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1.
Front Immunol ; 15: 1425076, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39221245

RESUMO

The optimal treatment for patients with severe aplastic anemia (SAA) who fail an initial course of antithymocyte globulin (ATG) plus cyclosporine has not yet been established. We compared the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) (n = 36) with repeated immunosuppressive therapy (IST) (n = 33) for relapsed/refractory SAA between 2007 and 2022. In the IST group, patients were retreated with ATG (n = 16) or high-dose cyclophosphamide (n = 17). The overall response rate was 57.6% at 6 months and 60.6% at 12 months. In the allo-HSCT group, patients received a transplant from a matched sibling donor (n = 6), matched unrelated donor (n = 7), or haploidentical donor (n = 23). All patients achieved neutrophil engraftment, and there were no cases of primary graft failure. The cumulative incidences (CIs) of grades II-IV and III-IV acute graft-versus-host disease (GVHD) were 36.1% ± 0.7% and 13.9% ± 0.3% at day +100, respectively. The 4-year CI of chronic GVHD (cGVHD) was 36.2% ± 0.7%, with moderate to severe cGVHD at 14.9% ± 0.4%. Compared with IST, HSCT recipients showed much higher hematologic recovery rate at 3, 6, and 12 months (63.9%, 83.3%, and 86.1%, respectively, p < 0.001). The estimated 4-year overall survival (OS) (79.8% ± 6.8% vs. 80.0% ± 7.3%, p = 0.957) was similar; however, the failure-free survival (FFS) was significantly better in the HSCT group (79.8% ± 6.8% vs. 56.6% ± 8.8%, p = 0.049). Of note, children in the HSCT cohort were all alive without treatment failures, exhibiting superior OS (100% vs. 50.0% ± 17.7%, p = 0.004) and FFS (100% vs. 50.0% ± 17.7%, p = 0.004) than children in the IST cohort. Subgroup analysis revealed that younger patients (age ≤ 35 years), especially children, and those with refractory SAA benefited more from HSCT. Therefore, for these patients, salvage HSCT may be more preferable than a second course of IST.


Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Imunossupressores , Recidiva , Humanos , Anemia Aplástica/terapia , Anemia Aplástica/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Masculino , Feminino , Adolescente , Adulto , Doença Enxerto-Hospedeiro/etiologia , Criança , Imunossupressores/uso terapêutico , Imunossupressores/administração & dosagem , Adulto Jovem , Pré-Escolar , Pessoa de Meia-Idade , Resultado do Tratamento , Soro Antilinfocitário/uso terapêutico , Soro Antilinfocitário/administração & dosagem , Transplante Homólogo , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Terapia de Imunossupressão/métodos , Estudos Retrospectivos , Ciclosporina/uso terapêutico , Ciclosporina/administração & dosagem
2.
Rev Cardiovasc Med ; 25(7): 267, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39139443

RESUMO

Background: Acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) carries a high mortality risk. Inflammation and nutrition are involved in the pathogenesis and prognosis of both AMI and CS. The advanced lung cancer inflammation index ratio (ALI) combines the inflammatory and nutritional status. Our present study aimed to explore the prognostic value of ALI in patients with CS following AMI. Methods: In total, 217 consecutive patients with AMI complicated by CS were divided into two groups based on the ALI admissions cut-off: ≤ 12.69 and > 12.69. The primary endpoint of this study was 30-day all-cause mortality. The secondary endpoints were gastrointestinal hemorrhage and major adverse cardiovascular events (MACEs), including 30-day all-cause mortality, atrioventricular block, ventricular tachycardia/ventricular fibrillation, and nonfatal stroke. The association of ALI with the study endpoints was analyzed by Cox regression analysis. Results: During the 30-day follow-up period after admission, 104 (47.9%) patients died and 150 (69.1%) suffered MACEs. The Kaplan-Meier analysis revealed significantly higher cumulative mortality and lower MACE rates in the low-ALI group compared to the high-ALI group (both log-rank p < 0.001). The 30-day mortality rate was significantly higher in patients with ALI ≤ 12.69 compared to ALI > 12.69 (72.1% vs. 22.6%; p < 0.001). Furthermore, the incidence of MACEs was higher in patients with ALI ≤ 12.69 (85.6% vs. 51.9%; p < 0.001). The receiver operating curve showed that ALI had a modest predictive value (area under the curve [AUC]: 0.789, 95% confidence interval [CI]: 0.729, 0.850). After multivariable adjustment, ALI ≤ 12.69 was an independent predictor for both 30-day all-cause mortality (hazard ratio [HR]: 3.327; 95% CI: 2.053, 5.389; p < 0.001) and 30-day MACEs (HR: 2.250; 95% CI 1.553, 3.260; p < 0.001). Furthermore, the addition of ALI to a base model containing clinical and laboratory data statistically improved the predictive value. Conclusions: Assessing ALI levels upon admission can provide important information for the short-term prognostic assessment of patients with AMI complicated by CS. A lower ALI may serve as an independent predictor of increased 30-day all-cause mortality and MACEs.

