Role of the P2X7 receptor in breast cancer progression.

Breast cancer is a common malignant tumor, whose incidence is increasing year by year, and it has become the malignant tumor with the highest incidence rate in women. Purine ligand-gated ion channel 7 receptor (P2X7R) is a cation channel receptor with Adenosine triphosphate ( ATP) as a ligand, which is widely distributed in cells and tissues, and is closely related to tumorigenesis and progression. P2X7R plays an important role in cancer by interacting with ATP. Studies have shown that P2X7R is up-regulated in breast cancer and can promote tumor invasion and metastasis by activating the protein kinase B (AKT) signaling pathway, promoting epithelial-mesenchymal transition (EMT), controlling the generation of extracellular vesicle (EV), and regulating the expression of the inflammatory protein cyclooxygenase 2 (COX-2). Furthermore, P2X7R was proven to play an essential role in the proliferation and apoptosis of breast cancer cells. Recently, inhibitors targeting P2X7R have been found to inhibit the progression of breast cancer. Natural P2X7R antagonists, such as rhodopsin, and the isoquinoline alkaloid berberine, have also been shown to be effective in inhibiting breast cancer progression. In this article, we review the research progress of P2X7R and breast cancer intending to provide new targets and directions for breast cancer treatment.

P2X7 receptor promotes migration and invasion of non-small cell lung cancer A549 cells through the PI3K/Akt pathways.

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.

Progress in the relationship between P2X7R and colorectal cancer.

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.

The Expression of P2X7 Receptor on Th1, Th17, and Regulatory T Cells in Patients with Systemic Lupus Erythematosus or Rheumatoid Arthritis and Its Correlations with Active Disease.

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.

Current Status of Endovascular Treatment for Acute Large Vessel Occlusion in China: A Real-World Nationwide Registry.

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.

Production, characterization, and application of a monoclonal antibody specific for the extracellular domain of human P2X7R.

This paper focuses on the production of a high-affinity monoclonal antibody (mAb) that can efficiently detect and block purinergic ligand-gated ion channel 7 receptor (P2X7R). To achieve this goal, the extracellular domain of human P2X7R, P2X7R-ECD, was used as an immunogen for BALB/c mice, inducing them to produce spleen lymphocytes that were subsequently fused with myeloma cells. Screening of the resultant hybridoma clones resulted in the selection of one stable positive clone that produced a qualified mAb, named 4B3A4. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis demonstrated that the purity of the purified 4B3A4 mAb was above 85%, with prominent bands corresponding to molecular weights of 55 kDa (heavy chain) and 25 kDa (light chain), and the BCA assay showed that the concentration of the purified 4B3A4 mAb was 0.3 mg/mL. Western blot analysis revealed that the 4B3A4 mAb could specifically recognize and bind both P2X7R-ECD and the full-length P2X7R protein. Laser scanning confocal microscopy (LSCM) revealed that the 4B3A4 mAb specifically bound to P2X7R on the membrane of human peripheral blood mononuclear cells (PBMCs). P2X7R expression was significantly different between healthy individuals and people with certain cancers as determined by flow cytometry (FCM). In addition, the 4B3A4 mAb significantly reduced ATP-stimulated Ca2+ entry and YO-PRO-1 uptake, which indicated that the 4B3A4 mAb effectively blocked P2X7R activity. These data indicate that the 4B3A4 mAb can be further used as not only an antibody to detect cell surface P2X7R but also as a therapeutic antibody to target P2X7R-related signaling pathways.

Overexpression of modified human TRß1 suppresses the growth of hepatocarcinoma SK-hep1 cells in vitro and in xenograft models.

Association studies suggest that TRß1 functions as a tumor suppressor. Thyroid hormone receptors (TRs) mediate transcriptional responses through a highly conserved DNA-binding domain (DBD). We previously constructed an artificially modified human TRß1 (m-TRß1) via the introduction of a 108-bp exon sequence into the corresponding position of the wild-type human TRß1 (TRß1) DBD. Studies confirmed that m-TRß1 was functional and could inhibit the proliferation of breast cancer MDA-MB-468 cells in vitro. To understand the role of m-TRß1 in liver tumor development, we adopted a gain-of-function approach by stably expressing TRß (m-TRß1 and TRß1) genes in a human hepatocarcinoma cell line, SK-hep1 (without endogenous TRß), and then evaluated the effects of the expressed TRß on cancer cell proliferation, migration, and tumor growth in cell-based studies and xenograft models. In the presence of 3,5,3-L-triiodothyronine (T3), the expression of TRß in SK-hep1 cells inhibited cancer cell proliferation and impeded tumor cell migration through the up-regulation of 4-1BB, Caspase-3, and Bak gene expression; down-regulation of Bcl-2 gene expression; and activation of the Caspase-3 protein. TRß expression in SK-hep1 led to less tumor growth in xenograft models. Additionally, the anti-tumor effect of m-TRß1 was stronger than that of TRß1. These data indicate that m-TRß1 can act as a tumor suppressor in hepatocarcinoma and its role was significantly better than that of TRß1.

Effect of Qigong exercise on motor function in stroke patients: a systematic review and meta-analysis of randomized controlled trials.

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.

The role of the purinergic ligand-gated ion channel 7 receptor in common digestive system cancers.

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.

Research Progress in the Relationship Between P2X7R and Cervical Cancer.

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.

Purinergic P2X7R as a potential target for pancreatic cancer.

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.

Effect of Qigong exercise on non-motor function and life quality in stroke patients: A systematic review and meta-analysis.

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.

Research progress on the P2X7 receptor in liver injury and hepatocellular carcinoma.

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.

Phasic regulation of the ATP/P2X7 receptor signaling pathway affects the function of antigen-presenting cells in experimental autoimmune uveitis.

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.

Predictive factors of poor outcome and mortality among anterior ischaemic stroke patients despite successful recanalisation in China: a secondary analysis of the CAPTURE trial.

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.

Selection of suitable reference genes for normalization of quantitative real-time PCR in cartilage tissue injury and repair in rabbits.

When studying the altered expression of genes associated with cartilage regeneration by quantitative real-time RT-PCR (RT-qPCR), reference genes with highly stable expression during different stages of chondrocyte developmental are necessary to normalize gene expression accurately. Until now, no reports evaluating expression changes of commonly used reference genes in rabbit articular cartilage have been published. In this study, defects were made in rabbit articular cartilage, with or without insulin-like growth factor 1 (IGF-1) treatment, to create different chondrocyte living environments. The stability and intensity of the expressions of the candidate reference genes glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 18S Ribosomal RNA (18S rRNA), cyclophilin (CYP), hypoxanthine phosphoribosyl transferase (HPRT1), and beta-2-microglobulin (B2M) were evaluated. The data were analyzed by geNorm and NormFinder. B2M and 18S rRNA were identified to be suitable reference genes for rabbit cartilage tissues.

ATP-gated P2X7 receptor as a potential target for prostate cancer.

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.

Endovascular treatment of acute ischemic stroke with a fully radiopaque retriever: A randomized controlled trial.

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.

P2X7 receptor: a critical regulator and potential target for breast cancer.

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.

Efficacy and Safety of a Novel Thrombectomy Device in Patients With Acute Ischemic Stroke: A Randomized Controlled Trial.

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.