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1.
Artigo em Inglês | MEDLINE | ID: mdl-33034853

RESUMO

In this study, the heterotrophic nitrification-aerobic denitrification activity of Pseudomonas aeruginosa (P-1) strain was investigated, and the N transformation pathway was revealed. The highest removal rates of NH4+, NO3-, and NO2- (9.29, 6.12, and 3.72 mg L-1 h-1, respectively) by this strain were higher than those by most reported bacteria and were achieved when the carbon source was glucose, C/N ratio was 15, pH was 8, temperature was 30 °C, and shaking speed was 200 rpm. The removal order and characteristics of three N sources were investigated in Pseudomonas aeruginosa for the first time. The results revealed that P-1 preferentially nitrified NH4+ and only began to denitrify NO2- and NO3- when NH4+ was almost entirely depleted. Isotopic labeling of N sources revealed that P-1 uses both partial and complete nitrification/denitrification pathways that can operate either simultaneously or independently, depending on the availability of different types of N compounds, with N2 as the final gaseous product and virtually no NO2- accumulation. Moreover, the P-1 strain could convert various nitrogen compounds under high salinity (40 g L-1) and high concentrations of Cu2+, Zn2+, Cr6+, Pb2+, and Cd2+ (50 mg L-1). Therefore, P-1 could be used as an alternative of inorganic N-removal bacteria in practical applications.

2.
Fertil Steril ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33066977

RESUMO

OBJECTIVE: To explore the relationship between couples' prepregnancy body mass index (BMI) and time to pregnancy (TTP) among those with no prior gravidity. DESIGN: Retrospective cohort study. SETTING: Local maternal/child health care or family-planning service institutions. PATIENT(S): A total of 2,301,782 eligible couples participating in the National Free Preconception Check-up Projects from January 1, 2015 to December 31, 2017. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Time to pregnancy. RESULT(S): Underweight, overweight, or obese status in women and underweight status in men were associated with couples' prolonged TTP. The optimal BMI levels were 20.61-23.06 kg/m2 and 22.69-27.74 kg/m2 for women and men, respectively. Compared with couples in whom both partners had a normal BMI, the pregnancy rates were reduced by 10% (fecundability odds ratio [FOR] 0.90; 95% confidence interval [CI], 0.88-0.92) and 19% (FOR 0.81; 95% CI, 0.78-0.84) for couples in whom both partners were underweight or obese, respectively. The combination of women with a normal BMI and overweight men had the greatest fertility (FOR 1.03; 95% CI, 1.02-1.03), and the combination of obese women and underweight men had the lowest fertility (FOR 0.70; 95% CI, 0.65-0.76). CONCLUSION(S): Abnormal prepregnancy BMIs in either women or men were associated with prolonged TTP among couples with no prior gravidity. Scientific management of couples' prepregnancy BMI could improve their fertility.

3.
BMC Med ; 18(1): 249, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32928217

RESUMO

BACKGROUND: The universal two-child policy in China which was announced in October 2015 might affect the caesarean birth rate. Few studies reported the caesarean birth rate affected by the policy especially after the universal two-child policy period. This study aimed to demonstrate the caesarean birth rate changes before and after the universal two-child policy and further elaborate the underlying influencing factors. METHODS: This nationwide, retrospective, population-based study was based on National Free Pre-Pregnancy Check-ups Project (NFPCP). Couples planning to conceive in next 6 months were encouraged to participate in NFPCP. Baseline information was collected using a standardized questionnaire with a face-to-face interview, and medical examinations were conducted. Two rounds of follow-up interviews were then conducted by trained nurses to update pregnancy status and outcomes. NFPCP participants who completed deliveries before December 31, 2018, were included in the current study. We used marginal effect of year to examine the trend of caesarean birth rate over time and interrupted time series (ITS) analysis to determine impacts of the universal two-child policy on the trend of caesarean birth rate. RESULTS: A total of 9,398,045 participants were included in the final analysis. High-risk factors to increase caesarean birth rate were identified. In the current study, the standardized caesarean birth rate declined from 34.1% in 2013 to 31.8% in 2015 and increased to 35.6% in 2018. ITS analysis showed the caesarean birth rate decreased by 0.1% (95% CI 0.1-0.1) per month before the release of universal two-child policy, 1.3% (95% CI 0.6-2.1%) absolute drop during the policy release month, and increased by 0.2% (95% CI 0.1-0.2%) per month after the policy implementation. For the period after the policy release, the increasing trends were observed in rural participants and urban primiparas. The prevalence of caesarean birth rates within China varied regionally. CONCLUSIONS: The decreasing trend of caesarean birth rate was reported after immediate release of the universal two-child policy. An increasing trend of caesarean birth rate was observed 2-3 years after the policy. It reminds us that the caesarean birth rate control is a long-lasting process and all the strategies need to be continually reinforced.

