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1.
Hepatol Int ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33821401

RESUMO

BACKGROUND: Microvascular invasion (MVI) is a risk factor for postoperative survival outcomes for hepatocellular carcinoma (HCC) after liver resection (LR). This study aims to investigate the actual long-term survival and its associated prognostic factors after LR for HCC patients with MVI. METHODS: This study was conducted on HCC patients with MVI who underwent LR from January 2009 to December 2012 at five major hospitals in China. The patients were divided into the 'long-term survivor group' and the 'short-term survivor group'. The clinicopathologic characteristics, perioperative data and survival outcomes were compared between these two groups. Univariate and multivariate regression analyses were performed to identify predictive factors associated with long-term survival outcomes. RESULTS: The study included 1517 patients with an actual 5-year survival rate of 33.3%. Multivariate regression analysis revealed that HBV DNA > 104 IU/mL, alanine aminotransferase > 44 U/L, alpha-fetoprotein > 400 ng/ml, anatomical hepatectomy, varices, intraoperative blood loss > 400 ml, tumor diameter > 5 cm, tumor number, satellite nodules, tumor encapsulation, wide resection margin and adjuvant transarterial chemoembolization (TACE) were independent prognostic factors associated with actual long-term survival. CONCLUSIONS: One-third of HCC patients with MVI reached the long-term survival milestone of 5 years after resection. Anatomical hepatectomy, controlling intraoperative blood loss, a wide resection margin, and postoperative adjuvant TACE should be considered for patients to achieve better long-term survival outcomes.

2.
Org Lett ; 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33797266

RESUMO

We report a promoter-assisted glycosidation approach for the stereoselective synthesis of the 6-deoxy-ß-d-manno-heptopyranose oligosaccharides. SphosAuNTf2-promoted glycosidation of 6-deoxy-d-manno-heptopyranosyl o-hexynylbenzoate with common alcohols afforded a range of 6-deoxy-d-manno-heptosides with good to excellent ß-selectivities. The counterion and the ligand of SPhosAuNTf2 were found to have a dramatic effect on the formation of the 1,2-cis-ß-linked 6-deoxy-d-manno-heptosides. This approach was effectively applied to the stereocontrolled synthesis of the 6-deoxy-ß-d-manno-heptopyranose oligosaccharides relevant to Burkholderia pseudomallei and Burkholderia mallei.

3.
Anal Chim Acta ; 1157: 338394, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33832585

RESUMO

Dopamine (DA) is a critical biomarker for a variety of neurological diseases. Methods for simple and rapid DA detection are crucial for clinical diagnosis and treatments for those diseases. In this work, we developed a novel pretreatment-free method for dopamine detection using carbon dots as a turn-on fluorescent probe synthesized in situ. The aminosilane-functionalized carbon dots (SiCDs) were produced in a mild condensation reaction between N-[3-(Trimethoxysilyl)propyl]ethylenediamine (AEATMS) and dopamine, which were directly used for probing of dopamine. The prepared SiCDs exhibited green fluorescence with excitation/emission maximum at 380/495 nm, the intensity of which can be measured to quantify the DA present in the reaction mixture. The linear range of the assay was between 0.1 and 100 µM with a limit of detection (LOD) of 56.2 nM. The probe is of good selectivity and the recoveries of the developed method were in the range of 101.77-119.91% with RSDs within 3.67% in human serum sample tests. The SiCDs were also synthesized within MN9D cells under 37 °C and generated bright fluorescence, which can probe the DA's distribution in the cells. The described method exhibit potential in DA detection and live-cell imaging for its feature of facility, inexpensiveness, and sensitivity.

