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1.
J Adv Prosthodont ; 16(3): 189-199, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38957293

RESUMO

PURPOSE: This study was conducted to evaluate the effects of plasma treatment of sandblasted and acid-etched (SLA) titanium implants on surface cleansing and osseointegration in a beagle model. MATERIALS AND METHODS: For morphological analysis and XPS analysis, scanning electron microscope and x-ray photoelectron spectroscopy were used to analyze the surface topography and chemical compositions of implant before and after plasma treatment. For this animal experiment, twelve SLA titanium implants were divided into two groups: a control group (untreated implants) and a plasma group (implants treated with plasma). Each group was randomly located in the mandibular bone of the beagle dog (n = 6). After 8 weeks, the beagle dogs were sacrificed, and volumetric analysis and histometric analysis were performed within the region of interest. RESULTS: In morphological analysis, plasma treatment did not alter the implant surface topography or cause any physical damage. In XPS analysis, the atomic percentage of carbon at the inspection point before the plasma treatment was 34.09%. After the plasma treatment, it was reduced to 18.74%, indicating a 45% reduction in carbon. In volumetric analysis and histometric analysis, the plasma group exhibited relatively higher mean values for new bone volume (NBV), bone to implant contact (BIC), and inter-thread bone density (ITBD) compared to the control group. However, there was no significant difference between the two groups (P > .05). CONCLUSION: Within the limits of this study, plasma treatment effectively eliminated hydrocarbons without changing the implant surface.

3.
Injury ; 55(10): 111711, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-39003882

RESUMO

INTRODUCTION: Recombinant human Bone morphogenetic proteins have been used for the treatment of nonunions with promising results. We have been investigating both experimentally and clinically the efficacy of the rhBMP-2 with the macro / micro-porous hydroxyapatite carrier granules on the potency on the reconstruction of long bone defect. The purpose of this study was to prospectively evaluate the efficacy and safety of this specific rhBMP-2 with HA carrier granules mixed with autologous cancellous bone in patients with nonunion and bone defect resulted from the fracture related infection. MATERIALS AND METHODS: This was a retrospective review of a prospective cohort at a university hospital. Patients diagnosed with nonunion under the definition of the United States Food and Drug Administration with bone defect after long bone fractures were enrolled from January 2020 to February 2021. We included patients with atrophic and oligotrophic nonunion, and hypertrophic nonunion with malalignment that needed to be corrected. The other patient group was consisted of segmental bone defect resulted from FRI. The maximum amount of rhBMP-2 allowed in this clinical study was 6 mg and was added to autologous bone at a 1:1 ratio. Autologous bone was added to the mixture if the volume of mixed graft was insufficient to fill the bone defect. Patients were followed 3, 6, and 12 months post-operatively. Each visit, a radiograph was taken for assessment. Visual analog scale (VAS), questionnaire for quality of life (SF-12 physical component summary [PCS], mental component summary [MCS]), and weight-bearing status were collected for functional outcome assessment. Drug safety was assessed by examining BMP-2 antibodies. RESULTS: Of the 24 enrolled patients (mean age: 57 years), 15 (62.5 %), 2 (8.33 %), and 7 (29.17 %) presented atrophic nonunion, hypertrophic nonunion with deformity, and bone defect after fracture related infection, respectively. Thirteen patients had nonunion in the femur, 9 in the tibia, and 1 in the humerus and radius. The average amount of harvested autologous bone was 9.25 g and 4.96 mg of rhBMP-2. All 24 patients achieved union after 1-year follow up. The union rate was 95.83 % and 100 % at 6 and 12 months postoperatively, respectively. Preoperative SF-12 PCS (mean: 34.71) improved at 6 and 12 months postoperatively, respectively. Preoperative SF-12 MCS (mean: 42.89) improved 12 months postoperatively (49.13, p = 0.0338). Change of VAS was statistically significant 3 months postoperatively (p = 0.0012). No adverse effects or development of BMP-2 antibodies were observed. CONCLUSION: BMP-2 combined with autogenous bone resulted in excellent radiographical and functional outcomes in a relatively small prospective series of patients with nonunion and bone defect, without adverse effects. Further investigations are necessary to support our finding and optimize treatment strategies in nonunion patients.

