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1.
Chem Soc Rev ; 53(10): 5291-5337, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38634467

RESUMO

Rechargeable batteries, typically represented by lithium-ion batteries, have taken a huge leap in energy density over the last two decades. However, they still face material/chemical challenges in ensuring safety and long service life at temperatures beyond the optimum range, primarily due to the chemical/electrochemical instabilities of conventional liquid electrolytes against aggressive electrode reactions and temperature variation. In this regard, a gel polymer electrolyte (GPE) with its liquid components immobilized and stabilized by a solid matrix, capable of retaining almost all the advantageous natures of the liquid electrolytes and circumventing the interfacial issues that exist in the all-solid-state electrolytes, is of great significance to realize rechargeable batteries with extended working temperature range. We begin this review with the main challenges faced in the development of GPEs, based on extensive literature research and our practical experience. Then, a significant section is dedicated to the requirements and design principles of GPEs for wide-temperature applications, with special attention paid to the feasibility, cost, and environmental impact. Next, the research progress of GPEs is thoroughly reviewed according to the strategies applied. In the end, we outline some prospects of GPEs related to innovations in material sciences, advanced characterizations, artificial intelligence, and environmental impact analysis, hoping to spark new research activities that ultimately bring us a step closer to realizing wide-temperature rechargeable batteries.

2.
Echocardiography ; 41(2): e15763, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38411366

RESUMO

Cardiac myxoma is the most common primary benign cardiac tumors, mostly found in the left atrium. It was previously reported that the main component of myxoma was myxoid stroma riched in acid-mucopolysaccharide, the blood vessels in which were sparsely distributed, being characterized as hypovascular tumor by contrast echocardiography (CE) and computed tomography angiography (CTA). There are few reports of myxoma with rich blood supply and we report one in the left atrium.


Assuntos
Neoplasias Cardíacas , Mixoma , Humanos , Neoplasias Cardíacas/diagnóstico por imagem , Angiografia , Ecocardiografia , Átrios do Coração/diagnóstico por imagem , Mixoma/diagnóstico por imagem
3.
Echocardiography ; 41(4): e15810, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38555578

RESUMO

The aortic short axis view demonstrated the widening of the pulmonary artery and the membrane-like echo in the pulmonary artery divided it into true lumen and false lumen. And the flow of the ruptured openings on the band-like echo was clearly revealed by Color Doppler.


Assuntos
Dissecção Aórtica , Comunicação Interventricular , Estenose da Valva Pulmonar , Humanos , Ecocardiografia , Artéria Pulmonar/diagnóstico por imagem , Comunicação Interventricular/complicações , Comunicação Interventricular/diagnóstico por imagem , Estenose da Valva Pulmonar/complicações , Estenose da Valva Pulmonar/diagnóstico por imagem
4.
J Clin Ultrasound ; 52(4): 435-436, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38168063

RESUMO

During the fetal period, the pulmonary artery bifurcation revealed the absence of the left pulmonary artery. Instead, an anomalous artery originated from the right pulmonary artery, coursing posteriorly the trachea to the left lung. The diagnosis of PAS was established following prenatal ultrasound screening, which was subsequently confirmed by postnatal echocardiography and CT after delivery.


Assuntos
Artéria Pulmonar , Ultrassonografia Pré-Natal , Humanos , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/anormalidades , Artéria Pulmonar/embriologia , Ultrassonografia Pré-Natal/métodos , Feminino , Gravidez , Recém-Nascido , Adulto , Ecocardiografia/métodos , Tomografia Computadorizada por Raios X/métodos
5.
J Clin Ultrasound ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38840562

RESUMO

Non-Hodgkin lymphoma (NHL) is a highly aggressive malignant tumor arising in lymph nodes or extra-nodal lymphoid tissues, with an incidence of 8.3 per million. It accounts for approximately 7% of childhood and adolescent malignancies, second only to leukemia and brain tumors. Despite the gastrointestinal tract being the most common extra-nodal site involved by lymphoma, primary intestinal lymphoma (PIL) is rare and typically affects middle-aged men without specific clinical symptoms. Here, we present the case of a 2-year-old child indicative of PIL with the informed consent of the parents.

