Autophagy is the general term of lysosomal degradation of substances in cells, which is considered the key to maintaining the normal structure and function of the heart. It also has a correlation with several heart diseases, in particular, myocardial ischemia/reperfusion (I/R) injury. At the stage of myocardial ischemia, autophagy degrades nonfunctional cytoplasmic proteins providing the critical nutrients for the critical life activities, thereby suppressing cell apoptosis and necrosis. However, autophagy is likely to affect the heart negatively in the reperfusion stage. Mammalian target of rapamycin (mTOR) and Beclin1 are two vital autophagy‐related molecules in myocardial I/R injury playing significant roles in different stages. In the ischemia stage, mTOR plays its roles through AMPK/mTOR and phosphoinositide 3‐kinase/Akt/mTOR pathway, whereas Beclin1 plays its roles through its upregulation in the reperfusion stage. A possible interaction between mTOR and Beclin1 has been reported recently, and further studies need to be done to find the underlying interaction between the two molecules in myocardial I/R injury

OBJECTIVE In recent years, some studies have indicated that a novel marker described as the stress hyperglycemia ratio (SHR) can reflect true acute hyperglycemic status and is associated with the short-term poor prognosis in patients with acute myocardial infarction. In the current study we evaluated the association of SHR with adverse cardiovascular events among patients with acute coronary syndrome (ACS). RESEARCH DESIGN AND METHODS We consecutively enrolled 5,562 ACS patients who underwent drug-eluting stent (DES) implantation. All subjects were divided into five groups according to SHR, which was determined by the following formula: ABG / [(28.7 × HbA1c %) − 46.7], where ABG is admission blood glucose level. The primary end point was major adverse cardiovascular and cerebrovascular events (MACCE) at the 2-year follow-up, and the secondary end point included major adverse cardiovascular events (MACE) at 2-year follow-up, cardiac death, and nonfatal myocardial infarction (MI) at 2-year follow-up and in-hospital cardiac death and nonfatal MI. RESULTS A total of 643 MACCE were recorded during a median follow-up of 28.3 months. Kaplan-Meier survival analysis showed the lowest MACCE incidence in quintile 3 (P < 0.001). Moreover, the outcomes of restricted cubic spline analysis suggested that there was a U-shaped or J-shaped association between the SHR and early and late cardiovascular outcomes even after adjustment for other confounding factors. CONCLUSIONS There were U-shaped associations of SHR with MACCE rate and MACE rate at 2-year follow-ups and J-shaped associations of SHR with in-hospital cardiac death and MI and that at 2-year follow-up in ACS patients who underwent DES implantation, and the inflection point of SHR for poor prognosis was 0.78.

Class III histone deacetylases (HDACs) belong to the proteasome family, comprising seven family members identified in mammalian cells, identified Sirt1-Sirt7. As an important member of HDACs, Sirt3 is hotly debated for its multiple functions. It was reported that Sirt3 got involved in the alleviation of multiple diseases, including myocardial infarction, neuron ischemia, hypertrophy, and diabetic myopathy. Through regulating many cellular mechanisms, such as apoptosis, autophagy, and clearance of reactive oxygen species (ROS), Sirt3 played an important role in the alleviation of myocardial ischemia-reperfusion injury. Nowadays Sirt3-induced autophagy was indicated to be involved in the process of the development of myocardial ischemiareperfusion injury. Sirt3 could both activate and inhibit autophagy process by activating different downstream signal pathways, such as Sirt3-AMP-activated protein kinase pathway, Sirt3-Foxo3a pathway, and Sirt3-superoxide dismutasemitochondrial ROS pathway. Whereas the Sirt3-induced autophagy in different phases of myocardial ischemia-reperfusion has not been systematically illustrated. In this review, we summarized the regulated mechanisms found in these years and listed the updated research about the relationship between Sirt3 and autophagy which are both positive and negative during myocardial ischemia-reperfusion phase. We anticipated that we may controlled the activation of autophagy by regulating the concentration of Sirt3 in myocyte. By maintaining a proper expression of autophagy in different phases of myocardial ischemia-reperfusion, we could reduce the morbidity of patients with myocardial infarction apparently in the future. K E Y W O R D SAMP-activated protein kinase, autophagy, mammalian target of rapamycin, mitophagy, myocardial ischemia-reperfusion injury, Sirt3