3.
Int J Surg Case Rep ; 123: 110214, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39208618

RESUMO

INTRODUCTION AND IMPORTANCE: Massage is a form of health care, but incorrect techniques can potentially harm the human body (Qin et al., 2023 [1]). While there have been no reported cases of lateral thoracic artery pseudoaneurysm and rupture induced by axillary massage, it is important to further explore how to address and prevent such potential risks. CASE PRESENTATION: This case study highlights a rare occurrence where a 61-year-old female patient experienced a lateral thoracic artery pseudoaneurysm and ruptured as a result of an axillary massage. The patient, self-taught in Chinese medicine and massage, regularly rubbed the Jiquan points in her armpits to promote heart health, with each session lasting 30-60 min for two years. She presented with symptoms such as dizziness, palpitations, left armpit pain, and oedema, leading to her admission to a nearby hospital. Despite receiving blood transfusions, her symptoms did not improve, necessitating her to refer to our hospital. A CT angiography scan of her upper limb arteries revealed the presence of a left lateral thoracic artery pseudoaneurysm and rupture, resulting in subcutaneous hematoma in the left axilla, chest, and back. Following angiography, successful embolisation was performed. Three months after surgery, the patient regained full mobility and was free from pain in her left upper limb. CLINICAL DISCUSSION: The armpit region contains a high concentration of nerves and blood vessels, making it crucial to have a thorough understanding of its anatomy and to use precise massage techniques. Damage to the axillary arteries can result in severe complications, which can be addressed through either open or endovascular interventional procedures. This article reviews existing literature and guides in managing these specific scenarios. CONCLUSION: Caution should be exercised when performing an armpit massage, as a thorough understanding of the anatomy of the axillary area is crucial. Injury to the lateral thoracic artery is a potential risk during axillary massage, and in such cases, endovascular intervention may be considered.

4.
CNS Neurosci Ther ; 30(7): e14875, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39072998

RESUMO

BACKGROUND: Angiogenesis is crucial in neuroprotection of secondary thalamic injury after cortical infarction. The p75 neurotrophin receptor (p75NTR) plays a key role in activating angiogenesis. However, the effects of p75NTR on angiogenesis in the thalamus after cortical infarction are largely unknown. Herein we investigate whether p75NTR facilitates angiogenesis to attenuate secondary thalamic damage via activating hypoxia-inducible factor 1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway mediated by Von Hippel-Lindau (VHL) after distal middle cerebral artery occlusion (dMCAO). METHODS: The male rat model of dMCAO was established. The effects of p75NTR on the angiogenesis was evaluated using RNA-sequencing, immunohistochemistry, western blot, quantitative real-time polymerase chain reaction, magnetic resonance imaging, behavior tests, viral and pharmacological interventions. RESULTS: We found that the p75NTR and vessel density were decreased in ipsilateral thalamus after dMCAO. The p75NTR-VHL interaction was reduced, which promoted the ubiquitination degradation of HIF-1α and reduced VEGF expression after dMCAO. Notably, p75NTR overexpression restrained the ubiquitination degradation of HIF-1α by inhibiting VHL-HIF-1α interaction, further promoted angiogenesis, increased cerebral blood flow of ipsilateral thalamus and improved neurological function after dMCAO. CONCLUSION: For the first time, we highlighted that the enhancement of p75NTR-VHL interaction promoted angiogenesis in attenuating secondary thalamic damage after dMCAO.


