound extracted from roots and barks of pharmaceutical plants, including Rheum palmatum, Aloe vera, Giant knotweed, Polygonum multiflorum and Polygonum cuspidatum. The review aims to provide a scientific summary of emodin in pharmacological activities and toxicity in order to identify the therapeutic potential for its use in human specific organs as a new medicine. Based on the fundamental properties, such as anticancer, anti-inflammatory, antioxidant, antibacterial, antivirs, anti-diabetes, immunosuppressive and osteogenesis promotion, emodin is expected to become an effective preventive and therapeutic drug of cancer, myocardial infarction, atherosclerosis, diabetes, acute pancreatitis, asthma, periodontitis, fatty livers and neurodegenerative diseases. This article intends to provide a novel insight for further development of emodin, hoping to reveal the potential of emodin and necessity of further studies in this field.

2.
Clin Infect Dis ; 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32392331

RESUMO

BACKGROUND: To illustrate the extent of transmission, identify affecting risk factors and estimate epidemiological modeling parameters of SARS-CoV-2 in household setting. METHODS: We enrolled 35 confirmed index cases and their 148 household contacts, January 2020-February 2020, in Zhuhai, China. All participants were interviewed and asked to complete questionnaires. Household contacts were then prospectively followed active symptom monitoring through the 21-day period and nasopharyngeal and/or oropharyngeal swabs were collected at 3-7 days intervals. Epidemiological, demographic and clinical data (when available) were collected. RESULTS: Assuming that all these secondary cases were infected by their index cases, the second infection rate (SIR) in household context is 32.4% (95% confidence interval [CI] 22.4%-44.4%), with 10.4% of secondary cases being asymptomatic. Multivariate analysis showed that household contacts with underlying medical conditions, a history of direct exposure to Wuhan and its surrounding areas, and shared vehicle with an index patient were associated with higher susceptibility. Household members without protective measures after illness onset of the index patient seem to increase the risk for SARS-CoV-2 infection. The median incubation period and serial interval within household were estimated to be 4.3 days (95% CI; 3.4 to 5.3 days) and 5.1 days (95% CI; 4.3 to 6.2 days), respectively. CONCLUSION: Early isolation of patients with COVID-19 and prioritizing rapid contact investigation, followed by active symptom monitoring and periodic laboratory evaluation, should be initiated immediately after confirming patients to address the underlying determinants driving the continuing pandemic.

3.
Chin J Integr Med ; 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32240476

RESUMO

OBJECTIVE: To evaluate the effectiveness and safety of Chinese herbal external umbilicus treatment with Modified Dinggui Powder (, MDGP) in patients with chronic nonbacterial prostatitis (CNP). METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted among 72 patients with CNP. Participants were randomly allocated to a treatment group and a placebo group using computer software in a 1:1 ratio, and received either MDGP external umbilicus treatment (MDGP group, 36 cases) or placebo control groupl (36 cases) at acupoints Shenque (CV 8), twice a week for 4 weeks. In addtion, patients all received herbal medicine treatment twice a day for 4 weeks. The primary outcomes was the US National Institutes of Health Chronic Prostatitis Symptom Scores Index (NIH-CPSI) with a questionnaire at weeks 2 and 4. The secondary outcomes including prostatic fluid examination (white blood cells and lecithin bodies), the clinical efficacy evaluation, and the adverse events were also assessed during the entire trial. RESULTS: The NIH-CPSI scores regarding pain or discomfort scores showed greater improvement in the MDGP group than placebo control group at weeks 2 (P0.001) and week 4 (P0.004), respectively. NIH-CPSI scores of symptom severity, total scores, the amount of leukocytes number in the prostatic fifluid in the MDGP group were significantly improved (P<0.05). There was no statistical difference in the urinary symptoms, quality of life, lecithin and other scores between two groups (P>0.05). The clinical effective rate was 73.53% (25/34) in the MDGP group, which was significally higher than the placebo control group with 48.39% (25/31, P<0.05). Patients were blinded successfully, and no serious adverse effects were found during the trial. CONCLUSION: A 4-week course of umbilicus treatment with modified Dinggui Powder seems to relieve pain and symptom severity effectively and increase the amount of leukocytes number in patients with CNP (Trial registration No. ChiCTR1800014687).

