[Pathogenesis of chronic heart failure in rats based on ferroptosis-mediated oxidative stress and intervention effect of Shenfu Injection].

This study aims to investigate the pathogenesis of chronic heart failure based on ferroptosis-mediated oxidative stress and predict the targets of Shenfu Injection in treating chronic heart failure. A rat model of chronic heart failure was established by the isoproterenol induction method. According to the random number table method, the modeled rats were assigned into three groups: a model group, a Shenfu Injection group, and a ferrostatin-1(ferroptosis inhibitor) group. In addition, a normal group was designed. After 15 days of intervention, the cardiac mass index and left ventricular mass index were determined. Echocardiography was employed to eva-luate the cardiac function. Hematoxylin-eosin staining and Masson staining were employed to reveal the pathological changes and fibrosis of the heart, and Prussian blue staining to detect the aggregation of iron ions in the myocardial tissue. Transmission electron microscopy was employed to observe the mitochondrion ultrastructure in the myocardial tissue. Colorimetry was adopted to measure the levels of iron metabolism, lipid peroxidation, and antioxidant indicators. Flow cytometry was employed to measure the content of lipid-reactive oxygen species(ROS) and the fluorescence intensity of ROS. Western blot and RT-qPCR were employed to determine the protein and mRNA levels, respectively, of ferroptosis-related factors in the myocardial tissue. The results showed that the rats in the model group had reduced cardiac function, elevated levels of total iron and Fe~(2+), lowered level of glutathione(GSH), increased malondialdehyde(MDA), decreased superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px), and rising levels of ROS and lipid-ROS. In addition, the model group showed fibrous tissue hyperplasia with inflammatory cell infiltration and myocardial fibrosis, iron ion aggregation, and characteristic mitochondrial changes specific for iron death. Moreover, the model group showcased upregulated protein and mRNA levels of p53 and COX2 and downregulated protein and mRNA levels of GPX4, FTH1, SLC7A11, and Nrf2 in the myocardial tissue. The intervention with Shenfu Injection significantly improved the cardiac function, recovered the iron metabolism, lipid peroxidation, and antioxidant indicators, decreased iron deposition, improved mitochondrial structure and function, and alleviated inflammatory cell infiltration and fibrosis. Furthermore, Shenfu Injection downregulated the mRNA and protein levels of p53 and COX2 and upregulated the mRNA and protein levels of GPX4, FTH1, SLC7A11, and Nrf2 in the myocardial tissue. Shenfu Injection can improve the cardiac function by regulating iron metabolism, inhibiting ferroptosis, and reducing oxidative stress injury.

A retrospective analysis of the care cascades for non-communicable disease and mental health among people living with HIV at a tertiary-care centre in Malaysia: opportunities to identify gaps and optimize care.

INTRODUCTION: The rapidly growing epidemic of non-communicable diseases (NCDs) including mental health among aging people living with HIV (PLWH) has put a significant strain on the provision of health services in many HIV clinics globally. We constructed care cascades for specific NCDs and mental health among PLWH attending our centre to identify potential areas for programmatic improvement. METHODS: This was a follow-up study of participants recruited in the Malaysian HIV & Aging study (MHIVA) from 2014 to 2016 at the University Malaya Medical Centre (n = 336). PLWH on suppressive antiretroviral therapy (ART) for a minimum of 12 months were invited to participate. At study entry, all participants underwent screening for diabetes (DM), hypertension (HTN) and dyslipidaemia; and completed assessments using the depression, anxiety and stress scale (DASS-21). Screening results were recorded in medical charts and clinical management provided as per standard of care. A subsequent review of medical records was performed at 24 months following study completion among participants who remained on active follow-up. Treatment pathways for NCD treatment and psychiatric referrals were assessed based on local practice guidelines to construct the care cascade. RESULTS: A total of 329 participants (median age = 43 years, 83% male, 100% on ART) completed follow-up at 24 months. The prevalence of diabetes was 13%, dyslipidaemia 88% and hypertension 44%, whereas 23% presented with severe/extremely severe symptoms of depression, anxiety and/or stress. More than 50% of participants with dyslipidaemia and hypertension were not diagnosed until study screening, whereas over 80% with prevalent psychiatric symptoms were not previously recognized clinically. Suboptimal control of fasting lipids, sugar and blood pressure were found in the majority of participants despite optimal HIV treatment outcomes maintained over this same period. Only 32% of participants with severe/extremely severe mental health symptoms received psychiatric referrals and 83% of these attended their psychiatry clinic appointments. CONCLUSIONS: Systematic screening must be introduced to identify NCDs and mental health issues among PLWH followed by proper linkage and referrals for management of screen-positive cases. Assessment of factors associated with attrition at each step of the care cascade is critically needed to improve health outcomes in our aging patients.