4.
Artigo em Inglês | MEDLINE | ID: mdl-39038229

RESUMO

Photorechargeable supercapacitors are promising next-generation renewable energy storage devices. Previously, a hybrid structure consisting of indium-tin oxide branched nanowires (ITO BRs) and poly(3-hexylthiophene) (P3HT) was demonstrated as a photorechargeable supercapacitor. However, the formation mechanism of photovoltage has not been studied. Herein, we experimentally investigated the photovoltage-determining parameters in the ITO BRs/P3HT photorechargeable supercapacitor by inserting a polyethylenimine ethoxylated (PEIE) interlayer or adding a phenyl-C61-butyric acid methyl ester (PCBM) electron acceptor. Coating the PEIE interlayer on ITO BRs decreased the work function by 0.5 eV and hindered the hole extraction from P3HT to ITO BRs, leading to interfacial recombination and a decrease in photovoltage. On the other hand, the addition of PCBM promoted the charge transfer of the electrons from P3HT to PCBM, enhanced the redox reaction at the PCBM/electrolyte interface, and reduced the number of accumulated electrons, leading to a decreased photovoltage. From these results, we found that two key parameters determine the photovoltage and charge storage capability; one is the interfacial recombination at the ITO BRs/P3HT interface and the other is the redox reaction at the P3HT/electrolyte interface.

5.
ACS Nano ; 2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39033415

RESUMO

For highly active electron transfer and ion diffusion, controlling the surface wettability of electrically and thermally conductive 3D graphene foams (3D GFs) is required. Here, we present ultrasimple and rapid superwettability switching of 3D GFs in a reversible and reproducible manner, mediated by solvent-exclusive microwave arcs. As the 3D GFs are prepared with vapors of nonpolar acetone or polar water exclusively, short microwave radiation (≤10 s) leads to plasma hotspot-mediated production of methyl and hydroxyl radicals, respectively. Upon immediate radical chemisorption, the 3D surfaces become either superhydrophobic (water contact angle = ∼170°) or superhydrophilic (∼0°), and interestingly, the wettability transition can be repeated many times due to the facile exchange between previously chemisorbed and newly introduced radicals via the formation of methanol-like intermediates. When 3D GFs of different surficial polarities are incorporated into electric double-layer capacitors with nonpolar ionic liquids or polar aqueous electrolytes, the polarity matching between graphene surfaces and electrolytes results in ≥548.0 times higher capacitance compared to its mismatching at ≥0.5 A g-1, demonstrating the significance of wettability-controlled 3D GFs.

6.
Curr Oncol ; 31(6): 3239-3251, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38920729

RESUMO

BACKGROUND: Interest in the oligometastatic prostate cancer (OMPC) is increasing, and various clinical studies have reported the benefits of metastasis-directed radiation therapy (MDRT) in OMPC. However, the recognition regarding the adopted definitions, methodologies of assessment, and therapeutic approaches is diverse among radiation oncologists. This study aims to evaluate the level of agreement for issues in OMPC among radiation oncologists. METHODS: We generated 15 key questions (KQs) for OMPC relevant to definition, diagnosis, local therapies, and endpoints. Additionally, three clinical scenarios representing synchronous metastatic prostate cancer (mPC) (case 1), metachronous mPC with visceral metastasis (case 2), and metachronous mPC with castration-resistance and history of polymetastasis (case 3) were developed. The 15 KQs were adapted according to each scenario and transformed into 23 questions with 6-9 per scenario. The survey was distributed to 80 radiation oncologists throughout the Republic of Korea. Answer options with 0.0-29.9%, 30-49.9%, 50-69.9%, 70-79.9%, 80-89.9%, and 90-100% agreements were considered as no, minimal, weak, moderate, strong, and near perfect agreement, respectively. RESULTS: Forty-five candidates voluntarily participated in this study. Among 23 questions, near perfect (n = 4), strong (n = 3), or moderate (n = 2) agreements were shown in nine. For the case recognized as OMPC with agreements of 93% (case 1), near perfect agreements on the application of definitive radiation therapy (RT) for whole metastatic lesions were achieved. While ≥70% agreements regarding optimal dose-fractionation for metastasis-directed RT (MDRT) has not been achieved, stereotactic body RT (SBRT) is favored by clinicians with higher clinical volume. CONCLUSION: For the case recognized as OMPC, near perfect agreement for the application of definitive RT for whole metastatic lesions was reached. SBRT was more favored as a MDRT by clinicians with a higher clinical volume.


