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1.
Adv Sci (Weinh) ; : e2403592, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39023171

RESUMEN

Endocrine-resistant ER+HER2- breast cancer (BC) is particularly aggressive and leads to poor clinical outcomes. Effective therapeutic strategies against endocrine-resistant BC remain elusive. Here, analysis of the RNA-sequencing data from ER+HER2- BC patients receiving neoadjuvant endocrine therapy and spatial transcriptomics analysis both show the downregulation of innate immune signaling sensing cytosolic DNA, which primarily occurs in endocrine-resistant BC cells, not immune cells. Indeed, compared with endocrine-sensitive BC cells, the activity of sensing cytosolic DNA through the cGAS-STING pathway is attenuated in endocrine-resistant BC cells. Screening of kinase inhibitor library show that this effect is mainly mediated by hyperactivation of AKT1 kinase, which binds to kinase domain of TBK1, preventing the formation of a trimeric complex TBK1/STING/IRF3. Notably, inactivation of cGAS-STING signaling forms a positive feedback loop with hyperactivated AKT1 to promote endocrine resistance, which is physiologically important and clinically relevant in patients with ER+HER2- BC. Blocking the positive feedback loop using the combination of an AKT1 inhibitor with a STING agonist results in the engagement of innate and adaptive immune signaling and impairs the growth of endocrine-resistant tumors in humanized mice models, providing a potential strategy for treating patients with endocrine-resistant BC.

2.
Sci Rep ; 14(1): 11899, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38789536

RESUMEN

The construction of underground cavern groups represents a particularly challenging task in current subsurface engineering due to a multitude of variable and often unknown factors, including diverse geological conditions. This study introduces a four-dimensional spatiotemporal model and formulates a dynamic safety information model for these underground systems. Developed using C# and Python, the model integrates the finite element analysis software ABAQUS and Microsoft SQL Server database. The framework allows for real-time visual management of monitoring data, dynamic coupling of construction phases with safety metrics, and continual updates correlating with construction progress. The theoretical findings offer valuable insights for enhancing the safety and efficiency of underground cavern group construction while also supplying methods for real-time safety feedback and control throughout the construction process.

3.
Infect Drug Resist ; 17: 1439-1445, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38628241

RESUMEN

Background: The HACEK group comprises Haemophilus spp., Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae, are Gram-negative bacteria that are slow-growing and fastidious. These organisms are common causes of culture-negative endocarditis. However, brain abscesses caused by Haemophilus aphrophilus and E. corrodens have been rarely reported. The case we describe, which was promptly identified and successfully treated, will be meaningful for the diagnosis and treatment of such infectious diseases. Case Presentation: Herein, we report a case of brain abscess in a young man who was infected with Haemophilus aphrophilus and E. corrodens. The patient was admitted to the hospital with sudden onset of vomiting, coma, and fever. Magnetic resonance imaging (MRI) of the brain and cerebrospinal fluid cell counts suggested cerebral abscess, he underwent drainage of the abscess and empirical antimicrobial therapy of meropenem (2 g every 8 hours) and linezolid (0.6 g every 12 hours) for more than 10 days without significant improvement. Metagenomic next-generation sequencing (mNGS) of drainage fluid and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) detection for isolated bacteria from samples suggested the presence of H. aphrophilus and E. corrodens. After 7 weeks of ceftriaxone (2 g every 12 hours) and meropenem (2 g every 8 hours) intravenously, the patient was discharged with a normal temperature and brain MRI showed improvement of the lesion. Conclusion: Similar cases reported in previous studies were always associated with bacterial blood dissemination after dental surgery or myocarditis; however, the patient in our case had no any associated risk factors. As far as we know, this is the only case of central nervous system infection caused by H. aphrophilus and E. corrodens that has utilized combined mNGS and MALDI-TOF MS in the diagnosis.

