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Background: Patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) are at high risk of thrombosis. However, bleeding-related complications during antithrombotic therapy remain a major barrier to effective treatment and can often lead to adverse outcomes. This meta-analysis aimed to determine the efficacy and safety of bivalirudin and heparin in patients with ACS after PCI. Methods: Randomized controlled trials (RCTs) on the efficacy and safety of bivalirudin versus heparin in patients with ACS after PCI were identified from the PubMed, Embase, Cochrane Library, CBM, CNKI, WanFang, and VIP database until August 2024. The outcomes included all-cause mortality, major adverse cardiovascular events (MACEs), incidence of recurrent myocardial infarction, stent thrombosis, short-term bleeding, revascularization, and retransfusion. Meta-analysis was performed using RevMan 5.3 and Stata 12.0 softwares. The included studies were assessed for risk of bias using the Cochrane risk-of-bias assessment tool. Results: A total of 70,199 patients from 27 randomized controlled trials (RCTs) were analyzed in this review. There were no significant differences between the bivalirudin and heparin groups in terms of all-cause mortality, major adverse cardiovascular events (MACEs), recurrent myocardial infarction, stent thrombosis within 30 days, or subacute stent thrombosis. Specifically, the incidence of short-term bleeding (P = 0.001) and retransfusion (P = 0.001) was significantly lower in the bivalirudin group compared to the heparin group. Conversely, the incidence of acute stent thrombosis (P < 0.0001) and revascularization (P = 0.009) was significantly higher in the bivalirudin group. Conclusions: Compared with heparin, bivalirudin has definite anticoagulant effect in patients with acute myocardial infarction after PCI, and the risk of bleeding and the incidence of retransfusion were lower in the bivalirudin group. This review helps doctors in PCI management choose bivalirudin or heparin more precisely based on patients' conditions for better treatment and fewer adverse events. [ABSTRACT FROM AUTHOR]

Background Poliovirus receptor interacts with 3 receptors: T-cell immunoglobulin immunoreceptor tyrosine-based inhibitory motif, CD96, and DNAX accessory molecule 1, which are predominantly expressed on T cells and natural killer (NK) cells. Many solid tumors, including IDH wild-type glioblastoma, have been reported to overexpress poliovirus receptor, and this overexpression is associated with poor prognosis. However, there are no preclinical or clinical trials investigating the use of cell-based immunotherapies targeting poliovirus receptor in IDH wild-type glioblastoma. Methods We analyzed poliovirus receptor expression in transcriptome sequencing databases and specimens from IDH wild-type glioblastoma patients. We developed poliovirus receptor targeting chimeric antigen receptor T cells using lentivirus. The antitumor activity of chimeric antigen receptor T cells was demonstrated in patient-derived glioma stem cells, intracranial and subcutaneous mouse xenograft models. Results We verified poliovirus receptor expression in primary glioma stem cells, surgical specimens from IDH wild-type glioblastoma patients, and organoids. Accordingly, we developed poliovirus receptor–based second-generation chimeric antigen receptor T cells. The antitumor activity of chimeric antigen receptor T cells was demonstrated in glioma stem cells and xenograft models. Tumor recurrence occurred in intracranial xenograft models because of antigen loss. The combinational therapy of tyrosine-based inhibitory motif extracellular domain–based chimeric antigen receptor T cells and NK-92 cells markedly suppressed tumor recurrence and prolonged survival. Conclusions Poliovirus receptor–based chimeric antigen receptor T cells were capable of killing glioma stem cells and suppressing tumor recurrence when combined with NK-92 cells. [ABSTRACT FROM AUTHOR]

Quantum process may conduce to brain function. Particularly, it was proposed that the Posner molecules, Cag(PO4)6, can serve as neural qubits, which can maintain quantum entanglement between phosphorus nuclei for quite a long time. We study the process from entangled Posner molecules to the synchronized activities of brain. A diffusion model of Posner molecules with appropriate boundary conditions and the mean first arriving time of Posner molecules from one area of brain to another are obtained. We establish linkages between the quantum entangled connectivity of brain and the remaining time of entangled Posner molecules before decoherence. Based on these results, we find direct correlations between entangled Posner molecules and the functional connectivity of human brain. Furthermore, we discover that the quantum entangled connectivity depends on age. [ABSTRACT FROM AUTHOR]

Background: Several studies suggested that depression was associated with poor prognosis following percutaneous coronary intervention (PCI) in coronary heart disease (CHD), whereas other studies showed that there were no associations between depression and poor outcomes. Objectives: Considering these problems, this meta-analysis was conducted to evaluate the relationship between depression and clinical outcomes after PCI. Methods: Articles published before July 2021 were analyzed from the databases: PubMed, Web of Science, EMBASE, Medline, and Google Scholar. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed to generate a pooled effect size and 95% CI with a random or fixed effects model. Q test and I2 were used to assess heterogeneities between studies. Results: The meta-analysis indicated that depression was associated with a higher risk of major adverse cardiac events (MACE) after PCI with a random effects model (HR = 1.89, 95% CI: 1.33–2.68, I2 = 57.0%, p = 0.023). The study indicated that depression was associated with a higher risk of all-cause mortality after PCI with a fixed effects model (HR = 1.71, 95% CI: 1.43–2.05, I2 = 0.0%, p = 0.756). The study indicated no significant association between depression and risk of repeat revascularization after PCI with a random effects model (HR = 2.10, 95% CI: 0.96–4.58, I2 = 68.9%, p = 0.022). Conclusion: Results indicated that depression is associated with adverse clinical outcomes in CHD patients' post-PCI. Appropriate mental health check and psychological treatment may be necessary for the prognosis of CHD patients who receive PCI. [ABSTRACT FROM AUTHOR]