Assuntos
Metástase Neoplásica , Neoplasias da Próstata , Radio-Oncologistas , Masculino , Humanos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , República da Coreia , Inquéritos e Questionários , Pessoa de Meia-Idade
7.
Biomedicines ; 12(6)2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38927380

RESUMO

This study aimed to investigate the impact of hypogonadism on bone mineral density (BMD) in children and adolescents with chronic diseases to determine the relationship between sex hormones and BMD. This retrospective study included 672 children and adolescents with chronic diseases such as hemato-oncologic, rheumatoid, gastrointestinal, and endocrinologic diseases. The relationship between the sex- and Tanner-stage-matched Z-scores for sex hormones and the sex- and age-matched lumbar spine BMD (LSBMD) Z-scores was evaluated. Adjustments were made for confounders such as underlying diseases, age at diagnosis, and age- and sex-matched body mass index Z-scores. Patients had a mean LSBMD Z-score of -0.55 ± 1.31. In the multivariate regression analysis, male testosterone showed a positive association with the LSBMD Z-score (p < 0.001), whereas female estradiol, luteinizing hormone, and follicular-stimulating hormone showed no significant association with the LSBMD Z-scores. In the male group, the testosterone level was associated with LSBMD Z-scores > -1.0 (p < 0.001), > -2.0 (p < 0.001), and > -3.0 (p = 0.002), while the estradiol level was associated with LSBMD Z-scores > -2.0 (p = 0.001) and > -3.0 (p = 0.002) in the female group. In conclusion, sex hormones are associated with BMD in children and adolescents with chronic diseases. Therefore, various measures may be necessary to predict future skeletal problems and improve bone health in these patients.

8.
Appl Radiat Isot ; 211: 111415, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38936285

RESUMO

Radioisotopes are widely used in the fields of medicine, science, and industry. The growing demand for medical radioisotopes has driven research on alternative production methods. In particular, both isotopes of 67Cu and 68Ge play vital roles in the medical environment in many countries to be used in the radio-immunotherapy and the positron emission tomography imaging, respectively. This study designed a multi-target system consisting of two Zn and one Ga2O3 plates to enable simultaneous production of the medical radioisotopes 67Cu and 68Ge using 100 MeV proton beams. To understand the thermal effect on the multi-targets, we examined the distribution of energy absorbed in each solid plate target when exposed to an accelerated proton beam through the thermal-fluid analysis based on ANSYS simulation. For confirming thermal stability for two Zn targets and one Ga2O3 target, the modified water flow path inside the multi-target system was designed effectively with the controlled distribution of multiple sub-holes between main inlet and the following four channels. It was confirmed that the newly designed multi-target system of Zn and Ga2O3 solid plates shows higher thermal stability than the case of uniform distribution of water inlet, which means it could be exposed to a higher current beam of 7.57% to decrease the processing time.

