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1.
Heliyon ; 10(11): e31775, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38947426

RESUMO

Diabetic nephropathy (DN) has emerged as the foremost cause of end-stage renal disease (ESRD) globally. Endoplasmic reticulum (ER) stress plays a critical role in DN progression. Triterpenoid saponin from Aralia taibaiensis (sAT) has been reported to possess anti-diabetic and anti-oxidant effects. The aim of this study was to examine the influence of sAT on DN treatment and elucidate potential underlying mechanisms. A high-fat diet (HFD) and Streptozotocin (STZ) were employed to induce DN in male Sprague Dawley (SD) rats which were subsequently treated with varying concentrations of sAT for 8 weeks. Our findings reveal that different doses of sAT significantly mitigated hyperglycemia, reduced urinary albumin excretion, and decreased plasma creatinine and blood urea nitrogen levels in DN rats. Moreover, sAT administration improved body weight, alleviated renal fibrosis and histopathological changes in the diabetic kidneys. Notably, sAT treatment partially restored increased Bax expression and decreased Bcl-2 expression. Additionally, sAT inhibited ER stress-related proteins, including GRP78, p-PERK, ATF4 and CHOP in kidneys of DN rats. These results suggest that sAT ameliorated experimental diabetic nephropathy, at least in part, through ER stress pathway. These findings provide a scientific basis for the potential development of sAT as a therapeutic agent for DN treatment.

2.
Dalton Trans ; 53(18): 7965-7970, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38647331

RESUMO

Organic crystal materials with metal-free feature and intrinsically low molecular mass are highly desirable for applications in flexible smart devices. Here, we reported a plastic crystal, tris(hydroxymethyl)aminomethane perchlorate (Tris-HClO4), which crystallizes in the R3̄ space group at room temperature and undergoes plastic phase transition at 369 K, showing a large entropy gain of 70.5 J mol-1 K-1, much higher than its fusion entropy gain (12.9 J mol-1 K-1). PXRD measurement indicates that it has cubic lattice symmetry in the high-temperature phase. Moreover, it exhibits excellent dielectric permittivity switching properties and robust cyclic stability. This work could be the pathway for chemical designing multifunctional switchable materials with the motive of combining the idea of symmetry breaking and plastic phase transition.

4.
Heliyon ; 10(4): e25258, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38375272

RESUMO

Objective: "Metabolism affects function" is the consensus of researchers at present. It has potential clinical application value to study the effects of regulating glutamine (Gln) metabolism on diabetes physiology or pathology. Our research aimed to summarize the latest research progress, frontier hot topics and future development trends in this field from the perspective of scientometrics. Methods: Relevant literatures and reviews were obtained from the Web of Science (WoS) between January 1, 2001 and May 31, 2022. An online analysis platform of bibliometrics, CiteSpace, and VOS viewer software were used to generate visual knowledge network graphs, including publication countries, institutions and authors partnership analysis, co-occurrence analysis, co-citation analysis, as well as citations and keywords burst detection to acquire research trends and hotspots. Results: Our results showed that a total of 945 publications in the WoS database met the analysis requirements, with articles being the main type. The overall characteristics showed an increasing trend in the number of publications and citations. The United States was leading the way in this research and was a hub for aggregating collaborations across countries. Vanderbilt University delivered high-quality impact with the most published articles. DeBerardinis, RJ in this field was the most representative author and his main research contents were Gln metabolism and mitochondrial glutaminolysis. Significantly, there was a relative lack of collaboration between institutions and authors. In addition, "type 2 diabetes", "glutamine", "metabolism", "gene expression" and "metabolomics" were the keywords categories with high frequency in co-citation references and co-occurrence cluster keywords. Analysis of popular keywords burst detection showed that "branched chain", "oxidative phosphorylation", "kinase", "insulin sensitivity", "tca cycle", "magnetic resonance spectroscopy" and "flux analysis" were new research directions and emerging methods to explore the link between Gln metabolism and diabetes. Overall, exploring Gln metabolism showed a gradual upward trend in the field of diabetes. Conclusion: This comprehensive scientometric study identified the general outlook for the field and provided valuable guidance for ongoing research. Strategies to regulate Gln metabolism hold promise as a novel target to treat diabetes, as well as integration and intersection of multidisciplinary provides cooperation strategies and technical guarantees for the development of this field.

