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1.
BMJ Open ; 13(12): e078917, 2023 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-38070920

RESUMO

OBJECTIVES: This work aimed to analyse the risk factors for poor outcomes and mortality among patients with anterior large vessel occlusion (LVO) ischaemic stroke, despite successful recanalisation. SETTING AND PARTICIPANTS: This study conducted a secondary analysis among patients who underwent successful recanalisation in the CAPTURE trial. The trial took place between March 2018 and September 2020 at 21 sites in China. The CAPTURE trial enrolled patients who had an acute ischaemic stroke aged 18-80 years with LVO in anterior circulation. INTERVENTIONS: Thrombectomy was immediately performed using Neurohawk or the Solitaire FR after randomisation in CAPTURE trial. Rescue treatment was available for patients with severe residual stenosis caused by atherosclerosis. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary goal was to predict poor 90-day survival or mortality within 90 days post-thrombectomy. Univariate analysis, using the χ2 test or Fisher's exact test, was conducted for each selected factor. Subsequently, a multivariable analysis was performed on significant factors (p≤0.10) identified through univariate analysis using the backward selection logistic regression approach. RESULTS: Among the 207 recruited patients, 79 (38.2%) exhibited poor clinical outcomes, and 26 (12.6%) died within 90 days post-thrombectomy. Multivariate analysis revealed that the following factors were significantly associated with poor 90-day survival: age ≥67 years, internal carotid artery (ICA) occlusion (compared with middle cerebral artery (MCA) occlusion), initial National Institutes of Health Stroke Scale (NIHSS) score ≥17 and final modified Thrombolysis in Cerebral Infarction (mTICI) score 2b (compared with mTICI 3). Additionally, the following factors were significantly associated with mortality 90 days post-thrombectomy: initial NIHSS score ≥17, ICA occlusion (compared with MCA occlusion) and recanalisation with more than one pass. CONCLUSIONS: Age, NIHSS score, occlusion site, mTICI score and the number of passes can be independently used to predict poor 90-day survival or mortality within 90 days post-thrombectomy. TRIAL REGISTRATION NUMBER: NCT04995757.


Assuntos
Arteriopatias Oclusivas , Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Lactente , Arteriopatias Oclusivas/etiologia , Isquemia Encefálica/cirurgia , Isquemia Encefálica/etiologia , Infarto da Artéria Cerebral Média/terapia , AVC Isquêmico/etiologia , Estudos Retrospectivos , Acidente Vascular Cerebral/cirurgia , Acidente Vascular Cerebral/etiologia , Trombectomia/efeitos adversos , Resultado do Tratamento
2.
Eur J Cancer Prev ; 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37942897

RESUMO

The incidence of digestive malignancies has increased in recent years, including colorectal cancer (CRC), hepatocellular carcinoma (HCC) and pancreatic cancer. Advanced stages of these cancers are prone to metastasis, which seriously reduce the standard of living of patients and lead to decline in the survival rate of patients. So far there are no good specific drugs to stop this phenomenon. It is very important and urgent to find new biomarkers and therapeutic targets. Purinergic ligand-gated ion channel 7 receptor (P2X7R) is ATP-gated and nonselective ion channel receptor involved in many inflammatory processes and cancer progression. P2X7R is present in many cancer cells and promotes or inhibits cancer development through signal transduction. Studies have presented that P2X7R plays a role in the proliferation and migration of digestive system cancers, such as CRC, HCC and pancreatic cancer. Therefore, P2X7R may serve as a biomarker or therapeutic target for digestive system cancers. This paper describes the structure and function of P2X7R, and mainly reviews the research progress on the role of P2X7R in CRC, HCC and pancreatic cancer.