9.
J Med Chem ; 67(13): 10687-10709, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38913701

RESUMO

UC and ALI are inflammatory diseases with limited treatment in the clinic. Herein, fragment-based anti-inflammatory agent designs were carried out deriving from cyclohexylamine/cyclobutylamine and several fragments from anti-inflammatory agents in our lab. AF-45 (IC50 = 0.53/0.60 µM on IL-6/TNF-α in THP-1 macrophages) was identified as the optimal molecule using ELISA and MTT assays from the 33 synthesized compounds. Through mechanistic studies and a systematic target search process, AF-45 was found to block the NF-κB/MAPK pathway and target IRAK4, a promising target for inflammation and autoimmune diseases. The selectivity of AF-45 targeting IRAK4 was validated by comparing its effects on other kinase/nonkinase proteins. In vivo, AF-45 exhibited a good therapeutic effect on UC and ALI, and favorable PK proprieties. Since there are currently no clinical or preclinical trials for IRAK4 inhibitors to treat UC and ALI, AF-45 provides a new lead compound or candidate targeting IRAK4 for the treatment of these diseases.


Assuntos
Lesão Pulmonar Aguda , Colite Ulcerativa , Quinases Associadas a Receptores de Interleucina-1 , Quinases Associadas a Receptores de Interleucina-1/antagonistas & inibidores , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Humanos , Animais , Colite Ulcerativa/tratamento farmacológico , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/uso terapêutico , Desenho de Fármacos , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Descoberta de Drogas , Masculino , NF-kappa B/metabolismo , NF-kappa B/antagonistas & inibidores , Relação Estrutura-Atividade , Células THP-1
10.
Nano Lett ; 24(23): 7100-7107, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38810235

RESUMO

Current-induced spin-orbit torque (SOT) offers substantial promise for the development of low-power, nonvolatile magnetic memory. Recently, a single-phase material concurrently exhibiting magnetism and the spin Hall effect has emerged as a scientifically and technologically interesting platform for realizing efficient and compact SOT systems. Here, we demonstrate external-magnetic-field-free switching of perpendicular magnetization in a single-phase ferromagnetic and spin Hall oxide SrRuO3. We delicately altered the local lattices of the top and bottom surface layers of SrRuO3, while retaining a quasi-homogeneous, single-crystalline nature of the SrRuO3 bulk. This leads to unbalanced spin Hall effects between the top and bottom layers, enabling net SOT performance within single-layer ferromagnetic SrRuO3. Notably, our SrRuO3 exhibits the highest SOT efficiency and lowest power consumption among all known single-layer systems under field-free conditions. Our method of artificially manipulating the local atomic structures will pave the way for advances in spin-orbitronics and the exploration of new SOT materials.

11.
Clin Nutr Res ; 13(2): 89-95, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38784854

RESUMO

Thickened beverages or swallowing aid jelly (SAJ), commonly used as tablet-swallowing aids for dysphagic patients, may influence the disintegration of orally administered tablets. With this in mind, we evaluated the disintegration times of therapeutic tablets immersed in thickened beverages or SAJ compared to immersion in ones without them. Thickened beverages and SAJs were prepared with various beverages (water, orange juice, and milk) using food thickeners and SAJ powders marketed in Korea. The tablet disintegration times were the same in thickened beverages and SAJs, and there was no statistically significant difference associated with the thickness levels of the thickened beverages. The disintegration times of Tylenol immersed in orange juice or milk were slightly higher compared to those immersed in water. Moreover, there was no difference in disintegration time when using the thickened beverages and SAJs. The disintegration times of Aspirin were similar in all of the thickened beverages or SAJs, and there were no differences between non-immersed and immersed tablets. These results demonstrate that the disintegration of Tylenol and Aspirin is not greatly affected by immersion in any of the thickened beverages and SAJs.