4.
Food Funct ; 11(4): 3610-3620, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32292961

RESUMO

Whole-wheat flour (WWF) is increasingly popular because of the health benefits of whole grains. This study investigated the effect of WWF particle size on dough properties, bread quality and in vitro starch digestibility. WWF was made from intact whole grain directly. Three WWF particle sizes were examined, including coarse, medium and fine with a mean size of 1315, 450 and 199 µm, respectively. The dough made from WWF of a larger particle size exhibited lower extensibility and stability, and subsequently the bread had a more compact structure (i.e. lower open porosity and thicker cell thickness), smaller specific volume and harder texture, which were regarded as poor quality attributes. On the other hand, the bread made from the fine WWF exhibited a higher amount of released glucose than those made from the coarse and medium WWFs. Moreover, the particle size of bread bolus showed no significant effect on in vitro starch digestion. The whole study demonstrated that the particle size of WWF plays a critical role in determining both bread quality and digestibility.

5.
Sci Rep ; 10(1): 4999, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32193438

RESUMO

Chlorpyrifos (CPF) and cadmium (Cd) are widespread environmental pollutants, which are often present in drinking water and foods. However, the combined effects of CPF and Cd were not entirely clear at present. There was also no biomarker available to diagnose the poisoning of the two chemicals at low dose for long-term exposures. In this study, we investigated the change of serum metabolites of rats with subchronic exposure to CPF, Cd, and CPF plus Cd using gas chromatography-mass spectrometer-based metabolomics approach. We performed a stepwise optimization algorithm based on receiver operating characteristic to identify serum metabolite biomarkers for toxic diagnosis of the chemicals at different doses after 90-day exposure. We found that aminomalonic acid was the biomarker for the toxicity of Cd alone administration, and serine and propanoic acid were unique biomarkers for the toxicities of CPF plus Cd administrations. Our results suggest that subchronic exposure to CPF and Cd alone, or in combination at their low doses, could cause disturbance of energy and amino acid metabolism. Overall, we have shown that analysis of serum metabolomics can make exceptional contributions to the understanding of the toxic effects following long-term low-dose exposure of the organophosphorus pesticide and heavy metal.

6.
Ecotoxicol Environ Saf ; 195: 110467, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32182532

RESUMO

Heavy metals and pesticides can be easily enriched in food chains and accumulated in organisms, thus pose significant threat to human health. However, their combined effects for long-term exposure at low dose has not been thoroughly investigated; especially there was no biofluid biomarker available to noninvasively diagnose the toxicosis of the combined exposure of the two chemicals at their low levels. In this study, we investigated the change of urine metabolites of rats with 90-day exposure to heavy metal cadmium (Cd) and/or organophosphorus pesticide chlorpyrifos (CPF) using gas chromatography-mass spectrometry (GC-MS)-based metabolomics approach. Our results showed that the interaction of Cd and CPF mainly displayed an antagonistic effect. We identified the panels of metabolite biomarkers in urine: benzoic acid and mannose were unique biomarkers for Cd exposure; creatinine and N-phenylacetyl glycine were unique biomarkers for CPF exposure; anthranilic acid, ribitol, and glucose were unique biomarkers for Cd plus CPF exposure. Our results suggest that 90-day exposure to Cd and/or CPF could cause a disturbance in energy and amino acid metabolism. And urine metabolomics analysis can help understand the toxicity of low dose exposure to mixed environmental chemicals.


Assuntos
Cádmio/toxicidade , Clorpirifos/toxicidade , Inseticidas/toxicidade , Animais , Ácido Benzoico/urina , Biomarcadores/urina , Creatinina/urina , Interações Medicamentosas , Cromatografia Gasosa-Espectrometria de Massas , Glicina/análogos & derivados , Glicina/urina , Masculino , Manose/urina , Metabolômica , Ratos
7.
Crit Care ; 24(1): 75, 2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131879