4.
HERD ; : 1937586720961311, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32990064

RESUMO

AIMS: This research aimed to investigate the major user behavior patterns of noise sources in healthcare environments and summarize such information as evidence that can inform the design of maternity wards for indoor noise control and patients' well-being. METHODS: Field investigations were conducted to identify users' behaviors as the major contributors of noises in the maternity wards of a typical hospital. A control experiment was set to test the feasibility of a noise control system that consisted of smart bracelets, mobile terminals, and monitors. Comparative studies were designed for statistical analysis of patients' sleep quality and satisfaction. Finally, a follow-up interview was conducted among the experts who were from the fields of healthcare environment design, medical treatments, and hospital administration to shed an insight into their concerns on the findings. RESULTS: The enclosed waiting areas, instead of open ones that were often seen in hospitals, around the entrances of operation rooms, were considered as the appropriate design strategy for maternity wards in China. Such a design could keep patients from being exposed to the excessive noises generated by visitors during nighttime, although it would occupy the floor area of wards and lead to a reduction of beds. Moreover, the statistical information of patients' behaviors could be used to moderate visitors' behaviors. CONCLUSIONS: It was necessary to include user behavior information in building information management and then make a good trade-off between the proportions of wards and enclosed waiting rooms in order to achieve a balance of medical efficiency and environmental satisfaction.

5.
Environ Res ; 191: 110137, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32861721

RESUMO

The nitrous oxide (N2O) flux and its possible production pathways from stormwater biofilters in response to moisture content (MC) due to a shift from dry to wet weather was investigated. In this study, we evaluated the changes in the composition of the bacterial community, the relative abundance of functional genes, and N2O emission rate in laboratory-scale stormwater biofilters in response to changes of MC. The results indicated that N2O flux correlated positively with soil MC (r = 0.722 p < 0.01). We observed a higher rates of N2O flux when shifting from dry to wet conditions. Notably, these values decreased substantially within 8-24 h in response to the rapid decline in MC, and then gradually decreased and stabilized at 4.4-12.0 µg/m2·h. The relative abundance of ammonia-oxidizing and denitrifying bacteria, as well as the relative abundance of functional groups associated with denitrification was higher under conditions of low soil MC than those in the high MC. Furthermore, the abundance of bacterial genes norB (r = 0.716 p < 0.01) and hao (r = 0.917 p < 0.01) was associated with higher N2O emission in high MC soils. Studies with the stable isotope (15N) revealed that 15N enrichment in N2O was primarily via denitrification pathways and labeled ammonium ion (15NH4+). Taken together, our results suggested that nitrifier denitrification is the main pathway generating N2O emission in soils with high MC, which may be caused by the high molar ratio of NH3 to total nitrogen in the influent.

7.
Water Sci Technol ; 81(9): 1870-1881, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32666942

RESUMO

The effect of change of hydraulic characteristic and microbial community on pollution removal efficiency of the infiltration systems in the bioclogging development process remain poorly understood. In this study, therefore, the pollutant removal as a response to hydraulic conductivity reduction and the change of diversity and structure of microbial communities in vertical flow constructed wetlands (VFCWs) was investigated. The results indicated that the richness and diversity of the bacterial communities in the columns at different depths were decreased, and the microbial communities of the genus level were changed in the process of bioclogging. However, the variation of microbial communities has a low impact on the purification performance of VFCWs because the abundance of function groups, respiratory activity, and degradation potentiality of microorganisms remain steady or even get improved in the columns after bioclogging. On the contrary, the hydraulic efficiency of VFCWs decreased greatly by 16.9%, 9.9%, and 57.1% for VFCWs filled with zeolite (Column I), gravel (Column II), and ceramsite (Column III), respectively. The existence of short-circuiting and dead zones in the filter media cause the poor pollution removal efficiency of VFCWs due to the short contact time and decrease of oxygenation renewal, as well as low activity in the dead zone.