12.
Neurosurgery ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38690884

RESUMO

BACKGROUND AND OBJECTIVES: The role of bypass surgery in intracranial atherosclerotic steno-occlusive diseases (ICADs) remains controversial. We aimed to analyze the surgical outcomes of bypass surgery in patients with the ICADs in a single tertiary institution. METHODS: Among 1018 cases of low-flow bypass surgery between 2003 and 2022, 215 patients with the ICAD refractory to medical treatment were finally enrolled in this study. Clinical and radiological outcomes were retrospectively evaluated, with survival analyses. RESULTS: All strokes, cerebral infarctions, and intracranial hemorrhages occurred in 12.1% (n = 26), 9.8% (n = 21), and 2.3% (n = 5), respectively, during the clinical follow-up of 54.6 ± 47.6 months (range, 0.6-237.8 months). Among all stroke events, 84.6% (n = 22) occurred within 30 postoperative days. The 2-year and 5-year cumulative risks of all strokes were 12.1% each. The mean modified Rankin Scale scores were 1.6 ± 1.1 (range, 0-5) preoperatively and 0.8 ± 1.2 (range, 0-6) at last (P < .01). The patency of direct bypass was 99.1% (n = 213) just before discharge and 96.3% (n = 184 of 191 patients with available tests) at the last angiographic follow-up of 27.0 ± 27.3 months (range, 2.3-97.3 months). All the patients with available data (n = 190) showed hemodynamic improvement on acetazolamide-challenged single-photon emission computed tomography with 99mTc-hexamethylpropyleneamine oxime during the follow-up of 38.6 ± 36.7 months (range, 2.3-158.6 months). CONCLUSION: Low-flow bypass surgery showed acceptable treatment outcomes in the prevention of recurrent stroke.

13.
Sci Rep ; 14(1): 10257, 2024 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704433

RESUMO

Endoscopic middle meatal antrostomy (MMA) is commonly used for maxillary sinus (MS) fungal ball removal. For challenging cases involving anterior or inferior recess, an additional inferior meatal approach (IMA) might be needed. We analyzed the differences in MS dimensions on CT scans according to the surgical approach to suggest preoperative variables that could facilitate an additional IMA. CT scans of 281 adult patients who underwent ESS for the MS fungal ball (139 MMA, 62 MMA & IMA) were evaluated for comparative analysis of 8 MS measurements based on the surgical approach. Complete removal was achieved in all cases. Age and sex didn't differ significantly (p > 0.05). The maximum distances between the anterior-posterior walls, the inferior ostium border to the lateral recess, and the ostium to the inferior wall of the MS were statistically greater in the MMA & IMA group compared to the MMA group (p = 0.003, p = 0.005, and p = 0.010, respectively), especially among females. This study underscores the clinical importance of specific measurements-anterior to posterior wall, medial wall to lateral recess, and ostium to inferior wall of the maxillary sinus-for guiding optimal surgical approaches in MS lesions.


Assuntos
Endoscopia , Seio Maxilar , Tomografia Computadorizada por Raios X , Humanos , Feminino , Masculino , Seio Maxilar/cirurgia , Seio Maxilar/diagnóstico por imagem , Seio Maxilar/microbiologia , Pessoa de Meia-Idade , Adulto , Endoscopia/métodos , Idoso , Estudos Retrospectivos , Maxila/cirurgia , Maxila/diagnóstico por imagem , Micoses/cirurgia , Micoses/diagnóstico por imagem
14.
Toxicology ; 505: 153827, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38729513

RESUMO

Pyroptosis is a form of programmed cell death characterized by gasdermin (GSDM)-mediated pore formation in the cell membrane, resulting in the release of pro-inflammatory cytokines and cellular lysis. Increasing evidence has shown that pyroptosis is responsible for the progression of various pulmonary disorders. The inhalation of polyhexamethylene guanidine (PHMG) causes severe lung inflammation and pulmonary toxicity; however, the underlying mechanisms are unknown. Therefore, in this study, we investigate the role of pyroptosis in PHMG-induced pulmonary toxicity. We exposed bronchial epithelial cells, BEAS-2B, to PHMG phosphate (PHMG-p) and evaluated cell death type, reactive oxygen species (ROS) levels, and relative expression levels of pyroptosis-related proteins. Our data revealed that PHMG-p reduced viability and induced morphological alterations in BEAS-2B cells. Exposure to PHMG-p induced excessive accumulation of mitochondrial ROS (mtROS) in BEAS-2B cells. PHMG-p activated caspase-dependent apoptosis as well as NLRP3/caspase-1/GSDMD-mediated- and caspase-3/GSDME-mediated pyroptosis through mitochondrial oxidative stress in BEAS-2B cells. Notably, PHMG-p reduced mitochondrial respiratory function and induced the translocation of Bax and cleaved GSDM into the mitochondria, leading to mitochondrial dysfunction. Our results enhanced our understanding of PHMG-p-induced lung toxicity by demonstrating that PHMG-p induces pyroptosis via mtROS-induced mitochondrial dysfunction in bronchial epithelial cells.