Assuntos
Infarto da Artéria Cerebral Média , Neovascularização Fisiológica , Ratos Sprague-Dawley , Tálamo , Animais , Masculino , Ratos , Tálamo/metabolismo , Tálamo/patologia , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/patologia , Neovascularização Fisiológica/fisiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Receptores de Fator de Crescimento Neural/metabolismo , Receptores de Fator de Crescimento Neural/genética , Infarto Cerebral/patologia , Angiogênese , Proteínas do Tecido Nervoso , Receptores de Fatores de Crescimento
5.
Front Bioeng Biotechnol ; 12: 1428446, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39040498

RESUMO

Background: All available methods for reconstruction after proximal humerus tumor resection have disadvantages, and the optimal reconstruction method remains uncertain. This study aimed to design a novel 3D-printed glenohumeral fusion prosthesis and verify its feasibility and safety using biomechanical methods. Methods: We verified the feasibility and safety of the 3D-printed glenohumeral fusion prosthesis by finite element analysis and biomechanical experimentation. In the finite element analysis, three reconstruction methods were used, and displacement and von Mises stress were observed; on this basis, in the biomechanical experiment, models constructed with sawbones were classified into two groups. The force‒displacement curve of the 3D-printed prosthesis was evaluated. Results: In terms of displacement, the finite element analysis showed greater overall stability for the novel prosthesis than traditional glenohumeral joint arthrodesis. There was no obvious stress concentration in the internal part of the 3D-printed glenohumeral fusion prosthesis; the stable structure bore most of the stress, and the force was well distributed. Adding lateral plate fixation improved the stability and mechanical properties of the prosthesis. Furthermore, the biomechanical results showed that without lateral plate fixation, the total displacement of the prosthesis doubled; adding lateral plate fixation could reduce and disperse strain on the glenoid. Conclusion: The design of the 3D-printed glenohumeral fusion prosthesis was rational, and its stability and mechanical properties were better than those of traditional glenohumeral joint arthrodesis. Biomechanical verification demonstrated the feasibility and safety of this prosthesis, indicating its potential for proximal humerus bone defect reconstruction after tumor resection.

6.
bioRxiv ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-39005289

RESUMO

Type 2 diabetics have an increased prevalence of hypertension and nondipping blood pressure (BP), which worsen cardiovascular outcomes. Exenatide, a short acting glucagon-like peptide-1 receptor agonist (GLP-1RA) used to treat type 2 diabetes, also demonstrates blood pressure (BP)-lowering effects. However, the mechanisms behind this and the impact of administration timing on BP dipping remain unclear. We investigated the effects of exenatide intraperitoneal injected at light onset (ZT0) or dark onset (ZT12) in diabetic (db/db) mice and nondiabetic controls. Using radio-telemetry and BioDAQ cages, we continuously monitored BP and food intake. Db/db mice exhibited non-dipping BP and increased food intake. ZT0 exenatide administration restored BP dipping by specifically lowering light-phase BP, while ZT12 exenatide reversed dipping by lowering dark-phase BP. These effects correlated with altered food intake patterns, and importantly, were abolished when food access was removed. Additionally, urinary norepinephrine excretion, measured by HPLC, was significantly reduced 6 hours post-exenatide at both ZT0 and ZT12, suggesting sympathetic nervous system involvement. Notably, combining exenatide with either ganglionic blocker mecamylamine or α-blocker prazosin did not enhance BP reduction beyond the individual effects of each blocker. These findings reveal that exenatide, when administered at light onset, restores BP dipping in db/db mice by suppressing light-phase food intake and sympathetic activity. Importantly, the efficacy of exenatide is dependent on food availability and its timing relative to circadian rhythms, highlighting the potential for chronotherapy in optimizing GLP-1RA- based treatments for type 2 diabetes and hypertension. Article Highlights: Maintaining a normal blood pressure (BP) circadian rhythm is vital for cardiovascular health, but diabetes often disrupts this rhythm. The effect of exenatide, a GLP-1 receptor agonist (GLP-1RA), on BP rhythm in diabetes is uncertain.This study investigates the impact of exenatide administration timing on BP patterns in diabetic db/db mice.Findings indicate that exenatide given at the onset of rest restores normal BP dipping, while at the start of the active phase worsens BP rhythm by modulating food intake and sympathetic activity.Timing GLP-1 RA administration may optimize BP control and provide cardiovascular benefits for type 2 diabetes patients.