4.
Microbes Infect ; : 104813, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33798714

RESUMO

Respiratory tract coinfections, specifically involving influenza A virus (IAV) and Streptococcus pneumoniae (S. pneumoniae), remain a major health problem worldwide. Secondary bacterial pneumonia is a common complication and an important cause of mortality related to seasonal and pandemic influenza infections. Vaccination is a basic control strategy against influenza and S. pneumoniae. The fusion protein DnaJ-ΔA146Ply is a vaccine candidate which can induce immune responses against pneumococcal infections via mucosal and subcutaneous immunization in mice. In the present study, we established a co-infection model using mouse-adapted laboratory strains of IAV (PR8) and S. pneumoniae (19F) in mice intranasally and subcutaneously immunized with DnaJ-ΔA146Ply. Our results showed that vaccinated mice suffered decreased weight loss compared with control mice. The survival rates were higher in intranasally and subcutaneously immunized mice than in control mice. In addition, the bacterial loads in nasal washes and lung homogenates were lower in vaccinated mice than in control mice. Furthermore, lung damage was alleviated in vaccinated mice compared with control mice, with less broken alveoli and less proinflammatory cytokine production. Taken together, these results indicate that vaccination with DnaJ-ΔA146Ply shows protective potential against influenza and S. pneumoniae co-infection in mice.

5.
J Pharm Pharmacol ; 73(1): 60-69, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33791810

RESUMO

OBJECTIVES: To explore the in vivo anti-obesity effect of chikusetsusaponin V and explore the underlying mechanism by transcriptomic and metabonomic methods. METHODS: The physiological parameters of high-fat-diet induced obese mice administered with or without 25 mg/kg and 100 mg/kg of chikusetsusaponin V by gavage for 16 weeks were recorded. In addition, the RNA-sequencing and UHPLC-Q-TOF techniques were applied to obtain the transcriptomic and metabolomic profiling, respectively. KEY FINDINGS: Chikusetsusaponin V could significantly alleviate the high-fat-diet induced increase in the weight of the whole body and obesity-related organs or tissues, and ameliorate the lipid content in the blood, the lipid accumulation in the livers, as well as the hypertrophy of the fat tissues. Importantly, transcriptomic results revealed that more than 30 genes involved in the pathway which closely associates with obesity, were significantly altered. Moreover, metabolomic data indicated the key differential metabolites enriched in the pathways such as the activated protein kinase signaling pathway which is a vital mediator of obesity and other processes. CONCLUSIONS: The integrative analysis highlighted that chikusetsusaponin V significantly influenced the activated protein kinase signaling pathway at both transcriptomic and metabolomic levels, thereby exerting anti-obesity effects.

6.
Curr Microbiol ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33792761

RESUMO

A Gram-stain-negative, aerobic, non-motile, white-pigmented, short rod-shaped, and alginate-degrading bacterium, designated B1Z28T, was isolated from the gut of the abalone Haliotis rubra obtained at Weihai, China. Strain B1Z28T was found to grow at 4-35 °C, pH 6.5-9.0, and in the presence of 0.5-8.0% (w/v) NaCl. Cells were positive for oxidase and catalase activity. The 16S rRNA-based phylogenetic analysis revealed that the nearest phylogenetic neighbors of strain B1Z28T were Tritonibacter scottomollicae MCCC 1A06440T (98.1%), Ruegeria faecimaris KCTC 23044T (98.0%), and Ruegeria meonggei KCTC 32450T (97.8%). Based on phylogenomic analysis, the average nucleotide identity (ANI) values between strain B1Z28T and the neighbor strains were 71.6, 77.2, and 78.1%, respectively; the digital DNA-DNA hybridization (dDDH) values based on the draft genomes between strain B1Z28T and its closest neighbors were 20.5, 20.8, and 21.6%, respectively. Ubiquinone-10 (Q-10) was detected as the predominant respiratory quinone. The dominant cellular fatty acids were Summed feature 8 (contained C18:1 ω7c and/or C18:1 ω6c). The polar lipids included phosphatidylethanolamine (PE), diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phospholipid (PL), aminolipid (AL), and three unidentified lipids. Based on the phylogenetic and phenotypic characteristics, strain B1Z28T is considered to represent a novel species of the genus Ruegeria, for which the name Ruegeria haliotis sp. nov. is proposed. The type strain is B1Z28T (= KCTC 72686T = MCCC 1H00393T).

