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1.
Infect Dis Ther ; 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34241831

RESUMO

BACKGROUND: No clinical study has investigated the use of ceftazidime-avibactam combination schemes with an in vitro non-susceptible antimicrobial that could be superior to ceftazidime-avibactam monotherapy against carbapenem-resistant Klebsiella pneumoniae. METHODS: We performed a retrospective cohort study at two tertiary hospitals in China for patients with carbapenem-resistant Klebsiella pneumoniae infection treated with ceftazidime-avibactam for at least 72 h. A Cox proportional hazards regression model was used to evaluate covariates that potentially affected 30-day mortality. RESULTS: Sixty-two patients were eligible for our study; 41 (66.1%) received ceftazidime-avibactam combination therapy and 21 (33.9%) received ceftazidime-avibactam monotherapy. The overall 30-day mortality was 33.9% (21 patients): 24.4% (10/41) and 47.6% (11/21), P = 0.028, in combination and monotherapy groups, respectively. Combination therapy was significantly associated with lower 30-day mortality (Hazard ratio, 0.167; 95% Confidence Interval, 0.060-0.465, P = 0.001). At the same time, a higher APACHE II score, use of vasoactive drugs and comorbidity of organ transplantation were considered factors that increased mortality. The propensity score showed no significant alterations with other variables after adding it to the final model. In the subgroup analysis, the protective effect was revealed when combined with carbapenems, tigecycline or fosfomycin were applied, and in the following subgroups of patients: with sepsis, with creatinine clearance > 50 mL/min, stayed in the intensive care unit ≤ 30 days or underwent mechanical ventilation. CONCLUSIONS: Ceftazidime-avibactam combined with another in vitro non-susceptible antimicrobial, especially carbapenems, fosfomycin and tigecycline, could significantly decrease the 30-day mortality rate for critically ill patients with carbapenem-resistant Klebsiella pneumoniae infection. Further investigation should be carried out to confirm this conclusion and identify autofit antimicrobials in ceftazidime-avibactam combination schemes.

2.
Chem Commun (Camb) ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34254065

RESUMO

A novel nanozyme comprised of graphene encapsuled Ru nanocrystals (Ru@G) with effective and stable peroxidase-like activity prepared using a chemical vapor deposition (CVD) method was used for the detection of glutathione at near-physiological pH.

3.
Am J Transplant ; 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34212503

RESUMO

Organ transplantation has become a mainstay of therapy for patients with end-stage organ diseases. However, long-term administration of immunosuppressive agents, a scheme for improving the survival of transplant recipients, has been compromised by severe side effects and posttransplant complications. Therapeutic delivery targeting immune organs has the potential to address these unmet medical issues. Here, through screening of a small panel of mammalian target of rapamycin complex kinase inhibitor (TORKinib) compounds, a TORKinib PP242 is identified to be able to inhibit T cell function. Further chemical derivatization of PP242 using polyunsaturated fatty acids (i.e., docosahexaenoic acid) transforms this water-insoluble hydrophobic agent into a self-assembling nanoparticle (DHA-PP242 nanoparticle [DPNP]). Surface PEGylation of DPNP with amphiphilic copolymers renders the nanoparticles aqueously soluble for preclinical studies. Systemically administered DPNP shows tropism for macrophages within peripheral immune organs. Furthermore, DPNP regulates differentiation of adoptively transferred T cells in a macrophage-dependent manner in Rag1-/- mouse model. In an experimental model of heart transplantation, DPNP significantly extends the survival of grafts through inducing immune suppression, thus reducing the inflammatory response of the recipients. These findings suggest that targeted delivery of TORKinibs exploiting prodrug-assembled nanoparticle scaffolds may provide a therapeutic option against organ rejection.