Assuntos
Brônquios , Células Epiteliais , Guanidinas , Mitocôndrias , Piroptose , Espécies Reativas de Oxigênio , Piroptose/efeitos dos fármacos , Humanos , Espécies Reativas de Oxigênio/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Brônquios/efeitos dos fármacos , Brônquios/patologia , Brônquios/metabolismo , Linhagem Celular , Guanidinas/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
15.
PLoS Biol ; 22(5): e3002596, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38718086

RESUMO

Autism spectrum disorders (ASD) frequently accompany macrocephaly, which often involves hydrocephalic enlargement of brain ventricles. Katnal2 is a microtubule-regulatory protein strongly linked to ASD, but it remains unclear whether Katnal2 knockout (KO) in mice leads to microtubule- and ASD-related molecular, synaptic, brain, and behavioral phenotypes. We found that Katnal2-KO mice display ASD-like social communication deficits and age-dependent progressive ventricular enlargements. The latter involves increased length and beating frequency of motile cilia on ependymal cells lining ventricles. Katnal2-KO hippocampal neurons surrounded by enlarged lateral ventricles show progressive synaptic deficits that correlate with ASD-like transcriptomic changes involving synaptic gene down-regulation. Importantly, early postnatal Katnal2 re-expression prevents ciliary, ventricular, and behavioral phenotypes in Katnal2-KO adults, suggesting a causal relationship and a potential treatment. Therefore, Katnal2 negatively regulates ependymal ciliary function and its deletion in mice leads to ependymal ciliary hyperfunction and hydrocephalus accompanying ASD-related behavioral, synaptic, and transcriptomic changes.


Assuntos
Transtorno do Espectro Autista , Cílios , Epêndima , Camundongos Knockout , Fenótipo , Animais , Masculino , Camundongos , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/metabolismo , Transtorno do Espectro Autista/fisiopatologia , Comportamento Animal , Cílios/metabolismo , Modelos Animais de Doenças , Epêndima/metabolismo , Hipocampo/metabolismo , Hidrocefalia/genética , Hidrocefalia/metabolismo , Hidrocefalia/patologia , Hidrocefalia/fisiopatologia , Katanina/metabolismo , Katanina/genética , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Sinapses/metabolismo , Transcriptoma/genética
16.
Eur J Med Chem ; 272: 116487, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38759452

RESUMO

Acute lung injury (ALI) and inflammatory bowel disease (IBD) are common inflammatory illnesses that seriously affect people's health. Herein, a series of 4-hydroxylcoumarin (4-HC) derivatives were designed and synthesized. The inhibitory effects of these compounds on LPS-induced interleukin-6 (IL-6) release from J774A.1 cells were then screened via ELISA assay, compound B8 showed 3 times more active than the lead compound 4-HC. The most active compound B8 had the IC50 values of 4.57 µM and 6.51 µM for IL-6 release on mouse cells J774A.1 and human cells THP-1, respectively. Furthermore, we also found that B8 could act on the MAPK pathway. Based on the target prediction results of computer virtual docking, kinase inhibitory assay was carried out, and it revealed that targeting IRAK1 was a key mechanism for B8 to exert anti-inflammatory activity. Moreover, B8 exerted a good therapeutic effect on the dextran sulfate sodium (DSS)-induced colitis model and liposaccharide (LPS)-induced ALI mouse models. The acute toxicity experiments indicated that high-dose B8 caused no adverse reactions in mice, confirming its safety in vivo. Additionally, the preliminary pharmacokinetic (PK) parameters of B8 in SD rats were also examined, revealing a bioavailability (F) of 28.72 %. In conclusion, B8 is a potential candidate of drug for the treatment of ALI and colitis.