6.
Anal Chem ; 95(39): 14686-14694, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37713524

RESUMO

The problem of corrosion-induced discoloration and embrittlement in silverware is a significant concern for the long-term preservation of excavated archeological silver artifacts, even after thermal restoration. The key to addressing this issue lies in the meticulous selection and evaluation of corrosion inhibitors that possess targeted corrosion inhibition capabilities. This study focuses on the evaluation of corrosion inhibitors for archeological silver artifacts using scanning electrochemical cell microscopy (SECCM) and X-ray photoelectron spectroscopy (XPS). The researchers aimed to compare the inhibition effects of four corrosion inhibitors [1,2,3-benzotriazole (BTA), 2-mercaptobenzimidazole (MBI), 2-mercaptobenzothiazole (MBT), and 2-mercaptobenzoxazole (MBO)] on a simulated Ag-Cu alloy sample and understand their mechanisms. The results showed that MBT exhibited better corrosion inhibition for microstructural regions with higher silver content due to its ability to form stable chelation structures with Ag(I). MBO exhibited better corrosion inhibition for microstructural regions with higher copper content due to its strong affinity with Cu(I). The targeted corrosion inhibition ability for the ß-phase was ranked as MBO > BTA ≈ MBI > MBT, while for the α-phase the ranking was MBT > MBO > MBI > BTA. The study demonstrated the feasibility and capabilities of SECCM in the targeted screening of corrosion inhibitors for different compositions and microstructural regions in archeological metal artifacts. This study highlights the potential of SECCM in corrosion inhibitor research for archeological metal artifacts and wider applications in metal material corrosion protection.

7.
BMC Med ; 21(1): 2, 2023 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-36600247

RESUMO

BACKGROUND: HL-085 is a selective, orally administered MEK1/2 inhibitor. We aimed to evaluate the safety and efficacy of HL-085 in patients with advanced melanoma harboring NRAS mutations. METHODS: This was a multicenter phase 1 study. HL-085 was administered twice daily in a standard 3 + 3 dose-escalation design (10 dose cohorts; 0.5-18 mg twice daily), followed by dose expansion at the recommended phase II dose (RP2D). The primary endpoints included tolerability, dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and RP2D. RESULTS: Between September 13, 2017, and January 18, 2021, 42 patients were enrolled (dose escalation phase: n = 30; dose expansion phase: n = 12). No DLT was reported during dose escalation and MTD was not reached with HL-085 doses up to 18 mg twice daily. The RP2D was 12 mg twice daily. The most common all-grade drug-related adverse events (AEs) across all dose levels were rash (61.9%), increased creatine phosphokinase (CK, 59.5%), face edema (50.0%), increased aspartate aminotransferase (47.6%), peripheral edema (40.5%), diarrhea (33.3%), alanine aminotransferase (33.3%), and paronychia (19.0%), most of which were grade 1 and 2. Most frequency of grade ≥ 3 AEs were CK (14.2%), asthenia (7.1%), peripheral edema (4.8%), and acneiform dermatitis (4.8%). In the cohort of 12 mg twice daily dose (15 patients), confirmed objective response rate was 26.7%; disease control rate was 86.7%; median duration of response was 2.9 months; median progression-free survival was 3.6 months. CONCLUSIONS: The HL-085 showed acceptable tolerability and substantial clinical activity in patients with advanced melanoma harboring NRAS mutations. TRIAL REGISTRATION: Trial registration ClinicalTrials.gov number: NCT03973151.


Assuntos
Melanoma , Quinases de Proteína Quinase Ativadas por Mitógeno , Humanos , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/genética , Proteínas de Membrana/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Mutação , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico
8.
Plant Biotechnol J ; 21(8): 1628-1641, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37154202

RESUMO

Traditional rice blast resistance breeding largely depends on utilizing typical resistance (R) genes. However, the lack of durable R genes has prompted rice breeders to find new resistance resources. Susceptibility (S) genes are potential new targets for resistance genetic engineering using genome-editing technologies, but identifying them is still challenging. Here, through the integration of genome-wide association study (GWAS) and transcriptional analysis, we identified two genes, RNG1 and RNG3, whose polymorphisms in 3'-untranslated regions (3'-UTR) affected their expression variations. These polymorphisms could serve as molecular markers to identify rice blast-resistant accessions. Editing the 3'-UTRs using CRISPR/Cas9 technology affected the expression levels of two genes, which were positively associated with rice blast susceptibility. Knocking out either RNG1 or RNG3 in rice enhanced the rice blast and bacterial blight resistance, without impacting critical agronomic traits. RNG1 and RNG3 have two major genotypes in diverse rice germplasms. The frequency of the resistance genotype of these two genes significantly increased from landrace rice to modern cultivars. The obvious selective sweep flanking RNG3 suggested it has been artificially selected in modern rice breeding. These results provide new targets for S gene identification and open avenues for developing novel rice blast-resistant materials.