3.
Brain Behav ; 13(11): e3246, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37667530

RESUMO

BACKGROUND: Qigong have a positive impact on the rehabilitation of motor function in stroke survivors, but there is no consensus on the effectiveness of Qigong on activities of daily living (ADL), neurological function, and life quality for patients with stroke. We aimed to quantitatively evaluate the effect of Qigong on non-motor function and life quality in stroke patients. METHODS: Electronic literature searches were performed for randomized controlled trials on this topic using PubMed and China National Knowledge Infrastructure through August 2022. The primary outcome measures were the Barthel Index, neurological deficit score (NDS), and Stroke-Specific Quality of Life Scale (SSQLS). A random-effects model was used to calculate the pooled mean difference (MD) with 95% confidence interval (CI). RevMan 5.4 software was used for meta-analysis. RESULTS: A total of 16 eligible randomized controlled trials with 1253 stroke patients were included. As indicated by the Barthel Index, Qigong was associated with the improvement in daily living activities of stroke patients (MD: 10.72, 95% CI: 5.88∼15.57). It was also found that Qigong was helpful in improving life quality (SSQLS, MD: 14.41, 95% CI: 5.56∼23.25) and reducing NDSs among them (NDS, MD: -4.56, 95% CI: -6.99∼-2.14). After sensitivity analysis, the effect of Qigong on these functions and life quality did not change significantly. By subgroup analysis of intervention duration, we found that long-term intervention (MD: 11.83, 95% CI: 2.80∼20.86) had a better effect on the improvement of daily living activities than short-term intervention (MD: 10.07, 95% CI: 6.15∼14.00) (pfor subgroup differences  = .001). CONCLUSIONS: Pooled results suggested that Qigong had beneficial effects on ADL, neurological function, and life quality in stroke patients, which may provide an option for their rehabilitation.


Assuntos
Qigong , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Atividades Cotidianas , Qualidade de Vida , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Clin. transl. oncol. (Print) ; 25(8): 2297-2305, aug. 2023. ilus
Artigo em Inglês | IBECS | ID: ibc-222409

RESUMO

Pancreatic cancer is one of the deadliest types of cancer, with a death rate nearly equal to the incidence. The P2X7 receptor (P2X7R) is a kind of extracellular adenosine triphosphate (ATP)-gated ion channel with special permeability, which exists in most tissues of human body and mediates inflammation-related signaling pathways and immune signal transduction after activation. P2X7R is also present on the surface of several tumor cells and is involved in tumor growth and progression. P2X7R expression in pancreatic cancer has also been identified in recent studies. Activation of P2X7R in pancreatic cancer can support the proliferation of pancreatic stellate cells, participate in protein interactions, and mediate ERK1/2, IL-6/STAT3, hCAP-18/LL-37, PI3K/AKT signaling pathways to promote pancreatic cancer progression. Inhibitors targeting P2X7R can inhibit the development of pancreatic cancer and are expected to be used in clinical therapy. Therefore, P2X7R is promising as a potential therapeutic target for pancreatic cancer. This article reviews the progress of research on P2X7R in pancreatic cancer (AU)


Assuntos
Humanos , Neoplasias Pancreáticas/patologia , Receptores Purinérgicos P2X7/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Transdução de Sinais/fisiologia
5.
Top Stroke Rehabil ; : 1-12, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37489736

RESUMO

BACKGROUND: Motor impairment is one of the most common defects after stroke, which could seriously affect the life quality of stroke patients. Exercise intervention gradually becomes a popular alternative rehabilitation therapy because of its safety and applicability. OBJECTIVES: To systematically assess the effect of Qigong exercise on motor function in stroke patients. METHODS: Randomized controlled trials that evaluated the effect of Qigong on motor function of stroke patients were obtained from PubMed and Chinese National Knowledge Infrastructure through May 2022. Mean values and standard deviations of the post-intervention score in both experimental group and control group were collected to calculate the mean difference (MD) and corresponkding 95% confidence interval (95% CI) of each study, which were quantificationally summarized using the Review Manager 5.3 software. RESULTS: Nineteen randomized controlled trials enrolling 1487 stroke patients were included. Pooled results indicated that Qigong exercise had beneficial effect on balance function (Berg Balance Scale [MD: 7.56, 95% CI: 4.09-11.02]), limb motor function (Fugl-Meyer Assessment [total score: MD: 7.54, 95% CI: 6.38-8.69; upper limb: MD: 3.57, 95% CI: 0.71-6.43; lower limb: MD: 2.44, 95% CI: 0.59-4.29]) and walking function (6-min walking test [MD: 62.21, 95% CI: 11.70-112.73]) of stroke patients. It was also found to be associated with an improvement in trunk function as indicated by the Trunk Impairment Scale. CONCLUSIONS: Available evidence supported potential benefits of Qigong exercise for improving motor functions of stroke patients. As a safe and widely applicable exercise, Qigong is worthy of further promotion in the rehabilitation of stroke patients.

