The correlation of atherogenic index of plasma with non-obstructive CAD and unfavorable prognosis among patients diagnosed with MINOCA.

BACKGROUND: The atherogenic index of plasma (AIP) is linked to lipid metabolism and has shown considerable prognostic value in cardiovascular disorders. However, its role in myocardial infarction with non-obstructive coronary arteries (MINOCA) has not been investigated. We assessed the relationship between AIP, the severity of coronary stenosis, and prognosis in MINOCA. METHODS: We included consecutive patients who were diagnosed with MINOCA. AIP was calculated using the base 10 logarithm of the ratio between the levels of TG and HDL-C. The patients were divided into four groups based on their AIP quartiles: Q1 (AIP<-0.145), Q2 (AIP≥-0.145and≤0.049), Q3 (AIP>0.049and≤0.253), and Q4 (AIP>0.253). All patients underwent follow-up for MACE. RESULTS: The final analysis included 421 patients, with 188 having normal coronaries (0 stenosis) and 233 exhibiting non-obstructive coronary artery disease (CAD) (<50 % stenosis). In the multivariate logistic analysis, highest AIP (Q4) group was significantly associated with increased risk of non-obstructive CAD in MINOCA (OR,1.994;95 % CI:1.075-3.698; P = 0.029). During the follow-up period, MACE occurred in 22.8 % of MINOCA patients. Q4 group exhibited a significantly higher rate of MACE (P = 0.021). Furthermore, when both AIP and coronary stenosis status were considered, the results revealed individuals in the Q4 group with non-obstructive CAD had the highest risk of MACE (log-rank P = 0.027). The adjusted Cox analysis indicated that the Q4 group was associated with a 2.052-fold increase in the HR of MACE. CONCLUSION: AIP exhibits a notable association with the incidence of MACE in MINOCA patients and serves as a substantial marker for non-obstructive CAD in this patient group.

Rechargeable Zinc-Air Batteries: Advances, Challenges, and Prospects.

Rechargeable zinc-air batteries (Re-ZABs) are one of the most promising next-generation batteries that can hold more energy while being cost-effective and safer than existing devices. Nevertheless, zinc dendrites, non-portability, and limited charge-discharge cycles have long been obstacles to the commercialization of Re-ZABs. Over the past 30 years, milestone breakthroughs have been made in technical indicators (safety, high energy density, and long battery life), battery components (air cathode, zinc anode, and gas diffusion layer), and battery configurations (flexibility and portability), however, a comprehensive review on advanced design strategies for Re-ZABs system from multiple angles is still lacking. This review underscores the progress and strategies proposed so far to pursuit the high-efficiency Re-ZABs system, including the aspects of rechargeability (from primary to rechargeable), air cathode (from unifunctional to bifunctional), zinc anode (from dendritic to stable), electrolytes (from aqueous to non-aqueous), battery configurations (from non-portable to portable), and industrialization progress (from laboratorial to practical). Critical appraisals of the advanced modification approaches (such as surface/interface modulation, nanoconfinement catalysis, defect electrochemistry, synergistic electrocatalysis, etc.) are highlighted for cost-effective flexible Re-ZABs with good sustainability and high energy density. Finally, insights are further rendered properly for the future research directions of advanced zinc-air batteries.

Screening and verifying the mutations in the LDLR and APOB genes in a Chinese family with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder. The primary objective of this study was to identify the major pathogenic mutations in a Chinese family with FH. METHODS: Whole-genome sequencing (WGS) was used to identify variants of FH-related genes, including low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9). Bioinformatics software was used to predict signal peptides, transmembrane structures, and spatial construction information of the mutated sequences. Western blotting was performed on the mutant protein to determine the presence of the major structural domains of the LDLR. The PCSK9 and APOB genes were screened and analyzed. Moreover, the proband and his brother were treated with a PCSK9 inhibitor for 1 year, and the effect of the treatment on lipid levels was assessed. RESULTS: WGS revealed two potentially pathogenic mutations in the LDLR gene. One was a novel mutation, c.497delinsGGATCCCCCAGCTGCATCCCCCAG (p. Ala166fs), and the other was a known pathogenic mutation, c.2054C>T (p. Pro685Leu). Bioinformatics prediction and in vitro experiments revealed that the novel mutation could not be expressed on the cell membrane. Numerous gene variants were identified in the APOB gene that may have a significant impact on the family members with FH. Thus, it is suggested that the severe manifestation of FH in the proband primarily resulted from the cumulative genetic effects of variants in both LDLR and APOB. However, a subsequent study indicated that treatment with a PCSK9 inhibitor (Evolocumab) did not significantly reduce the blood lipid levels in the proband or his brother. CONCLUSIONS: The cumulative effect of LDLR and APOB variants was the primary cause of elevated blood lipid levels in this family. However, PCSK9 inhibitor therapy did not appear to be beneficial for the proband. This study emphasizes the importance of genetic testing in determining the most suitable treatment options for patients with FH.