Assuntos
Genes de Plantas , Oryza , Oryza/genética , Oryza/microbiologia , Estudo de Associação Genômica Ampla , Edição de Genes , Resistência à Doença/genética , Melhoramento Vegetal
9.
J Bone Miner Metab ; 41(4): 457-469, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37036534

RESUMO

INTRODUCTION: Osteoporosis invariably manifests as loss of bone, which is replaced by adipose tissue; this can easily lead to fractures, accompanied by delayed and poor healing. Adiponectin (APN) balances osteogenesis and adipogenesis in bone marrow mesenchymal stem cells (BMSCs). Therefore, this study explored whether adiponectin promotes bone fracture healing by regulating the balance between osteogenesis and adipogenesis. MATERIALS AND METHODS: We used adenovirus overexpression vectors carrying APN (Ad-APN-GFP) to treat ovariectomized (OVX) mouse BMSCs and osteoporotic bone fractures to investigate the role of APN in bone microenvironment metabolism in osteoporotic fractures. We subsequently established an OVX mice and bone fracture model using Ad-APN-GFP treatment to investigate whether APN could promote bone fracture healing in osteoporotic mice. RESULTS: The experimental results showed that APN is a critical molecule in diverse differentiation directions in OVX mouse BMSCs, with pro-osteogenesis and anti-adipogenesis properties. Importantly, our study revealed that Ad-APN-GFP treatment facilitates bone generation and healing around the osteoporotic fracture ends. Moreover, we identified that Sirt1 and Wnt signaling were closely related to the pro-osteogenesis and anti-adipogenesis commitment of APN in OVX mouse BMSCs and femoral tissues. CONCLUSION: We demonstrated that APN overexpression facilitates bone fracture healing in osteoporosis. Furthermore, APN overexpression promoted bone formation in OVX mouse BMSCs and bone fracture ends by regulating the balance between osteogenesis and adipogenesis both in vitro and in vivo.


Assuntos
Fraturas Ósseas , Osteoporose , Camundongos , Animais , Osteogênese , Adiponectina/genética , Consolidação da Fratura , Diferenciação Celular , Osteoporose/metabolismo
10.
Arch Insect Biochem Physiol ; 113(2): e22005, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36802092

RESUMO

N6-methyladenosine (m6A) is a ubiquitous reversible epigenetic RNA modification that plays an important role in regulating many biological processes, especially embryonic development. However, regulation of m6A methylation during silkworm embryonic development and diapause remains to be investigated. In this study, we analyzed the phylogeny of subunits of methyltransferases BmMettl3 and BmMettl14, and detected the expression patterns of BmMettl3 and BmMettl14 in different tissues and at different developmental stages in silkworm. To investigate the function of m6A on the development of silkworm embryo, we analyzed the m6A/A ratio in diapause and diapause termination eggs. The results showed that BmMettl3 and BmMettl14 were highly expressed in gonads and eggs. Moreover, the expression of BmMettl3 and BmMettl14 and the m6A/A ratio were significantly increased in diapause termination eggs compared with diapause eggs in the early stage of silkworm embryonic development. Furthermore, in BmN cell cycle experiments, the percentage of cells in the S phase increased when lacking BmMettl3 or BmMettl14. This work contributes to understanding the role of m6A methylation during insect embryogenesis and gametogenesis. It also provides a research orientation to further analyze the role of m6A methylation in diapause initiation and termination during insect embryonic development.


Assuntos
Bombyx , Metiltransferases , Animais , Metiltransferases/genética , Metiltransferases/metabolismo , Bombyx/metabolismo , RNA/metabolismo , Epigênese Genética , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica no Desenvolvimento , Óvulo/metabolismo
11.
Mar Drugs ; 21(7)2023 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-37504904

RESUMO

The concise and highly convergent synthesis of the isodityrosine unit of seongsanamide A-D and its derivatives bearing a diaryl ether moiety is described. In this work, the synthetic strategy features palladium-catalyzed C(sp3)-H functionalization and a Cu/ligand-catalyzed coupling reaction. We report a practical protocol for the palladium-catalyzed mono-arylation of ß-methyl C(sp3)-H of an alanine derivative bearing a 2-thiomethylaniline auxiliary. The reaction is compatible with a variety of functional groups, providing practical access to numerous ß-aryl-α-amino acids; these acids can be converted into various tyrosine and dihydroxyphenylalanine (DOPA) derivatives. Then, a CuI/N,N-dimethylglycine-catalyzed arylation of the already synthesized DOPA derivatives with aryl iodides is described for the synthesis of isodityrosine derivatives.