Assuntos
4-Hidroxicumarinas , Lesão Pulmonar Aguda , Colite , Desenho de Fármacos , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Colite/tratamento farmacológico , Colite/induzido quimicamente , Camundongos , Humanos , Relação Estrutura-Atividade , 4-Hidroxicumarinas/farmacologia , 4-Hidroxicumarinas/química , 4-Hidroxicumarinas/síntese química , Estrutura Molecular , Sulfato de Dextrana , Masculino , Relação Dose-Resposta a Droga , Ratos , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Interleucina-6/metabolismo , Interleucina-6/antagonistas & inibidores , Quinases Associadas a Receptores de Interleucina-1/antagonistas & inibidores , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Simulação de Acoplamento Molecular , Camundongos Endogâmicos C57BL , Linhagem Celular
17.
JAMA Oncol ; 10(6): 737-743, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38662364

RESUMO

Importance: Prospective data assessing the safety of hypofractionated (40 Gy in 16 fractions) radiotherapy (RT) among patients who receive postoperative concurrent chemoradiotherapy for cervical cancer are lacking. Objective: To evaluate the acute toxic effects of hypofractionated pelvic intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy among women with cervical cancer who underwent radical hysterectomy. Design, Setting, and Participants: The POHIM-CCRT (Postoperative Hypofractionated Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy in Cervical Cancer) study was designed as a multicenter, phase 2 nonrandomized controlled trial that accrued and followed up patients from June 1, 2017, to February 28, 2023. In total, 84 patients were enrolled from 5 institutions affiliated with the Korean Radiation Oncology Group. Eligible patients experienced lymph node metastasis, parametrial invasion, or positive resection margins after radical hysterectomy for treatment of confirmed cervical cancer. Intervention: Postoperative pelvic radiation using hypofractionated IMRT with 40 Gy in 16 fractions to the whole pelvis combined with concurrent chemotherapy. Main Outcomes and Measures: The primary end point was incidence of acute grade 3 or higher gastrointestinal tract, genitourinary, and hematologic toxic effects (based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) in the evaluable population during RT or within 3 months after RT completion. Results: Of 84 patients enrolled, 5 dropped out prior to RT, and data from 79 patients were analyzed. The patients' median (IQR) age was 48 (42-58) years, and the median (IQR) tumor size was 3.7 (2.7-4.5) cm. Of these patients, 31 (39.7%) had lymph node metastasis, 4 (5.1%) had positive resection margins, and 43 (54.4%) had parametrial invasion. Grade 3 or higher acute toxic effects occurred in 2 patients (2.5% [90% CI, 0%-4.8%]). After a median (IQR) follow-up of 43.0 (21.1-59.0) months, the 3-year disease-free survival rate was 79.3%, and the overall survival rate was 98.0%. Conclusions: Findings from this nonrandomized control trial indicated that postoperative pelvic irradiation combined with concurrent chemotherapy using hypofractionated IMRT with 40 Gy in 16 fractions was safe and well-tolerated in women with cervical cancer. Studies assessing long-term toxic effects and oncological outcomes with longer follow-up periods are needed. Trial Registration: ClinicalTrials.gov Identifier: NCT03239613.


Assuntos
Quimiorradioterapia , Hipofracionamento da Dose de Radiação , Radioterapia de Intensidade Modulada , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Pessoa de Meia-Idade , Adulto , Quimiorradioterapia/efeitos adversos , Histerectomia , Estudos Prospectivos , Idoso
18.
Sci Rep ; 14(1): 8358, 2024 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600292