Association between the atherogenic index of plasma and adverse long-term prognosis in patients diagnosed with chronic coronary syndrome.

BACKGROUND: The Atherogenic Index of Plasma (AIP) is a newly identified biomarker associated with lipid metabolism, demonstrating significant prognostic capabilities in individuals diagnosed with cardiovascular disease. However, its impact within the context of chronic coronary syndromes (CCS) remains unexplored. Thus, the present investigation sought to examine the potential association between AIP levels and long-term clinical outcomes in patients diagnosed with CCS. METHODS: A total of 404 patients diagnosed with CCS and who underwent coronary angiography were included in this study. The AIP index was calculated as log (triglycerides / high-density lipoprotein-cholesterol). The patients were categorized into four groups based on their AIP values: Q1 (< -0.064), Q2 (-0.064 to 0.130), Q3 (0.130 to 0.328), and Q4 (> 0.328). The occurrence of major adverse cardiovascular events (MACE) was monitored during the follow-up period for all patients. Cox regression analysis and Kaplan-Meier curve analysis were employed to examine the relationship between AIP and MACE. Furthermore, ROC analysis was utilized to determine the optimal cut-off value of AIP for predicting clinical MACE. RESULTS: During the median 35 months of follow-up, a total of 88 patients experienced MACE. Notably, the group of patients with higher AIP values (Q4 group) exhibited a significantly higher incidence of MACE compared to those with lower AIP values (Q1, Q2, and Q3 groups) (31.7% vs. 16.8%, 15.7%, and 23.0% respectively; P = 0.023). The Kaplan-Meier curves illustrated those patients in the Q4 group had the highest risk of MACE relative to patients in the other groups (log-rank P = 0.014). Furthermore, the multivariate Cox regression analysis demonstrated that individuals in the Q4 group had a 7.892-fold increased risk of MACE compared to those in the Q1 group (adjusted HR, 7.892; 95% CI 1.818-34.269; P = 0.006). Additionally, the ROC curve analysis revealed an optimal AIP cut-off value of 0.24 for predicting clinical MACE in patients with CCS. CONCLUSION: Our data indicate, for the first time, that AIP is independently associated with poor long-term prognosis in patients suffering from CCS. The optimal AIP cut-off value for predicting clinical MACE among CCS patients was 0.24.

Association between the triglyceride-glucose index and the presence and prognosis of coronary microvascular dysfunction in patients with chronic coronary syndrome.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a strong determinant of prognosis in patients with chronic coronary syndrome (CCS). The triglyceride-glucose index (TyG index), an alternative method to evaluate insulin resistance, is positively correlated with the incidence and adverse outcomes of cardiovascular diseases. However, the relationship between the TyG index and the presence and prognosis of CMD in CCS patients has not been investigated. Therefore, we aimed to evaluate the association between the TyG index and the presence and clinical outcomes of CMD among CCS patients. METHODS: CCS patients who underwent coronary angiography between June 2015 to June 2019 were included. The TyG index was calculated as Ln[fasting triglycerides (mg/dL) × fasting blood glucose (mg/dL)/2]. Coronary angiography­derived index of microvascular resistance (caIMR) was used to measure microvascular function, and CMD was defined as caIMR ≥ 25U. Patients with CMD were divided into three groups (T1, T2, and T3 groups) according to TyG tertiles. The primary endpoint was major adverse cardiac event (MACE). RESULTS: Of 430 CCS patients, 221 patients had CMD. CMD patients had significantly higher TyG index than those without CMD. Sixty-three MACE was recorded during the follow-up duration among CMD patients, and the incidence rate of MACE was higher in the T3 group compared to T1/T2 groups (39.2% vs. 20.5% vs. 25.7%; P = 0.035). Multivariable logistic regression analysis showed that the TyG index was an independent predictor of CMD (OR, 1.436; 95% CI, 1.014-2.034; P = 0.042). Compared to the T1 group, the T3 group strongly correlated with the risk of MACE in CMD patients even after adjusting for additional confounding risk factors (HR, 2.132; 95%CI, 1.066-4.261; P = 0.032). CONCLUSION: TyG index is significantly associated with the risk of CMD, and it is an independent predictor of MACE among CMD patients with CCS. This study suggests that the TyG index has important clinical significance for the early prevention and risk stratification of CMD.