7.
iScience ; 27(6): 110045, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38947529

RESUMO

Aging is closely associated with inflammation, which affects renal function reserve (RFR) in the kidneys. This study aims to investigate the impact of reduced RFR reduction on kidney aging and the influence of renal inflammation and RFR reduction on this process. Natural aging rats and those subjected to unilateral nephrectomy (UNX), 1/6 nephrectomy (1/6NX), and unilateral ureteral obstruction (UUO) were observed at 6, 12, 18, and 21 months. Our findings suggest that RFR reduction and renal inflammation can accelerate kidney aging, and inflammation contributes more. Metabolomics analysis revealed alterations in amino acid metabolism contribute to RFR decline. Furthermore, experiments in vitro confirmed the involvement of pentose phosphate pathway (PPP) in promoting aging though inflammation. Our research provides novel insights into for the mechanism of kidney aging and provides indirect support for clinical treatment decisions, such as addressing kidney inflammation, stones, or tumors that may necessitate partial or complete nephrectomy.

8.
Planta Med ; 90(11): 885-895, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38857860

RESUMO

5(S)-5-carboxystrictosidine (5-CS) is a compound found in the root of Mappianthus iodoides, a traditional Chinese medicine used for the treatment of coronary artery disease. The aim of the present study was to investigate the protective effect of 5-CS against oxidative stress-induced apoptosis in H9c2 cardiomyocytes and the underlying mechanisms. 5-CS pretreatment significantly protected against H2O2-induced cell death, LDH leakage, and malondialdehyde (MDA) production, which are indicators for oxidative stress injury. 5-CS also enhanced the activity of SOD and CAT. In addition, 5-CS pretreatment significantly inhibited H2O2-induced apoptosis, as determined by flow cytometer, suppressed the activity of caspase-3 and caspase-9, and attenuated the activation of cleaved caspase-3 and caspase-9. 5-CS also increased Akt and ERK activation altered by H2O2 using Western blot analysis. The PI3K-specific inhibitor LY294002 abolished 5-CS-induced Akt activation. The ERK-specific inhibitor PD98059 abolished 5-CS-induced ERK activation. Both LY294002 and PD98059 attenuated the protective effect of 5-CS on H9c2 cardiomyocytes against H2O2-induced apoptosis and cell death. Taken together, these results demonstrate that 5-CS prevents H2O2-induced oxidative stress injury in H9c2 cells by enhancing the activity of the endogenous antioxidant enzymes, inhibiting apoptosis, and modulating PI3K/Akt and ERK signaling pathways.


Assuntos
Apoptose , Peróxido de Hidrogênio , Miócitos Cardíacos , Estresse Oxidativo , Fosfatidilinositol 3-Quinases , Raízes de Plantas , Proteínas Proto-Oncogênicas c-akt , Miócitos Cardíacos/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Peróxido de Hidrogênio/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Estresse Oxidativo/efeitos dos fármacos , Raízes de Plantas/química , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Linhagem Celular , Transdução de Sinais/efeitos dos fármacos , Caspase 9/metabolismo
9.
J Clin Invest ; 134(15)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900572

RESUMO

Androgen has long been recognized for its pivotal role in the sexual dimorphism of cardiovascular diseases, including aortic aneurysms (AAs), a devastating vascular disease with a higher prevalence and fatality rate in men than in women. However, the mechanism by which androgen mediates AAs is largely unknown. Here, we found that male, not female, mice developed AAs when exposed to aldosterone and high salt (Aldo-salt). We revealed that androgen and androgen receptors (ARs) were crucial for this sexually dimorphic response to Aldo-salt. We identified programmed cell death protein 1 (PD-1), an immune checkpoint, as a key link between androgen and AAs. Furthermore, we demonstrated that administration of anti-PD-1 Ab and adoptive PD-1-deficient T cell transfer reinstated Aldo-salt-induced AAs in orchiectomized mice and that genetic deletion of PD-1 exacerbated AAs induced by a high-fat diet and angiotensin II (Ang II) in nonorchiectomized mice. Mechanistically, we discovered that the AR bound to the PD-1 promoter to suppress the expression of PD-1 in the spleen. Thus, our study unveils a mechanism by which androgen aggravates AAs by suppressing PD-1 expression in T cells. Moreover, our study suggests that some patients with cancer might benefit from screenings for AAs during immune checkpoint therapy.