5.
Int Orthop ; 48(3): 773-783, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37964157

RESUMO

PURPOSE: The objective of this study was to investigate the efficacy of an artificial intelligence-assisted 3D planning system (AIHIP) in total hip arthroplasty by direct anterior approach and assess the reliability of the AIHIP preoperative program in terms of both interobserver and intraobserver agreement. METHODS: A retrospective analysis was conducted on patients who underwent unilateral primary THA via direct anterior approach from June 2019 to March 2022. Participants were randomly assigned to receive either the AIHIP system (n = 220) or the 2D template (control group) (n = 220) for preoperative planning. The primary outcome aimed to evaluate the correspondence between the prosthesis selected intro-operation and the one planned preoperatively, as well as to calculate the intraclass correlation coefficient (ICC). Secondary outcomes included operation time, intraoperative blood loss, fluoroscopy times, Harris hip score (HHS), lower limb length difference (LLD), femoral offset (FO), and bilateral femoral offset difference. RESULTS: No significant differences were observed in gender, age, body mass index (BMI), aetiology, and American Society of Anesthesiologists (ASA) score between the two groups. Both planning methods exhibited good intraobserver agreement for component planning (ICC: 0.941-0.976). Interobserver agreement for component planning was comparable between the two methods (ICC: 0.882-0.929). In the AIHIP group, the accuracy of acetabular cup and femoral stem prosthetics planning significantly improved, with accuracies within the size range of ± 0 and ± 1 being 76.8% and 90.5% and 79.5% and 95.5%, respectively. All differences between two groups were statistically significant (p < 0.05). Patients receiving AIHIP preoperative planning experienced shorter operation times, reduced intraoperative blood loss, fewer fluoroscopy times, and lower leg length discrepancy (LLD) (p < 0.05). Moreover, they demonstrated a higher Harris hip score (HHS) at three days post-surgery (p < 0.05). However, no significant differences were found in femoral offset (FO), difference of bilateral femoral offsets, and HHS at 1 month after the operation. CONCLUSION: Utilizing AIHIP for preoperative planning of direct anterior approach THA can significantly enhance the accuracy of prosthetic sizing with good reliability, decrease operation time, reduce intraoperative blood loss, and more effectively restore the length of both lower limbs. This approach has greater clinical application value.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Humanos , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos , Inteligência Artificial , Estudos Retrospectivos , Reprodutibilidade dos Testes , Perda Sanguínea Cirúrgica , Desigualdade de Membros Inferiores , Resultado do Tratamento
6.
Clin Cancer Res ; 30(3): 489-497, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37982848

RESUMO

PURPOSE: Cachexia is common in patients with advanced cancer and is associated with elevated serum growth differentiation factor 15 (GDF-15) concentrations. This first-in-patient (phase Ib), 24-week study assessed use of ponsegromab, a mAb against GDF-15, in adults with advanced cancer, cachexia, and elevated GDF-15 serum concentration. PATIENTS AND METHODS: Participants (n = 10) received open-label ponsegromab subcutaneous 200 mg every 3 weeks for 12 weeks in addition to standard-of-care anticancer treatment. Ponsegromab safety, tolerability, and pharmacokinetics were assessed in addition to serum GDF-15 concentrations and exploratory measures of efficacy. RESULTS: No treatment-related treatment-emergent adverse events, injection site reactions, or adverse trends in clinical laboratory tests, vital signs, or electrocardiogram parameters attributable to ponsegromab were identified. Median serum unbound GDF-15 concentration at baseline was 2.269 ng/mL. Following initiation of study treatment, median unbound GDF-15 concentrations were below the lower limit of quantification (0.0424 ng/mL) from day 1 (3 hours postdose) through week 15. Increases in body weight were observed at all time points during the treatment and follow-up periods. A least-squares mean (SE) increase of 4.63 (1.98) kg was observed at week 12, an increase of approximately 6.6% relative to baseline. Ponsegromab-mediated improvements in actigraphy-based assessments of physical activity and in quality of life, including appetite as assessed by Functional Assessment of Anorexia-Cachexia Therapy total and subscale scores, were also observed. CONCLUSIONS: Ponsegromab was well tolerated, suppressed serum GDF-15 concentrations, and demonstrated preliminary evidence of efficacy. These findings support the continued development of ponsegromab for the treatment of cachexia.