6.
Int Immunopharmacol ; 119: 110241, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37141671

RESUMO

Purinergic ligand-gated ion channel 7 receptor (P2X7R) is a purine type P2 receptor that is expressed on a variety of immune cells. Recent studies have shown that P2X7R signaling is required to trigger an immune response, and P2X7R antagonist-oxidized ATP (oxATP) effectively blocks P2X7R activation. In this study, we investigated the effect of phasic regulation of the ATP/P2X7R signaling pathway on antigen-presenting cells (APCs) by constructing an experimental autoimmune uveitis (EAU) disease model. Our results demonstrated that APCs isolated from the 1st, 4th, 7th and 11th days of EAU presented antigen function and could stimulate the differentiation of naive T cells. Moreover, after stimulation by ATP and BzATP (a P2X7R agonist), antigen presentation, promoting differentiation and inflammation were enhanced. The regulation of the Th17 cell response was significantly stronger than that of the Th1 cell response. In addition, we verified that oxATP blocked the P2X7R signaling pathway on APCs, attenuated the effect of BzATP, and significantly improved the adoptive transfer EAU induced by antigen-specific T cells cocultured with APCs. Our results demonstrated that at an early stage of EAU, the ATP/P2X7R signaling pathway regulation of APCs was time dependent, and the treatment of EAU could be achieved by intervening in P2X7R function on APCs.


Assuntos
Doenças Autoimunes , Receptores Purinérgicos P2X7 , Transdução de Sinais , Uveíte , Trifosfato de Adenosina/farmacologia , Células Apresentadoras de Antígenos , Receptores Purinérgicos P2X7/metabolismo , Animais , Modelos Animais de Doenças
7.
Clin Transl Oncol ; 25(8): 2297-2305, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36856920

RESUMO

Pancreatic cancer is one of the deadliest types of cancer, with a death rate nearly equal to the incidence. The P2X7 receptor (P2X7R) is a kind of extracellular adenosine triphosphate (ATP)-gated ion channel with special permeability, which exists in most tissues of human body and mediates inflammation-related signaling pathways and immune signal transduction after activation. P2X7R is also present on the surface of several tumor cells and is involved in tumor growth and progression. P2X7R expression in pancreatic cancer has also been identified in recent studies. Activation of P2X7R in pancreatic cancer can support the proliferation of pancreatic stellate cells, participate in protein interactions, and mediate ERK1/2, IL-6/STAT3, hCAP-18/LL-37, PI3K/AKT signaling pathways to promote pancreatic cancer progression. Inhibitors targeting P2X7R can inhibit the development of pancreatic cancer and are expected to be used in clinical therapy. Therefore, P2X7R is promising as a potential therapeutic target for pancreatic cancer. This article reviews the progress of research on P2X7R in pancreatic cancer.


Assuntos
Neoplasias Pancreáticas , Receptores Purinérgicos P2X7 , Humanos , Receptores Purinérgicos P2X7/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Pancreáticas/patologia , Transdução de Sinais/fisiologia , Neoplasias Pancreáticas
8.
Purinergic Signal ; 19(4): 685-697, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36854856

RESUMO

It has been demonstrated that the ATP-gated ion channel P2X7 receptor is involved in tumor progression and plays an important role in regulating tumor cell growth, invasion, migration and angiogenesis. However, P2X7 receptors have been relatively poorly studied in non-small cell lung cancer (NSCLC) cells. Therefore, the aim of this study was to investigate the effects of P2X7 receptor on A549 cells (NSCLC cell line) migration and invasion and to reveal the molecular mechanisms mediated by it. We detected the expression and function of P2X7 receptor in A549 cells. The effects and mechanisms of P2X7 receptor on A549 cells migration, invasion, and epithelial-mesenchymal transition were detected in vitro and in vivo. The results showed P2X7 receptor expressed by A549 cells had ion channel and macropore formation function. In addition, activation of P2X7 receptor by adenosine triphosphate (ATP) or 2'(3')-O-(4-Benzoylbenzoyl)-adenosine-5'-triphosphate (BzATP) promoted Epithelial-mesenchymal transition (EMT), migration and invasion of A549 cells, which was attenuated by treatment of cells with P2X7 receptor antagonist A438079 and Oxidized ATP. Furthermore, activation of P2X7 receptor increased phosphorylated protein kinase B (p-Akt) levels, and the phosphatidylinositol-tris-phosphate kinase 3 (PI3K)/protein kinase B (Akt) inhibitor LY294002 blocked migration and invasion of A549 cells induced by ATP or BzATP. At the same time, in vivo results showed that P2X7 receptor could also promote EMT and PI3K/Akt expression in transplanted tumors. Our study indicated that P2X7 receptor promotes A549 cells migration and invasion through the PI3K/Akt signaling pathway, suggesting that P2X7 receptor may be a potential therapeutic target for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Células A549 , Trifosfato de Adenosina/farmacologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Pulmonares/metabolismo , Fosfatos/metabolismo , Fosfatos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/farmacologia , Receptores Purinérgicos P2X7
9.
Reprod Sci ; 30(3): 823-834, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35799022