Assuntos
Paládio , Tirosina , Paládio/química , Catálise , Di-Hidroxifenilalanina
12.
Biomed Chromatogr ; 37(5): e5607, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36802077

RESUMO

HSK7653 is a novel super long-acting dipeptidyl peptidase-4 inhibitor, which is promising for the treatment of type 2 diabetes mellitus with the twice-monthly dosing regimen. In this article, a robust and sensitive HPLC coupled with tandem mass spectrometry method for determining the concentration of HSK7653 in human plasma and urine was developed and validated for the first time. Plasma and urine samples were prepared by protein precipitation. After that, the extracts were analyzed using an LC-20A HPLC system coupled with API 4000 tandem MS equipped with an electrospray ionization source in positive mode. Separation was obtained using an XBridge Phenyl column (2.1 × 50 mm, 3.5 µm) with a gradient elution of acetonitrile and water containing 0.1% formic acid and 5% acetonitrile at room temperature. This bioanalysis method has been fully validated and the results showed good sensitivity and specificity. In brief, the standard curves were linear over the concentration range of 2.00-2000 ng/ml for plasma and 20.0-20,000 ng/ml for urine, respectively. In addition, the precisions of inter- and intra-run of HSK7653 were less than 12.7% and the accuracies were -3.3% to 6.3% for both plasma and urine. Finally, this method was successfully applied to explore the pharmacokinetic characteristics of HSK7653 in Chinese healthy volunteers in a first-in-human study.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Reprodutibilidade dos Testes , Hipoglicemiantes , Dipeptidil Peptidases e Tripeptidil Peptidases
13.
Sensors (Basel) ; 23(9)2023 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-37177724

RESUMO

The mobile node location method can find unknown nodes in real time and capture the movement trajectory of unknown nodes in time, which has attracted more and more attention from researchers. Due to their advantages of simplicity and efficiency, intelligent optimization algorithms are receiving increasing attention. Compared with other algorithms, the black hole algorithm has fewer parameters and a simple structure, which is more suitable for node location in wireless sensor networks. To address the problems of weak merit-seeking ability and slow convergence of the black hole algorithm, this paper proposed an opposition-based learning black hole (OBH) algorithm and utilized it to improve the accuracy of the mobile wireless sensor network (MWSN) localization. To verify the performance of the proposed algorithm, this paper tests it on the CEC2013 test function set. The results indicate that among the several algorithms tested, the OBH algorithm performed the best. In this paper, several optimization algorithms are applied to the Monte Carlo localization algorithm, and the experimental results show that the OBH algorithm can achieve the best optimization effect in advance.

14.
J Clin Ultrasound ; 51(6): 1067-1069, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37130036

RESUMO

The giant prostatic utricle cyst, located behindthe bladder with removable irregular mixed echo, communicating with the urethraat the level of the seminal colliculus, was diagnosed by ultrasound andverified by pathology and surgery.


Assuntos
Cistos , Doenças Prostáticas , Masculino , Humanos , Doenças Prostáticas/diagnóstico por imagem , Doenças Prostáticas/patologia , Próstata/diagnóstico por imagem , Pelve/patologia , Bexiga Urinária , Cistos/diagnóstico por imagem , Cistos/cirurgia
15.
J Clin Ultrasound ; 51(8): 1364-1365, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37817347

RESUMO

Morning glory syndrome (MGS) and persistent hyperplastic primary vitreous (PHPV) are congenital abnormity, which may be related to the increased incidence of systemic abnormalities and retinal detachment,diagnosed by ultrasound, identified by CT, MRI, and with the confirmation of fundus examination.