Assuntos
Androgênios , Aneurisma Aórtico , Receptor de Morte Celular Programada 1 , Receptores Androgênicos , Animais , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/imunologia , Camundongos , Masculino , Feminino , Androgênios/farmacologia , Androgênios/metabolismo , Receptores Androgênicos/metabolismo , Receptores Androgênicos/genética , Aneurisma Aórtico/metabolismo , Aneurisma Aórtico/genética , Aneurisma Aórtico/patologia , Aldosterona/metabolismo , Camundongos Knockout , Humanos , Angiotensina II/farmacologia
10.
iScience ; 27(6): 110075, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38868208

RESUMO

Postoperative acute kidney injury (AKI) is a common complication in patients undergoing deep hypothermic circulatory arrest (HCA); however, its underlying pathogenesis is unclear. In this study, we established a rat cardiopulmonary bypass model and demonstrated that hypothermia during HCA, rather than circulatory arrest, was responsible for the occurrence of AKI. By recruiting 56 patients who underwent surgery with HCA and analyzing the blood samples, we found that post-HCA AKI was associated with an increase in bradykinin. Animal experiments confirmed this and showed that hypothermia during HCA increased bradykinin levels by increasing kallikrein expression. Mechanistically, bradykinin inhibited the Nrf2-xCT pathway through B2R and caused renal oxidative stress damage. Application of Icatibant, a B2R inhibitor, reversed changes in the Nrf2-xCT pathway and oxidative stress damage. Finally, Icatibant reversed hypothermia-induced AKI in vivo. This finding reveals the pathogenesis of AKI after HCA and helps to provide therapeutic strategy for patients with post-HCA AKI.

11.
Sci Rep ; 14(1): 14057, 2024 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890451

RESUMO

This study aimed to explore the mediating effects of ADL and depression on the relationship between sleep quality and HRQOL among older people in rural China, while also exploring the moderating impact of loneliness. The study gathered data from a household survey conducted among 1587 Chinese rural older adults (mean age = 73.63 years). The collected data was analyzed using SPSS version 23.0 software (IBM, New York, USA) and the PROCESS macro version 4.0 program. The findings indicated a significant correlation between sleep quality, ADL, depression, loneliness and HRQOL. ADL and depression exhibited a chain mediation effect on the relationship between sleep quality and HRQOL. Notably, the association between sleep quality and HRQOL was entirely mediated by ADL and depression. Additionally, loneliness acted as a moderator in the relationship between ADL and HRQOL. The findings of this study suggest that interventions focusing on sleep quality should prioritize strategies for enhancing older adults' ADL and depression as integral components of promoting older adults' HRQOL.


Assuntos
Atividades Cotidianas , Depressão , Qualidade de Vida , Qualidade do Sono , Humanos , Idoso , Depressão/psicologia , Masculino , Feminino , Idoso de 80 Anos ou mais , China/epidemiologia , Solidão/psicologia , Pessoa de Meia-Idade , População Rural , Inquéritos e Questionários
12.
Nano Lett ; 24(19): 5754-5760, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38708987

RESUMO

Two-dimensional (2D) FenGeTe2, with n = 3, 4, and 5, has been realized in experiments, showing strong magnetic anisotropy with enhanced critical temperature (Tc). The understanding of its magnetic anisotropy is crucial for the exploration of more stable 2D magnets and its spintronic applications. Here, we report a quantitative reconstruction of the magnetization magnitude and its direction in ultrathin Fe4GeTe2 using nitrogen vacancy centers. Through imaging stray magnetic fields, we identified the spin-flop transition at approximately 80 K, resulting in a change of the easy axis from the out-of-plane direction to the in-plane direction. Moreover, by analyzing the thermally activated escape behavior of the magnetization near Tc in terms of the Ginzburg-Landau model, we observed the in-plane magnetic anisotropy effect and the formation capability of magnetic domains at ∼0.4 µm2 µT-1. Our findings contribute to the quantitative understanding of the magnetic anisotropy effect in a vast range of 2D van der Waals magnets.

