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Objective To investigate the effect of blood pressure telemonitoring management mode, blood pressure self-monitoring management mode, and outpatient blood pressure management mode on the level of blood pressure and the rate of reaching the standard for blood pressure in patients with essential hypertension. Methods A total of 441 patients with essential hypertension were recruited and randomly divided into telemonitoring group with 156 patients, non-telemonitoring group with 144 patients, and conventional group with 141 patients. The patients in the telemonitoring group and the non-telemonitoring group were provided with the same model of intelligent electronic blood pressure monitor, and they were managed in accordance with the telemonitoring management mode and the self-monitoring management mode, respectively. The patients in the conventional group received blood pressure management according to the outpatient blood pressure management mode and were asked to go to the community clinic regularly to have their blood pressure measured by a physician. Related data were recorded before management and after 6 months of management, including office blood pressure, the rate of reaching the standard for blood pressure, medication, body mass index, waist circumference, and lifestyle. Results After 6 months of management, all three groups had significant reductions in systolic blood pressure and diastolic blood pressure (t=5.611-14.434,P0.05). There was no significant difference in the improvement of life style between the three groups before ma-nagement and after 6 months of management (P>0.05). Conclusion Compared with blood pressure self-monitoring management mode and outpatient blood pressure management mode, blood pressure telemonitoring management mode can better manage blood pressure, improve the rate of reaching the standard for blood pressure, and increase the proportion of patients with combined medication.

Objective To investigate the value of plasma neutrophil-to-lymphocyte ratio (NLR) combined with global registry of acute coronary events (GRACE) score in evaluating the long-term prognosis of patients with non-ST-elevation myocar-dial infarction (NSTEMI). Methods An analysis was performed for 278 patients with NSTEMI who were hospitalized in The Affiliated Hospital of Qingdao University in 2018 and received long-term follow-up after discharge, and related clinical data were collected to calculate plasma NLR and GRACE score. With the onset of major adverse cardiovascular events (MACE) during follow-up as the endpoint, the patients were divided into MACE group and non-MACE group, and clinical data were compared between the two groups. A multivariate logistic regression analysis was used to investigate the risk factors for MACE, and a receiver operating characteristic (ROC) curve analysis was performed for plasma NLR and GRACE score to investigate their value in eva-luating patient prognosis. The multivariate Cox regression model was used to explore the impact of plasma NLR and GRACE score on the specific survival time of patients. Results There were significant differences between the two groups in age, composition ratio of male patients, composition ratio of diabetic patients, plasma lymphocyte count, plasma NLR, serum low-density lipoprotein cholesterol, plasma B-type natriuretic peptide, left ventricular ejection fraction, and GRACE score (t=-2.748-5.054,χ2=5.067,8.952,Z=-3.108-4.442,P

The aberrant changes of fussion/fission-related proteins can trigger mitochondrial dynamics imbalance, which cause mitochondrial dysfunctions and result insulin resistance (IR). However, the relationship between the inner mitochondrial membrane fusion protein optic atrophy 1 (Opa1) and hepatic IR as well as the specific molecular mechanisms of signal transduction has not been fully elucidated. In this study, we explore whether abnormalities in the Opa1 cause hepatic IR and whether berberine (BBR) can prevent hepatic IR through the SIRT1/Opa1 signalling pathway. High-fat diet (HFD)-fed mice and db/db mice are used as animal models to study hepatic IR in vivo. IR, morphological changes, and mitochondrial injury of the liver are examined to explore the effects of BBR. SIRT1/Opa1 protein expression is determined to confirm whether the signalling pathway is damaged in the model animals and is involved in BBR treatment-mediated mitigation of hepatic IR. A palmitate (PA)-induced hepatocyte IR model is established in HepG2 cells in vitro. Opa1 silencing and SIRT1 overexpression are induced to verify whether Opa1 deficiency causes hepatocyte IR and whether SIRT1 improves this dysfunction. BBR treatment and SIRT1 silencing are employed to confirm that BBR can prevent hepatic IR by activating the SIRT1/Opa1 signalling pathway. Western blot analysis and JC-1 fluorescent staining results show that Opa1 deficiency causes an imbalance in mitochondrial fusion/fission and impairs insulin signalling in HepG2 cells. SIRT1 and BBR overexpression ameliorates PA-induced IR, increases Opa1, and improves mitochondrial function. SIRT1 silencing partly reverses the effects of BBR on HepG2 cells. SIRT1 and Opa1 expressions are downregulated in the animal models. BBR attenuates hepatic IR and enhances SIRT1/Opa1 signalling in db/db mice. In summary, Opa1 silencing-mediated mitochondrial fusion/fission imbalance could lead to hepatocyte IR. BBR may improve hepatic IR by regulating the SIRT1/Opa1 signalling pathway, and thus, it may be used to treat type-2 diabetes.

Background: Breast cancer remains a leading cause of mortality among women worldwide, with existing therapeutic options often accompanied by significant side effects and a persistent risk of disease recurrence. This highlights the need for novel drug candidates with new mechanisms of action by targeting alternative signaling pathways. While hERG channel is notoriously regarded as an off-target due to drug-induced cardiotoxicity, its therapeutic potential as a drug target remains largely unexplored. Methods: This study investigated the role of hERG in breast cancer progression and its impact on patient survival. The anti-proliferative, anti-migratory, anti-invasive and pro-apoptotic effects of hERG activators were evaluated using the Cell Counting Kit-8, wound healing assay, transwell assay and cell apoptosis assay, respectively. Western blotting, Ca2+ imaging and immunofluorescence assays were employed to study their antitumor mechanisms of actions. Results: We identified two novel hERG activators, SDUY429 and SDUY436 , which effectively inhibited the proliferation and migration of MDA-MB-231 and MCF-7 cells. In addition, SDUY436 demonstrated significant anti-invasive and pro-apoptotic effects in MDA-MB-231 cells. Mechanistically, the anti-proliferative activity of hERG activators were mediated through calcineurin activation via enhanced calcium ion influx, which facilitated the nuclear translocation of nuclear factor of activated T cells (NFAT) and upregulated p21Waf/Cip expression. Furthermore, both SDUY429 and SDUY436 remarkably suppressed the migration and invasion of MDA-MB-231 cells by downregulating the protein kinase B (AKT)/glycogen synthase kinase-3 beta (GSK3β)/β-catenin signaling pathway. The observed reduction in phospho-AKT-Ser473 (p AKTS473) expression resulted in the decreased levels of phospho-GSK3β-Ser9 (p GSK3βS9), thereby limiting the nuclear localization of β-catenin, which led to the inhibition of cell migration and invasion. Notably, combining SDUY429 or SDUY436 with the AKT inhibitor MK-2206 produced synergistic anti-proliferative effects. Conclusion: These findings suggest that hERG activators hold promise as new potential therapeutic agents for the treatment of breast cancer, paving the way for future investigations into their clinical applications. [ABSTRACT FROM AUTHOR]