Assuntos
Caquexia , Neoplasias , Adulto , Humanos , Caquexia/tratamento farmacológico , Caquexia/etiologia , Fator 15 de Diferenciação de Crescimento/uso terapêutico , Qualidade de Vida , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico
7.
Biochem Pharmacol ; 220: 115968, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38104671

RESUMO

Ischemic stroke (IS) can cause severe harm, inducing oxidative stress, inflammation, and pyroptotic death. IS treatment efficacy remains limited, and microglia are important regulators of IS-related blood-brain barrier (BBB) damage. It is thus vital that new therapeutic agents capable of targeting microglia be identified to treat IS-related damage to the BBB. Acteoside (ACT), which is a compound derived from Cistanche tubulosa (Schenk) Wight., offers promising bioactivity, but its ability to protect against central nervous system injury remains to be documented. To clarify the protective benefits and mechanisms through which ACT can protect against damage to the BBB, a rat middle cerebral artery occlusion (MCAO) model system was herein employed. These in vivo analyses demonstrated that ACT was able to significantly reduce cerebral infarct size while improving their neurological scores and altering neurotrophic and inflammatory factor release. RNA sequencing and molecular docking studies highlighted the ability of ACT to exert its protective benefits via the HMGB1/TLR4/NLRP3 axis. Western immunoblotting and immunofluorescent staining for tight junction proteins additionally confirmed the ability of ACT to preserve BBB integrity. The underlying mechanisms were then explored with an oxygen-glucose deprivation (OGD) model in vitro with BV2 cells. This strategy thus confirmed that the ability of ACT to suppress microglial inflammatory and pyroptotic activity was HMGB1/TLR4/NLRP3 pathway-dependent. These data thus offer novel evidence that ACT can protect against IS-related damage to the BBB through the abrogation of inflammatory and pyroptotic activity, underscoring its promise as a novel lead compound for the therapeutic treatment of IS.


Assuntos
Isquemia Encefálica , Glucosídeos , Proteína HMGB1 , AVC Isquêmico , Polifenóis , Traumatismo por Reperfusão , Acidente Vascular Cerebral , Ratos , Animais , Barreira Hematoencefálica/metabolismo , Microglia/metabolismo , Receptor 4 Toll-Like/metabolismo , AVC Isquêmico/tratamento farmacológico , Proteína HMGB1/metabolismo , Simulação de Acoplamento Molecular , Proteína 3 que Contém Domínio de Pirina da Família NLR , Acidente Vascular Cerebral/tratamento farmacológico
8.
World J Psychiatry ; 13(11): 912-918, 2023 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-38073906

RESUMO

BACKGROUND: The psychological state of patients with post stroke limb movement disorders undergoes a series of changes that affect rehabilitation training and recovery of limb motor function. AIM: To determine the correlation between motor rehabilitation and the psychological state of patients with limb movement disorders after stroke. METHODS: Eighty patients with upper and lower limb dysfunction post stroke were retrospectively enrolled in our study. Based on Hospital Anxiety and Depression Scale (HADS) scores measured before rehabilitation, patients with HADS scores ≥ 8 were divided into the psychological group; otherwise, the patients were included in the normal group. Motor function and daily living abilities were compared between the normal and psychological groups. Correlations between the motor function and psychological status of patients, and between daily living ability and psychological status of patients were analyzed. RESULTS: After 1, 2, and 3 wk of rehabilitation, both the Fugl-Meyer assessment and Barthel index scores improved compared to their respective baseline scores (P < 0.05). A greater degree of improvement was observed in the normal group compared to the psychological group (P < 0.05). There was a negative correlation between negative emotions and limb rehabilitation (-0.592 ≤ r ≤ -0.233, P < 0.05), and between negative emotions and daily living ability (-0.395 ≤ r ≤ -0.199, P < 0.05). CONCLUSION: There is a strong correlation between motor rehabilitation and the psychological state of patients with post stroke limb movement disorders. The higher the negative emotions, the worse the rehabilitation effect.