13.
Nat Commun ; 15(1): 4250, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762497

RESUMO

Axion insulators possess a quantized axion field θ = π protected by combined lattice and time-reversal symmetry, holding great potential for device applications in layertronics and quantum computing. Here, we propose a high-spin axion insulator (HSAI) defined in large spin-s representation, which maintains the same inherent symmetry but possesses a notable axion field θ = (s + 1/2)2π. Such distinct axion field is confirmed independently by the direct calculation of the axion term using hybrid Wannier functions, layer-resolved Chern numbers, as well as the topological magneto-electric effect. We show that the guaranteed gapless quasi-particle excitation is absent at the boundary of the HSAI despite its integer surface Chern number, hinting an unusual quantum anomaly violating the conventional bulk-boundary correspondence. Furthermore, we ascertain that the axion field θ can be precisely tuned through an external magnetic field, enabling the manipulation of bonded transport properties. The HSAI proposed here can be experimentally verified in ultra-cold atoms by the quantized non-reciprocal conductance or topological magnetoelectric response. Our work enriches the understanding of axion insulators in condensed matter physics, paving the way for future device applications.

14.
Am J Chin Med ; 52(3): 799-819, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38752843

RESUMO

Subarachnoid hemorrhage (SAH), a specific subtype of cerebrovascular accident, is characterized by the extravasation of blood into the interstice between the brain and its enveloping delicate tissues. This pathophysiological phenomenon can precipitate an early brain injury (EBI), which is characterized by inflammation and neuronal death. Rutaecarpine (Rut), a flavonoid compound discovered in various plants, has been shown to have protective effects against SAH-induced cerebral insult in rodent models. In our study, we used a rodent SAH model to evaluate the effect of Rut on EBI and investigated the effect of Rut on the inflammatory response and its regulation of SIRT6 expression in vitro. We found that Rut exerts a protective effect on EBI in SAH rats, which is partly due to its ability to inhibit the inflammatory response. Notably, Rut up-regulated Sirtuin 6 (SIRT6) expression, leading to an increase in H3K9 deacetylation and inhibition of nuclear factor-kappa B (NF-[Formula: see text]B) transcriptional activation, thereby mediating the inflammatory response. In addition, further data showed that SIRT6 was proven to mediate the regulation of Rut on the microglial inflammatory response. These findings highlight the importance of SIRT6 in the regulation of inflammation and suggest a potential mechanism for the protective effect of Rut on EBI. In summary, Rut may have the potential to prevent and treat SAH-induced brain injury by interacting with SIRT6. Our findings may provide a new therapeutic strategy for the treatment of SAH-induced EBI.


Assuntos
Alcaloides Indólicos , NF-kappa B , Quinazolinas , Ratos Sprague-Dawley , Sirtuínas , Hemorragia Subaracnóidea , Animais , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/complicações , Sirtuínas/metabolismo , Sirtuínas/genética , Alcaloides Indólicos/farmacologia , NF-kappa B/metabolismo , Masculino , Quinazolinas/farmacologia , Quinazolinas/uso terapêutico , Modelos Animais de Doenças , Lesões Encefálicas/etiologia , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/metabolismo , Ratos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Fitoterapia , Transdução de Sinais/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Quinazolinonas
15.
Natl Sci Rev ; 11(6): nwad262, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38715704

RESUMO

Surface electrons in axion insulators are endowed with a topological layer degree of freedom followed by exotic transport phenomena, e.g., the layer Hall effect. Here, we propose that such a layer degree of freedom can be manipulated in a dissipationless way based on the antiferromagnetic [Formula: see text] with tailored domain structure. This makes [Formula: see text] a versatile platform to exploit the 'layertronics' to encode, process and store information. Importantly, the layer filter, layer valve and layer reverser devices can be achieved using the layer-locked chiral domain wall modes. The dissipationless nature of the domain wall modes makes the performance of the layertronic devices superior to those in spintronics and valleytronics. Specifically, the layer reverser, a layer version of the Datta-Das transistor, also fills up the blank in designing the valley reverser in valleytronics. Our work sheds light on constructing new generation electronic devices with high performance and low-energy consumption in the framework of layertronics.