Assuntos
Microbiota , Áreas Alagadas , Bactérias , Nitrogênio
8.
J Clin Oncol ; 38(24): 2753-2761, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32614698

RESUMO

PURPOSE: Targeted therapies against non-small-cell lung cancer (NSCLC) harboring HER2 mutations remain an unmet need. In this study, we assessed the efficacy and safety of pyrotinib in patients with HER2-mutant advanced NSCLC in a prospective, multicenter, open-label, single-arm, phase II study. PATIENTS AND METHODS: Patients with stage IIIB or IV HER2-mutant lung adenocarcinoma who were previously treated with platinum-based chemotherapy were enrolled to receive pyrotinib at a dose of 400 mg/d for 21-day cycles. The primary end point was objective response rate per independent review committee (IRC). RESULTS: Between October 20, 2016, and December 10, 2018, 60 patients received pyrotinib monotherapy. At baseline, 58 (96.7%) were stage IV, and 25 (41.7%) received at least 2 lines of prior chemotherapy. As of data cutoff on June 20, 2019, IRC-assessed objective response rate was 30.0% (95% CI, 18.8% to 43.2%). All subgroups of patients with different HER2 mutation types showed a favorable objective response rate. The objective response rates were similar between patients with and without brain metastases (25.0% v 31.3%). The median duration of response was 6.9 months (95% CI, 4.9 to 11.1 months). The median progression-free survival was 6.9 months (95% CI, 5.5 to 8.3 months) per IRC. The median overall survival was 14.4 months (95% CI, 12.3 to 21.3 months). Treatment-related adverse events of grade 3 or 4 occurred in 28.3% of patients, with the most common being diarrhea (20.0%; all grade 3). No treatment-related deaths were reported. CONCLUSION: Pyrotinib showed promising antitumor activity and an acceptable safety profile in chemotherapy-treated patients with HER2-mutant NSCLC.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32621338

RESUMO

Here an efficient copper-catalyzed cascade cyclization of azide-ynamides via α-imino copper carbene intermediates is reported, representing the first generation of α-imino copper carbenes from alkynes. This protocol enables the practical and divergent synthesis of an array of polycyclic N-heterocycles in generally good to excellent yields with broad substrate scope and excellent diastereoselectivities. Moreover, an asymmetric azide-ynamide cyclization has been achieved with high enantioselectivities (up to 98:2 e.r.) by employing BOX-Cu complexes as chiral catalysts. Thus, this protocol constitutes the first example of an asymmetric azide-alkyne cyclization. The proposed mechanistic rationale for this cascade cyclization is further supported by theoretical calculations.