9.
Cureus ; 15(11): e48312, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37933319

RESUMO

In this case report, we discuss a young female who presented to the emergency department with a recent onset of weakness, paraesthesia, and gait disturbance suggestive of peripheral neuropathy and gait ataxia. This was attributed to the occasional use of recreational nitrous oxide (N2O) over the past 10 months. Subacute combined degeneration of the spinal cord is a condition affecting the lateral and posterior columns of the spinal cord, mainly caused by demyelination. The use of recreational N2O depletes the levels of vitamin B12 thus leading to this demyelination of the nervous system. Physical examination revealed T6 and T7 and L3 and L4 sensory deficits bilaterally with hyporeflexia in bilateral knee and ankle reflexes with reduced power in the left lower limb as well as a spastic gait. Her vitamin B12 levels were low (98 g/dL). MRI spine showed a high signal in the posterior cord/ dorsal column. The patient made good recovery post-intramuscular B12 administration and physiotherapy with planned outpatient neurology rehabilitation.

10.
Inorg Chem ; 62(49): 19930-19936, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37990884

RESUMO

Organic-inorganic hybrid perovskites (OIHPs) have been emerging as a hot research topic due to their potential applications in energy storage, semiconductors, and electronic devices. Herein, we systematically investigated the synthesis and phase transition behaviors of the enantiomeric OIHPs, (R) and (S)-N,N-dimethyl-3-fluoropyrrolidinium cadmium bromide ([DMFP][CdBr3]), and the hybrid trigonal structure [DMFP]3 (CdBr3)(CdBr4). The enantiomers have a mirror-symmetric structure and enhanced solid-state phase transition points of 417 and 443 K, in contrast to the nonfluorinated parent compound, N,N-dimethyl-pyrrolidinium cadmium bromide ([DMP][CdBr3], 385 K). Moreover, racemic H/F substitution on the pyrrolidinium cations leads to the formation of a trigonal compound, showing above-room-temperature structural phase transition and dominant ferroelasticity. This work discovers chiral enantiomeric OIHPs through H/F substitution, demonstrating a useful chemical synthesis strategy for exploring novel phase transition materials.

11.
BMC Surg ; 23(1): 320, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37872509

RESUMO

BACKGROUND: Colorectal cancer (CRC) patients undergoing surgery are at a high risk of developing surgical site infections (SSIs), which contribute to increased morbidity, prolonged hospitalization, and escalated healthcare costs. Understanding the incidence, risk factors, and impact of SSIs is crucial for effective preventive strategies and improved patient outcomes. METHODS: This retrospective study analyzed data from 431 CRC patients who underwent surgery at Huangshan Shoukang Hospital between 2014 and 2022. The clinical characteristics and demographic information were collected. The incidence and impact of SSIs were evaluated, and independent risk factors associated with SSIs were identified using multivariable logistic regresison. A nomogram plot was constructed to predict the likelihood of SSIs occurrence. RESULTS: The overall incidence rate of SSIs was 7.65% (33/431). Patients with SSIs had significantly longer hospital stays and higher healthcare costs. Risk factors for SSIs included elevated Body Mass Index (BMI) levels (odds ratio, 1.12; 95% CI, 1.02-1.23; P = 0.017), the presence of diabetes (odds ratio, 3.88; 95% CI, 1.42 - 9.48; P = 0.01), as well as specific surgical factors such as open surgical procedures (odds ratio, 2.39; 95% CI [1.09; 5.02]; P = 0.031), longer surgical duration (odds ratio, 1.36; 95% CI [1.01; 1.84]; P = 0.046), and the presence of a colostomy/ileostomy (odds ratio, 3.17; 95% CI [1.53; 6.62]; P = 0.002). Utilizing multivariable regression analysis, which encompassed factors such as open surgical procedures, the presence of diabetes and colostomy/ileostom, the nomogram plot functions as a visual aid in estimating the individual risk of SSIs for patients. CONCLUSIONS: Risk factors for SSIs included higher BMI levels, the presence of diabetes, open surgical procedures, longer surgical duration, and the presence of colostomy/ileostomy. The nomogram plot serves as a valuable tool for risk assessment and clinical decision-making.