RESUMO

Cervical cancer is one of the most common and serious tumors in women. Finding new biomarkers and therapeutic targets plays an important role in the diagnosis, prognosis, and treatment of cervical cancer. Purinergic ligand-gated ion channel 7 receptor (P2X7R) is a purine ligand cation channel, activated by adenosine triphosphate (ATP). Studies have shown that P2X7R plays an important role in a variety of diseases and cancers. More and more studies have shown that P2X7R is also closely related to cervical cancer; therefore, the role of P2X7R in the development of cervical cancer deserves further discussion. The expression level of P2X7R in uterine epithelial cancer tissues was lower than that of the corresponding normal tissues. P2X7R plays an important role in the apoptotic process of cervical cancer through various mechanisms of action, and both antagonists and agonists of P2X7R can inhibit the proliferation of cervical cancer cells, while P2X7R is involved in the antitumor effect of Atr-I on cervical cancer cells. This review evaluates the current role of P2X7R in cervical cancer in order to develop more specific therapies for cervical cancer. In conclusion, P2X7R may become a biomarker for cervical cancer screening, and even a new target for clinical treatment of cervical cancer.


Assuntos
Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/tratamento farmacológico , Detecção Precoce de Câncer , Colo do Útero/metabolismo , Biomarcadores , Apoptose , Receptores Purinérgicos P2X7 , Trifosfato de Adenosina/metabolismo , Antagonistas do Receptor Purinérgico P2X/farmacologia , Antagonistas do Receptor Purinérgico P2X/uso terapêutico
10.
Chem Biol Drug Des ; 101(3): 794-808, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36403102

RESUMO

Purinergic ligand-gated ion channel 7 receptor (P2X7 receptor) is an adenosine triphosphate (ATP)-gated ion channel that is widely distributed on the surfaces of immune cells and tissues such as those in the liver, kidney, lung, intestine, and nervous system. Hepatocellular carcinoma (HCC) is one of the most common malignancies with increasing incidence and mortality. Although many treatments for liver cancer have been studied, the prognosis for liver cancer is still very poor. Therefore, new liver cancer treatments are urgently needed. P2X7 receptor activation can secrete proinflammatory factors through the P2X7 receptor-NLRP3 signaling pathway, thereby affecting the progression of liver injury. The P2X7 receptor may be a target for growth inhibition of HCC cells and may affect the invasion and migration of HCC cells through the PI3K/AKT and AMPK signaling pathways. In recent years, P2X7 receptor antagonists or inhibitors have attracted widespread attention as therapeutic targets for hepatocellular carcinoma and liver injury. Therefore, this review covers the basic concepts of the P2X7 receptor and role of the P2X7 receptor in liver cancer and liver injury, providing new potential therapeutic targets for hepatocellular carcinoma and liver injury.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Receptores Purinérgicos P2X7 , Neoplasias Hepáticas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Trifosfato de Adenosina/metabolismo
11.
Mol Biol Rep ; 50(2): 1687-1699, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36417079

RESUMO

Purinergic ligand-gated ion channel 7 receptor (P2X7R) is a nonselective cation channel of the purinergic receptor family. P2X7R is activated by adenosine triphosphate (ATP) and plays a significant role in inflammatory and autoimmune diseases by triggering cellular signal transduction. More importantly, P2X7R is abnormally expressed in many tumor cells and is involved in the progression of various tumor cells. Studies have shown that the irregular expression of P2X7R in colorectal cancer (CRC) can not only indirectly affect the occurrence and development of CRC by promoting inflammatory bowel disease but also directly affect the proliferation and metastasis of CRC cells. P2X7R plays a bidirectional role in cancer induction and inhibition by mediating complex signaling pathways in CRC, and its expression level is closely related to the overall survival of CRC patients. Therefore, P2X7R may be a biomarker and potential therapeutic target for the development and prognosis of CRC. In this paper, we review the research progress on P2X7R in CRC.