Assuntos
Disco Óptico , Vítreo Primário Hiperplásico Persistente , Humanos , Vítreo Primário Hiperplásico Persistente/diagnóstico por imagem , Disco Óptico/anormalidades , Disco Óptico/diagnóstico por imagem , Ultrassonografia , Síndrome , Imagem Multimodal
16.
Molecules ; 28(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36677606

RESUMO

The anode-free lithium metal battery (AFLMB) is attractive for its ultimate high energy density. However, the poor cycling lifespan caused by the unstable anode interphase and the continuous Li consumption severely limits its practical application. Here, facile one-step heat treatment of the Cu foil current collectors before the cell assembly is proposed to improve the anode interphase during the cycling. After heat treatment of the Cu foil, homogeneous Li deposition is achieved during cycling because of the smoother surface morphology and enhanced lithiophilicity of the heat-treated Cu foil. In addition, Li2O-riched SEI is obtained after the Li deposition due to the generated Cu2O on the heat-treated Cu foil. The stable anode SEI can be successfully established and the Li consumption can be slowed down. Therefore, the cycling stability of the heat-treated Cu foil electrode is greatly improved in the Li|Cu half-cell and the symmetric cell. Moreover, the corresponding LFP|Cu anode-free full cell shows a much-improved capacity retention of 62% after 100 cycles, compared to that of 43% in the cell with the commercial Cu foil. This kind of facile but effective modification of current collectors can be directly applied in the anode-free batteries, which are assembled without Li pre-deposition on the anode.

17.
BMC Oral Health ; 23(1): 554, 2023 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-37568132

RESUMO

BACKGROUND: Bioceramic cements have been widely used in endodontic treatment. This study aimed to compare the microhardness, elastic modulus, internal microstructure and chemical compositions of Biodentine, WMTA, ERRM Putty, iRoot FS and IRM after exposure to PBS, butyric acid, and butyric acid followed by PBS. METHODS: Specimens of each material were prepared and randomly divided into 5 subgroups (n = 5): subgroup A: PBS (pH = 7.4) for 4 days, subgroup B: PBS (pH = 7.4) for 14 days, subgroup C: butyric acid (pH = 5.4) for 4 days, subgroup D: butyric acid (pH = 5.4) for 14 days, subgroup E: butyric acid for 4 days followed by 10 days in contact with PBS. The surface microhardness, elastic modulus, internal morphologic and chemical compositions of specimens were analyzed. RESULTS: The microhardness and elastic modulus values of all materials were significantly higher in the presence of PBS compared to exposure to butyric acid, with the same setting time (P < 0.01). After 4-day exposure to butyric acid followed by 10-day exposure to PBS, the microhardness values returned to the same level as 4-day exposure to PBS (P > 0.05). Biodentine showed significantly higher microhardness and elastic modulus values than other materials, while IRM displayed the lowest (P < 0.01). CONCLUSION: Biodentine seems the most suitable bioceramic cements when applied to an infected area with acidic pH. Further storage at neutral pH, e.g. PBS reverses the adverse effects on bioceramic cements caused by a low pH environment.


Assuntos
Compostos de Cálcio , Óxidos , Humanos , Compostos de Alumínio/química , Ácido Butírico , Cálcio , Compostos de Cálcio/farmacologia , Compostos de Cálcio/química , Fosfatos de Cálcio , Cimentos Dentários/química , Combinação de Medicamentos , Teste de Materiais , Óxidos/química , Silicatos/farmacologia , Silicatos/química
18.
Entropy (Basel) ; 25(2)2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36832680

RESUMO

Inspired by the bamboo growth process, Chu et al. proposed the Bamboo Forest Growth Optimization (BFGO) algorithm. It incorporates bamboo whip extension and bamboo shoot growth into the optimization process. It can be applied very well to classical engineering problems. However, binary values can only take 0 or 1, and for some binary optimization problems, the standard BFGO is not applicable. This paper firstly proposes a binary version of BFGO, called BBFGO. By analyzing the search space of BFGO under binary conditions, the new curve V-shaped and Taper-shaped transfer function for converting continuous values into binary BFGO is proposed for the first time. A long-mutation strategy with a new mutation approach is presented to solve the algorithmic stagnation problem. Binary BFGO and the long-mutation strategy with a new mutation are tested on 23 benchmark test functions. The experimental results show that binary BFGO achieves better results in solving the optimal values and convergence speed, and the variation strategy can significantly enhance the algorithm's performance. In terms of application, 12 data sets derived from the UCI machine learning repository are selected for feature-selection implementation and compared with the transfer functions used by BGWO-a, BPSO-TVMS and BQUATRE, which demonstrates binary BFGO algorithm's potential to explore the attribute space and choose the most significant features for classification issues.