The associations between diode laser (810 nm) therapy and chronic wound healing and pain relief: Light into the chronic wound patient's life.

Chronic wounds have become one of the major issues in medicine today, the treatments for which include dressing changes, negative pressure wound therapy, hyperbaric oxygen, light irradiation, surgery and so forth. Nevertheless, the application of diode lasers in chronic wounds has rarely been reported. This retrospective cohort study aimed to evaluate the therapeutic effect of diode laser (810 nm) irradiation on chronic wounds. Eighty-nine patients were enrolled in the study. The control group (41 patients) received traditional dressing change therapy, while the diode laser treatment group (48 patients) were patients received additional treatment with diode laser (810 nm) irradiation for 10 min at each dressing change. Wound healing time was compared between two groups, while the pain relief index was creatively introduced to evaluate the effect of relieving wound pain, which was calculated by the difference in pain scores between the first and last dressing changes divided by the number of treatment days. The wound healing time of the diode laser treatment group was 22.71 ± 8.99 days, which was significantly shorter than that of the control group (37.44 ± 23.42 days). The pain relief index of the diode laser treatment group was 0.081 ± 0.055, which was significantly increased compared with that of the control group (0.057 ± 0.033). Our findings suggest that diode laser irradiation has the potential to promote healing in chronic wounds and relieve wound pain.

Effect of nonobstructive coronary stenosis on coronary microvascular dysfunction and long-term outcomes in patients with INOCA.

BACKGROUND: Ischemic pain with no-obstructive coronary artery (INOCA) is clinically significant and defined by nonobstructive coronary stenosis <50%. Coronary microvascular dysfunction (CMD) is a relevant cause associated with adverse outcomes. OBJECTIVES: Investigated the effect of no-stenosis (0% stenosis) and non-obstructive (0% < stenosis < 50%) on the prognostic impact of CMD in INOCA. METHOD: A retrospective study assessed the coronary microvascular function in 151 INOCA patients who underwent invasive angiography by the coronary angiography-derived index of microcirculation-resistance (caIMR). CZT-SPECT was performed to evaluate myocardial perfusion imaging (MPI) abnormalities. Chi-square test/Fisher exact test, Student t-test, Kaplan-Meier curve, and Uni-multivariable Cox proportional models were used for analysis. Clinical outcomes were major adverse cardiovascular events (MACE) during a median follow-up of 35 months. RESULT: No-stenosis was present in 71 (47%) INOCA patients, and 80 (53%) were with nonobstructive. CMD (caIMR ≥ 25) was more prevalent in patients with no-stenosis than nonobstructive (76.1% vs. 48.8%, p = .001), along with abnormal MPI (39.4% vs. 22.5%, p = .024). The MACE rates were not different between no-stenosis and nonobstructive stenosis. CMD showed an increased risk of MACE for all INOCA. No-stenosis with CMD had the worst prognosis. Cox regression analysis identified CMD and abnormal MPI as predictors of MACE in all INOCA and patients with no-stenosis. However, no-stenosis and nonobstructive stenosis were not predictors of MACE in INOCA. CONCLUSION: CMD was more frequently present in INOCA with no-stenosis. However, there was no difference in long-term clinical outcomes between no-stenosis and nonobstructive stenosis. CMD could independently predict poor outcomes in INOCA, particularly in patients with no-stenosis.

Prognostic implication of coronary slow flow assessed by cTFC in patients with myocardial infarction with Non-obstructive coronary arteries.