Assuntos
Neoplasias Colorretais , Receptores Purinérgicos P2X7 , Humanos , Trifosfato de Adenosina , Biomarcadores , Carcinogênese , Neoplasias Colorretais/metabolismo , Receptores Purinérgicos P2X7/genética , Receptores Purinérgicos P2X7/metabolismo , Transdução de Sinais
12.
Hum Cell ; 35(5): 1346-1354, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35657562

RESUMO

Prostate cancer is the most common malignancy of the male genitourinary system and is one of the leading causes of male cancer death. The P2X7 receptor is an important member of purine receptor family. It is a gated ion channel with adenosine triphosphate (ATP) as the ligand, which exists in a variety of immune tissues and cells and can be involved in tumorigenesis and tumor progression. Studies have shown that the P2X7 receptor is abnormally expressed in prostate cancer, and is related to the level of prostate-specific antigen, P2X7 receptor may be an early biomarker of prostate cancer. The P2X7 receptor is essential in the occurrence and development of prostate cancer. The P2X7 receptor mainly affects the invasion and metastasis of prostate cancer cells through epithelial mesenchymal transition/invasion-related genes and the PI3K/AKT and ERK1/2 signaling pathways. The P2X7 receptor could be a promising therapeutic target for prostate cancer.


Assuntos
Trifosfato de Adenosina , Neoplasias da Próstata , Receptores Purinérgicos P2X7 , Trifosfato de Adenosina/metabolismo , Humanos , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias da Próstata/patologia , Receptores Purinérgicos P2X7/genética , Receptores Purinérgicos P2X7/metabolismo , Transdução de Sinais/genética
13.
Front Neurol ; 13: 962987, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36588884

RESUMO

Objective: The Neurohawk retriever is a new fully radiopaque retriever. A randomized controlled non-inferiority trial was conducted to compare the Neurohawk and the Solitaire FR in terms of safety and efficacy. In order to evaluate the efficacy and safety of endovascular treatment in acute ischemic stroke (AIS) caused by intracranial atherosclerotic disease (ICAD) larger vessel occlusion (LVO), a sub-analysis was performed. Methods: Acute ischemic stroke patients aged 18-80 years with LVO in the anterior circulation were randomly assigned to undergo thrombectomy with either the Neurohawk or the Solitaire FR. The primary efficacy endpoint was successful reperfusion (mTICI 2b-3) rate by the allocated retriever. A relevant non-inferiority margin was 12.5%. Safety outcomes were symptomatic intracranial hemorrhage (sICH) and all-cause mortality within 90 days. Secondary endpoints included first-pass effect (FPE), modified FPE, and favorable outcomes at 90 days. In subgroup analysis, the patients were divided into the ICAD group and non-ICAD group according to etiology, and baseline characteristics, angiographic, and clinical outcomes were compared. Results: A total of 232 patients were involved in this analysis (115 patients in the Neurohawk group and 117 in the Solitaire group). The rates of successful reperfusion with the allocated retriever were 88.70% in the Neurohawk group and 90.60% in the Solitaire group (95%CI of the difference, -9.74% to 5.94%; p = 0.867). There were similar results in FPE and mFPE in both groups. The rate of sICH seemed higher in the Solitaire group (13.16% vs. 7.02%, p = 0.124). All-cause mortality and favorable outcome rates were comparable as well. In subgroup analysis, 58 patients were assigned to the ICAD group and the remaining 174 to the non-ICAD group. The final successful reperfusion and favorable outcome rates showed no statistically significant differences in two groups. Mortality within 90 days was relatively lower in the ICAD group (6.90% vs. 17.24%; p = 0.054). Conclusion: The Neurohawk retriever is non-inferior to the Solitaire FR in the mechanical thrombectomy of large vessel occlusion-acute ischemic stroke (LVO-AIS). The sub-analysis suggested that endovascular treatment including thrombectomy with the retriever and essential rescue angioplasty is effective and safe in AIS patients with intracranial atherosclerotic disease-larger vessel occlusion (ICAD-LVO). Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04995757, number: NCT04995757.