10.
Lancet Respir Med ; 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32479794

RESUMO

BACKGROUND: We evaluated the efficacy and safety of tepotinib, a potent and highly selective oral MET inhibitor, plus gefitinib in patients with epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) with MET overexpression (immunohistochemistry [IHC]2+ or IHC3+) or MET amplification having acquired resistance to EGFR inhibition. METHODS: In this open-label, phase 1b/2, multicentre, randomised trial (the INSIGHT study), we enrolled adult patients (≥18 years) with advanced or metastatic NSCLC, and Eastern Cooperative Oncology Group performance status of 0 or 1, from academic medical centres and community clinics in six Asian countries. In phase 1b, patients received oral tepotinib 300 mg or 500 mg plus gefitinib 250 mg once daily. In phase 2, patients with EGFR-mutant, T790M-negative NSCLC MET overexpression or MET amplification were randomly assigned (initially in a 1:1 ratio and then 2:1 following a protocol amendment) to tepotinib plus gefitinib at the recommended phase 2 dose or to standard platinum doublet chemotherapy. Randomisation was done centrally via an interactive voice-response system. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety. Subgroup analyses were preplanned in patients with high MET overexpression (IHC3+) or MET amplification (mean gene copy number ≥5 or MET to centromere of chromosome 7 ratio ≥2). Efficacy and patient characteristics were assessed on an intention-to-treat basis and safety was assessed for all patients who received at least one dose of study medication. Low recruitment led to early termination of phase 2, so all analyses are considered to be exploratory. This study is registered with ClinicalTrials.gov, NCT01982955, and the European Union Drug Regulating Authorities Clinical Trials Database, Eudra-CT 2016-001604-28. FINDINGS: From Dec 23, 2013, to May 25, 2017, 18 patients were enrolled in phase 1b (n=6 in the 300 mg tepotinib group; n=12 in the 500 mg tepotinib group) and 55 patients in phase 2 (n=31 in the tepotinib plus gefitinib group; n=24 in the chemotherapy group). No dose-limiting toxicities were observed in phase 1b, so tepotinib 500 mg was used as the recommended phase 2 dose. In phase 2, survival outcomes were similar between groups: median PFS was 4·9 months in the tepotinib plus gefitinib group (90% CI 3·9-6·9) versus 4·4 months in the chemotherapy group (90% CI 4·2-6·8; hazard ratio [HR] 0·67, 90% CI 0·35-1·28). Median OS was 17·3 months in the tepotinib plus gefitinib group (12·1-37·3) versus 18·7 months in the chemotherapy group (15·9-20·7; HR 0·69, 0·34-1·41). PFS and OS were longer with tepotinib plus gefitinib than with chemotherapy in patients with high (IHC3+) MET overexpression (n=34; median PFS 8·3 months [4·1-16·6] vs 4·4 months [4·1-6·8]; HR 0·35, 0·17-0·74; median OS 37·3 months [90% CI 24·2-37·3] vs 17·9 months [12·0-20·7]; HR 0·33, 0·14-0·76) or MET amplification (n=19; median PFS 16·6 months [8·3-not estimable] vs 4·2 months [1·4-7·0]; HR 0·13, 0·04-0·43; median OS 37·3 months [90% CI not estimable] vs 13·1 months [3·25-not estimable]; HR 0·08, 0·01-0·51). The most frequent treatment-related grade 3 or worse adverse events were increased amylase (5 [16%] of 31 patients) and lipase (4 [13%]) concentrations in the tepotinib plus gefitinib group and anaemia (7 [30%] of 23 patients) and decreased neutrophil count (3 [13%]) in the chemotherapy group. INTERPRETATION: Despite early study termination, in a preplanned subgroup analysis, our findings suggest improved anti activity for tepotinib plus gefitinib compared with standard chemotherapy in patients with EGFR-mutant NSCLC and MET amplification, warranting further exploration. FUNDING: Merck KGaA.

11.
Environ Int ; 142: 105851, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32585501

RESUMO

BACKGROUND: Little is known about the effect of ambient temperature on preterm birth, especially for the trimester-specific effects. OBJECTIVE: To evaluate whether exposure to relatively low or high temperature during pregnancy is associated with increasing risk of preterm birth or not. METHOD: We analysed the data of a birth cohort with 1,281,859 singleton pregnancies during 2013-2014 and matched the home address of each pregnant women to the model based daily meteorological and air pollution data. Then we used the Cox proportional hazard regression models with random effect to estimate the non-linear associations between exposure to relatively low or high temperature at each trimester of pregnancy and the risk of preterm birth, after controlling for air pollution and individual-level covariates. FINDING: The overall preterm birth rate was 8.1% (104,493 preterm births). Exposure to relatively low or high temperatures during the entire pregnancy significantly increase the risk of preterm birth, with hazard ratios (HRs) [95% confidence intervals (CIs)] of 1.03 (95%CI: 1.02, 1.04) for relatively low (9.1 ℃, the 5th percentile) temperature and 1.55 (95%CI: 1.48, 1.61) for relatively high (23.0 ℃, the 95th percentile) temperature in comparison with the thresholds (12.0 ℃). Pregnant women at the early pregnancy (the 1st and 2nd trimester) are more susceptible to high temperatures while pregnant women at the late pregnancy (the 3rd trimester) are more susceptible to low temperatures. CONCLUSION: These findings provide new evidence that exposure to relatively low or high temperatures during pregnancy increases the risk of preterm birth, which can serve as scientific evidence for prevention of preterm birth.