7.
Chem Commun (Camb) ; 57(28): 3508-3511, 2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33690772

RESUMO

A novel mitochondria-targeting molecular rotator FD was designed to visualize changes in viscosity under hypoxic conditions in vitro and in vivo. Importantly, FD can be used to detect changes in the blood viscosity of liver cancer and liver cirrhosis patients, and also rehabilitation of liver disease.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33740125

RESUMO

BACKGROUND: Rationale exists for combining immune checkpoint inhibitors and PARP inhibitors (PARPi), and results of clinical trials in ovarian cancer are promising, but data in other cancers are limited. METHOD: Efficacy and safety of PARPi/anti-PD-1 in advanced solid tumors were retrospectively analyzed. The efficacy measures included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). RESULTS: This retrospective study included data from 40 patients. The ORR was 27.5% (95% CI, 13.0-42.0%), with a DCR of 85.0% (95% CI, 73.4-96.6%). Except four patients in first-line treatment (three with PR and one with SD), the ORR of ≥second-line treatment, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) was 22.2%, 23.1% and 28.6%, and the DCR was 83.3%, 84.6% and 71.4%, separately. The median PFS of all patients, ≥second-line treatment, NSCLC and SCLC was 4.6 m, 4.2 m, 4.5 m and 3.7 m. The median OS was 9.4 m, 11.4 m, 12.7 m and 5.4 m, respectively. Multivariable analysis revealed that BRCA1/2 mutation was positively correlated with ORR (P = 0.008), and LDH≥250U/L was negatively correlated with lowered DCR (P = 0.018), while lymphocyte number, ECOG and LDH significantly influenced both PFS and OS. We found that the possible resistant mechanisms were sarcomatous degeneration and secondary mutation, including BRCA2 truncation mutation, A2M, JAK1,T790M, KEAP1 and mTOR mutation. 37.5% patients had ≥grade 3 adverse events. CONCLUSION: PARPi/anti-PD-1 is an effective and tolerable method for patients with advanced solid tumors, and BRCA1/2 is a potential biomarker.

9.
Spectrochim Acta A Mol Biomol Spectrosc ; 254: 119628, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-33706115

RESUMO

A glutathione stabilized Au nanoclusters (GSH-Au NCs) was synthesized here and used to selective detection of cobalt ion. The as-prepared GSH-Au NCs had strong green light emission around 500 nm, and the features of the NCs have been systematically characterized by UV-vis absorption, X-ray photoelectronic spectroscopic, Fourier transform infrared spectroscopy and transmission electron microscope characterization. The interactions between the GSH-Au NCs and metal ions was studied, and the results indicated that the fluorescence of the GSH-Au NCs could be quenched in the presence of Co2+ ion at pH of 6.0. The quenching ratio was linear with the concentration of Co2+ ions, and the calibration curve was I0/I = 0.1187cco + 0.6085 in the Co2+ concentration ranges from 2.0 to 50.0 µM with correlation coefficient (R2) of 0.9950 and the limit of detection (LOD, 3σ) of 0.124 µM. In addition, we collected environmental water samples to test the reliability of the method and demonstrated this method is simple, rapid, and selective.

10.
Nano Lett ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33710893

RESUMO

Electrocatalytic CO2 reduction reaction is regarded as an intriguing route for producing renewable chemicals and fuels, but its development is limited by the lack of highly efficient and stable electrocatalysts. Herein, we propose the pipet-like bismuth (Bi) nanorods semifilled in nitrogen-doped carbon nanotubes (Bi-NRs@NCNTs) for highly selective electrocatalytic CO2 reduction. Benefited from the prominent capillary and confinement effects, the Bi-NRs@NCNTs act as nanoscale conveyors that can significantly facilitate the mass transport, adsorption,and concentration of reactants onto the active sites, realizing rapid reaction kinetics and low cathodic polarization. The spatial encapsulation and separation by the NCNT shells prevents the self-aggregation and surface oxidation of Bi-NRs, increasing the dispersity and stability of the electrocatalyst. As a result, the Bi-NRs@NCNTs exhibit high activity and durable catalytic stability for CO2-to-formate conversion over a wide potential range. The Faradaic efficiency for formate production reaches 90.9% at a moderate applied potential of -0.9 V vs reversible hydrogen electrode (RHE).