4.
Skeletal Radiol ; 53(4): 697-707, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37843585

RESUMEN

OBJECTIVE: To perform a meta-analysis comparing the MRI features of tuberculous and pyogenic spondylitis, using histopathological results and/or blood culture as the standard reference. MATERIALS AND METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched for English-language studies on the MRI features of tuberculous and pyogenic spondylitis published between January 2010 and February 2023. Risk for bias and concerns regarding applicability were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Pooled MRI features' proportions were calculated using a bivariate random-effects model. RESULTS: Thirty-two studies met the inclusion criteria: 21 for tuberculous spondylitis, three for pyogenic spondylitis, and eight for both. Of the nine informative MRI features comparing tuberculous spondylitis to pyogenic spondylitis, involvement of ≥ 2 vertebral bodies (92% vs. 88%, P = .004), epidural extension (77% vs. 25%, P < .001), paravertebral collection (91% vs. 84%, P < .001), subligamentous spread (93% vs. 24%, P < .001), thin and regular abscess wall (94% vs. 18%, P < .001), vertebral collapse (68% vs. 24%, P < .001), and kyphosis (39% vs. 3%, P < .01) were more suggestive of tuberculous spondylitis, while disc signal change (82% vs. 95%, P < .001) and disc height loss (22% vs. 59%, P < .001) were more suggestive of pyogenic spondylitis. CONCLUSION: Involvement of ≥ 2 vertebral vertebral bodies, soft tissue attribution, thin and regular abscess wall, vertebral collapse, and kyphosis were MRI features more common in tuberculous spondylitis, while disc signal change and height loss were more common in pyogenic spondylitis.


Asunto(s)
Cifosis , Espondiloartritis , Espondilitis , Tuberculosis de la Columna Vertebral , Humanos , Absceso , Estudios Retrospectivos , Espondilitis/diagnóstico por imagen , Espondilitis/patología , Tuberculosis de la Columna Vertebral/diagnóstico por imagen , Tuberculosis de la Columna Vertebral/patología , Imagen por Resonancia Magnética/métodos
5.
Stem Cell Res ; 74: 103272, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38100915

RESUMEN

South Asians, which represent around 25% of the world's population, have a disproportionately high risk of cardiometabolic disease, two-fold higher risk of myocardial infarction, and 4- to 6-fold higher risk for diabetes compared to Caucasians. We generated two induced pluripotent stem cell (iPSC) lines from healthy South Asian donors and validated the pluripotency and ability of these cell lines to differentiate into three germ layers. These iPSC lines can be applied to generate many cardiovascular cell types such as cardiomyocytes, endothelial cells, and mural cells to investigate different cardiovascular disease mechanisms triggered by environmental risk factors or drugs in vitro.


Asunto(s)
Células Madre Pluripotentes Inducidas , Infarto del Miocardio , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Etnicidad , Células Endoteliales , Infarto del Miocardio/metabolismo , Miocitos Cardíacos , Diferenciación Celular
6.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1014523

RESUMEN

More than 300 million people worldwide suffer from asthma, and the incidence is increasing year by year. As one of the most common chronic diseases, asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity. With the in-depth study of physiological and pathological mechanisms, therapeutic small molecule and hormone drugs have been introduced to control and treat most patients, but about 5% - 10% of patients still suffer from various subtypes of difficult to control and treat asthma, that is, severe asthma. In the past decade, with the rapid development of bio-pharmaceutical research, protein and antibody have become the key drugs for the treatment of severe asthma with high efficacy, high specificity and high safety. However, biological drugs are usually administered by injection, they cannot be noninvasive and directly delivered into the lung to quickly absorb and take effect. Therefore, there is an urgent need for the introduction of inhaled biologics with quick effectiveness, convenience, economy and safety in clinical. The review summarizes the existing small molecule, hormone and biological therapy drugs, and summarizes the development of inhalable biological agents of asthma, and analyzes the future prospects of the inhalable biological drugs, which is designed to deepen the perception of the direction of the inhalable biological drugs research, and update the information of the field, in order to provide reference for the development of more inhalable biologics.

7.
Basic & Clinical Medicine ; (12): 389-392, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1018626

RESUMEN

The activation of the P2X7 receptor as an ATP-gated ion channel,triggers the release of pro-inflammato-ry cytokines in tumor carring individuals and stimulate excitation of injury-causing neurons,thereby exacerbating the transmission of pain.In preclinical cancer pain models,it has the potential to serve as a new therapeutic target for cancer pain management.