RESUMO

BACKGROUND: Although current guidelines for AKI suggested against the use of furosemide in AKI management, the effect of furosemide on outcomes in real-world clinical settings remains uncertain. The aim of the present study was to investigate the association between furosemide administration and outcomes in critically ill patients with AKI using real-world data. METHODS: Critically ill patients with AKI were identified from the Medical Information Mart for Intensive Care (MIMIC)-III database. Propensity score (PS) matched analysis was used to match patients receiving furosemide to those without diuretics treatment. Linear regression, logistic regression model, and Cox proportional hazards model were used to assess the associations between furosemide and length of stay, recovery of renal function, and in-hospital and 90-day mortality, respectively. RESULTS: A total of 14,154 AKI patients were included in the data analysis. After PS matching, 4427 pairs of patients were matched between the patients who received furosemide and those without diuretics treatment. Furosemide was associated with reduced in-hospital mortality [hazard ratio (HR) 0.67; 95% CI 0.61-0.74; P < 0.001] and 90-day mortality [HR 0.69; 95% CI 0.64-0.75; P < 0.001], and it was also associated with the recovery of renal function [HR 1.44; 95% CI 1.31-1.57; P < 0.001] in over-all AKI patients. Nevertheless, results illustrated that furosemide was not associated with reduced in-hospital mortality in patients with AKI stage 0-1 defined by UO criteria, AKI stage 2-3 according to SCr criteria, and in those with acute-on-chronic (A-on-C) renal injury. CONCLUSIONS: Furosemide administration was associated with improved short-term survival and recovery of renal function in critically ill patients with AKI. Furosemide was especially effective in patients with AKI UO stage 2-3 degree. However, it was not effective in those with AKI SCr stage 2-3 and chronic kidney disease. The results need to be verified in randomized controlled trials.

8.
JAMA Intern Med ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32065604

RESUMO

Importance: Use of empirical broad-spectrum antibiotics for pneumonia has increased owing to concern for resistant organisms, including methicillin-resistant Staphylococcus aureus (MRSA). The association of empirical anti-MRSA therapy with outcomes among patients with pneumonia is unknown, even for high-risk patients. Objective: To compare 30-day mortality among patients hospitalized for pneumonia receiving empirical anti-MRSA therapy vs standard empirical antibiotic regimens. Design, Setting, and Participants: Retrospective multicenter cohort study was conducted of all hospitalizations in which patients received either anti-MRSA or standard therapy for community-onset pneumonia in the Veterans Health Administration health care system from January 1, 2008, to December 31, 2013. Subgroups of patients analyzed were those with initial intensive care unit admission, MRSA risk factors, positive results of a MRSA surveillance test, and positive results of a MRSA admission culture. Primary analysis was an inverse probability of treatment-weighted propensity score analysis using generalized estimating equation regression; secondary analyses included an instrumental variable analysis. Statistical analysis was conducted from June 14 to November 20, 2019. Exposures: Empirical anti-MRSA therapy plus standard pneumonia therapy vs standard therapy alone within the first day of hospitalization. Main Outcomes and Measures: Risk of 30-day all-cause mortality after adjustment for patient comorbidities, vital signs, and laboratory results. Secondary outcomes included the development of kidney injury and secondary infections with Clostridioides difficile, vancomycin-resistant Enterococcus species, or gram-negative bacilli. Results: Among 88 605 hospitalized patients (86 851 men; median age, 70 years [interquartile range, 62-81 years]), empirical anti-MRSA therapy was administered to 33 632 (38%); 8929 patients (10%) died within 30 days. Compared with standard therapy alone, in weighted propensity score analysis, empirical anti-MRSA therapy plus standard therapy was significantly associated with an increased adjusted risk of death (adjusted risk ratio [aRR], 1.4 [95% CI, 1.3-1.5]), kidney injury (aRR, 1.4 [95% CI, 1.3-1.5]), and secondary C difficile infections (aRR, 1.6 [95% CI, 1.3-1.9]), vancomycin-resistant Enterococcus spp infections (aRR, 1.6 [95% CI, 1.0-2.3]), and secondary gram-negative rod infections (aRR, 1.5 [95% CI, 1.2-1.8]). Similar associations between anti-MRSA therapy use and 30-day mortality were found by instrumental variable analysis (aRR, 1.6 [95% CI, 1.4-1.9]) and among patients admitted to the intensive care unit (aRR, 1.3 [95% CI, 1.2-1.5]), those with a high risk for MRSA (aRR, 1.2 [95% CI, 1.1-1.4]), and those with MRSA detected on surveillance testing (aRR, 1.6 [95% CI, 1.3-1.9]). No significant favorable association was found between empirical anti-MRSA therapy and death among patients with MRSA detected on culture (aRR, 1.1 [95% CI, 0.8-1.4]). Conclusions and Relevance: This study suggests that empirical anti-MRSA therapy was not associated with reduced mortality for any group of patients hospitalized for pneumonia. These results contribute to a growing body of evidence that questions the value of empirical use of anti-MRSA therapy using existing risk approaches.