BACKGROUND: Coronary slow flow (CSF) is common and linked to worse cardiovascular events and life-threatening arrhythmias. However, the clinical implication of CSF among myocardial infarction with the non-obstructive coronary artery (MINOCA) has never been studied. We aimed to evaluate the impact of CSF on the MINOCA population. METHODS: Patients diagnosed with MINOCA were consecutively selected. The corrected TIMI frame count (cTFC) was used to evaluate the coronary flow. CSF was defined as cTFC greater than 27 frames per second (FPS) in any of the three coronary arteries. Major adverse cardiovascular events (MACE) are the primary endpoint. Cox regression analysis was used to evaluate the association between CSF and MACE. RESULTS: A total of 158 patients with MINOCA were enrolled, of which 54 (34.2%) patients had CSF. Forty incidents of MACE occurred during the median 28 months of follow-up. The MACE incidence was higher among patients who presented with CSF than the normal coronary flow patients (35.2% vs. 20.2%, p = 0.040). In the Kaplan-Meier analysis, CSF patients had significantly higher rates of MACE (log-rank P = 0.034). Multivariate Cox regression analysis showed that CSF was an independent predictor linked to an increased hazard of MACE (adjusted HR, 2.76; 95% CI, 1.34-5.67; P = 0.006). CONCLUSION: The presence of CSF is associated with a higher risk of adverse events and is an independent predictor of clinical outcomes among patients with MINOCA. This result suggests that CSF might serve as a robust tool to stratify MINOCA patients.

Prognostic value of combined coronary angiography-derived IMR and myocardial perfusion imaging by CZT SPECT in INOCA.

BACKGROUND: A significant proportion of ischemia with non-obstructive coronary artery disease (INOCA) demonstrate coronary microvascular dysfunction (CMD), a condition associated with abnormal myocardial perfusion imaging (MPI) and adverse outcomes. Coronary angiography-derived index of microvascular resistance (caIMR) is a novel non-invasive technique to assess CMD. We aimed to investigate the prognostic value of combined caIMR and MPI by CZT SPECT in INOCA patients. METHODS: Consecutive 151 patients with chest pain and < 50% coronary stenosis who underwent coronary angiography and MPI within 3 months were enrolled. caIMR was calculated by computational pressure-flow dynamics. CMD was defined as caIMR ≥ 25. The endpoint was major adverse cardiac events (MACE: cardiovascular death, nonfatal myocardial infarction, revascularization, angina-related rehospitalization, heart failure, and stroke). RESULTS: Of all INOCA patients, CMD was present in 93 (61.6%) patients. The prevalence of abnormal MPI was significantly higher in CMD compared with non-CMD patients (40.9% vs 13.8%, P < .001). CMD showed a higher risk of MACE than non-CMD patients. Patients with both CMD and abnormal MPI had the worst prognosis, followed by patients with CMD and normal MPI (log-rank P < .001). Cox regression analysis identified CMD (HR 3.121, 95%CI 1.221-7.974, P = .017) and MPI (HR 2.704, 95%CI 1.030-7.099, P = .043) as predictive of MACE. The prognostic value of INOCA patients enhanced significantly by adding CMD and MPI to the model with clinical risk factors (AUC = 0.777 vs 0.686, P = .030). CONCLUSION: caIMR-derived CMD is associated with increased risk of MACE among INOCA patients. Patients with abnormalities on both caIMR and MPI had the worse outcomes.

Interaction of basic diseases and low red blood cell count as critical murderer of wound infection after osteosarcoma resection: Wound infection after osteosarcoma resection.

BACKGROUND: Surgical wound infection is one of the common complications in patients after osteosarcoma resection. It is imperative to grasp the risk factors comprehensively. Therefore, this study aimed to explore the risk factors of wound infection and deeply analyze the correlation between risk factors and wound infection. METHODS: The study subjects were 101 patients who underwent osteosarcoma resection between April 2018 and August 2021. The diagnosis of postoperative wound infection was confirmed by postoperative observation of the incision, ultrasound imaging, and pathogenic examination. This study included a series of potential factors, mainly laboratory examination indicators and patients' general information. The statistical methods had Pearson Chi-square test, Spearman-rho correlation test, multifactorial linear regression model, logistic regression analysis, and receiver operating characteristic (ROC) curve. RESULTS: Pearson Chi-square test and Spearman correlation test showed that red blood cell (RBC) count (P = .033) and basic diseases (P = .020) were significantly correlated with a surgical wound infection after osteosarcoma resection. Logistic regression analysis manifested that basic disease (OR = 0.121, 95% CI: 0.015-0.960, P = .046) and RBC (OR = 0.296, 95% CI: 0.093-0.944, P = .040) have a clear correlation with whether the patients have surgical wound infection after osteosarcoma resection. And the interaction of basic diseases and RBC could diagnose the surgical wound infection sensitively and accurately (AUC = 0.700, P = .014, 95% CI = 0.564-0.836) via the ROC analysis. CONCLUSION: Patients with basic diseases and low RBC were risk factors for surgical wound infection after osteosarcoma resection.