4.
J Clin Neurosci ; 90: 171-177, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34275545

RESUMO

Cervical and thoracic or lumbar intramedullary spinal cavernous malformations (ISCMs) may behave differently. We conducted this retrospective study by using data from adult ISCMs to compare their natural histories and explore prognostic factors for improved clinical outcomes. Neurological functions were assessed by using the Modified McCormick Scale (MMCS) and Aminoff-Logue Disability Scale. A total of 111 study-eligible adult patients were included in this study. Patients with cervical ISCMs mostly demonstrated a shorter duration of symptoms (P = 0.026), an acute onset pattern with some recovery (P = 0.026), and a larger lesion size (P = 0.033) than their thoracic or lumbar counterparts. Thoracic or lumbar lesions had a higher proportion of motor symptoms (P = 0.001) and sphincter problems (P = 0.005), and they were usually associated with an aggressive clinical course (P = 0.001, OR = 9.491, 95% CI = 2.555-35.262) in multivariate analysis. There was no difference in age, sex distribution, hemorrhage risk between the cervical and thoracic-lumbar groups. A better preoperative neurological status (P = 0.034, OR = 2.768, 95% CI = 1.081-7.177) and improvement immediately after surgery (P < 0.001, OR = 8.756, 95% CI = 4.837-72.731) were identified as indicators for long-term improvement by multivariate analysis. Cervical lesions had a high proportion for long-term improvement, but it was not a predictor for improvement in multivariate analysis. ISCMs in the thoracic or lumbar location should be considered for surgical removal more aggressively than those in the cervical location. Surgical removal of symptomatic ISCMs can avoid further neurological deterioration and usually result in satisfactory long-term outcomes.

5.
BMC Genomics ; 22(1): 521, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34238252

RESUMO

BACKGROUND: Chinese sprangletop [Leptochloa chinensis (L.) Nees] is an annual malignant weed, which can often be found in paddy fields. Cyhalofop-butyl is a specialized herbicide which is utilized to control L. chinensis. However, in many areas, L. chinensis has become tolerant to this key herbicide due to its continuous long-term use. RESULTS: In this study, we utilized a tolerant (LC18002) and a sensitive (LC17041) L. chinensis populations previously identified in our laboratory, which were divided into four different groups. We then employed whole transcriptome analysis to identify candidate genes which may be involved in cyhalofop-butyl tolerance. This analysis resulted in the identification of six possible candidate genes, including three cytochrome P450 genes and three ATP-binding cassette transporter genes. We then carried out a phylogenetic analysis to identify homologs of the differentially expressed cytochrome P450 genes. This phylogenetic analysis indicated that all genes have close homologs in other species, some of which have been implicated in non-target site resistance (NTSR). CONCLUSIONS: This study is the first to use whole transcriptome analysis to identify herbicide non-target resistance genes in L. chinensis. The differentially expressed genes represent promising targets for better understanding herbicide tolerance in L. chinensis. The six genes belonging to classes already associated in herbicide tolerance may play important roles in the metabolic resistance of L. chinensis to cyhalofop-butyl, although the exact mechanisms require further study.


Assuntos
Acetil-CoA Carboxilase , Herbicidas , Acetil-CoA Carboxilase/genética , Butanos , China , Perfilação da Expressão Gênica , Resistência a Herbicidas/genética , Herbicidas/toxicidade , Nitrilas , Filogenia , Proteínas de Plantas/genética
6.
Genes Genomics ; 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: covidwho-1296973

RESUMO

BACKGROUND: COVID-19, as a novel coronavirus disease caused by new coronavirus SARS-CoV-2, spreads all over the world, and brings harm to human in many countries. Humans suffered a lot from both SARS-CoV-2 now and by SARS-CoV in the year 2003. It is important to understand the differences and the relationships between these two types of viruses. OBJECTIVE: To compare relative synonymous codon usage of ORF1ab gene in SARS-CoV-2 and SARS-CoV, relative synonymous codon usage of their genomes are studied in this paper from the bioinformatics perspective. METHODS: The ORF1ab gene, which is an important non-structural polyprotein coding gene and now used for nucleic acid detection markers in many measurement method, in both SARS-CoV-2 (30 strains) and SARS-CoV (20 strains) are considered to be the research object in the present paper. The relative synonymous codon usage values of the ORF1ab gene are calculated to characterize the differences and the evolutionary characteristics among 50 strains. RESULTS: There is a significant difference between SARS-CoV and SARS-CoV-2 when the relative synonymous codon usage value of ORF1ab genes is concerned. The results suggest that codon usage pattern of SARS-CoV is more similar to human than that of the SARS-CoV-2, and that the inner difference in SARS-CoV-2 strains is larger than that of SARS-CoV, which denote the larger diversity exits in the SARS-CoV-2 virus. CONCLUSION: These results show that the relative synonymous codon usage values in the coronavirus could be used for further research on their evolutionary phenomenon.