9.
Cell Prolif ; 53(3): e12773, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32020692

RESUMO

OBJECTIVES: SIRT1 is an antioxidative factor, but its mechanism in methamphetamine (MA)-induced lung injury remains unclear. The purpose of this study is to determine whether MA can disrupt the integrity of alveolar epithelial barrier, whether SIRT1 is involved in MA-induced chronic lung injury and whether Resveratrol (Res) can protect the integrity of alveolar epithelial cells by regulating ROS to activate SIRT1/PTEN/p-Akt pathway. MATERIALS AND METHODS: The rats were randomly divided into control group and MA group. Extracted lungs were detected by Western blot, HE staining and immunohistochemistry. The alveolar epithelial cells were treated with MA or/and Res, following by Western blot, LDH leakage assay and flow cytometry. MOE is used for bio-informatics prediction. RESULTS: Chronic exposure to MA can cause slower growth ratio of weight, increased RVI and induced lung injury including the reduced number of alveolar sacs and the thickened alveolar walls. MA-induced apoptosis was associated with SIRT1-related oxidative stress. Res suppressed ROS levels, activated SIRT1, negatively regulated PTEN, phosphorylated Akt, reduced LDH leakage, increased the expression of ZO-1 and E-cadherin and inhibited the apoptosis of alveolar epithelial cells to attenuate MA-induced higher permeability of alveolar epithelium. CONCLUSIONS: MA disrupted the integrity of alveolar epithelial barrier. Res inhibited oxidative stress and reversed MA-induced higher permeability and apoptosis of alveolar epithelium by the activation of SIRT1/PTEN/p-Akt pathway.


Assuntos
Células Epiteliais Alveolares/efeitos dos fármacos , Antioxidantes/uso terapêutico , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico , Metanfetamina/efeitos adversos , Resveratrol/uso terapêutico , Células A549 , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Animais , Apoptose/efeitos dos fármacos , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo
12.
Am J Kidney Dis ; 75(1): 84-104, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31473020

RESUMO

The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) are currently willing to consider a 30% to 40% glomerular filtration rate (GFR) decline as a surrogate end point for kidney failure for clinical trials of kidney disease progression under appropriate conditions. However, these end points may not be practical for early stages of kidney disease. In March 2018, the National Kidney Foundation sponsored a scientific workshop in collaboration with the FDA and EMA to evaluate changes in albuminuria or GFR as candidate surrogate end points. Three parallel efforts were presented: meta-analyses of observational studies (cohorts), meta-analyses of clinical trials, and simulations of trial design. In cohorts, after accounting for measurement error, relationships between change in urinary albumin-creatinine ratio (UACR) or estimated GFR (eGFR) slope and the clinical outcome of kidney disease progression were strong and consistent. In trials, the posterior median R2 of treatment effects on the candidate surrogates with the clinical outcome was 0.47 (95% Bayesian credible interval [BCI], 0.02-0.96) for early change in UACR and 0.72 (95% BCI, 0.05-0.99) when restricted to baseline UACR>30mg/g, and 0.97 (95% BCI, 0.78-1.00) for total eGFR slope at 3 years and 0.96 (95% BCI, 0.63-1.00) for chronic eGFR slope (ie, the slope excluding the first 3 months from baseline, when there might be acute changes in eGFR). The magnitude of the relationships of changes in the candidate surrogates with risk for clinical outcome was consistent across cohorts and trials: a UACR reduction of 30% or eGFR slope reduction by 0.5 to 1.0mL/min/1.73m2 per year were associated with an HR of ∼0.7 for the clinical outcome in cohorts and trials. In simulations, using GFR slope as an end point substantially reduced the required sample size and duration of follow-up compared with the clinical end point when baseline eGFR was high, treatment effects were uniform, and there was no acute effect of the treatment. We conclude that both early change in albuminuria and GFR slope fulfill criteria for surrogacy for use as end points in clinical trials for chronic kidney disease progression under certain conditions, with stronger support for change in GFR than albuminuria. Implementation requires understanding conditions under which each surrogate is likely to perform well and restricting its use to those settings.