8.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1031387

RESUMEN

This case report summarizes the experience from diagnosis and treatment of a patient with repeated high fever, hepatosplenomegaly and pancytopenia. Following exclusion of bacterial, viral, fungal infections and hematological diseases, metagenomic next-generation sequencing of the patient’s peripheral blood revealed Leishmania infantum infection, and rK39 rapid diagnostic test showed positive for anti-Leishmania antibody, while microscopic examination of bone marrow smears identified Leishmania amastigotes. Therefore, the case was definitively diagnosed as visceral leishmaniasis, and given anti-infective treatment with sodium antimony gluconate and hormone, hepatoprotection, elevation of white blood cell counts and personalized nursing. Then, the case was cured and discharged from hospital. Metagenomic next-generation sequencing is of great value in etiological detection of fever patients with unknown causes, which deserves widespread clinical applications.

9.
Chinese Health Economics ; (12): 8-10,37, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1025213

RESUMEN

As an important healthcare service to cope with the aging population and slow disease characterization,the quality and development mode of the successive healthcare service has gradually attracted attention as to how to adapt to the existing hierarchical diagnosis and treatment system.It will sort out the supportive policies and development status of the successive medical services un-der China's hierarchical diagnosis and treatment system,and find out the problems in the development of the successive medical ser-vices under the hierarchical diagnosis and treatment system in the new period,in order to provide references and suggestions for the further sustainable development of the successive medical services in China.

10.
Chinese Health Economics ; (12): 21-23, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1025237

RESUMEN

At present,China's multi-level Traditional Chinese medicine(TCM)Medical Alliance has been gradually formed,the sinking effect of resource sharing is obvious.The level of medical services homogenization has been improved,the operation guarantee mechanism has been continuously improved,and the diagnosis and treatment capacity of each member unit has continued to improve.However,in the construction of various regions,there are still government departments'weak cognition and planning of TCM Medical Alliance,and the characteristics are insufficient.It is recommended to strengthen the functional positioning and connotation construction of TCM Medical Alliance,improve the operation and management mechanism,and give full play to the"baton"role of performance evaluation,so as to effectively promote the sinking and balanced distribution of TCM high-quality resources.

11.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1028976

RESUMEN

Objective:To explore whether the degree of skeletal muscle atrophy in obese individuals under the influence of colorectal cancer is more severe than that in non-obese individuals.Methods:The clinical data of patients who underwent radical resection of colorectal cancer in our department from Jul 2020 to Dec 2021 was collected. Sixty-four obese patients were included and 64 non-obese patients were matched according to propensity score. At the same time, 51 obese patients were collected from non-tumor patients and matched with 51 non-obese patients. The psoas muscle index (PMI) of included patients was analyzed and compared.Results:The PMI of patients with colorectal cancer was significantly lower than that of corresponding non-tumor patients, regardless of gender and body weight (both P<0.05). The PMI of obese patients with colorectal cancer was significantly lower than that of non-obese patients ( P<0.05). Conclusions:The impact of colorectal cancer on skeletal muscle atrophy in obese individuals is greater than that in normal weight individuals. Therefore, the skeletal muscle status of obese patients with colorectal cancer should be evaluated more comprehensively.

12.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1030569

RESUMEN

ObjectiveTo analyze the satisfaction of service recipients with the preliminary assessment service of the unified elderly care needs evaluation in Shanghai, so as to provide reference for further optimization of the service system. MethodsA multi-stage random sampling method was employed to recruit participants. A total of 110 individuals who had received unified elderly care needs evaluation service in six districts of Shanghai were investigated using a structured questionnaire. SPSS 25.0 was used to analyze the data. Univariate analyses were conducted using the Chi-square test and Fisher’s precision probability test, while multivariate analysis was performed using ordinal regression. ResultsThere were differences in satisfaction with various aspects of the preliminary assessment process among participants from different areas, with those from outer suburbs generally exhibiting lower satisfaction (P<0.01). Multivariate analysis results indicated that satisfaction with the timing of the preliminary assessment was related to the service recipients’ residential area and their primary source of income; satisfaction with the service attitude and capability of the assessment personnel was only related to the residential area. Satisfaction with the preliminary evaluation results was related to the participants’ marital status, educational level, income level, and the specific rating results. ConclusionThe satisfaction level with the preliminary assessment of the unified elderly care needs assessment in Shanghai is relatively high. In the process of evaluation, a deeper analysis and exploration of individual needs based on various personal information are essential to ensure the appropriateness of the provided elderly care services, and thereby effectively enhancing recipient satisfaction.