11.
ACS Appl Mater Interfaces ; 13(9): 11195-11204, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33645961

RESUMO

Metal-organic frameworks (MOFs), especially those made by biological molecules (bio-MOFs), have been proved to be prospective candidates for biomedical applications. However, a simple and universal bio-MOF to load different substances for precise targeting is still lacking. In this work, we propose a facile one-pot method to prepare a peptide-doped bio-MOF for general encapsulation and targeted delivery. This bio-MOF is constructed by 9-fluorenylmethyloxycarbonyl-modified histidine (Fmoc-His) as a bridging linker that coordinates with Zn2+ ions, denoted as ZFH. The Fmoc-His-Asp-Gly-Arg peptide (Fmoc-HDGR) can be easily doped into the ZFH structure with different ratios to modulate the targeting ability of ZFH-DGR. Containing both hydrophobic Fmoc and hydrophilic His moieties, this framework is compatible with encapsulating various types of payloads, including hydrophobic chemotherapeutic, hydrophilic protein, and positively/negatively charged inorganic nanoparticles. It has also been proved to be highly biocompatible and stable in circulation, exhibit the capabilities to target ανß3 integrin overexpressed on tumor cells, and trigger drug release in a low pH microenvironment at the tumor site. As a proof of concept, Doxorubicin (Dox)-loaded ZFH-DGR (ZFH-DGR/Dox) demonstrated high cell selectivity between liver hepatocellular carcinoma (HepG2) cells and normal liver (L02) cells, which express high and low ανß3 integrin, respectively. This selectivity endows ZFH-DGR/Dox precise treatment and low toxicity in Heps-bearing liver cancer mice. This work develops a de novo approach to construct a peptide-doped bio-MOF system for universal load, precise delivery, and peptide drug combination therapy in the future.

12.
J Neuroinflammation ; 18(1): 80, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33757547

RESUMO

BACKGROUND: Increasing evidence suggests a causal link between periodontitis and cognitive disorders. Systemic inflammation initiated by periodontitis may mediate the development of cognitive impairment. Our study aims to investigate the effect of ligature-induced periodontitis on cognitive function and the role of signal transducers and activators of transcription 3 (STAT3) in this process. MATERIALS AND METHODS: Ligature-induced periodontitis was established, and the rats were treated intraperitoneally with/without the pSTAT3 inhibitor cryptotanshinone (CTS). Alveolar bone resorption and periodontal inflammation were detected by micro-computed tomography analysis and histopathological evaluation. Locomotor activity and cognitive function were evaluated by the open field test and the Morris water maze test, respectively. The activation of microglia and astrocytes in the hippocampus and cortex was assessed by immunohistochemistry (IHC). The expression of interleukins (IL-1ß, IL-6, IL-8, IL-21) in both the periphery and cortex was evaluated by RT-PCR and ELISA. The expression of TLR/NF-κB and ROS cascades was evaluated by RT-PCR. The expression of pSTAT3 and the activation of the STAT3 signaling pathway (JAK2, STAT3, and pSTAT3) in the periodontal tissue and cortex were assessed by IHC and Western blot. The expression of amyloid precursor protein (APP) and its key secretases was evaluated by RT-PCR. The level of amyloid ß-protein (Aß) and the ratio of Aß1-40/1-42 were measured via ELISA in the plasma and cortex while IHC was used to detect the level of Aß1-42 in the brain. RESULTS: In periodontal ligature rats, significant alveolar bone resorption and local inflammatory cell infiltration were present. Apparent increases in inflammatory cytokines (IL-1ß, IL-6, IL-8, and IL-21) were detected in peripherial blood and brain. Additionally, spatial learning and memory ability was impaired, while locomotor activity was not affected. Activated microglia and astrocytes were found in the cortex and hippocampus, presenting as enlarged cell bodies and irregular protrusions. Levels of TLR/NF-kB, PPAR and ROS were altered. The STAT3 signaling pathway was activated in both the periodontal tissue and cortex, and the processing of APP by ß- and γ-secretases was promoted. The changes mentioned above could be relieved by the pSTAT3 inhibitor CTS. CONCLUSIONS: Ligature-induced periodontitis in rats resulted in systemic inflammation and further abnormal APP processing, leading to cognitive impairments. In this progress, the activation of the STAT3 signaling pathway may play an important role by increasing inflammatory load and promoting neuroinflammation.