7.
ACS Synth Biol ; 10(7): 1775-1784, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34213891

RESUMO

Malate is an essential intermediate in the tricarboxylic acid (TCA) cycle; it also has valuable uses in medicine and food. The production of malate with a microbial synthesis method is still in its early stages. One of the key problems in metabolic engineering is that the dynamic and subtle changes in malate are difficult to detect. It remains critical to develop techniques with direct and precise detection of malate in microbial metabolism, which facilitates high-throughput screening of the engineered strains. In this study, a genetically encoded biosensor in response to malate was constructed in B. licheniformis. Key regulator MalR and the action site of the biosensor were first identified. Then, the output of the reporter gene expression was amplified by introducing a strong constitutive promoter and iteratively tuning the action sites. The engineered biosensor can respond to malate from 5 to 15 g/L; within this range, it shows a linear correlation between eGFP fluorescence and malate concentration. This biosensor enrich our toolbox of synthetic biology in pathway engineering for malate production in microorganisms.

8.
Int J Nanomedicine ; 16: 4351-4369, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234430

RESUMO

Purpose: Multifunctional nanoparticles with targeted therapeutic function and diagnostic-imaging are of great interest in the domain of precision therapy. NIR laser responsive nanoparticles (PLGA-PEG-FA encapsulating Bi2S3, PFP, and Dox (designed as FBPD NPs)) are synthesized for ovarian cancer targeted combination therapy with CT/PA dual-modal imaging guidance (PA: photoacoustic; CT: X-ray computed tomography). Methods and Results: The FBPD NPS prepared by the double emulsification method revealed excellent dispersity, great stability, outstanding optical properties. The temperature of FBPD NPs increased rapidly after laser irradiation, inducing liquid-to-gas conversion of perfluoropentane (PFP), and promoting the release of Dox up to 86.7%. These FBPD NPs demonstrated their outstanding imaging capability for both PA and CT imaging both in vitro and in vivo, providing the potential for therapeutic guidance and monitoring. Assisted by folic acid, these nanoparticles could highly enrich in ovarian tumor tissue and the accumulation peaked at 3 h after intravenous administration. The desirable photothermal-conversion efficiency of the nanoparticles combined with chemotherapy achieved highly efficient therapy, which was demonstrated both in vitro and in vivo. Conclusion: We successfully constructed multifunctional theranostic FBPD NPs for highly efficient PTT/chemotherapy combined therapy with dual CT/PA imaging guidance/monitoring. The unique nanoparticles with multiple abilities pave an emerging way toward precise treatment of ovarian cancer.


Assuntos
Raios Infravermelhos , Lasers , Nanopartículas/uso terapêutico , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/terapia , Técnicas Fotoacústicas , Tomografia Computadorizada por Raios X , Animais , Terapia Combinada , Feminino , Ácido Fólico/química , Humanos , Nanopartículas/química , Poliésteres/química , Polietilenoglicóis/química
9.
Front Public Health ; 9: 665282, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249837

RESUMO

Introduction: Gatekeeping mechanism of primary care institutions (PCIs) is essential in promoting tiered healthcare delivery system in China. However, patients seeking for higher-level institutions instead of gatekeepers as their first contact has persisted in the past decade. This study aims to explain patients' choice and willingness and to provide potential solutions. Methods: A survey was conducted among residents who had received medical care within the previous 14 days. Patients' choice and willingness of PCIs for first contact together with influencing factors were analyzed using binary logistic regression. Results: Of 728 sampled patients in Hubei, 55.22% chose PCIs for first contact. Patients who are older, less educated, with lower family income, not living near non-PCIs, with better self-perceived health status, only buying medicines, and living in rural instead of urban area had significantly higher probability of choosing PCIs. As of willingness, over 90% of the patients inclined to have the same choice for their first contact under similar health conditions. Service capability was the primary reason limiting patients' choice of PCIs. Conclusions: The gatekeeper system did not achieve its goal which was 70% of PCIs among all kinds of institutions for first contact. Future measures should aim to improve gate-keepers' capability.

10.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207153

RESUMO

Aerobic denitrification is considered as a promising biological method to eliminate the nitrate contaminants in waterbodies. However, the molecular mechanism of this process varies in different functional bacteria. In this study, the nitrogen removal characteristics for a newly isolated aerobic denitrifier Bacillus subtilis JD-014 were investigated, and the potential functional genes involved in the aerobic denitrification process were further screened through transcriptome analysis. JD-014 exhibited efficient denitrification performance when having sodium succinate as the carbon source with the range of nitrate concentration between 50 and 300 mg/L. Following the transcriptome data, most of the up-regulated differentially expressed genes (DEGs) were associated with cell motility, carbohydrate metabolism, and energy metabolism. Moreover, gene nirsir annotated as sulfite reductase was screened out and further identified as a regulator participating in the nitrogen removal process within JD-014. The findings in present study provide meaningful information in terms of a comprehensive understanding of genetic regulation of nitrogen metabolism, especially for Bacillus strains.