19.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 48(4): 581-593, 2023 Apr 28.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-37385621

RESUMO

OBJECTIVES: With the increasing detection rate of lung nodules, the qualitative problem of lung nodules has become one of the key clinical issues. This study aims to evaluate the value of combining dynamic contrast-enhanced (DCE) MRI based on time-resolved imaging with interleaved stochastic trajectories-volume interpolated breath hold examination (TWIST-VIBE) with T1 weighted free-breathing star-volumetric interpolated breath hold examination (T1WI star-VIBE) in identifying benign and malignant lung nodules. METHODS: We retrospectively analyzed 79 adults with undetermined lung nodules before the operation. All nodules of patients included were classified into malignant nodules (n=58) and benign nodules (n=26) based on final diagnosis. The unenhanced T1WI-VIBE, the contrast-enhanced T1WI star-VIBE, and the DCE curve based on TWIST-VIBE were performed. The corresponding qualitative [wash-in time, wash-out time, time to peak (TTP), arrival time (AT), positive enhancement integral (PEI)] and quantitative parameters [volume transfer constant (Ktrans), interstitium-to-plasma rate constant (Kep), and fractional extracellular space volume (Ve)] were evaluated. Besides, the diagnostic efficacy (sensitivity and specificity) of enhanced CT and MRI were compared. RESULTS: There were significant differences in unenhanced T1WI-VIBE hypo-intensity, and type of A, B, C DCE curve type between benign and malignant lung nodules (all P<0.001). Pulmonary malignant nodules had a shorter wash-out time than benign nodules (P=0.001), and the differences of the remaining parameters were not statistically significant (all P>0.05). After T1WI star-VIBE contrast-enhanced MRI, the image quality was further improved. Compared with enhanced CT scan, the sensitivity (82.76% vs 80.50%) and the specificity (69.23% vs 57.10%) based on MRI were higher than that of CT (both P<0.001). CONCLUSIONS: T1WI star-VIBE and dynamic contrast-enhanced MRI based on TWIST-VIBE were helpful to improve the image resolution and provide more information for clinical differentiation between benign and malignant lung nodules.


Assuntos
Imageamento por Ressonância Magnética , Plasma , Adulto , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Pulmão
20.
BMC Med ; 20(1): 453, 2022 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-36424628

RESUMO

BACKGROUND: Conteltinib (CT-707) is a potent second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) showing promising anti-tumor activities in preclinical studies. This study aimed to assess the safety, pharmacokinetic (PK), and efficacy of conteltinib in patients with ALK-positive non-small cell lung cancer (NSCLC). METHODS: In this multicenter, single-arm, open-label, first-in-human phase 1 study, conteltinib was taken orally at doses of 50 to 800 mg quaque die (QD) in a dose-escalation phase. If the response was observed in a dose cohort of the dose-escalation phase, dose expansion was started. The primary endpoints were maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and adverse events assessed by investigators. RESULTS: Between April 13, 2016, and February 8, 2020, 64 ALK-positive NSCLC patients were enrolled, including 41 (64.1%) patients with ALK TKI-naïve and 23 (35.9%) patients who received crizotinib previously. In the dose-escalation phase, 26 patients were treated with conteltinib at doses of 50 mg, 100 mg, 200 mg, 300 mg, 450 mg, 600 mg, and 800 mg QD. One DLT event was reported at the dose of 600 mg. MTD was not reached. Overall, 58 (90.6%) patients experienced treatment-related adverse events (TRAEs) and 9 (14.1%) patients had grade ≥ 3 TRAEs. The most common TRAEs were diarrhea (46 [71.9%]), serum creatinine elevated (29 [45.3%]), aspartate aminotransferase elevated (25 [39.1%]), and nausea (24 [37.5%]). Among 39 ALK TKI-naïve patients, the overall response rate (ORR) was 64.1% (25 of 39; 95% confidence interval [CI], 47.2-78.8), median progression-free survival (PFS) was 15.9 months (95% CI, 9.26-23.3), and median duration of response (DoR) was 15.0 months (95% CI, 9.06-25.8). Among 21 patients who received crizotinib previously, the ORR was 33.3% (7 of 21; 95% CI, 14.6-57.0), median PFS was 6.73 months (95% CI, 4.73-8.54), and median DoR was 6.60 months (95% CI, 3.77-13.3). CONCLUSIONS: In this study, conteltinib showed manageable safety profile, favorable PK properties, and anti-tumor activity in advanced ALK-positive NSCLC patients. The recommended phase 2 dose was determined to be 600 mg QD for ALK TKI-naïve patients and 300 mg bis in die (BID) for patients who received crizotinib previously. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02695550.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Crizotinibe/efeitos adversos , Quinase do Linfoma Anaplásico , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Tirosina Quinases
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