BackgroundThe triglyceride-glucose index (TyG index) is a valuable marker for predicting adverse cardiovascular events in diabetic patients. However, for nondiabetic patients, whether the TyG index is independently related to poor prognosis remains unclear. This cohort study assessed the association of the TyG index with future cardiovascular risk in nondiabetic subjects who received percutaneous coronary intervention (PCI).MethodsWe consecutively enrolled 5,489 nondiabetic patients who underwent PCI. All experimental subjects were divided into three groups based on their TyG index, which was determined by the equation ln (fasting triglyceride (mg/dl) × fasting blood glucose (mg/dl)/2). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, and target vessel revascularization (TVR).ResultsA total of 386 MACCE were documented during a median 29-month follow-up. The Kaplan–Meier survival results indicated that among the three groups, there was no obvious difference in any endpoints. Further Cox regression analyses suggested that the TyG index was not independently related to adverse cardiovascular outcomes for nondiabetic patients who underwent PCI (HR: 0.77, 95% CI 0.56–1.16, P = 0.210 for MACCE). Subgroup analysis suggested that the TyG index was independently relevant to MACCE for patients with low-density lipoprotein cholesterol (LDL-C) lower than 1.8 mmol/L.ConclusionThe TyG index is not an effective predictive factor for adverse cardiovascular prognosis in nondiabetic patients who underwent PCI. However, in subjects with LDL-C lower than 1.8mmol/L, it may predict future cardiovascular risk.

Background Non-diabetic coronary artery disease (CAD) patients are thought to encounter metabolic dysfunction and while these changes may be imperceptible to the patient they probably influence outcomes. At present, there is no system to support patients sensing these subtle changes, nor is there an established model for prognoses. The Atherogenic Index of Plasma (AIP) index has already proven useful for atherosclerosis although further research is needed, especially for those without hyperglycemia. Methods This is a prospective study of 5538 non-diabetic CAD patients who had received percutaneous coronary intervention (PCI). Participants were assigned to one of three groups according to their AIP index. High AIP index cases were then compared to low index patients according to major adverse cardiac events (MACE). Restricted cubic spline (RCS) analysis was also conducted to investigate interrelations between AIP index levels and hazard ratios (HR) for MACEs. Results Patients with a high AIP index encountered metabolic dysfunction compared to those with a low AIP index i.e., higher Body Mass Index (BMI), Total Cholesterol (TC), Triglycerides (TG), and uric acid as well as lower HDL-C. Each of the aforementioned interrelations were significant with p values of less than 0.001. There was also a significant increase in the number of MACEs in the high AIP index group compared to the low AIP index group (HR: 1.37, 95% CI 1.04–1.81; p = 0.025). A J-shaped RCS curve highlighted a change in the HR after the 0.18 juncture (HR per SD: 1.20, 95% CI 0.96–1.50). Further subgroup analysis supported the main findings, all with HRs greater than one. Conclusion The AIP index could be used in prognostics for non-diabetic CAD patients 2 years after PCI. The relationship between hazard ratio and the AIP index appears to be J-shaped. Although, further multi-center studies designed for non-diabetic patients with potential metabolic dysfunction should be conducted to determine the value of the AIP index.