16.
Bone Marrow Transplant ; 59(7): 997-1005, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38580777

RESUMO

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers rapid hematopoietic and immune reconstitution for aplastic anemia (AA). As a non-malignant disorder, attenuation of GVHD remains a clinical priority in AA patients. Our study sought to investigate the safety and efficacy of the prophylactic use of ruxolitinib in allogeneic HSCT. A total of 35 AA patients were retrospectively consecutively treated with allo-HSCT whereby ruxolitinib was added to the standard GVHD prophylaxis regimen (rux group). The addition of peri-transplant ruxolitinib did not impact the engraftment and graft function, while better recovery of CD4+ Tregs in the rux group was observed. Interestingly, the rux group demonstrated significantly lower incidence of bacterial/fungal infections (17.14% vs 45.71%). Compared to the control group, the rux group exhibited significantly lower incidence of moderate to severe aGVHD (17.1% vs 48.6%) with a trend toward lower severe aGVHD (8.6% vs 20%) and cGVHD (26.2 vs 38.3). The rux group also demonstrated a trend toward higher GVHD and failure-free survival (GFFS: 85.7% vs 68.6%) and lower TRM (2.9% vs 14.3%). Addition of ruxolitinib to standard GVHD prophylaxis regimen, thus, represents a safe and highly efficient method for the attenuation of GVHD with better outcome of allo-HSCT.


Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Nitrilas , Pirazóis , Pirimidinas , Humanos , Pirazóis/uso terapêutico , Nitrilas/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/etiologia , Pirimidinas/uso terapêutico , Adulto , Masculino , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Anemia Aplástica/terapia , Pessoa de Meia-Idade , Adolescente , Estudos Retrospectivos , Adulto Jovem , Transplante Homólogo/métodos , Aloenxertos
17.
Sci Rep ; 14(1): 8088, 2024 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582794

RESUMO

The Amur tiger is currently confronted with challenges of anthropogenic development, leading to its population becoming fragmented into two geographically isolated groups: smaller and larger ones. Small and isolated populations frequently face a greater extinction risk, yet the small tiger population's genetic status and survival potential have not been assessed. Here, a total of 210 samples of suspected Amur tiger feces were collected from this small population, and the genetic background and population survival potentials were assessed by using 14 microsatellite loci. Our results demonstrated that the mean number of alleles in all loci was 3.7 and expected heterozygosity was 0.6, indicating a comparatively lower level of population genetic diversity compared to previously reported studies on other subspecies. The genetic estimates of effective population size (Ne) and the Ne/N ratio were merely 7.6 and 0.152, respectively, representing lower values in comparison to the Amur tiger population in Sikhote-Alin (the larger group). However, multiple methods have indicated the possibility of genetic divergence within our isolated population under study. Meanwhile, the maximum kinship recorded was 0.441, and the mean inbreeding coefficient stood at 0.0868, both of which are higher than those observed in other endangered species, such as the African lion and the grey wolf. Additionally, we have identified a significant risk of future extinction if the lethal equivalents were to reach 6.26, which is higher than that of other large carnivores. Further, our simulation results indicated that an increase in the number of breeding females would enhance the prospects of this population. In summary, our findings provide a critical theoretical basis for further bailout strategies concerning Amur tigers.


Assuntos
Leões , Tigres , Animais , Feminino , Tigres/genética , Espécies em Perigo de Extinção , Heterozigoto , Densidade Demográfica , Repetições de Microssatélites/genética , Leões/genética , Conservação dos Recursos Naturais , Variação Genética
18.
Front Surg ; 11: 1329771, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655210

RESUMO

Objectives: The diameter, area, and volume of the true lumen and false lumen (FL) have been measured in previous studies to evaluate the extent of DeBakey type I aortic dissection. However, these indicators have limitations because of the irregular shapes of the true and false lumens and the constant oscillation of intimal flap during systole and diastole. The ratio of arch lengths seems to be a more reliable indicator. FL% was defined as the ratio of the arch length of FL to the circumference of the aorta at the different levels of the aorta. The purpose of this article was to investigate whether FL% is a predictor of the severity of acute DeBakey type I aortic dissection in patients undergoing frozen elephant trunk (FET) and total arch replacement. Methods: In this retrospective observational study, we analyzed a total of 344 patients with acute DeBakey type I aortic dissection that underwent FET and total arch replacement at our center from October 2015 to October 2019. The patients were divided into two groups by cluster analysis according to the perioperative course. Binary logistic regression analyses were performed to determine whether FL% could predict the severity of acute DeBakey type I aortic dissection. The area under the receiver operating characteristic curve (AUROC) was used to assess the power of the multivariate logistic regression model for the severity of acute DeBakey type I aortic dissection. Results: The patients in the ultra-high-risk group (109 patients) had significantly more severe clinical comorbidities and complications than the patients in the high-risk group (235 patients). The ascending aortic FL% [odds ratio (OR), 11.929 (95% CI: 1.421-100.11); P = 0.022], location of initial tear [OR, 0.68 (95% CI: 0.47-0.98); P = 0.041], the degree of left iliac artery involvement [OR, 1.95 (95% CI: 1.15-3.30); P = 0.013], and the degree of right coronary artery involvement [OR, 1.46 (95% CI: 1.01-2.12); P = 0.045] on preoperative computed tomography angiography were associated with the severity of acute DeBakey type I aortic dissection. The AUROC value of this multivariate logistic regression analysis was 0.940 (95% CI: 0.914-0.967; P < 0.001). The AUROC value of ascending aortic FL% was 0.841 (95% CI: 0.798-0.884; P < 0.001) for the severity of acute DeBakey type I aortic dissection in patients undergoing FET and total arch replacement. Conclusions: Ascending aortic FL% was validated as an essential radiologic index for assessing the severity of acute DeBakey type I aortic dissection in patients undergoing FET and total arch replacement. Higher values of ascending aortic FL% were more severe.