13.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1030570

RESUMEN

ObjectiveTo clarify the perception of the work and satisfaction levels among personnel conducting unified elderly care needs assessment in Shanghai, to analyze the factors influencing their job satisfaction, and to provide references for optimizing the job satisfaction of unified elderly care needs assessment personnel in Shanghai. MethodsA survey was conducted among 93 assessment personnel randomly selected from 29 elderly care needs assessment agencies in Shanghai. The personnel’s perception of their work and their levels of job satisfaction were examined. Chi-square test and Fisher’s precision probability test were used to compare regional differences, while the two-factor theory was employed to analyze the factors influencing job satisfaction. ResultsRegarding perception of the work, 92.5% of the surveyed personnel believed their work was important. Moreover, 87.1% were interested in their assessment tasks, and 84.9% believed they made a positive contribution to the assessment work and the assessment position was in line with their personal preferences. Regarding job satisfaction, 83.9% of the participants were satisfied with their assessment work, 78.5% considered the workload appropriate, and 74.2% found the working hours suitable. Additionally, 65.6% expressed satisfaction with the level of cooperation from the assessment subjects, while 94.6% and 91.4% of the personnel were satisfied with the support provided by the assessment agencies and had a sense of belonging, respectively. Furthermore, 65.6% of the personnel expressed satisfaction with their job compensation and benefits. Hygiene factors affecting job satisfaction included salary and compensation, workload, time spent on the job and institutional support related to external assistance, job suitability, teamwork, and client cooperation (P<0.05), while motivational factors included recognition of the significance of the job, sense of achievement, interest in the job, sense of belonging, and opportunities for personal growth (P<0.05). ConclusionThe overall work cognition and satisfaction of unified elderly care needs assessment personnel in Shanghai towards their work are relatively positive. Main issues include the heavy workload and actual job subsidies not meeting expectations. It is recommended to improve the standardization of the assessment process, establish a professional team of assessment personnel, and enhance the compensation and incentive mechanisms to continuously increase staff satisfaction.

14.
World J Gastrointest Surg ; 15(8): 1684-1692, 2023 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-37701706

RESUMEN

BACKGROUND: The liver hemodynamic changes caused by portal hypertension (PH) are closely related to various complications such as gastroesophageal varices and portosys-temic shunts, which may lead to adverse clinical outcomes in these patients, so it is of great clinical significance to find treatment strategies with favorable clinical efficacy and low risk of complications. AIM: To study the clinical efficacy of total laparoscopic splenectomy (TLS) for PH and its influence on hepatic hemodynamics and liver function. METHODS: Among the 199 PH patients selected from October 2016 to October 2020, 100 patients [observation group (OG)] were treated with TLS, while the remaining 99 [reference group (RG)] were treated with open splenectomy (OS). We observed and compared the clinical efficacy, operation indexes [operative time (OT) and intraoperative bleeding volume], safety (intraperitoneal hemorrhage, ascitic fluid infection, eating disorders, liver insufficiency, and perioperative death), hepatic hemodynamics (diameter, velocity, and flow volume of the portal vein system), and liver function [serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and serum total bilirubin (TBil)] of the two groups. RESULTS: The OT was significantly longer and intraoperative bleeding volume was significantly lesser in the OG than in the RG. Additionally, the overall response rate, postoperative complications rate, and liver function indexes (ALT, AST, and TBil) did not differ significantly between the OG and RG. The hepatic hemodynamics statistics showed that the pre- and postoperative blood vessel diameters in the two cohorts did not differ statistically. Although the postoperative blood velocity and flow volume reduced significantly when compared with the preoperative values, there were no significant inter-group differences. CONCLUSION: TLS contributes to comparable clinical efficacy, safety, hepatic hemodynamics, and liver function as those of OS in treating PH, with a longer OT but lesser intraoperative blood loss.