12.
Lung Cancer ; 146: 252-262, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32592986

RESUMO

OBJECTIVES: Fruquintinib is an orally active kinase inhibitor that selectively targets the vascular endothelial growth factor (VEGF) receptor. A Phase II trial has demonstrated a significant benefit in progression-free survival (PFS) for fruquintinib-treated patients with locally advanced/metastatic nonsquamous non-small-cell lung cancer (NSCLC) who have progressed after second-line chemotherapy. This Phase III trial is a randomized, double-blind, multicenter trial to confirm fruquintinib's efficacy in the same patient population. MATERIALS AND METHODS: From December 2015 to February 2018, 730 patients were screened, of whom 527 were enrolled into the study. Participants were randomized 2:1 to receive fruquintinib (n = 354) or placebo (n = 173) once daily for 3 weeks on-treatment, and 1 week off-treatment. Patients were stratified according to epidermal growth factor receptor mutation status and prior use of VEGF inhibitors. Primary endpoint was overall survival (OS). RESULTS: Median OS was 8.9 months for the fruquintinib group and 10.4 months for placebo group (hazard ratio [HR] 1.02; 95 % confidence interval [CI], 0.82-1.28; P = 0.841), with median PFS of 3.7 months and 1.0 months, respectively (HR 0.34; 95 % CI, 0.28-0.43; P < 0.001). Objective response rate and disease control rate were 13.8 % and 66.7 % for fruquintinib, and 0.6 % and 24.9 % for placebo, respectively (P < 0.001). Hypertension was the most frequent treatment-emergent adverse event (≥grade 3) observed in fruquintinib-treated patients (21.0 %). Post hoc analysis revealed that fruquintinib prolonged the median OS for patients who did not receive subsequent antitumor therapy: 7.0 months versus 5.1 months for placebo (HR 0.65; 95 % CI, 0.46-0.91; P = 0.012). Patients receiving fruquintinib also reported improvements in quality of life for most functional scales measured by EORTC QLQ-C30 and LC13 questionnaires. CONCLUSION: Although the study did not meet its primary endpoint, fruquintinib could be effective in combination with other agents for the treatment of patients with NSCLC who have failed second-line chemotherapy.

13.
Int J Biol Macromol ; 160: 531-537, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32479935

RESUMO

Self-assembly behavior of charged-starches significantly influenced core-shell structures of layer-by-layer assembled particles. In this study, insulin (IN)-loaded nanoparticles with structured shell features were fabricated to investigate how the interactions of carboxymethyl starch (CMS) with spermine-modified starch (SS) influenced IN release properties of the particles (IN/CMS/SS/CMS) within the gastrointestinal tract (GIT). Results indicated that the assembly action of CMS and SS could be controlled by simply tailoring the ratio of CMS/SS content. An intermediate CMS/SS ratio (1:4) was required to construct nanoparticles with compact shell structure and desirable IN release properties in the colon (74.23%). However, a higher CMS/SS ratio (1:2) yielded particles with loose shell structure and an excessive IN release in the upper GIT (58.89%), and a lower CMS/SS ratio (1:8) rather resulted in particles with higher compactness shell structure along with limited IN release in the colon (29.01%). The interactions between CMS and SS should be the key factor influencing core-shell structures and in turn the IN-release properties of the carrier. The shell structure and release properties of layer-by-layer assembled particles could be tailored by controlling the interactions between starches.

15.
Food Chem ; 328: 127113, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32474239

RESUMO

In view of the high polarity and ubiquitous occurrence of perchlorate, achieving an ultra-trace analysis has become a challenging task. The present study aimed to develop a simple and generic pretreatment protocol based on cold-induced liquid-liquid extraction to efficiently extract perchlorate from tea and dairy products and remarkably decrease potential matrix interferences and laborious cleanup. By optimizing the pretreatment conditions, the enrichment factor of perchlorate increased by 7.79 times under the compromise between the matrix effect and extraction recovery. The validated method presented satisfactory selectivity, linearity, accuracy, precision, and matrix effect, providing recoveries of 78.2%-106.2% with RSDr ranging from 1.2% to 7.9% and RSDR less than 10.7% for tea and dairy products. This pretreatment protocol depended only on shaking, freezing, and centrifugation in one step, without additional equipment or tedious operations, which will be explored to a greater extent in complex biological or food matrices.


Assuntos
Laticínios/análise , Análise de Alimentos/métodos , Contaminação de Alimentos/análise , Extração Líquido-Líquido/métodos , Percloratos/análise , Chá/química , Centrifugação/métodos , Análise Custo-Benefício , Análise de Alimentos/economia , Congelamento , Extração Líquido-Líquido/economia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fatores de Tempo
16.
Food Chem ; 329: 127159, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32497845