Assuntos
Albuminúria/metabolismo , Taxa de Filtração Glomerular , Falência Renal Crônica/metabolismo , Insuficiência Renal Crônica/metabolismo , Teorema de Bayes , Biomarcadores , Creatinina/urina , Progressão da Doença , Aprovação de Drogas , Europa (Continente) , Humanos , Estados Unidos , United States Food and Drug Administration
13.
Biomarkers ; 25(1): 94-99, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31762333

RESUMO

Background: Permethrin is a type of widely used pyrethroid pesticide. Although acute toxicity of permethrin has been well-characterised, the non-acute toxicity of permethrin upon long-term exposure at low dose has been seldom studied yet. The current study investigates the time-course change of the metabolomic profiles of urine following the low level long-term exposure of permethrin and identified biomarkers of the chronic toxicity of permethrin.Methods: Male Wistar rats were administrated orally with permethrin (75 mg/kg body weight/day, 1/20 LD50) daily for consecutive 90 days. The urine samples from day 30, day 60, and day 90 after the first dosing were collected and analysed by 1H NMR spectrometry. Serum biochemical analysis was also carried out.Results: Permethrin caused significant changes in the urine metabolites such as taurine, creatinine, acetate, lactate, dimethylamine, dimethylglycine, and trimethylamine-N-oxide. These biological markers indicated prominent kidney and liver toxicity induced by permethrin. However, there was no change in serum biochemical parameters for the toxicity, indicating that metabolomic approach was much more sensitive in detecting the chronic toxicity.Conclusion: The time-course alteration of metabolomic profiles of the urine based on 1H NMR reflects the progressive development of the chronic toxicity with the long-term low-level exposure of permethrin.

14.
Surg Endosc ; 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823049

RESUMO

OBJECTIVES: Adenocarcinoma of the esophagogastric junction (AEG) is one of the most aggressive and poor prognosis cancers. To date, no standard procedures have been established for the surgical treatment of Siewert type II. In this study, we proposed the approach of thoracoscopic-laparoscopic Ivor-Lewis surgery plus D2 celiac lymphadenectomy (TLILD2) and aimed to investigate the patterns of lymph node metastasis and long-term survival. METHODS: From June 2015 to June 2018, 72 patients accepted TLILD2 and enrolled in this study. Relevant patient characteristics and postoperative variables were collected and evaluated. The disease-free survival (DFS) and disease-specific survival (DSS) were determined by the Kaplan-Meier method and compared by log-rank tests. RESULTS: There was no case of postoperative death in this study, and the most common complication was anastomotic mediastinal fistula (5/72, 6.9%). A total of 2811 lymph nodes were retrieved, and the positivity rate was 11.9% (334/2811). The positivity rate of celiac and mediastinal lymph nodes was 14.4% (314/2186) and 3.2% (20/625), respectively. The percentage of patients who had positive celiac and mediastinal lymph nodes reached up to 58.3% (42/72) and 8.3% (6/72), respectively. The DFS and DSS of these 72 patients were 94% and 93.4% at 1 year after surgery and 59.8% and 62% at 3 years after surgery, respectively. The pTNM stage showed a significant difference between DFS and DSS. CONCLUSIONS: TLILD2 could be a potential way to promote long-term survival of AEG patients. On the basis of the patterns of lymph nodes metastasis, we suggest that lower mediastinal and D2 celiac lymphadenectomy is necessary to improve the oncological outcome.