14.
Front Neurol ; 12: 686253, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456847

RESUMO

Purpose: The Tonbridge stent is a novel retriever with several design improvements which aim to achieve promising flow reperfusion in the treatment of acute ischemic stroke (AIS). We conducted a randomized controlled, multicenter, non-inferiority trial to compare the safety and efficacy of the Tonbridge stent with the Solitaire FR. Methods: AIS patients aged 18-85 years with large vessel occlusion in anterior circulation who could undergo puncture within 6 h of symptom onset were included. Randomization was performed on a 1:1 ratio to thrombectomy with either the Tonbridge stent or the Solitaire FR. The primary efficacy endpoint was successful reperfusion using a modified thrombolysis in cerebral infarction score (mTICI) of 2b/3. Safety outcomes were symptomatic intracranial hemorrhage (sICH) within 24 ± 6 h and all-cause mortality within 90 days. A clinically relevant non-inferiority margin of 12% was chosen as the acceptable difference between groups. Secondary endpoints included time from groin puncture to reperfusion, National Institutes of Health Stroke Scale (NIHSS) score at 24 h and at 7 days, and a modified Rankin Scale (mRS) score of 0-2 at 90 days. Results: A total of 220 patients were enrolled; 104 patients underwent thrombectomy with the Tonbridge stent and 104 were treated with the Solitaire FR. In all test group patients, the Tonbridge was used as a single retriever without rescuing by other thrombectomy devices. Angioplasty with balloon and/or stent was performed in 26 patients in the Tonbridge group and 16 patients in the Solitaire group (p = 0.084). Before angioplasty, 86.5% of those in the Tonbridge group and 81.7% of those in the Solitaire group reached successful reperfusion (p = 0.343). Finally, more patients in the Tonbridge group achieved successful reperfusion (92.3 vs. 84.6%, 95% CI of difference value 0.9-16.7%, p < 0.0001). There were no significant differences on sICH within 24 ± 6 h between the two groups. All-cause mortality within 90 days was 13.5% in the Tonbridge group and 16.3% in the Solitaire group (p = 0.559). We noted no significant differences between groups on the NIHSS at either 24 h or 7 days and the mRS of 0-2 at 90 days. Conclusion: The trial indicated that the Tonbridge stent was non-inferior to the Solitaire FR within 6 h of symptom onset in cases of large vessel occlusion stroke. Clinical Trial Registration:ClinicalTrials.gov, number: NCT03210623.

15.
Stroke ; 52(4): 1203-1212, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33596674

RESUMO

BACKGROUND AND PURPOSE: The benefit of endovascular treatment (EVT) for large vessel occlusion in clinical practice in developing countries like China needs to be confirmed. The aim of the study was to determine whether the benefit of EVT for acute ischemic stroke in randomized trials could be generalized to clinical practice in Chinese population. METHODS: We conducted a prospective registry of EVT at 111 centers in China. Patients with acute ischemic stroke caused by imaging-confirmed intracranial large vessel occlusion and receiving EVT were included. The primary outcome was functional independence at 90 days defined as a modified Rankin Scale score of 0 to 2. Outcomes of specific subgroups in the anterior circulation were reported and logistic regression was performed to predict the primary outcome. RESULTS: Among the 1793 enrolled patients, 1396 (77.9%) had anterior circulation large vessel occlusion (median age, 66 [56-73] years) and 397 (22.1%) had posterior circulation large vessel occlusion (median age, 64 [55-72] years). Functional independence at 90 days was reached in 45% and 44% in anterior and posterior circulation groups, respectively. For anterior circulation population, underlying intracranial atherosclerotic disease was identified in 29% of patients, with higher functional independence at 90 days (52% versus 44%; P=0.0122) than patients without intracranial atherosclerotic disease. In the anterior circulation population, after adjusting for baseline characteristics, procedure details, and early outcomes, the independent predictors for functional independence at 90 days were age <66 years (odds ratio [OR], 1.733 [95% CI, 1.213-2.476]), time from onset to puncture >6 hours (OR, 1.536 [95% CI, 1.065-2.216]), local anesthesia (OR, 2.194 [95% CI, 1.325-3.633]), final modified Thrombolysis in Cerebral Infarction 2b/3 (OR, 2.052 [95% CI, 1.085-3.878]), puncture-to-reperfusion time ≤1.5 hours (OR, 1.628 [95% CI, 1.098-2.413]), and National Institutes of Health Stroke Scale score 24 hours after the procedure <11 (OR, 9.126 [95% CI, 6.222-13.385]). CONCLUSIONS: Despite distinct characteristics in the Chinese population, favorable outcome of EVT can be achieved in clinical practice in China. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03370939.


Assuntos
Procedimentos Endovasculares/métodos , AVC Isquêmico/cirurgia , Idoso , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/cirurgia , China , Feminino , Humanos , AVC Isquêmico/etiologia , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Resultado do Tratamento
16.
J Mol Med (Berl) ; 99(3): 349-358, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33486566