RESUMO

The widespread use of neonicotinoids (NEOs) and fipronils (FIPs) as insecticides in modern agriculture has been widely investigated because of their adverse effects on human health. This study aimed to develop an accurate quantitative approach to analyze NEOs and FIPs in tea by using a modified QuEChERS method based on dispersive solid-phase extraction procedure coupled with liquid chromatography-high resolution mass spectrometry. To minimize matrix interferences largely, we selected polyvinylpolypyrrolidone (PVPP) and strong cationic exchange adsorbent (PCX) as dispersive adsorbents to eliminate polyphenols and caffeine from tea extract, respectively. Under optimal conditions, a slight matrix effect was observed for NEOs and FIPs due to the highest reductions of polyphenols and caffeine (94% and 88%, respectively). The method was validated by the European Medicines Agency and Eurachem guidelines and was successfully applied to tea samples for NEOs and FIPs analysis. NEOs and FIPs were commonly detected in tea.


Assuntos
Contaminação de Alimentos/análise , Neonicotinoides/análise , Pirazóis/análise , Chá/química , Cafeína/química , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Análise de Alimentos/métodos , Inseticidas/análise , Polifenóis/química , Reprodutibilidade dos Testes , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos
17.
Transl Oncol ; 13(8): 100784, 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32428850

RESUMO

OBJECTIVE: This study investigated the feasibility of using malignant pleural effusion (MPE) supernatant and paired cell blocks (precipitate) for gene profiling in patients with non-small cell lung cancer (NSCLC) using next-generation sequencing (NGS) technique. METHODS: Stage IV non-squamous NSCLC patients with MPE were eligible in this prospective study and recruited from Zhejiang Cancer Hospital between May 2014 and October 2015. MPE supernatant and paired precipitate sample gene alterations were determined with NGS containing 14 cancer-related genes. Progression free survival (PFS) was evaluated using Kaplan-Meier method and compared using log-rank test. RESULTS: A total of 102 patients were enrolled in the present study. All pleural effusions were confirmed as malignant with cytological smears. A total of 77 paired MPE supernatant and precipitate samples were acquired from the 102 patients. The results revealed that there were no statistically significant differences in the detection rate and maximum allelic fraction between supernatant and precipitate samples (P = 1.0 and P = .6). Collectively, 172 and 158 genomic alterations with 112 shared mutations were identified in supernatant and precipitate samples, respectively. Comparable PFS was found in EGFR mutation patients according to the supernatant and precipitate sample results (14.0 vs.13.9 months, P = .90). CONCLUSIONS: These results demonstrated that MPE supernatants were comparable to precipitate samples for detection of genetic alterations. However, gene mutation heterogeneity was found between these two media types.

18.
J Pharm Biomed Anal ; 187: 113350, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32403061

RESUMO

Pholidota chinensis Lindl. is commonly used as functional tea or folk medicine in China, but few studies have been conducted on its phenolic composition and bioactivities. This study was aimed to investigate the phenolic profiles of P. chinensis extracts by different solvents (petroleum ether, ethyl acetate, n-butanol and water) and their in vitro antioxidant, antidiabetic, and anti-inflammatory activities. The results showed that a total of 42 phenolic compounds were accurately identified, 30 of them were further quantified in P. chinensis extracts by UPLC-MS/MS. Among four extracts, ethyl acetate extract not only had the highest contents of total phenolics and 21 individual phenolic compounds, but also possessed the strongest antioxidant (DPPH, 1.43 mmol AAE/g; ABTS, 5.38 mmol TE/g; FRAP, 2.58 mmol FSHE/g), α-glucosidase inhibition (13.29 mmol ACAE/g) and anti-inflammation (IC50 = 18.71 µg/ml) activities. Also, the antioxidant, antidiabetic, and anti-inflammatory activities were significantly correlated with total phenolics and individual phenolic compounds. Orientin and vitexin can be considered as the potential quality markers of P. chinensis. This study will provide a comprehensive phenolic profile of P. chinensis and relates them to their antioxidant, antidiabetic, and anti-inflammatory activities.