Assuntos
Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Regulação Bacteriana da Expressão Gênica , Nitrogênio/metabolismo , Carbono/metabolismo , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Regulação Enzimológica da Expressão Gênica , Ontologia Genética , Nitratos/metabolismo , Nitrificação , Reprodutibilidade dos Testes
11.
Mol Cell Endocrinol ; 535: 111378, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34216644

RESUMO

PURPOSE: We previously found the mutation frequency of cytoskeleton-associated protein 2 (CKAP2) was significantly increased in proliferative diabetic retinopathy (PDR) patients through whole exome sequencing. The present study was conducted to explore the expression and possible mechanism of CKAP2 in PDR patients and human retinal capillary endothelial cells (HRCECs) under high-glucose (HG) conditions. METHODS: Expression of CKAP2 and p53 in the vitreous fluid and fibrovascular membrane (FVM) of PDR patients and HRCECs under HG conditions was observed. Cell proliferation, migration and tubule formation were assessed. Ranibizumab and siRNA transfection were used in the inhibition assay. RESULTS: CKAP2 and p53 were significantly increased in the ocular tissues of PDR patients. HG combined with VEGF treatment significantly up-regulated expression of CKAP2 and p53 in HRCECs. Inhibition of CKAP2 attenuated the abilities of cell proliferation, migration and tube formation under HG conditions. Blocking VEGF or p53 significantly decreased CKAP2 expression, whereas inhibition of CKAP2 failed to alter the level of VEGF or p53. CONCLUSIONS: CKAP2 is involved in the pathogenesis of PDR and regulated by VEGF and p53 under HG conditions.

12.
J Struct Biol ; 213(3): 107767, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34214602

RESUMO

The enzymes exopolyphosphatase/guanosine pentaphosphate phosphohydrolase (PPX/GppA) play important roles in the bacterial stringent response. PPX degrades inorganic polyphosphate (polyP), a polymer composed of a few to hundreds of phosphate residues supporting cell survival in the stationary phase. The crystal structure of PPX from Porphyromonas gingivalis (PgPPX) in complex with catalytic magnesium ions and several sulfate ions was solved. PgPPX contained two domains and represented a "closed" configuration. Four sulfate ions forming a linear dispersed chain were observed in the aqueduct of the PPX dimer, which the long polyP chain most likely occupied. The side chain of R255 stretched into the cavity where polyP could be located, obstructing the entrance of larger substrates such as NTP and NDP. This study provided the first view into the structure of the PPX/GppA homolog in complex with magnesium ions and substrate analogs and explained how PgPPX implemented its functionality.

13.
Water Res ; 202: 117373, 2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34243051

RESUMO

Biochemical oxidation and reduction are the principle of biological water and wastewater treatment, in which electron donor and/or acceptor shall be provided. Elemental sulfur (S0) as a non-toxic and easily available material with low price, possesses both reductive and oxidative characteristics, suggesting that it is a suitable material for water and wastewater treatment. Recent advanced understanding of S0-respiring microorganisms and their metabolism further stimulated the development of S0-based technologies. As such, S0-based biotechnologies have emerged as cost-effective and attractive alternatives to conventional biological methods for water and wastewater treatment. For instance, S0-driven autotrophic denitrification substantially lower the operational cost for nitrogen removal from water and wastewater, compared to the conventional process with exogenous carbon source supplementation. The introduction of S0 can also avoid secondary pollution commonly caused by overdose of organic carbon. S0 reduction processes cost-effectively mineralize organic matter with low sludge production. Biological sulfide production using S0 as electron acceptor is also an attractive technology for metal-laden wastewater treatment, e.g. acid mine drainage. This paper outlines an overview of the fundamentals, characteristics and advances of the S0-based biotechnologies and highlights the functional S0-related microorganisms. In particular, the mechanisms of microorganisms accessing insoluble S0 and feasibility to improve S0 bio-utilization efficiency are critically discussed. Additionally, the research knowledge gaps, current process limitations, and required further developments are identified and discussed.