Assuntos
Neoplasias Colorretais , Diabetes Mellitus , Humanos , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/prevenção & controle , Fatores de Risco , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/complicações , Diabetes Mellitus/epidemiologia
12.
J Am Chem Soc ; 145(42): 23292-23299, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37819908

RESUMO

Fullerenes offer versatile functionalities and are promising materials for a widespread range of applications from biomedicine and energy to electronics. Great efforts have been made to manipulate the symmetries of fullerene and its derivatives for studying material properties and novel effects, such as ferroelectricity with polar symmetry; however, no documentary report has been obtained to realize their ferroelectricity. Here, for the first time, we demonstrated clear ferroelectricity in a fullerene adduct formed by C60 and S8. More is different: the combination of the most symmetric molecule C60 with the highest Ih symmetry and molecule S8 with high D4d symmetry resulted in the polar C60S8 adduct with a low crystallographic symmetry of the C2v (mm2) point group at room temperature. The presented C60S8 undergoes polar-to-polar ferroelectric phase transition with the mm2Fm notation, whose ferroelectricity was confirmed by a ferroelectric hysteresis loop and ferroelectric domain switching. This finding opens up a new functionality for fullerenes and sheds light on the exploration of more ferroelectric fullerenes.

13.
Medicine (Baltimore) ; 102(40): e35427, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37800829

RESUMO

RATIONALE: Posterior occipito-cervical spinal fusion (OCF) is a common surgical method for atlantoaxial dislocation, but postoperative airway complications may occur. Reintubation has been reported in the past, but the failure of reintubation is rare. PATIENT CONCERNS: A 54-year-old woman who underwent OCF due to rheumatoid cervical spondylosis and atlantoaxial dislocation. In the postanesthesia care unit, the patient developed upper respiratory tract obstruction after extubation. DIAGNOSES AND INTERVENTIONS: It is an upper respiratory tract obstruction due to anatomical changes because of surgery. Emergency airway management was activated, but it did not work. OUTCOMES: Emergency reintubation failed, and the patient was finally saved after tracheotomy. LESSONS: For patients who underwent OCF due to cervical spondylosis caused by rheumatoid arthritis, great attention should be paid to the perioperative airway management, especially during the recovery period. And more important, adequate reintubation preparatory work should be done before extubation.


Assuntos
Obstrução das Vias Respiratórias , Luxações Articulares , Doenças da Coluna Vertebral , Fusão Vertebral , Espondilose , Feminino , Humanos , Pessoa de Meia-Idade , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos , Vértebras Cervicais/cirurgia , Doenças da Coluna Vertebral/cirurgia , Pescoço , Luxações Articulares/etiologia , Luxações Articulares/cirurgia , Obstrução das Vias Respiratórias/etiologia , Espondilose/complicações , Complicações Pós-Operatórias
14.
Front Endocrinol (Lausanne) ; 14: 1115893, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37745701

RESUMO

Background: Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis and limited treatment options for metastases. However, new effective regimens are emerging for specific conditions in metastatic ACC. Case presentation: We report a case of a 36-year-old man diagnosed with metastatic ACC who had a large left adrenal mass (158 mm × 112 mm) and multiple metastases in the liver and lungs. Genetic testing revealed a microsatellite instability-high (MSI-H) tumor, a splice mutation in MLH1, and a high tumor mutational burden (TMB). After the left adrenalectomy, he received sequential treatment with a combination of mitotane, etoposide, paraplatin (EP-M), and sintilimab. His condition has been assessed as a stable disease since the sixth cycle of the combined regimen. Conclusion: This case highlights the remarkable response of our patient's ACC with MSI-H tumor, MLH1 spice mutation, and high TMB to treatment with a novel combination of EP-M and sintilimab. Our findings suggest a promising therapeutic option for patients with similar molecular profiles.


Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Masculino , Humanos , Adulto , Carcinoma Adrenocortical/tratamento farmacológico , Carcinoma Adrenocortical/genética , Mitotano , Carboplatina , Etoposídeo , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Neoplasias do Córtex Suprarrenal/genética
15.
Cancer Rep (Hoboken) ; 6(9): e1857, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37404200