19.
Lancet Oncol ; 21(6): 832-842, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32416073

RESUMO

BACKGROUND: Patients with advanced or metastatic oesophageal squamous cell carcinoma have poor prognosis and few treatment options after first-line therapy. We aimed to assess efficacy and safety of the anti-PD-1 antibody camrelizumab versus investigator's choice of chemotherapy in previously treated patients. METHODS: ESCORT is a randomised, open-label, phase 3 study of patients aged 18 to 75 years with a histological or cytological diagnosis of advanced or metastatic oesophageal squamous cell carcinoma done at 43 hospitals in China. Eligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and had progressed on, or were intolerant to, first-line standard therapy. Patients were randomly assigned (1:1) to camrelizumab (200 mg every 2 weeks) or chemotherapy with docetaxel (75 mg/m2 every 3 weeks) or irinotecan (180 mg/m2 every 2 weeks), all given intravenously. Central randomisation was done using the Randomization and Trial Supply Management system with block size randomly generated as four or six and stratified by disease and ECOG performance status. The primary endpoint was overall survival, assessed in randomised patients who had received at least one dose of treatment. Safety was assessed in all treated patients. The trial is registered with ClinicalTrials.gov, NCT03099382, and is closed to new participants. FINDINGS: From May 10, 2017, to July 24, 2018, 457 (75%) of 607 screened patients were randomly assigned to treatment, of whom 228 received camrelizumab treatment and 220 received chemotherapy. As of data cutoff on May 6, 2019, with a median follow-up time of 8·3 months (IQR 4·1-12·8) in the camrelizumab group and 6·2 months (3·6-10·1) in the chemotherapy group, median overall survival was 8·3 months (95% CI 6·8-9·7) in the camrelizumab group and 6·2 months (5·7-6·9) in the chemotherapy group (hazard ratio 0·71 [95% CI 0·57-0·87]; two-sided p=0·0010). The most common treatment-related adverse events of grade 3 or worse were anaemia (camrelizumab vs chemotherapy: six [3%] vs 11 [5%]), abnormal hepatic function (four [2%] vs one [<1%]), and diarrhoea (three [1%] vs nine [4%]). Serious treatment-related adverse events occurred in 37 (16%) of 228 patients in the camrelizumab group, and in 32 (15%) of 220 patients in the chemotherapy group. Ten treatment-related deaths occurred, seven (3%) in the camrelizumab group (three deaths from unknown causes, one enterocolitis, one hepatic function abnormal, one pneumonitis, and one myocarditis) and three (1%) in the chemotherapy group (two deaths from unknown causes, and one gastrointestinal haemorrhage). INTERPRETATION: Second-line camrelizumab significantly improved overall survival in patients with advanced or metastatic oesophageal squamous cell carcinoma compared with chemotherapy, with a manageable safety profile. It might represent a potential option of standard second-line treatment for patients with oesophageal squamous cell carcinoma in China. FUNDING: Jiangsu Hengrui Medicine.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel/administração & dosagem , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Irinotecano/administração & dosagem , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , China , Progressão da Doença , Docetaxel/efeitos adversos , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/imunologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/secundário , Feminino , Humanos , Irinotecano/efeitos adversos , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Intervalo Livre de Progressão , Transdução de Sinais , Fatores de Tempo , Adulto Jovem
20.
Appl Microbiol Biotechnol ; 104(14): 6149-6159, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32436033

RESUMO

Brasiliamides are a class of piperazine-containing alkaloids produced by Penicillium brasilianum with a range of pharmaceutical activities. The mechanism of brasiliamide biosynthesis, including piperazine ring formation and multiple tailoring modifications, still remains unclear. In this study, the biosynthetic gene cluster of brasiliamides, brs, was identified from the marine-derived fungal strain Penicillium brasilianum WZXY-M122-9. Deletion of a histone deacetylase-encoding gene using a CRISPR/Cas9 gene editing system led to the production of a new compound, namely brasiliamide I (1). The brs-encoded single-module nonribosomal peptide synthetase (NRPS) BrsA is involved in the formation of the piperazine skeleton of brasiliamides. Full-length BrsA protein (113.6 kDa) was purified, and reconstitution of enzymatic activity in vitro confirmed that BrsA stereoselectively accepts L-phenylalanine as the substrate. Multiple deletion of tailoring genes and analysis of purified proteins in vitro enabled us to propose a brasiliamide biosynthetic pathway. In the tailoring steps, an α-ketoglutarate (KG)-dependent nonheme iron dioxygenase, BrsJ, was identified to catalyze piperazine ring cleavage during biosynthesis of brasiliamide A (2). KEY POINTS: The gene cluster encoding brasiliamide biosynthesis, brs, is identified. Deletion of a histone deacetylase-encoding gene produces brasiliamide I. BrsA catalyzes brasiliamide piperazine skeleton formation. BrsJ catalyzes piperazine ring cleavage to produce brasiliamide A. Graphical abstract.

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