14.
Ecotoxicol Environ Saf ; 222: 112487, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34252681

RESUMO

The residual behaviors and dietary risk probability of 12 pesticides in Dendrobium officinale Kimura et Migo cultivated at two representative locations under green house conditions were investigated using liquid chromatography-tandem mass spectrometry. Field trials showed that the half-lives of 12 pesticides ranged from 0.9 to 14.4 days in fresh D. officinale stems. Based on maximum residue levels (MRLs), the ultimate residues of imidacloprid, dimethomorph, metalaxyl, tebuconazole, and cyazofamid at a pre-harvest interval (PHI) of 28 days were within acceptable limits. For abamectin, indoxacarb, and difenoconazole, 35-day PHIs were needed. The PHIs of trifloxystrobin and fluopyram were 42 days, the time required for their residues to be reduced to an MRL of 4 mg/kg. The chronic and acute risk quotients of target pesticides at PHIs of 28-42 days were below 5.929% and 0.532%, respectively, showing that the evaluated D. officinale exhibited an acceptably low dietary risk to the general population.

15.
J Colloid Interface Sci ; 604: 650-659, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34280763

RESUMO

Developing an efficient bifunctional catalyst for Hydrogen Evolution Reaction (HER) and Oxygen Evolution Reaction (OER) in water splitting technology is very attractive for clean energy. Here, a new Co-Fe-B ternary catalyst with improved crystallinity is successfully synthesized by combining the chemical reduction and subsequent solid-state reaction method. Synchrotron-based X-ray absorption near-edge structure (XANES) and X-ray photoelectron spectroscopy (XPS) indicate the electronic structure redistribution is favor for the improved performance. The overpotential is only 129 mV and 280 mV for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in alkaline condition, the corresponding Tafel slope is 67.3 mV dec-1 and 38.9 mV dec-1. Density functional theory calculations distinguish that the ternary crystalline Co-Fe-B catalysts are thermodynamically favorable for HER and OER. The actual active species of the ternary catalyst in OER is the CoOOH and FeOOH as indicated in ex situ Raman spectra. The present work may introduce promising crystallinity borides material for the anode and cathode of water splitting device.

16.
Sci Transl Med ; 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285130

RESUMO

Multiple safe and effective vaccines that elicit immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are necessary to respond to the ongoing coronavirus disease 2019 (COVID-19) pandemic. Here, we developed a protein subunit vaccine comprised of spike ectodomain protein (StriFK) plus a nitrogen bisphosphonate-modified zinc-aluminum hybrid adjuvant (FH002C). StriFK-FH002C generated substantially higher neutralizing antibody titers in mice, hamsters, and cynomolgus monkeys than those observed in plasma isolated from COVID-19 convalescent individuals. StriFK-FH002C also induced both Th1- and Th2-polarized helper T cell responses in mice. In hamsters, StriFK-FH002C immunization protected animals against SARS-CoV-2 challenge, as shown by absence of virus-induced weight loss, fewer symptoms of disease, and reduced lung pathology. Vaccination of hamsters with StriFK-FH002C also reduced within-cage virus transmission to unvaccinated, cohoused hamsters. In summary, StriFK-FH002C represents an effective, protein subunit-based SARS-CoV-2 vaccine candidate.

17.
Genes Genomics ; 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34228320

RESUMO

BACKGROUND: COVID-19, as a novel coronavirus disease caused by new coronavirus SARS-CoV-2, spreads all over the world, and brings harm to human in many countries. Humans suffered a lot from both SARS-CoV-2 now and by SARS-CoV in the year 2003. It is important to understand the differences and the relationships between these two types of viruses. OBJECTIVE: To compare relative synonymous codon usage of ORF1ab gene in SARS-CoV-2 and SARS-CoV, relative synonymous codon usage of their genomes are studied in this paper from the bioinformatics perspective. METHODS: The ORF1ab gene, which is an important non-structural polyprotein coding gene and now used for nucleic acid detection markers in many measurement method, in both SARS-CoV-2 (30 strains) and SARS-CoV (20 strains) are considered to be the research object in the present paper. The relative synonymous codon usage values of the ORF1ab gene are calculated to characterize the differences and the evolutionary characteristics among 50 strains. RESULTS: There is a significant difference between SARS-CoV and SARS-CoV-2 when the relative synonymous codon usage value of ORF1ab genes is concerned. The results suggest that codon usage pattern of SARS-CoV is more similar to human than that of the SARS-CoV-2, and that the inner difference in SARS-CoV-2 strains is larger than that of SARS-CoV, which denote the larger diversity exits in the SARS-CoV-2 virus. CONCLUSION: These results show that the relative synonymous codon usage values in the coronavirus could be used for further research on their evolutionary phenomenon.