RESUMO

Breast cancer is currently the most common cancer and the leading cause of cancer death among women worldwide. Advanced breast cancer is prone to metastasis, and there is currently no drug to cure metastatic breast cancer. The purinergic ligand-gated ion channel 7 receptor is an ATP-gated nonselective cation channel receptor and is involved in signal transduction, growth regulation, cytokine secretion, and tumor cell development. Recent studies have shown that upregulation of the P2X7 receptor in breast cancer can mediate AKT signaling pathways, Ca2 þ-activated SK3 potassium channels, and EMT and regulate the secretion of small extracellular vesicles to promote breast cancer invasion and migration, which are affected by factors such as hypoxia and ATP. In addition, studies have shown that microRNAs can bind to the 3' untranslated region of the P2X7 receptor, which affects the occurrence and development of breast cancer by upregulating and downregulating P2X7 receptor expression. Studies have shown that new P2X7 receptor inhibitors, such as emodin and Uncaria tomentosa, can inhibit P2X7 receptor-mediated breast cancer invasion and are expected to be used clinically. This article reviews the research progress on the relationship between the P2X7 receptor and breast cancer to provide new ideas and a basis for clinical diagnosis and treatment.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/metabolismo , Terapia de Alvo Molecular/métodos , Proteínas de Neoplasias/fisiologia , Antagonistas do Receptor Purinérgico P2X/uso terapêutico , Receptores Purinérgicos P2X7/fisiologia , Trifosfato de Adenosina/metabolismo , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Unha-de-Gato , Cátions/metabolismo , Progressão da Doença , Emodina/uso terapêutico , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Transporte de Íons , Invasividade Neoplásica , Metástase Neoplásica , Proteínas de Neoplasias/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Antagonistas do Receptor Purinérgico P2X/farmacologia , Receptores Purinérgicos P2X7/química , Receptores Purinérgicos P2X7/efeitos dos fármacos , Transdução de Sinais/fisiologia , Relação Estrutura-Atividade , Regulação para Cima
17.
PLoS One ; 15(10): e0240959, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33085709

RESUMO

As a novel concept of responding to disease epidemics, Fangcang shelter hospitals were deployed to expand the health system's capacity and provide medical services for non-severe COVID-19 patients during the outbreak in Wuhan. To give insights on patient management within Fangcang hospitals, we conducted a retrospective analysis to: 1) describe the characteristics of the patients admitted to Fangcang hospitals and 2) explore risk factors for longer length of stay (LOS). We enrolled 136 confirmed COVID-19 patients, including asymptomatic patients and those with mild symptoms, who were hospitalized in the Wuti Fangcang Hospital. 58 patients completed the treatment and discharged before 1 March 2020. After describing patients' demographic and clinical characteristics, exposure history, treatment received and time course of the disease, we conducted linear regression analysis to identify factors influencing LOS. We found that patients having fever before admission were hospitalized 3.5 days (95%CI 1.39 to 5.63, p = 0.002) longer than those without fever and that patients having bilateral pneumonia were hospitalized 3.4 days (95%CI 0.49 to 6.25, p = 0.023) longer than those with normal CT scan results. We also found weak evidence suggesting that patients with diabetes were hospitalized 3.2 days longer than those without diabetes (95%CI -0.2 to 6.56, p = 0.065). However, we observed no significant differences in LOS between symptomatic and asymptomatic patients and between patients who received treatment and those without treatment. Longer duration of hospitalization among non-severe COVID-19 patients is associated with having fever, bilateral pneumonia on CT scan and diabetes. However, being asymptomatic and using supportive medications at the early stage of infection do not have significant influences on LOS. Our study is a single-centered study with relatively small sample size. The findings provide evidence for predicting hospital bed demand in a novel response scenario and may help decision-makers in preparing for ramping up the health system capacity.


Assuntos
Betacoronavirus/genética , Doenças Cardiovasculares/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Diabetes Mellitus/epidemiologia , Tempo de Internação , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Índice de Gravidade de Doença , Adulto , Idoso , COVID-19 , Comorbidade , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/virologia , Feminino , Febre , Humanos , Contagem de Linfócitos , Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/virologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Fatores Sexuais , Tomografia Computadorizada por Raios X
18.
J Cancer Res Clin Oncol ; 146(11): 2731-2741, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32892231