15.
Surg Endosc ; 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31828499

RESUMO

BACKGROUND: Chylothorax remains a challenging and potentially life-threatening postoperative complication after minimally invasive esophagectomy (MIE). The effect of intraoperative prophylactic thoracic duct ligation on preventing postoperative chylothorax still remains controversial. Moreover, the potential impact of thoracic duct ligation on long-term outcome after MIE has not been well established. METHODS: From September 2009 to July 2018, a total of 600 consecutive patients suffering from thoracic esophageal cancer who underwent thoracoscopic-laparoscopic McKeown esophagectomy in the Department of Thoracic surgery at Daping hospital were eligible. Among them, 559 patients received esophagectomy with preventive thoracic duct ligation and 41 patients did not. Propensity score matching (PSM) was performed to improve comparability between the two groups. Log-rank test was used to assess the survival differences between groups. RESULTS: Postoperative chylothorax occurred in five patients in the preservation group (PG) and in seven patients in the ligation group (LG) (12.2% vs. 1.3%, P = 0.001). The median age of the patients in the preservation group (PG) was 57.78 (range, 37-76) years, while the median age in the ligation group (LG) was 62.75 (range, 39-87) years. The PG had more patients with tumor located in middle thoracic esophagus and stage T3 than LG, 82.9% vs. 55.6%, 70.7% vs. 45.6%, respectively. After PSM (40 matched patients in PG and 134 in LG), there was no significant between-group difference with respect to age, tumor location, and T stage. The median survival times for patients in the PG and LG were 69.5 months (95% interval confidence, CI 54.6-84.3) and 65.2 months (95% CI 56.3-74.1), respectively (P = 0.977). The 5-year survival rates were comparable between PG and LG (54.9% vs. 54.4%, P = 0.977). CONCLUSION: On the basis of the present results, routine thoracic duct ligation during minimally invasive McKeown esophagectomy for cancer is an effective and safe method for prevention of postoperative chylothorax, and does not exert unfavourable effect on long-term survival.

16.
Cancer Med ; 8(18): 7637-7643, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31677253

RESUMO

BACKGROUND: The optimal treatment sequence for patients with advanced BRAF V600 mutant melanoma is unknown. BRAF/MEK inhibition (BRAF/MEKi), single agent anti-PD-1 (aPD-1) antibodies and combination immune checkpoint inhibition with nivolumab and ipilimumab (niv/ipi) are all approved; however, they have not been prospectively compared. Therefore, we sought to compare overall survival of patients with advanced BRAF mutant melanoma treated with either front-line BRAF/MEKi, aPD-1, or niv/ipi. METHODS: Patients with advanced BRAF mutant melanoma who had received BRAF/MEKi, niv/ipi, or aPD-1 in the front-line setting were identified from a nationwide database comprising de-identified patient-level structured and unstructured data derived from electronic health records. Survival was compared using Kaplan-Meier curves and log-rank analysis. Univariate and multivariate Cox regression models were used to measure the effect of front-line treatment, age (>64 or not), LDH (elevated or not), and Eastern Cooperative Oncology Group (ECOG) performance status (>1 or not) on survival. RESULTS: Five hundred and sixty seven patients with advanced disease and treated with front-line aPD-1 (n = 162), BRAF/MEKi (n = 297) or niv/ipi (n = 108) were identified. With a median follow-up of 22.4 months, median overall survival (OS) for patients treated with front-line niv/ipi was not reached (NR) while median OS for patients treated with aPD-1 or BRAF/MEKi was 39.5 months and 13.2 months, respectively. Front-line treatment with PD-1 and niv/ipi were associated with statistically longer survival than BRAF/MEKi in multivariate analyses. CONCLUSIONS: In our real-world retrospective analysis, patients with advanced BRAF mutant melanoma treated with front-line niv/ipi or aPD-1 had longer survival compared to those treated with front-line BRAF/MEKi.

17.
Sci Rep ; 9(1): 16989, 2019 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-31740703

RESUMO

As a major kind of carbamate insecticide, propoxur plays an important role in agriculture, veterinary medicine, and public health. The acute toxicity of propoxur is mainly neurotoxicity due to the inhibition of cholinesterase. However, little is known regarding the toxicity of propoxur upon long-term exposure at low dose. In this study, Wistar rats were orally administrated with low dose (4.25 mg/kg body weight/day) for consecutive 90 days. And the urine samples in rats treated with propoxur for 30, 60, and 90 days were collected and analyzed by employing 1H NMR-based metabolomics approach. We found that propoxur caused significant changes in the urine metabolites, including taurine, creatinine, citrate, succinate, dimethylamine, and trimethylamine-N-oxide. And the alteration of the metabolites was getting more difference compared with that of the control as the exposure time extending. The present study not only indicated that the changed metabolites could be used as biomarkers of propoxur-induced toxicity but also suggested that the time-course alteration of the urine metabolomic profiles could reflect the progressive development of the toxicity following propoxur exposure.