13.
Micromachines (Basel) ; 12(2)2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33672210

RESUMO

Thermophoresis of charged colloids in aqueous media has wide applications in biology. Most existing studies of thermophoresis focused on spherical particles, but biological compounds are usually non-spherical. The present paper reports a numerical analysis of the thermophoresis of a charged spheroidal colloid in aqueous media. The model accounts for the strongly coupled temperature field, the flow field, the electric potential field, and the ion concentration field. Numerical simulations revealed that prolate spheroids move faster than spherical particles, and oblate spheroids move slower than spherical particles. For the arbitrary electric double layer (EDL) thickness, the thermodiffusion coefficient of prolate (oblate) spheroids increases (decreases) with the increasing particle's dimension ratio between the major and minor semiaxes. For the extremely thin EDL case, the hydrodynamic effect is significant, and the thermodiffusion coefficient for prolate (oblate) spheroids converges to a fixed value with the increasing particle's dimension ratio. For the extremely thick EDL case, the particle curvature's effect also becomes important, and the increasing (decreasing) rate of thermodiffusion coefficient for prolate (oblate) spheroids is reduced slightly.

14.
Cancer Biol Med ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33710815

RESUMO

OBJECTIVE: This phase 3 study aimed to test equivalence in efficacy and safety for QL1101, a bevacizumab analogue in Chinese patients with untreated locally advanced non-squamous non-small cell lung cancer (NSCLC). METHODS: Eligible patients were randomly assigned 1:1 to receive carboplatin and paclitaxel in combination with either QL1101 or bevacizumab, 15 mg/kg every 3-week for 6 cycles. This was followed by maintenance treatment with single agent QL1101 every 3-week. The primary end-point was objective response rate (ORR), with secondary end-points being progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events (AEs). RESULTS: Of 675 patients, 535 eligible patients were randomized to the QL1101 group (n = 269) and bevacizumab group (n = 266). ORRs were 52.8% and 56.8%, respectively, for the QL1101 and bevacizumab groups, with an ORR hazard ratio 0.93 (95% confidence interval: 0.8-0131.1). The PFS, OS, DCR, and AEs were comparable between the 2 groups, which remained the same after stratification according to epidermal growth factor receptor mutation or smoking history. CONCLUSIONS: QL1101 showed similar efficacy and safety profiles as compared to bevacizumab among Chinese patients with untreated locally advanced non-squamous NSCLC.

15.
J Nucl Cardiol ; 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33751472

RESUMO

BACKGROUND: A low appropriate therapy rate indicates that a minority of patients will benefit from their implantable cardioverter defibrillator (ICD). Quantitative measurements from 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) may predict ventricular arrhythmia (VA) occurrence after ICD placement. METHODS: We performed a prospective observational study and recruited patients who required ICD placement. Pre-procedure image scans were performed. Patients were followed up for VA occurrence. Associations between image results and VA were analyzed. RESULTS: In 51 patients (33 males, 53.9 ± 17.2 years) analyzed, 17 (33.3%) developed VA. Compared with patients without VA, patients with VA had significantly larger values in scar area (17.7 ± 12.4% vs. 7.0 ± 7.9%), phase standard deviation (51.4° ± 14.0° vs. 34.0° ± 15.0°), bandwidth (172.9° ± 39.8° vs. 128.7° ± 49.9°), sum thickening score (STS, 29.5 ± 11.1 vs. 17.8 ± 13.2), and sum motion score (42.9 ± 11.5 vs. 33.0 ± 19.0). Cox regression analysis and receiver operating characteristic curve analysis showed that scar size, dyssynchrony, and STS were associated with VA occurrence (HR, 4.956, 95% CI 1.70-14.46). CONCLUSION: Larger left ventricular scar burden, increased dyssynchrony, and higher STS quantified by 18F-FDG PET may indicate a higher VA incidence after ICD placement.