15.
Cancer Lett ; 564: 216186, 2023 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-37105392

RESUMEN

Evading immune destruction is an emerging hallmark of cancer and a potential key step in tumorigenesis. Immune checkpoint blocker (ICB)-based combination therapies revolutionize the landscape of systemic therapy for HCC. However, the molecular underpinnings governing immune evasion and responses remain unclear. Our study aims to find new regulatory molecules that drive HCC immune escape and tumorigenesis and find new promising immunotherapeutic approaches for HCC. In our study, laser capture microdissection (LCM) and miRNA sequencing combined with in vitro and in vivo experiments identified miR-93-5p as a crucial initiating oncogene during liver progenitor cell (LPC) malignant transformation and immune escape. Mechanistically, miR-93-5p could directly target canonical tumour suppressors such as APC to promote LPC malignant transformation and hepatocarcinogenesis. More importantly, miR-93-5p could induce deviant GAL-9 augmentation to inactivate infiltrated CD8(+) T cells and induce immune evasion by targeting several epigenetic regulators, such as AEBP2, and then regulating H3K4me3/H3K27me3 bivalency. Experiments in C57BL/6 mice demonstrated that blockade of Gal-9 abrogated miR-93-5p-induced HCC progression and improved their prognosis. Clinically, we identified a unique subtype of HCC closely associated with high GAL-9 expression and anti-PD1 treatment resistance. Our study highlights the pivotal role of the miR-93-5p/Gal-9 axis in driving HCC immune escape and tumorigenesis. Blocking GAL-9 is an effective and promising immunotherapeutic approach for HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Animales , Ratones , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/metabolismo , Linfocitos T CD8-positivos/metabolismo , Ratones Endogámicos C57BL , MicroARNs/genética , MicroARNs/metabolismo , Inmunoterapia , Carcinogénesis/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral
16.
J Pharm Biomed Anal ; 229: 115346, 2023 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-37001272

RESUMEN

Ferroptosis, an iron-dependent cell death process, is a potential therapeutic strategy for Lung squamous cell carcinoma (LUSC). Resveratrol (RES) is an anti-tumor polyphenol. However, whether and how RES treats LUSC is not yet known. This study aimed to investigate the effect of RES on LUSC and to explore its potential mechanism. This study used a combination of proteomics, bioinformatics, clinical samples, and cell experiments to study the interaction between HMMR and the ferroptosis signaling pathway and investigate the role of RES in regulating tumor immune microenvironment and anti-tumor by cytotoxic CD8 +T cells in LUSC. Ferroptosis signaling pathway and HMMR were involved in the LUSC tumor immune microenvironment and correlated with worse prognosis of LUSC patients. RES+H520 cells induced a higher level of ferroptosis and MDA, mainly by reducing the expression of GPX4 and SLC7A11, inducing the expression of ACSL4 and TFRC. HMMR, GSH, and SOD contents were lower observed than in H520 cells. When HMMR was expressed, SLC7A11 was also highly expressed in LUSC, and there was an interaction between HMMR expression and SLC7A11. In addition, RES increased the TNF-α, IFN-γ, IL-12, and IL-2 expression and increased the cytotoxic effects of CD8 +T cells expressions in LUSC. Resveratrol regulates SLC7A11-HMMR interaction, activates ferroptosis, enhances the cytotoxic effect of CD8 +T cells, and regulates the tumor immune microenvironment. Based on the pathogenesis of LUSC and the clinical efficacy of RES, this study explored the influence of RES on LUSC, clarified its biological effects, and further provided cell biological basis for the clinical application of RES, which could guide clinical combination and personalized medicine, improve the response rate of immunotherapy and benefit more patients with LUSC.


Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Ferroptosis , Neoplasias Pulmonares , Humanos , Resveratrol/farmacología , Resveratrol/uso terapéutico , Microambiente Tumoral , Carcinoma de Células Escamosas/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Linfocitos T CD8-positivos , Neoplasias Pulmonares/tratamiento farmacológico , Pulmón
17.
Neuroscience Bulletin ; (6): 1050-1068, 2023.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-982460

RESUMEN

The axon initial segment (AIS) is a highly specialized axonal compartment where the action potential is initiated. The heterogeneity of AISs has been suggested to occur between interneurons and pyramidal neurons (PyNs), which likely contributes to their unique spiking properties. However, whether the various characteristics of AISs can be linked to specific PyN subtypes remains unknown. Here, we report that in the prelimbic cortex (PL) of the mouse, two types of PyNs with axon projections either to the contralateral PL or to the ipsilateral basal lateral amygdala, possess distinct AIS properties reflected by morphology, ion channel expression, action potential initiation, and axo-axonic synaptic inputs from chandelier cells. Furthermore, projection-specific AIS diversity is more prominent in the superficial layer than in the deep layer. Thus, our study reveals the cortical layer- and axon projection-specific heterogeneity of PyN AISs, which may endow the spiking of various PyN types with exquisite modulation.


Asunto(s)
Ratones , Animales , Segmento Inicial del Axón , Sinapsis/fisiología , Células Piramidales/fisiología , Corteza Cerebral , Axones/fisiología
18.
Neuroscience Bulletin ; (6): 1789-1806, 2023.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1010642

RESUMEN

Brachial plexus avulsion (BPA) is a combined injury involving the central and peripheral nervous systems. Patients with BPA often experience severe neuropathic pain (NP) in the affected limb. NP is insensitive to the existing treatments, which makes it a challenge to researchers and clinicians. Accumulated evidence shows that a BPA-induced pain state is often accompanied by sympathetic nervous dysfunction, which suggests that the excitation state of the sympathetic nervous system is correlated with the existence of NP. However, the mechanism of how somatosensory neural crosstalk with the sympathetic nerve at the peripheral level remains unclear. In this study, through using a novel BPA C7 root avulsion mouse model, we found that the expression of BDNF and its receptor TrκB in the DRGs of the BPA mice increased, and the markers of sympathetic nervous system activity including α1 and α2 adrenergic receptors (α1-AR and α2-AR) also increased after BPA. The phenomenon of superexcitation of the sympathetic nervous system, including hypothermia and edema of the affected extremity, was also observed in BPA mice by using CatWalk gait analysis, an infrared thermometer, and an edema evaluation. Genetic knockdown of BDNF in DRGs not only reversed the mechanical allodynia but also alleviated the hypothermia and edema of the affected extremity in BPA mice. Further, intraperitoneal injection of adrenergic receptor inhibitors decreased neuronal excitability in patch clamp recording and reversed the mechanical allodynia of BPA mice. In another branch experiment, we also found the elevated expression of BDNF, TrκB, TH, α1-AR, and α2-AR in DRG tissues from BPA patients compared with normal human DRGs through western blot and immunohistochemistry. Our results revealed that peripheral BDNF is a key molecule in the regulation of somatosensory-sympathetic coupling in BPA-induced NP. This study also opens a novel analgesic target (BDNF) in the treatment of this pain with fewer complications, which has great potential for clinical transformation.


Asunto(s)
Humanos , Ratones , Animales , Hiperalgesia/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Hipotermia/metabolismo , Neuralgia , Plexo Braquial/lesiones , Edema/metabolismo
19.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1011003

RESUMEN

Natural products are essential sources of antitumor drugs. One such molecule, β-elemene, is a potent antitumor compound extracted from Curcuma wenyujin. In the present investigation, a series of novel 13,14-disubstituted nitric oxide (NO)-donor β-elemene derivatives were designed, with β-elemene as the foundational compound, and subsequently synthesized to evaluate their therapeutic potential against leukemia. Notably, the derivative labeled as compound 13d demonstrated a potent anti-proliferative activity against the K562 cell line, with a high NO release. In vivo studies indicated that compound 13d could effectively inhibit tumor growth, exhibiting no discernible toxic manifestations. Specifically, a significant tumor growth inhibition rate of 62.9% was observed in the K562 xenograft tumor mouse model. The accumulated data propound the potential therapeutic application of compound 13d in the management of leukemia.