18.
Am J Epidemiol ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31781743

RESUMO

Head and neck cancer (HNC) risk prediction models based on risk factor profiles have not yet been developed. We took advantage of the large database including 14 studies (1981-2010) in the US from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium to develop risk prediction models. Seventy percent of the data were used to develop HNC risk prediction models; the remaining 30% were used to validate the models. We used competing risk models to calculate absolute risks. The predictors included age, sex, education, race/ethnicity, alcohol drinking intensity, cigarette smoking duration and intensity or family history of HNC. The 20-year absolute HNC risk was 7.61% for a 60-year-old woman who smoked >20 cigarettes/day for >20 years, drank 3+ alcoholic drinks/day, was a high school graduate, with family history of HNC and was non-Hispanic White. The 20-year risk for men with a similar profile was 6.85%. The absolute risks of oropharyngeal and hypopharyngeal cancers were generally lower than those of oral cavity and laryngeal cancers. The AUC statistics were 0.70 or higher except for oropharyngeal cancer in men. The HNC risk prediction model may be useful in promoting healthier behaviors such as smoking cessation, or in aiding individuals with family history of HNC to evaluate their risks.

19.
Thorac Cancer ; 10(11): 2071-2080, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31496055

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive and lethal cancers lacking valid prognostic biomarkers. As an essential component of a large ribonucleoprotein complex, U Three Protein 14a (UTP14a) might play important roles in human tumorigenesis. However, the clinical significance and functions of UTP14a in ESCC still remain unclear. METHODS: From September 2009 to August 2015, 210 patients with ESCC of the thoracic esophagus underwent thoracoscopic esophagectomy in our institute. The corresponding 210 tissue samples and 30 cancer-distant mucosa (CDM) samples were tested for UTP14a expression by immunohistochemical staining. The long-term survival was analyzed by the Kaplan-Meier method and Cox proportional hazards regression analyses. CCK8, cell colony formation, cell cycle, apoptosis, cell invasion, and wound healing assays were carried out with ECA109 cells to evaluate the effects of UTP14a on ESCC in vitro. RESULTS: UTP14a was positively expressed in 88.1% (185/210) of the ESCC samples. UTP14a expression in ESCC was significantly higher than in CDM, as further confirmed by Western blot analysis. High expression of UTP14a in ESCC correlated significantly with tumor invasive depth (pT stage), which predicts poor disease-free survival and disease-specific survival, as indicated by the log-rank test and Cox proportional hazards regression analysis. Additionally, our in vitro experiments further demonstrated that knockdown of UTP14a inhibits cell proliferation and invasion in ECA109 cells. CONCLUSIONS: Our results suggest that UTP14a is aberrantly expressed in ESCC, plays a critical role in cancer progression and could be a potential prognosis predictor of ESCC.

20.
J Am Soc Nephrol ; 30(9): 1735-1745, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31292197

RESUMO

BACKGROUND: Surrogate end points are needed to assess whether treatments are effective in the early stages of CKD. GFR decline leads to kidney failure, but regulators have not approved using differences in the change in GFR from the beginning to the end of a randomized, controlled trial as an end point in CKD because it is not clear whether small changes in the GFR slope will translate to clinical benefits. METHODS: To assess the use of GFR slope as a surrogate end point for CKD progression, we performed a meta-analysis of 47 RCTs that tested 12 interventions in 60,620 subjects. We estimated treatment effects on GFR slope (mean difference in GFR slope between the randomized groups), for the total slope starting at baseline, chronic slope starting at 3 months after randomization, and on the clinical end point (doubling of serum creatinine, GFR<15 ml/min per 1.73 m2, or ESKD) for each study. We used Bayesian mixed-effects analyses to describe the association of treatment effects on GFR slope with the clinical end point and to test how well the GFR slope predicts a treatment's effect on the clinical end point. RESULTS: Across all studies, the treatment effect on 3-year total GFR slope (median R 2=0.97; 95% Bayesian credible interval [BCI], 0.78 to 1.00) and on the chronic slope (R 2 0.96; 95% BCI, 0.63 to 1.00) accurately predicted treatment effects on the clinical end point. With a sufficient sample size, a treatment effect of 0.75 ml/min per 1.73 m2/yr or greater on total slope over 3 years or chronic slope predicts a clinical benefit on CKD progress with at least 96% probability. CONCLUSIONS: With large enough sample sizes, GFR slope may be a viable surrogate for clinical end points in CKD RCTs.

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