Protective Effects of 4-Trifluoromethyl-(E)-cinnamoyl]-L-4-F-phenylalanine Acid against Chronic Cerebral Hypoperfusion Injury through Promoting Brain-Derived Neurotrophic Factor-Mediated Neurogenesis.

Vascular dementia (VaD), one of the major consequences after stroke, is the second reason for the cognitive decline in aged people. Chronic cerebral hypoperfusion (CCH) is considered as the main cause for cognitive impairment in VaD patients. In our previous study, a synthetic compound, 4-trifluoromethyl-(E)-cinnamoyl]-L-4-F-phenylalanine acid (AE-18), has been proven to decrease infarct volume and to recover the insufficient blood supply after ischemia-reperfusion in rats, which was reminded that AE-18 may possess the ameliorative effect in CCH. In this study, the bilateral common carotid artery occlusion was performed to establish the CCH model in rats to evaluate the effect and mechanisms of AE-18 in CCH. Results showed that AE-18 (5 and 10 mg/kg, i.g.) could recover the learning and memory and increase the number of neurons in the hippocampus, which may be attributed to its neurogenesis effects and its recovery of cerebral blood flow in CCH rats. In addition, the in vitro studies showed that AE-18 promoted neuronal proliferation, induced differentiation of Neuro-2a cells into a neuron-like morphology, and accelerated the establishment of axon-dendrite polarization of primary hippocampal neurons through upregulating brain-derived neurotrophic factor via the PI3K/Akt/CREB pathway. In conclusion, AE-18 is a promising candidate for the treatment of cognitive decline after CCH injury by restoring blood supply to the brain and promoting neurogenesis in the hippocampus.

Prognostic value of coronary microvascular dysfunction assessed by coronary angiography-derived index of microcirculatory resistance in diabetic patients with chronic coronary syndrome.

BACKGROUND: Coronary microvascular dysfunction (CMD) is common and is associated with unfavorable cardiovascular events in patients with diabetes mellitus (DM). Coronary angiography-derived index of microcirculatory resistance (caIMR) is a recently developed wire- and hyperemic agent-free method to assess CMD. We aimed to investigate the prognostic impact of CMD assessed by caIMR on clinical outcomes in patients with DM and chronic coronary syndrome (CCS). METHODS: CCS patients who underwent coronary angiography between June 2015 to May 2018 were included. Coronary microvascular function was measured by caIMR, and CMD was defined as caIMR ≥ 25U. The primary endpoint was major adverse cardiac events (MACE). Kaplan-Meier analysis and Cox proportional hazards models were used to assess the relationship between caIMR and the risk of MACE. RESULTS: Of 290 CCS patients, 102 patients had DM. Compared with non-diabetic patients, CMD (caIMR ≥ 25U) was higher among DM patients (57.8% vs. 38.3%; p = 0.001). During a mean 35 months follow-up, 40 MACE had occurred. Patients with caIMR ≥ 25 had a higher rate of MACE than patients with caIMR < 25 (20.6% vs. 8.2%, p = 0.002). Of these, the MACE rate was higher among DM patients with caIMR ≥ 25 than those with caIMR < 25 (33.9% vs. 14.0%; p = 0.022). In multivariable Cox analysis, caIMR ≥ 25 was independently associated with MACE in the DM patients but not in non-DM patients (HR, 2.760; 95% CI, 1.066-7.146; P = 0.036). CONCLUSION: CMD assessed by caIMR was common and is an independent predictor of MACE among diabetic patients with CCS. This finding potentially enables a triage of higher-risk patients to more intensive therapy.

A Novel Energy Planning Scheme Based on PGA Algorithm and Its Application.