RESUMO

The necessity of bilateral bypass in adult moyamoya disease (MMD) remains unclear despite its recommendation for pediatric and hemorrhagic cases. We aimed to investigate the natural course of hemodynamically stable unoperated hemispheres after bypass surgery for symptomatic and hemodynamically unstable hemispheres in adult patients with ischemic MMD. Among 288 patients, the mean age at the first operation of the unstable hemispheres was 40.8 ± 12.2 years. The mean follow-up period was 62.9 ± 46.5 months. 45 patients (15.6%) experienced stroke events in the unoperated hemisphere, consisting of hemorrhagic stroke in 8 (2.8%) and ischemic stroke in 37 (12.8%), including progressive transient ischemic attack in 25 (8.7%) and infarction in 12 (4.2%). Among them, 39 patients (13.5%) underwent bypass surgery. The annual risk of total stroke is 3.0%/patient-year, with 2.5% for ischemic stroke and 0.5% for hemorrhagic stroke. The 5- and 10-year cumulative risks of ischemic stroke were 13.4% and 18.3%, respectively, and those of hemorrhagic stroke were each 3.2%. The natural course of hemodynamically stable hemispheres contralateral to the operated ones appeared fairly good. Additional bypass surgery on the unoperated hemispheres should be considered for symptomatic and hemodynamically unstable hemispheres in adult patients with ischemic MMD during the follow-up.


Assuntos
Revascularização Cerebral , Acidente Vascular Cerebral Hemorrágico , AVC Isquêmico , Doença de Moyamoya , Acidente Vascular Cerebral , Adulto , Humanos , Criança , Pessoa de Meia-Idade , Doença de Moyamoya/cirurgia , Resultado do Tratamento , Estudos Retrospectivos
19.
Sci Rep ; 14(1): 8364, 2024 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600312

RESUMO

This study retrospectively assessed radiographic outcomes and risk factors associated with non-union in femoral shaft fragmentary segmental fractures (AO/OTA 32C3) treated with reamed antegrade intra-medullary nailing. Radiological outcomes, including union and alignment, were evaluated. The risk factors for non-union were investigated, including demographics and treatment-related characteristics, such as the number of interlocking screws, segmentation length, main third fragment length, distance of the main third fragment, width ratio and exposed nail length in one cortex from immediate post-operative radiographs. Multivariate logistic regression was used for statistical analysis. Among 2295 femoral shaft fracture patients from three level-1 trauma centers, 51 met the inclusion criteria. The radiological union was achieved in 37 patients (73%) with a mean union time of 10.7 ± 4.8 months. The acceptable axial alignment was observed in 30 patients (59%). Multiple logistic regression analysis identified only exposed nail length as a significant risk factor for non-union (odds ratio: 1.599, p = 0.003) and the cut-off value was 19.1 mm (sensitivity, 0.786; specificity, 0.811). The study revealed high rates of non-union (27%) and malalignment (41%). Therefore, patients who underwent intramedullary nailing with an exposed nail length greater than 19.1 mm or about twice the nail diameter should be cautioned of the potential non-union.


Assuntos
Fraturas do Fêmur , Fixação Intramedular de Fraturas , Humanos , Fixação Intramedular de Fraturas/efeitos adversos , Estudos Retrospectivos , Pinos Ortopédicos/efeitos adversos , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/cirurgia , Fraturas do Fêmur/etiologia , Radiografia , Resultado do Tratamento , Consolidação da Fratura
20.
Nature ; 628(8007): 293-298, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38570686

RESUMO

Phase-change memory (PCM) has been considered a promising candidate for solving von Neumann bottlenecks owing to its low latency, non-volatile memory property and high integration density1,2. However, PCMs usually require a large current for the reset process by melting the phase-change material into an amorphous phase, which deteriorates the energy efficiency2-5. Various studies have been conducted to reduce the operation current by minimizing the device dimensions, but this increases the fabrication cost while the reduction of the reset current is limited6,7. Here we show a device for reducing the reset current of a PCM by forming a phase-changeable SiTex nano-filament. Without sacrificing the fabrication cost, the developed nano-filament PCM achieves an ultra-low reset current (approximately 10 µA), which is about one to two orders of magnitude smaller than that of highly scaled conventional PCMs. The device maintains favourable memory characteristics such as a large on/off ratio, fast speed, small variations and multilevel memory properties. Our finding is an important step towards developing novel computing paradigms for neuromorphic computing systems, edge processors, in-memory computing systems and even for conventional memory applications.

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