16.
Molecules ; 26(3)2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33573149

RESUMO

The precise operation of molecular motion for constructing complicated mechanically interlocked molecules has received considerable attention and is still an energetic field of supramolecular chemistry. Herein, we reported the construction of two tris[2]pseudorotaxanes metallacycles with acid-base controllable molecular motion through self-sorting strategy and host-guest interaction. Firstly, two hexagonal Pt(II) metallacycles M1 and M2 decorated with different host-guest recognition sites have been constructed via coordination-driven self-assembly strategy. The binding of metallacycles M1 and M2 with dibenzo-24-crown-8 (DB24C8) to form tris[2]pseudorotaxanes complexes TPRM1 and TPRM2 have been investigated. Furthermore, by taking advantage of the strong binding affinity between the protonated metallacycle M2 and DB24C8, the addition of trifluoroacetic acid (TFA) as a stimulus successfully induces an acid-activated motion switching of DB24C8 between the discrete metallacycles M1 and M2. This research not only affords a highly efficient way to construct stimuli-responsive smart supramolecular systems but also offers prospects for precisely control multicomponent cooperative motion.


Assuntos
Compostos Organoplatínicos/química , Platina/química , Rotaxanos/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Éteres de Coroa/química , Estrutura Molecular , Compostos Organoplatínicos/síntese química , Polímeros/síntese química , Polímeros/química , Rotaxanos/síntese química , Ácido Trifluoracético/química
17.
Medicine (Baltimore) ; 100(7): e24737, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607818

RESUMO

ABSTRACT: Early hematoma expansion of hypertensive cerebral hemorrhage is affected by various factors. This study aimed to clarify the risk factors and develop a nomogram to predict early hematoma expansion.A retrospective analysis was carried out in patients with hypertensive cerebral hemorrhage admitted to our institution between January 1, 2012 and December 31, 2018; the patients were divided into 2 groups according to the presence of early hematoma expansion. Univariate and multivariate analyses were performed to analyze the risk factors of hematoma expansion. The nomogram was developed based on a multivariate logistic regression model, and the discriminative ability of the model was analyzed.A total of 477 patients with hypertensive cerebral hemorrhage and with a baseline hematoma volume <30 ml were included in our retrospective analysis. The hematoma expansion rate was 34.2% (163/477). After multivariate logistic regression, 9 variables (alcohol history, Glasgow coma scale score, total serum calcium, blood glucose, international normalized ratio, hematoma shape, hematoma density, volume of hematoma on initial computed tomography scan, and presence of intraventricular hemorrhage) identified as independent predictors of hematoma expansion were used to generate the nomogram. The area under the receiver operating characteristic curve of the nomogram was 0.883 (95% confidence interval 0.851-0.914), and the cutoff score was -0.19 with sensitivity of 75.5% and specificity of 87.3%.The nomogram can accurately predict the risk of early hematoma expansion.


Assuntos
Hematoma/etiologia , Hemorragia Intracraniana Hipertensiva/complicações , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Estudos de Casos e Controles , Hemorragia Cerebral/complicações , Progressão da Doença , Feminino , Escala de Coma de Glasgow , Hematoma/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Nomogramas , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodos
18.
Helicobacter ; 26(2): e12784, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33534148