18.
Clin Lung Cancer ; 2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34247986

RESUMO

BACKGROUND: Several studies have suggested that patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) might benefit from the use of tyrosine kinase inhibitors (TKIs) in combination with antiangiogenic agents. This study aimed to comprehensively review the available evidence regarding the efficacy and safety of first-line TKI plus antiangiogenic agents versus TKIs alone in EGFR-mutated advanced NSCLC. MATERIALS AND METHODS: A literature search was performed using PubMed to identify studies published up to Feb. 2020. Abstracts from major international conferences reported over the last 5 years were searched. The primary outcome was progression-free survival (PFS), and the secondary outcomes included overall survival (OS), the objective response rate (ORR), and toxicity. RESULTS: In total, 7 relevant trials comprising 1612 patients were identified. TKIs plus antiangiogenic agents led to significant improvements in PFS regardless of the EGFR mutation subtype and presence of brain metastasis. In particular, in the subgroup with the L858R mutation, the hazard ratio (HR) of PFS was 0.58 (95% confidence interval [CI], 0.48-0.71, P < .001). The OS following combined treatment was similar to that following TKI monotherapy. The ORR was increased with the use of TKIs plus antiangiogenic agents (HR 1.10, 95% CI, 1.01-1.20, P = .029). In the safety analyses, TKIs plus antiangiogenic agents exhibited a significantly increased incidence of adverse events of grade 3 or higher. CONCLUSION: The use of TKIs plus antiangiogenic agents is associated with significantly improved PFS and ORR compared with TKIs alone in untreated EGFR-mutated NSCLC. The toxicities of combination therapy should be considered when making treatment choices.

19.
World Neurosurg ; 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34224885

RESUMO

OBJECTIVE: In spinal surgery, considerable blood loss is increasingly treated with local application of TXA. However, little is known about the cytotoxicity and effect on human fibroblasts. This study was to identify the effect of TXA solutions on human fibroblast at different concentrations and exposure times in vitro. METHODS: To mimic the actual clinical situation, human fibroblast was subjected to both limited and chronic exposure to various clinically relevant concentrations of TXA to mimic different ways of topical administration. At timepoint after treatment, the viability, proliferation, apoptosis, collagen synthesis, adhesion and migration of fibroblasts were analyzed in vitro. RESULTS: The limited exposure (10 min) to even high concentration of TXA (100 mg/ml) does not affect the viability, proliferation and apoptosis of fibroblasts and the chronic exposure to low concentration of TXA (≤ 12.5 mg/ml) exerted little effect on viability, proliferation, apoptosis, collagen synthesis, adhesion and migration of human fibroblast (P>0.05). However, the chronic exposure to high concentration of TXA (≥25 mg/ml) can inhibit the viability, proliferation, collagen synthesis, adhesion and migration and induce apoptosis of fibroblasts. CONCLUSIONS: Although limited exposure to high concentration of TXA and chronic exposure to low concentration of TXA exerted little effect on fibroblasts, chronic exposure to high concentration of TXA can lead fibroblasts injury.

20.
Asian J Surg ; 2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34148753

RESUMO

BACKGROUND: We sought to evaluate the safety and feasibility of single-stage treatment with left iliac vein stenting and saphenous stripping in patients with left iliac vein compression (LIVC) and left great saphenous vein (GSV) incompetence. METHOD: s: We conducted a prospective cohort study of 72 patients diagnosed with LIVC and left GSV incompetence between June 2012 to Oct 2018. We evaluated the periprocedural, 30-day, and 1-year outcomes of venous clinical severity score (VCSS), Chronic Venous Insufficiency Questionnaire 2 (CIVIQ2), the success rate of stent placement, duration of intervention, length of hospital stay, duplex recurrence, and clinically visible recurrence. RESULTS: There were 43 patients in the two-staged group and 29 patients in the single-staged group. The clinical characteristics of the two groups were similar. There were no differences between the two groups in the technical success rate, perioperative mortality, and surgical morbidity. There was no significant difference in the duplex and clinically visible recurrence. The length of hospital stay was significantly lower in the single-staged group. The single-staged group was associated with a higher complication rate of ecchymosis. There was no death, pulmonary embolism, or contrast-induced nephropathy among the patients. The 1-year primary patency rate was similar. CONCLUSIONS: Both treatment approaches were equally effective and had a high technical success rate. The single-staged group had a higher complication rate of ecchymosis due to heparin applying during the procedure.

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