Preoperative MRI is one of the most important clinical results for the diagnosis and treatment of glioma patients. The objective of this study was to construct a stable and validatable preoperative T2-weighted MRI-based radiomics model for predicting the survival of gliomas. A total of 652 glioma patients across three independent cohorts were covered in this study including their preoperative T2-weighted MRI images, RNA-seq and clinical data. Radiomic features (1731) were extracted from preoperative T2-weighted MRI images of 167 gliomas (discovery cohort) collected from Beijing Tiantan Hospital and then used to develop a radiomics prediction model through a machine learning-based method. The performance of the radiomics prediction model was validated in two independent cohorts including 261 gliomas from the The Cancer Genomae Atlas database (external validation cohort) and 224 gliomas collected in the prospective study from Beijing Tiantan Hospital (prospective validation cohort). RNA-seq data of gliomas from discovery and external validation cohorts were applied to establish the relationship between biological function and the key radiomics features, which were further validated by single-cell sequencing and immunohistochemical staining. The 14 radiomic features-based prediction model was constructed from preoperative T2-weighted MRI images in the discovery cohort, and showed highly robust predictive power for overall survival of gliomas in external and prospective validation cohorts. The radiomic features in the prediction model were associated with immune response, especially tumour macrophage infiltration. The preoperative T2-weighted MRI radiomics prediction model can stably predict the survival of glioma patients and assist in preoperatively assessing the extent of macrophage infiltration in glioma tumours. [ABSTRACT FROM AUTHOR]

Background: Domperidone has long been used as a prokinetic agent in the treatment of epigastric distress symptoms. This study aimed to provide adequate evidence for registration approval of a new generic dry suspension formulation of domperidone by comparing the safety and pharmacokinetic profiles between the test and branded reference formulation in the context of fasted and fed condition., Materials and Methods: This was designed as a randomized, open-label, single-dose, two-period, two-treatment crossover study. 32 and 28 eligible healthy subjects were enrolled in the fasted and fed study, respectively. Each subject was randomly assigned to receive either the test or reference formulation in the first period, followed by a 1-week washout period and dosing of the alternate formulation in the second period. A series of blood samples were collected at scheduled timepoints within 48 hours after administration during each treatment period. Plasma concentrations of domperidone were determined by validated HPLC-MS/MS. Pharmacokinetic parameters, including C max , t max , AUC 0-t , AUC 0-∞ , and T 1/2 , were acquired based on the concentration vs. time profiles by non-compartmental analysis using WinNonlin software. Then the geometric mean ratios (GMR) of C max , AUC 0-t , and AUC 0-∞ between the two formulations and corresponding 90% confidence intervals (CIs) were calculated for bioequivalence determination. Safety was assessed as routine., Results: The two formulations showed similar pharmacokinetic profiles. Under fasted condition, the GMR and corresponding 90% CIs of AUC 0-t , AUC 0-∞ , and C max were 101.48% (96.79 - 106.38%), 101.17% (96.66 - 105.90%), and 104.61% (96.73 - 113.14%), respectively. Under fed condition, the GMR and corresponding 90% CIs were 105.46% (99.19 - 112.12%), 104.21% (98.19 - 110.61%), and 112.78% (103.64 - 122.73%), respectively, for AUC 0-t , AUC 0-∞ , and C max . All values fell within the accepted bioequivalence range of 80 - 125%. Both the test and the reference products were well tolerated without any serious or unexpected adverse reactions., Conclusion: Pharmacokinetic bioequivalence was established between the two dry suspension formulations of domperidone in healthy Chinese subjects. Both products were safe and well tolerated.

Leuprolide acetate microspheres developed by Shanghai Livzon Pharmaceutical Co., Ltd. (T) have been marketed in China for more than 10 years, benefiting a large number of patients, and will continue to play an important role in China. However, as a generic drug, it is unclear whether there is a difference in efficacy between T and the original product Enantone ® (R). This study compared the differences in efficacy and safety of two 1-month depot formulations in 48 healthy Chinese male subjects by comparing multiple pharmacokinetic (PK) and pharmacodynamic (PD) parameters. The main research indicators were the PK parameters of leuprolide (C max , AUC 0-t , AUC 0-D7 , and AUC D7-t ) and the PD parameters of testosterone (E max , AUEC 0-t , AUEC 0-D7 , and AUEC D7-t ) after 42 days of administration. The C max , AUC 0-t , AUC 0-D7 and AUC D7-t of leuprolide were slightly higher in the T group than in the R group with 90% confidence intervals (CIs) of 94.43-118.53%, 109.13-141.88%, 109.53-139.54%, and 105.17-145.74%, respectively. No significant differences in the PD parameters (E max , AUEC 0-t , AUEC 0-D7 , and AUEC D7-t ) existed between the T and R groups, and 90% CIs were 62.80-93.57%, 88.17-110.55, 95.72%-118.50%, and 79.77-105.63, respectively. At 672 h (D28), the castration rate of T was 91.30% (21/23) and that of R was 60.87% (14/23). The PK characteristics were consistent and the inhibitory effects on testosterone levels were similar in both T and R groups; further, clinical safety was observed for both T and R formulations, suggesting that these two products can replace each other in clinical practice. Clinical Trial Registration: http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml, identifier CTR20200641., Competing Interests: Author LW was employed by the company Shanghai Livzon Pharmacy Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, Zhang, Zheng, Zhai, Xu, Zhao, Liu, Wan and Luo.)