RESUMO

INTRODUCTION: Obesity is a major risk factor in the development of endometrial cancer (EC) in young patients of reproductive age. Fertility sparing treatment is a viable option for a select group of patients with early EC, and involves systemic and intra-uterine hormonal therapy. Weight loss has been associated with improved outcomes in this group. Bariatric surgery (BS) has been shown to be the most efficient and durable method of weight loss in obese patients. However, there is a paucity of data studying the benefit of BS as part of fertility sparing treatment. METHODS: We present a retrospective case series of five patients who are undergoing fertility sparing treatment for early EC, who also underwent BS for treatment of obesity and related comorbidities. We aim to show early regression of EC for all the patients and also report on the other health benefits of BS. RESULTS: All five patients in the series achieved regression of EC within 6 months of undergoing BS. They also achieved significant weight loss consistent with previous studies, and three patients who had comorbidities related to obesity had remission of these conditions. One of the patients with EC regression also managed to conceive with IVF (In-vitro Fertilisation). CONCLUSION: Patients on fertility sparing treatment for early EC who underwent BS was associated with early regression within 6 months, significant weight loss and resolution of comorbidities. BS could be a promising component of fertility sparing treatment. Long term, prospective studies are required to confirm the benefits reported in this case series.


Assuntos
Cirurgia Bariátrica , Hiperplasia Endometrial , Neoplasias do Endométrio , Preservação da Fertilidade , Feminino , Humanos , Estudos Retrospectivos , Hiperplasia Endometrial/complicações , Preservação da Fertilidade/métodos , Neoplasias do Endométrio/complicações , Obesidade/complicações
16.
Adv Sci (Weinh) ; 10(24): e2302426, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37328441

RESUMO

Inorganic ferroelectrics have long dominated research and applications, taking advantage of high piezoelectric performance in bulk polycrystalline ceramic forms. Molecular ferroelectrics have attracted growing interest because of their environmental friendliness, easy processing, lightweight, and good biocompatibility, while realizing the considerable piezoelectricity in their bulk polycrystalline forms remains a great challenge. Herein, for the first time, through ring enlargement, a molecular ferroelectric 1-azabicyclo[3.2.1]octonium perrhenate ([3.2.1-abco]ReO4 ) with a large piezoelectric coefficient d33 up to 118 pC/N in the polycrystalline pellet form is designed, which is higher than that of the parent 1-azabicyclo[2.2.1]heptanium perrhenate ([2.2.1-abch]ReO4 , 90 pC/N) and those of most molecular ferroelectrics in polycrystalline or even single crystal forms. The ring enlargement reduces the molecular strain for easier molecular deformation, which contributes to the higher piezoelectric response in [3.2.1-abco]ReO4 . This work opens up a new avenue for exploring high piezoelectric polycrystalline molecular ferroelectrics with great potential in piezoelectric applications.

17.
J Asian Nat Prod Res ; 25(12): 1217-1222, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37163366

RESUMO

A new abietane diterpenoid, 1ß, 11-epoxyabieta-12-hydroxy-8, 11, 13-triene-7-one (1), along with three known compounds (2-4), was isolated from Lycopodium complanatum. Their structures were confirmed by the analysis of 1D, 2D NMR and HRESIMS data, and comparison with previous spectral data. All compounds were tested for inhibitory activities against A549, HepG2 and MCF-7 tumor cell lines. [Figure: see text].


Assuntos
Antineoplásicos Fitogênicos , Lycopodium , Humanos , Abietanos/farmacologia , Abietanos/química , Estrutura Molecular , Lycopodium/química , Linhagem Celular Tumoral , Células MCF-7 , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química
18.
Cancer Sci ; 114(7): 2951-2960, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37158138

RESUMO

D-1553 is a small molecule inhibitor selectively targeting KRASG12C and currently in phase II clinical trials. Here, we report the preclinical data demonstrating antitumor activity of D-1553. Potency and specificity of D-1553 in inhibiting GDP-bound KRASG12C mutation were determined by thermal shift assay and KRASG12C -coupled nucleotide exchange assay. In vitro and in vivo antitumor activity of D-1553 alone or in combination with other therapies were evaluated in KRASG12C mutated cancer cells and xenograft models. D-1553 showed selective and potent activity against mutated GDP-bound KRASG12C protein. D-1553 selectively inhibited ERK phosphorylation in NCI-H358 cells harboring KRASG12C mutation. Compared to the KRAS WT and KRASG12D cell lines, D-1553 selectively inhibited cell viability in multiple KRASG12C cell lines, and the potency was slightly superior to sotorasib and adagrasib. In a panel of xenograft tumor models, D-1553, given orally, showed partial or complete tumor regression. The combination of D-1553 with chemotherapy, MEK inhibitor, or SHP2 inhibitor showed stronger potency on tumor growth inhibition or regression compared to D-1553 alone. These findings support the clinical evaluation of D-1553 as an efficacious drug candidate, both as a single agent or in combination, for patients with solid tumors harboring KRASG12C mutation.