In order to actively respond to the "14th Five-Year Plan," the PGA algorithm is used to develop a new energy planning strategy in this paper. The project can make full use of my country's abundant renewable energy resources, encourage energy conservation and reduction of emissions, improve the energy structure's low-carbon level, support the development of smart green energy, and achieve ecological civilization construction. This solution can show users how much greenhouse gas emissions can be reduced through some environmental changes, as well as the basic issues of meeting the future energy needs. It can display the benefits, costs, and emissions data under different scenarios in the future and use the scenario demonstration method to show energy planning to make energy data more vivid. It allows people, technicians, and decision makers to understand what will happen to China's carbon emissions over time in the next 15 years. This paper innovatively combines a particle swarm optimization algorithm with a genetic algorithm and designs a PGA algorithm for path optimization. In terms of carbon emission reduction, comparative trials demonstrate that the PGA algorithm's path optimization is 58.06 percent greater than the genetic algorithm; In terms of cost, the PGA algorithm's path optimization is 15.72% less expensive than the genetic algorithm's. This article provides a reference path for selecting the best results for future energy planning schemes and provides a new strategy for the "14th Five-Year" energy plan.

Prognostic impact of coronary microvascular dysfunction assessed by caIMR in overweight with chronic coronary syndrome patients.

Objective: Coronary microvascular dysfunction (CMD) may associate with adverse cardiovascular events in obese patients. Coronary angiography-derived index of microcirculatory resistance (caIMR) is proposed as a less-invasive and pressure-wire-free index to assess CMD. We aimed to investigate the impact of coronary microvascular function assessed by caIMR in patients with overweight and chronic coronary syndrome (CCS). Methods: CCS patients who underwent coronary angiography between 2015 to 2018 were included. Overweight was defined as BMI≥24.0kg/m². Impaired coronary microvascular function was defined as caIMR≥25U. The patients were classified according to BMI and caIMR. The primary endpoint was major adverse cardiac events (MACE). Kaplan-Meier and Cox regression analyses evaluated the association between caIMR and MACE. Results: Two hundred and eighty-two CCS patients were enrolled. Among these, 169 (59.93%) were overweight. Impaired coronary microvascular function was higher in overweight patients than in patients with normal weight (49.70% vs. 38.05%; P=0.035). During 35 months of follow-up, 33 MACE had occurred. Among the total CCS population, MACE was higher in patients with high caIMR than in low caIMR (18.11% vs. 6.45%, P=0.003). In subgroups analysis, MACE was higher in overweight patients with high caIMR than low caIMR (20.24% vs. 7.06%, P=0.014), while there were no significant differences in normal-weight patients. Multivariate Cox analysis demonstrated that caIMR≥25 was independently associated with MACE in overweight patients (HR, 2.87; 95% CI, 1.12-7.30; P=0.027) but not in the normal-weight patients. In addition, caIMR showed a significant predictive value for adverse outcomes in overweight patients and provided an incremental prediction when added to a prediction model with BMI. Conclusions: Impaired coronary microvascular function assessed by caIMR was common and is an independent predictor of MACE in overweight patients with CCS.

4-Trifluoromethyl-(E)-cinnamoyl]-L-4-F-phenylalanine acid exerts its effects on the prevention, post-therapeutic and prolongation of the thrombolytic window in ischemia-reperfusion rats through multiple mechanisms of action.

Ischemic stroke is one of the leading causes of death and disability worldwide. The severe sequelae caused by ischemic thrombolysis and the narrow time window are now the main clinical challenges. Our previous study has reported 4-Trifluoromethyl-(E)-cinnamoyl]-L-4-F-phenylalanine Acid (AE-18) was a promising candidate for Parkinson's Disease. In this study, the preventive and therapeutic effects of AE-18 on focal cerebral ischemia-reperfusion injury and the mechanisms are explored. In oxygen glucose deprivation/reoxygenation (OGD/R)-induced well-differentiated PC12 cells model, AE-18 (10 or 20 µM) can significantly reduce nerve damage when administered before or after molding. In middle cerebral artery occlusion-reperfusion (MCAO/R) rat model, pre-modelling, or post-modelling administration of AE-18 (5 or 10 mg/kg) was effective in reducing neurological damage, decreasing infarct volume and improving motor disturbances. In addition, AE-18 (5 mg/kg) given by intravenous injection immediately after occlusion significantly reduce the infarct volume caused by reperfusion for different durations, indicating that AE-18 could extend the time window of thrombolytic therapy. Further studies demonstrate that AE-18 exerts the effects in the prevention, treatment, and prolongation of the time window of cerebral ischemic injury mainly through inhibiting excitotoxicity and improving BBB permeability, VEGF and BDNF. These results suggest that AE-18 is a good candidate for the treatment of ischemic stroke.