RESUMO

PURPOSE: Purinergic P2X7 receptor (P2X7R) is a gated ion channel for which adenosine triphosphate (ATP) is a ligand. Activated P2X7R is widely expressed in a variety of immune cells and tissues and is involved in a variety of physiological and pathological processes. Studies have confirmed that P2X7R is involved in the regulation of tumor cell growth, stimulating cell proliferation or inducing apoptosis. Recent studies have found that P2X7R is abnormally expressed in lung cancer and is closely related to the carcinogenesis and development of lung cancer. In this paper, we comprehensively describe the structure, function, and genetic polymorphisms of P2X7R. In particular, the role and therapeutic potential of P2X7R in lung cancer are discussed to provide new targets and new strategies for the treatment and prognosis of clinical lung cancer. METHODS: The relevant literature on P2X7R and lung cancer from PubMed databases is reviewed in this article. RESULTS: P2X7R regulates the function of lung cancer cells by activating multiple intracellular signaling pathways (such as the JNK, Rho, HMGB1 and EMT pathways), thereby affecting cell survival, growth, invasion, and metastasis and patient prognosis. Targeting P2X7R with inhibitors effectively suppresses the growth and metastasis of lung cancer cells. CONCLUSION: In summary, P2X7R is expected to become a potential target for the treatment of lung cancer, and more clinical research is needed in the future to explore the effectiveness of P2X7R antagonists as treatments.


Assuntos
Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Antagonistas do Receptor Purinérgico P2X/farmacologia , Receptores Purinérgicos P2X7/fisiologia , Animais , Humanos
19.
J Immunol ; 205(7): 1752-1762, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32868411

RESUMO

P2X7 receptor (P2X7R) is highly expressed on immune cells, triggering the release of cytokines and regulating autoimmune responses. To investigate P2X7R surface expression on T helper (Th) 1, Th17, and regulatory T (Treg) cells in patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) and correlations with disease activity, 29 SLE and 29 RA patients and 18 healthy controls (HCs) were enrolled. We showed that SLE and RA patients had significantly higher levels of plasma cytokines (IFN-γ, IL-1ß, IL-6, IL-17A, and IL-23), frequencies of Th1 and Th17 cells, and expression of P2X7R on Th1 and Th17 than HCs, and the Th17/Treg ratio was significantly increased, whereas Treg cell levels were significantly decreased. The Ca2+ influx increase following BzATP stimulation was significantly higher in CD4+PBMCs from SLE and RA patients than in HCs. Blood levels of shed P2X7R were increased in SLE and RA patients. Furthermore, 28-joint Disease Activity Score and SLE Disease Activity Index score showed negative correlations with Treg cell levels and positive correlations with Th17/Treg ratio and Th17 cell P2X7R expression. Interestingly, Th17 cell P2X7R expression was closely correlated with IL-1ß, C-reactive protein, the erythrocyte sedimentation rate, anticyclic citrullinated peptide Abs, albumin, and C4. These data indicate that increased Th17 cell P2X7R expression is functionally and positively related to disease activity and some inflammatory mediators in SLE and RA patients, and P2X7R could be critical in promoting the Th17 immune response and contributing to the complex pathogenesis of SLE and RA.


Assuntos
Artrite Reumatoide/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Receptores Purinérgicos P2X7/metabolismo , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologia , Doença Aguda , Adulto , Idoso , Progressão da Doença , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Purinérgicos P2X7/genética
20.
J Food Sci ; 85(5): 1418-1426, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32304227

RESUMO

As a major product of linoleic acid-rich oils, 2,4-decadienal has unique reactivity that may be potentially toxic to human body. In this study, a reliable reversed-phase liquid chromatography method for the determination of carbonyls was developed, and 2,4-decadienal as the target aldehyde was validated. Furthermore, the possibility of 2,4-decadienal as a lipid oxidation marker was evaluated. The optimal sample pretreatment method was extraction by 2 mL of acetonitrile three times, followed by derivatization at 40 °C for 30 min. The method was linear, sensitive, and accurate with detection and quantification limits of 15 and 50 nmol/L, respectively, and had good average recoveries for 2,4-decadienal in oil samples. In tested edible oils, during heating at 180 °C, the level of 2,4-decadienal rose faster than other aldehydes, including one of the characteristic aldehydes, hexanal. Moreover, good linear relationships between the 2,4-decadienal content and other oxidation indices (R2 = 0.858 to 0.984 for the anisidine value; R2 = 0.876 to 0.986 for the total oxidation value) were observed in sunflower and corn oils under 8 hr heating at three temperatures (120, 150, and 180 °C), indicating that 2,4-decadienal can predict the oxidation of oil. PRACTICAL APPLICATION: 2,4-Decadienal is a toxic aldehyde produced by the oxidation of linoleic acid-rich oils, which is closely related to human health. This work is the first to demonstrate that 2,4-decadienal can be used as an alternative oxidation indicator for linoleic acid-rich oils and is of great significance for the quality control of edible oil in the food industry.


Assuntos
Aldeídos/análise , Óleos de Plantas/química , Cromatografia de Fase Reversa/métodos , Culinária , Temperatura Alta , Oxirredução
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