Limited studies have focused on the impact of high-sensitivity C-reactive protein (hsCRP) to albumin ratio (CAR) on cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI). Hence, the present study evaluates the association between CAR and cardiovascular outcomes in patients undergoing drug-eluting stent (DES) implantation. We consecutively enrolled 9375 CHD patients undergoing DES implantation. All patients were divided into 3 groups according to their CAR: tertile 1 (CAR ≤.02, n=3125), tertile 2 (.02<CAR≤.06, n = 3125), and tertile 3 (CAR >.06, n = 3125). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). Kaplan-Meier analysis indicated that the incidences of MACCE and MI increased with high tertiles of the CAR (MACCE: 8.7 vs 10.5 vs 12.3%, log-rank P < .001; MI: 3.3 vs 4.0 vs 4.7%, long-rank P = .015). Cox regression analysis suggested that CAR was an independent risk factors for MACCE (HR per standard deviation (SD) increase: 1.07, 95% CI, 1.01–1.14, P = .024), and MI (HR per SD increase: 1.11, 95% CI, 1.01–1.22, P = .028). In conclusion, the CAR is an independent predictor of MACCE and MI in CHD patients.

Background Limited studies have focused on the impact of SHyper on poor prognosis in patients with known coronary artery disease (CAD). Hence, we implemented the present study to explore the association between SHyper and adverse cardiovascular events in CAD patients who underwent drug-eluting stent (DES) implantation. Methods We consecutively recruited 8,283 CAD patients undergoing percutaneous coronary intervention (PCI). All subjects were divided into 2 groups according to their thyroid function: group 1 (euthyroidism group, n = 7,942) and group 2 (SHyper group, n = 341). After 1:4 propensity score (PS) matching, 1,603 patients (332 SHyper group and 1,271 euthyroidism group) were selected. The primary endpoint was major adverse cardiovascular events (MACE), a composite of cardiac mortality, nonfatal myocardial infarction (MI), and target vessel revascularization (TVR). Results Kaplan-Meier (K-M) survival analyses suggested that there was no significant difference in the primary endpoint and secondary endpoints (MACE: 11.4% vs. 8.8%, log-rank P = 0.124; cardiac death: 1.2% vs. 0.9%, log-rank P = 0.540; nonfatal MI: 5.7% vs. 4%, log-rank P = 0.177; and TVR: 6% vs. 4.7%, log-rank P = 0.303) in the PS-matched population. Besides, Cox regression analysis indicated that SHyper was not an independent risk factor for MACE (HR: 1.33, 95% CI, 0.92–1.92, P = 0.127). Conclusion SHyper is not independently associated with adverse cardiovascular events in CAD patients undergoing PCI. More studies should be implemented in the future to assess the long-term predictive value of SHyper with thyrotropin (TSH) levels &lt; 0.1 mIU/L for CAD patients undergoing PCI.

Objective The incidence rate of thyroid diseases increased worldwide. This study aims to overview the changing landscape of drug clinical trials on thyroid disease during 2009–2022. Methods The detailed information of thyroid disease drug trials registered on the National Medical Products Administration (NMPA) Registration and Information Disclosure Platform for Drug Clinical Studies was searched and collected. The thyroid drug clinical trials were analyzed by the characteristics, time trends, indications, and geographical distribution. Results Sixty-five thyroid disease drug clinical trials were launched from 2009 to 2022 in China, which included 21 trials in nontumorous thyroid disease and 44 trials in thyroid carcinoma. The number of registered trials of thyroid diseases including thyroid carcinoma and nontumorous thyroid disease increased steadily from 2009 to 2020. Bioequivalence studies accounted for the largest proportion (32[49.2%]), while phase I and Phase II studies both only accounted for 18.5% (12/65). A significant difference was observed in the trials phase, and randomization between thyroid carcinoma and nontumorous thyroid disease. In terms of clinical indications and drug mechanisms, the number of trials in multi-target tyrosine kinase inhibitors for thyroid carcinoma (n=35) ranked first, followed by thyroid hormone for hypothyroidism (n=7), thyrotropin for thyroid carcinoma (n=6). Sixty-five trials were led by 36 principal investigator (PI) units, and more than 30% of PI-leading units were located in Shanghai (n=7) and Beijing (n=4). Conclusion During the past 13 years, the development of thyroid diseases drugs trials has achieved certain progress in thyroid carcinoma, especially the molecular targeted therapy, yet the development of drug trials on nontumorous thyroid disease was very slow.