19.
Front Immunol ; 15: 1327779, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38596674

RESUMO

Neoadjuvant chemoimmunotherapy has revolutionized the therapeutic strategy for non-small cell lung cancer (NSCLC), and identifying candidates likely responding to this advanced treatment is of important clinical significance. The current multi-institutional study aims to develop a deep learning model to predict pathologic complete response (pCR) to neoadjuvant immunotherapy in NSCLC based on computed tomography (CT) imaging and further prob the biologic foundation of the proposed deep learning signature. A total of 248 participants administrated with neoadjuvant immunotherapy followed by surgery for NSCLC at Ruijin Hospital, Ningbo Hwamei Hospital, and Affiliated Hospital of Zunyi Medical University from January 2019 to September 2023 were enrolled. The imaging data within 2 weeks prior to neoadjuvant chemoimmunotherapy were retrospectively extracted. Patients from Ruijin Hospital were grouped as the training set (n = 104) and the validation set (n = 69) at the 6:4 ratio, and other participants from Ningbo Hwamei Hospital and Affiliated Hospital of Zunyi Medical University served as an external cohort (n = 75). For the entire population, pCR was obtained in 29.4% (n = 73) of cases. The areas under the curve (AUCs) of our deep learning signature for pCR prediction were 0.775 (95% confidence interval [CI]: 0.649 - 0.901) and 0.743 (95% CI: 0.618 - 0.869) in the validation set and the external cohort, significantly superior than 0.579 (95% CI: 0.468 - 0.689) and 0.569 (95% CI: 0.454 - 0.683) of the clinical model. Furthermore, higher deep learning scores correlated to the upregulation for pathways of cell metabolism and more antitumor immune infiltration in microenvironment. Our developed deep learning model is capable of predicting pCR to neoadjuvant chemoimmunotherapy in patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Aprendizado Profundo , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/terapia , Terapia Neoadjuvante , Resposta Patológica Completa , Estudos Retrospectivos , Imunoterapia , Tomografia Computadorizada por Raios X , Microambiente Tumoral
20.
ESC Heart Fail ; 11(4): 2405-2409, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38520316

RESUMO

Left ventricular assist device (LVAD) implantation is an effective alternative treatment to heart transplantation, especially for end-stage heart failure patients who are ineligible for or unable to await a heart transplant. This report describes a complex and innovative surgery where LVAD implantation was performed alongside multiple concomitant cardiac and aortic procedures. A 62-year-old male patient with complicated comorbidities developed acute myocardial infarction and subsequent refractory advanced heart failure. Given his critically ill condition and intractable anatomical malformations, the CH-VAD left ventricular assist system implantation was performed concomitantly with the Bentall procedure, coronary artery bypass grafting, tricuspid valvuloplasty, and foramen ovale closure. The patient was successfully discharged. This case details the medical decision-making process and surgical strategy and demonstrates the feasibility of LVAD implantation combined with multiple additional cardiac and aortic procedures in expert cardiac centres. Success relies on experienced cardiac surgeons and a multidisciplinary LVAD Heart Team, ensuring excellence in surgical techniques, preoperative evaluation, post-operative care, and rehabilitation.


Assuntos
Ponte de Artéria Coronária , Insuficiência Cardíaca , Coração Auxiliar , Humanos , Masculino , Pessoa de Meia-Idade , Ponte de Artéria Coronária/métodos , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/complicações , Ventrículos do Coração/anormalidades , Ventrículos do Coração/fisiopatologia
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