RESUMO

BACKGROUND: The efficacy and safety of reverse hybrid therapy in the treatment of Helicobacter pylori (H. pylori) infection remained unclear. MATERIALS AND METHODS: This systematic review was performed in accordance with the PRISMA 2009 guidelines. A systematic search of the Pubmed, Embase, and Cochrane database was conducted using the combination of "Helicobacter pylori or H. pylori or Hp" and "hybrid". The primary endpoint of this meta-analysis was to evaluate the efficacy of reverse hybrid therapy; the second endpoint was to evaluate the efficacy of reverse hybrid therapy among the strains with antibiotic resistance and the compliance, safety of reverse hybrid therapy. RESULTS: Four studies with 1530 participants were included. The crude H. pylori eradication rate of reverse hybrid therapy was 95.5% (737/772) and 96.2% (701/729) by ITT and PP analysis, respectively. There is no statistical significance of efficacy between reverse hybrid therapy and control according to ITT (pooled rate: 96% vs. 94%, RR = 1.02, 95% CI, 0.95-1.05, p = .28) and PP (pooled rate: 96% vs. 94%, RR = 1.02, 95% CI, 0.99-1.06, p = .23) analysis. The effect of reverse hybrid therapy in strains with isolated clarithromycin resistance (pooled rate: 89% vs. 65%, RR = 1.13, 95% CI, 0.77-1.66, p = .53), metronidazole resistance (pooled rate: 91% vs. 81%, RR = 1.00, 95% CI, 0.96-1.05, p = .85), and dual clarithromycin-metronidazole resistance (pooled rate: 86% vs. 83%, RR = 0.94, 95% CI, 0.69-1.27, p = .69) showed no superior to that of control. The compliance of reverse hybrid therapy is 96%, and side effect is slightly lower to that of control group. CONCLUSION: Reverse hybrid therapy shows good efficacy, safety, and compliance in the treatment of H. pylori infection. However, its application for H. pylori treatment in regions with high antibiotic resistance need to be further explored.

19.
J Thorac Oncol ; 2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33588113

RESUMO

INTRODUCTION: By implementing dynamic circulating tumor DNA (ctDNA) analysis, we explored the impact of TP53 mutations on tumor evolution and resistance mechanisms to ensartinib in patients with ALK-positive NSCLC. METHODS: In a multicenter phase 2 trial, patients with ALK-positive NSCLC who progressed on crizotinib were treated with ensartinib. Blood samples for ctDNA analysis were collected at baseline, cycle 3 day 1, and progression disease (PD) and analyzed with a 212-gene panel. RESULTS: A total of 440 samples were collected from 168 patients. Baseline TP53 mutations (20.2%) significantly correlated with inferior progression-free survival (4.2 mo versus 11.7 mo, p < 0.0001). Patients with TP53 mutations had higher mutation load than those without TP53 mutations at baseline (13.79 ± 3.72 versus 4.67 ± 0.39, p < 0.001). Although there was no significant difference in mutation load between these groups at cycle 3 day 1 (5.89 ± 2.25 versus 3.72 ± 0.62, p = 0.425), patients with mutated TP53 developed more mutations at PD (7.07 ± 1.25 versus 3.20 ± 0.33, p = 0.003). Frequency and abundance of secondary ALK mutations G1269A, G1202R, and E1210K increased markedly at PD than baseline. In patients without secondary ALK mutations, we identified ALK-independent resistance mechanisms including bypass signaling activation, downstream effector protein reactivation, epithelial-mesenchymal transformation, and epigenetic dysregulation. CONCLUSIONS: Our study highlighted the advantage of ctDNA analysis for monitoring tumor evolution. TP53 mutations promoted genetic evolution and accelerated occurrence of resistance. We also unveiled ALK-dependent resistance mechanisms, mainly by G1269A, G1202R, and E1210K mutations, and ALK-independent resistance mechanisms to ensartinib.

20.
Chem Commun (Camb) ; 57(24): 3038-3041, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33624637

RESUMO

The DNAzyme activity of G-quadruplex/hemin in mitochondria has not been characterized. Herein, we report an unexpected difference in the DNAzyme activity between in vitro assays and in mitochondria. Molecular dynamic simulations illustrate how the interaction of the G-quadruplex with hemin may modulate the DNAzyme activity. These results might facilitate a better understanding of the catalytic mechanism of the DNAzyme and help the rational design of stable and active DNAzymes suitable for intracellular catalysis.

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