Assuntos
Neoplasias Pulmonares , Proteínas Proto-Oncogênicas p21(ras) , Animais , Humanos , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Linhagem Celular Tumoral , Modelos Animais de Doenças , Neoplasias Pulmonares/patologia
19.
Medicine (Baltimore) ; 102(14): e33484, 2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-37026923

RESUMO

RATIONALE: It is emergency and vital during neurosurgical procedure in traumatic intracranial when an acute intraoperative brain bulge (AIBB) is occurred. It is important to get a diagnosis quickly. PATIENT CONCERNS: A 44-year-old man was undergone a neurosurgical procedure for the left side of traumatic intracranial hematoma. An AIBB was occurred during the surgery. Computed tomography (CT) is always used in diagnosis when an AIBB is occurred, but more time is needed when CT is conducted. DIAGNOSES: We diagnosed the AIBB through bedside real-time ultrasound, and a delayed hematoma which caused the AIBB was found. INTERVENTIONS: A further neurosurgical procedure of right intracranial hematoma was performed for the patient. OUTCOMES: The surgical effect and the patient's prognosis were significantly improved. LESSONS: Through this patient, we should pay more attention to the application of perioperative of real-time ultrasonic monitoring, to provide more convenience for surgical patients, and improve the prognosis of them.


Assuntos
Hematoma , Hemorragia Intracraniana Traumática , Masculino , Humanos , Adulto , Hematoma/diagnóstico por imagem , Hematoma/etiologia , Hematoma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Tomografia Computadorizada por Raios X , Hemorragia Intracraniana Traumática/diagnóstico por imagem , Hemorragia Intracraniana Traumática/etiologia , Hemorragia Intracraniana Traumática/cirurgia , Ultrassonografia
20.
BMC Musculoskelet Disord ; 24(1): 319, 2023 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-37087443

RESUMO

OBJECTIVE: To investigate whether the application of a curved rasp on the femoral side is effective in reducing the incidence of stem malalignment in total hip replacement with direct anterior approach (DAA-THA), followed by the analysis of the independent risk factors affecting stem malalignment. METHODS: Retrospective analysis was carried out covering 160 patients undergoing DAA-THA from January 2019 to December 2021, with Tri-Lock (BPS, Depuy) stem applied in all 113 patients were screened according to inclusion and exclusion criteria. The data of gender, age, body mass index, preoperative diagnoses, Dorr classification, FAR ratio, pelvic morphology ratio, WOMAC scores, were analyzed to explore the independent factors influencing the malalignment of the femoral prosthesis implantation. Then data of patients were divided into group A and group B according to whether the curved rasp was taken during the operation. The chi-square test was performed to compare the incidence of femoral stem malalignment between the two groups. RESULTS: There revealed two independent risk factors: BMI and FAR ratio that affected femoral stem malalignment. The increased BMI was associated with a higher probability of femoral stem malalignment (P<0.05), the probability of malalignment of femoral stem in FAR ratio<1 was 1.15 times higher than that in FAR>1(OR = 1.15, 95% CI: 1.03-1.28, P<0.05). Further grouping analysis showed that the incidence of femoral stem malalignment in patients with intraoperative application of curved rasp was 27%, while in patients without curved rasp, the incidence of femoral stem malalignment increased significantly to 48.7%(P<0.05). The placement angle of prosthesis in group A was significantly better than that in group B, especially mild femoral stem malalignment (0%) and severe femoral stem malalignment (2.70%), and the difference was statistically significant (P < 0.05). There found no significant difference in age, gander, intraoperative complications and last follow-up assessment of WOMAC scores between the two groups of patients. CONCLUSIONS: In DAA-THA, BMI and FAR ratio act as the independent risk factors for femoral stem malalignment. Intraoperative use of a curved rasp significantly reduces the incidence of malalignment of the femoral stem.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Humanos , Artroplastia de Quadril/efeitos adversos , Prótese de Quadril/efeitos adversos , Estudos Retrospectivos , Fêmur/cirurgia , Resultado do Tratamento
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