Defect-rich cobalt pyrophosphate hybrids decorated Cd0.5Zn0.5S for efficient photocatalytic hydrogen evolution: Defect and interface engineering.

Photocatalysts with highly efficient charge separation are of critical significance for improving photocatalytic hydrogen production performance. Herein, a cost-effective and high-performance composite photocatalyst, cobalt-phosphonate-derived defect-rich cobalt pyrophosphate hybrids (CoPPi-M) modified Cd0.5Zn0.5S is rationally devised via defect and interface engineering, in which the co-catalyst CoPPi-M delivers a strong interaction with host photocatalyst Cd0.5Zn0.5S, rendering Cd0.5Zn0.5S/CoPPi-M with a remarkably improved efficiency of charge separation and migration. Besides, Cd0.5Zn0.5S/CoPPi-M exhibits a hydrophilic surface with ample access to electrons and a strong reduction ability of electrons. Benefiting from these advantages, the integration of defect-rich cobalt pyrophosphate and Cd0.5Zn0.5S enables Cd0.5Zn0.5S/CoPPi-M-5% with high photocatalytic H2 production rate of 6.87 mmol g-1h-1, which is 2.46 times higher than that of pristine Cd0.5Zn0.5S, and the notable apparent quantum efficiency (AQE) is 20.7% at 420 nm. This work provides a promising route for promoting the photocatalytic performance of non-precious hybrid photocatalyst via defect and interface engineering, and advances energy-generation and environment-restoration devices.

Does Sex Influence Outcomes in Myocardial Infarction With Nonobstructive Coronary Arteries?

We examined differences in clinical profiles, predictors, and outcomes among patients with myocardial infarction (MI) with nonobstructive coronary arteries (MINOCAs) by sex. Data of 259 (132 males and 127 females) patients with MINOCA were consecutively collected. The primary clinical end point was major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal MI, stroke, heart failure, and angina rehospitalization. Female patients with MINOCA were likely to be older than male patients with higher non-ST elevation myocardial infarction rate. Total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels were higher in female patients while male patients were more likely to have a smoking history, greater ST elevation myocardial infarction rate, higher diastolic blood pressure, and more alcohol use. During the 2-year follow-up, the incidence of MACE in males and females was similar (18% vs 20.2%, respectively; P = .673). The multivariable predictors of MACE in the female group were age, hypertension, and left ventricular ejection fraction (LVEF), whereas diabetes, smoking, and LVEF were multivariable predictors of MACE in the male group. In conclusion, there were differences in the clinical profiles between sexes. Clinical outcome was similar between male and female patients with MINOCA, whereas predictive risk factors varied.

Higher TYROBP and lower SOX6 as predictive biomarkers for poor prognosis of clear cell renal cell carcinoma: A pilot study.

BACKGROUND: Clear cell renal carcinoma (ccRCC) is the most common subtype of renal cancer, accounting for approximately 75% of all histological types of renal cancer, and is the leading cause of death from renal cancer. However, the molecular mechanism of tyrosine kinase binding protein (TYROBP) and sex-determining region Y Box-6 (SOX6) in the ccRCC was not precise. METHODS: Bioinformatics analysis was performed to explore the hub role of TYROBP and SOX6 on the ccRCC. A total of 6 patients with clear cell renal cell carcinoma (ccRCC) were recruited. HE staining was performed to observe the pathology result of ccRCC. Immunohistochemistry and Immunofluorescence assay was made to detect the protein expression of TYROBP. Total RNA was extracted using TRIzol to examine the mRNA expression of TYROBP via the Real time quantitative polymerase chain reaction. The strong correlation between the expression of TYROBP and the survival time of ccRCC patients was performed by the BP neural network and support vector machine. RESULTS: Compared with the control group, the expression of SOX6 was downregulated in the samples with ccRCC. However, the expression of TYROBP was higher in the samples with ccRCC than in the control group. Compared with the patients with high SOX6 expression, the patients with low SOX6 expression have a poor survival prognosis (HR=0.39, P < .05). However, the patients with high TYROBP expression have a shorter survival time than the patients with low TYROBP expression (HR=1.66, P < .05). The genes related with TYROBP and SOX6 are mainly enriched in the regulation of cell activation, leukocyte activation, negative regulation of cell activation, myeloid leukocyte activation, positive regulation of response to external stimulus, immune response-regulating signaling pathway. The interaction between TYROBP, SOX6, and kidney neoplasms was drawn, and the inference score of TYROBP and SOX6 on the kidney neoplasms was high. CONCLUSION: In conclusion, TYROBP is highly expressed in renal clear cell carcinoma, and when this molecule is highly expressed, the survival prognosis of renal carcinoma is poor. TYROBP and SOX6 may be potential targets for diagnosing and treating renal clear cell carcinoma.