Asunto(s)
Humanos , Ratones , Animales , Línea Celular Tumoral , Donantes de Óxido Nítrico/farmacología , Sesquiterpenos/farmacología , Leucemia/tratamiento farmacológico , Bioensayo , Proliferación Celular
20.
Chinese Journal of Cardiology ; (12): 851-858, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1046029

RESUMEN

Objective: To investigate the impact of combined use and timing of arterial-venous extracorporeal membrane oxygenation (VA-ECMO) with intra-aortic balloon pump (IABP) on the prognosis of patients with acute myocardial infarction complicated with cardiogenic shock (AMICS). Methods: This was a prospective cohort study, patients with acute myocardial infarction and cardiogenic shock who received VA-ECMO support from the Heart Center of Lanzhou University First Hospital from March 2019 to March 2022 in the registration database of the Chinese Society for Extracorporeal Life Support were enrolled. According to combination with IABP and time point, patients were divided into VA-ECMO alone group, VA-ECMO+IABP concurrent group and VA-ECMO+IABP non-concurrent group. Data from 3 groups of patients were collected, including the demographic characteristics, risk factors, ECG and echocardiographic examination results, critical illness characteristics, coronary intervention results, VA-ECMO related parameters and complications were compared among the three groups. The primary clinical endpoint was all-cause death, and the safety indicators of mechanical circulatory support included a decrease in hemoglobin greater than 50 g/L, gastrointestinal bleeding, bacteremia, lower extremity ischemia, lower extremity thrombosis, acute kidney injury, pulmonary edema and stroke. Kaplan-Meier survival curves were used to analyze the survival outcomes of patients within 30 days of follow-up. Using VA-ECMO+IABP concurrent group as reference, multivariate Cox regression model was used to evaluate the effect of the combination of VA-ECMO+IABP at different time points on the prognosis of AMICS patients within 30 days. Results: The study included 68 AMICS patients who were supported by VA-ECMO, average age was (59.8±10.8) years, there were 12 female patients (17.6%), 19 cases were in VA-ECMO alone group, 34 cases in VA-ECMO+IABP concurrent group and 15 cases in VA-ECMO+IABP non-concurrent group. The success rate of ECMO weaning in the VA-ECMO+IABP concurrent group was significantly higher than that in the VA-ECMO alone group and the VA-ECMO+IABP non-concurrent group (all P<0.05). Compared with the ECMO+IABP non-concurrent group, the other two groups had shorter ECMO support time, lower rates of acute kidney injury complications (all P<0.05), and lower rates of pulmonary edema complications in the ECMO alone group (P<0.05). In-hospital survival rate was significantly higher in the VA-ECMO+IABP concurrent group (28 patients (82.4%)) than in the VA-ECMO alone group (9 patients) and VA-ECMO+IABP non-concurrent group (7 patients) (all P<0.05). The survival rate up to 30 days of follow-up was also significantly higher surviving patients within were in the ECMO+IABP concurrent group (26 cases) than in VA-ECMO alone group (9 patients) and VA-ECMO+IABP non-concurrent group (4 patients) (all P<0.05). Multivariate Cox regression analysis showed that compared with the concurrent use of VA-ECMO+IABP, the use of VA-ECMO alone and non-concurrent use of VA-ECMO+IABP were associated with increased 30-day mortality in AMICS patients (HR=2.801, P=0.036; HR=2.985, P=0.033, respectively). Conclusions: When VA-ECMO is indicated for AMICS patients, combined use with IABP at the same time can improve the ECMO weaning rate, in-hospital survival and survival at 30 days post discharge, and which does not increase additional complications.


Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Anciano , Choque Cardiogénico/complicaciones , Oxigenación por Membrana Extracorpórea/métodos , Edema Pulmonar/complicaciones , Cuidados Posteriores , Estudios Prospectivos , Alta del Paciente , Infarto del Miocardio/terapia , Contrapulsador Intraaórtico/métodos , Resultado del Tratamiento , Estudios Retrospectivos
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