Objective: To explore the clinical application of PTEN-induced kinase 1 (PINK1) and acyl-CoA synthetase long chain family 4 (ACSL4) protein levels in patients with acute myocardial infarction (AMI) and the prognosis evaluation after percutaneous coronary intervention (PCI). Methods: 152 AMI patients who underwent PCI at our hospital from October 2021 to February 2023 were selected as the study group. They were divided into a MACE group (31 cases) and a non MACE group (121 cases) based on the major adverse cardiovascular events (MACE) within 28 days after PCI. Additionally, 152 angina pectoris patients admitted during the same period were selected as the control group. Measure and analyze the levels and clinical significance of PINK1 and ACSL4 proteins in all study subjects. Results: The PINK1 protein level in the study group was lower than that in the control group, while the PINK1 protein level in the MACE group was lower than that in the non MACE group (P<0.05), while the ACSL4 protein level was the opposite (P<0.05); PINK1 expression was negatively correlated with SYNTAX score (r=-0.602, P<0.05), while ACSL4 expression was positively correlated with SYNTAX score (r=0.683, P<0.05); Age, LVEF, and ACSL4 were risk factors for poor prognosis in AMI patients after PCI, while PINK1 was a protective factor (P<0.05); The combined prediction of PINK1 and ACSL4 for the postoperative prognosis of AMI patients after PCI was superior to the individual detection of PINK1 and ACSL4 (P<0.05). Conclusion: The expression levels of PINK1 and ACSL4 are related to the occurrence of AMI, and their combined detection has high predictive power for the prognosis of AMI patients after PCI.

ABSTRACT Background VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part Phase 2 study evaluated the tolerability, safety and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD). Methods In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50 and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50 or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus. Results The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during Weeks 1–2 of treatment). Most gastrointestinal disorders resolved without intervention, and none was serious. In Part 1, serum phosphorus significantly improved (mean change −2.0 mg/dL; 95% confidence interval −2.7, −1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day [mean change −1.6 (−2.2, −1.0), −1.8 (−2.4, −1.2) and −1.4 (−2.2, −0.5) mg/dL, respectively]. In both parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation. Conclusion VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. Clinical Trial registration number NCT04551300

Background Pegmolesatide, a synthetic peptide-based erythropoietin (EPO) receptor agonist, is being evaluated as an alternative to epoetin alfa for treating anemia of chronic kidney disease (CKD) in Chinese dialysis patients. There is a critical need for a long-acting, cost-effective erythropoiesis-stimulating agent that does not produce EPO antibodies.Methods A randomized, open-label, active-comparator, non-inferiority phase three trial was conducted at 43 dialysis centers in China between May 17th, 2019, and March 28th, 2022. Eligible patients aged 18-70 years were randomly assigned (2:1) to receive pegmolesatide once every four weeks or epoetin alfa one to three times per week, with doses adjusted to maintain a hemoglobin level between 10.0 and 12.0 g/dL. The primary efficacy endpoint was the mean change in hemoglobin level from baseline to the efficacy evaluation period in the per-protocol set (PPS) population. Non-inferiority of pegmolesatide to epoetin alfa was established if the lower limit of the two-sided 95% confidence interval for the between-group difference was >= -1.0 g/dL. Safety assessment included adverse events and potential anaphylaxis reactions. This trial is registered at ClinicalTrials.gov, NCT03902691.Findings Three hundreds and seventy-two patients were randomly assigned to the pegmolesatide group (248 patients) or the epoetin alfa group (124 patients). A total of 347 patients (233 in the pegmolesatide group and 114 in the epoetin alfa group) were included in the PPS population. In the PPS, the mean change (standard deviation, SD) in hemoglobin level from baseline to the efficacy evaluation period was 0.07 (0.92) g/dL in the pegmolesatide group and -0.22 (0.97) g/dL in the epoetin alfa group. The between-group difference was 0.29 g/ dL (95% confidence interval: 0.11-0.47), verifying non-inferiority of pegmolesatide to epoetin alfa. Adverse events occurred in 231 (94%) participants in the pegmolesatide group and in 110 (89%) in the epoetin alfa group. Hypertension was the most common treatment-related adverse event. No fatal cases of anaphylaxis or hypotension were reported.Interpretation Monthly subcutaneously injection of pegmolesatide was as effective and safe as conventional epoetin alfa administrated one to three times a week in treating anemia in Chinese dialysis patients.

Objective:To investigate the effects of connective tissue growth factor(CTGF)in pathogenesis of diabetic nephropathy(DN),and to observe curative effects and mechanism of fluvastatin on DN by influencing CTGF expression.Methods:Thirty-eight DN patients whose 24-hour urinary albumin(24h-UA)was between 150 and 500mg,were randomly divided into 3 groups:Valsartan treated group(group Val),fluvastatin treated group(group Flu),and fluvastatin+Valsartan treated group(group FV).Their 24h-UR excretion rates(UAER)and blood CTGF concentrations were determined by using ELISA before and after 3 months of the treatments,and the results were analyzed.Results:Fluvastatin reduced serum CTGF concentrations and 24h-UA excretion rates,and the curative effects were more obvious when combination of fluvastatin and valsartan was used.Conclusion:Fluvastatin has protective effect on kidney,and can delay DN development.