Prognostic Significance of Uric Acid in Patients with Obstructive and Nonobstructive Coronary Artery Disease Undergoing D-SPECT.

PURPOSE: The association of serum uric acid (SUA) levels with cardiovascular outcomes in patients with coronary artery disease (CAD) has been extensively studied and yielded conflicting results. We aimed to investigate whether the severity of coronary stenosis and ischemia influences the prognostic impact of SUA levels in patients with CAD undergoing D-SPECT. PATIENTS AND METHODS: This study consecutively included patients who were admitted for CAD in Shanghai Tenth People's Hospital between June 2014 and August 2018, had complete SUA data and underwent both coronary angiography and D-SPECT within 3 months. Hyperuricemia was defined as an SUA level of >7 mg/dL in men and >6 mg/dL in women. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiac death, unplanned coronary revascularization, nonfatal myocardial infarction, ischemic stroke, heart failure, and angina-related hospitalization. RESULTS: A total of 695 patients were included, of whom 432 (62.2%) presented with obstructive CAD and 117 (16.8%) had hyperuricemia. During a median follow-up of 26 months, the incidence rates of MACE in patients with hyperuricemia and normouricemia were 15.2% and 21.1%, respectively. After a multivariable adjustment, hyperuricemia was significantly associated with an increased risk of MACE (HR: 1.39, 95% CI: 1.03-1.87, p = 0.033) when compared with normouricemia. When repeating the primary analysis in patients with and without obstructive CAD, we showed that hyperuricemia was independently associated with an 80% increased risk of MACE among patients with nonobstructive CAD (HR: 1.80, 95% CI: 1.04-3.11, p = 0.035), while such a significant association was not found among those with obstructive CAD (HR: 1.18, 95% CI: 0.82-1.72, p = 0.373). Moreover, we uncovered a U-shaped and linear trajectory of SUA levels with MACE in the obstructive and nonobstructive CAD, respectively. The sex-specific analysis showed that the adverse impact of hyperuricemia was only pronounced in males (HR: 1.73, 95% CI: 1.18-2.53, p = 0.005) but not in females (HR: 0.98, 95% CI: 0.57-1.66, p = 0.933). CONCLUSION: Hyperuricemia is significantly associated with increased risk of MACE in the nonobstructive CAD rather than in the obstructive CAD.

Prognostic Value of Diastolic Dysfunction Derived From D-SPECT in Coronary Artery Disease Patients With Normal Ejection Fraction.

Diastolic dysfunction (DD) with normal systolic function has been elucidated to be associated with heart failure and worse prognosis. The recently introduced single photon emission computed tomography (SPECT) with dedicated cardiac cadmium-zinc-telluride (CZT) cameras (D-SPECT) is a novel method to quantitate left ventricular functional parameters. We aimed to evaluate the prognostic value of DD derived from D-SPECT in coronary artery disease (CAD) patients with normal ejection fraction. All CAD patients who underwent D-SPECT and invasive coronary angiography within 3 months were considered. DD was defined as peak filling rate (PFR) <2.1 end diastolic volume (EDV, ml)/s according to the D-SPECT results. Patients were divided into three groups: group 1 (n = 226)-normal PFR; group 2 (n = 67)-ischemia-related DD (abnormal stress PFR and normal rest PFR); and group 3 (n = 106)-rest DD (abnormal rest PFR). The primary clinical endpoint of the present study was a composite of heart failure events (HFE). A total of 399 consecutive CAD patients with normal systolic function undergoing stress D-SPECT were analyzed. The incidence rates of HFE among the three groups were 4.0, 7.5, and 11.3%, respectively. Cox regression analysis showed that the multivariate predictors of HFE were rest PFR, diabetes mellitus, obesity, and old age. DD derived from D-SPECT in CAD patients with normal ejection fraction is predictive of HFE.