Optimized gated a SPECT-derived myocardial salvage index: its prognostic significance in predicting major adverse cardiac events following acute myocardial infarction percussion.

PURPOSE: Estimate myocardial salvage index (MSI) using a single-gated Single-Photon Emission Computed Tomography (SPECT) myocardial perfusion imaging (GSMPI) early after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) and compare its predictive value with the traditional method especially for post-PCI left ventricular ejection fraction (LVEF) improvement and major adverse cardiac events (MACEs). METHODS: GSMPI was performed in 62 patients with AMI early after PCI (3-10 days). The MSI and the conventional parameters were obtained, including total perfusion deficit, LVEF, peak ejection rate (PER), and peak filling rate (PFR). The new calculation method (scoring evaluation method means the extent of abnormality is the percentage of the total scores of abnormal segments divided by the sum of the maximum scores of all myocardial segments using 4-point and 5-point scale semi-quantitative scoring method) and the reference method (number evaluation method means the extent of abnormality is the percentage of the number of abnormal segments divided by the total number of myocardial segments) were applied to acquire the MSI. We compared the predictive ability of the 2 methods based on the area under the receiver operating characteristic curve for LVEF improvement 6 months after PCI using MSI. The Kaplan-Meier method was used for depicting survival curves for predicting MACEs by the 2 methods. Cox proportional-hazards regression was applied to confirm the independent predictors of MACEs. RESULTS: The MSI obtained by the new method indicated stronger prognostic significance in LVEF improvement [area under the curve (AUC): 0.793, 95% confidence interval (CI) 0.620-0.912, P < .001] compared with the reference method (AUC: 0.634, 95%CI 0.452-0.792, P = .187). Delong's test revealed a statistically significant difference in AUCs between the 2 methods (P < .05, 95%CI 0.003-0.316). The diagnostic value of the scoring evaluation method was higher than that of the number evaluation method. The Cox prevalence of MACEs was substantially higher in the < median MSI group than in the ≥ median MSI group (hazard ratio: 0.172; 95% CI 0.041-0.724; P < .05] using the new method, whereas no considerable differences were observed between the 2 groups using the reference method (P = .12). Further, the multivariate Cox regression analysis revealed that MSI was an independent indicator for predicting MACEs (P < .05). CONCLUSION: The MSI obtained from a simple GSMPI early after PCI, using the scoring evaluation method, was a reliable prognostic indicator for predicting LVEF improvement and MACEs in AMI. It remarkably improved the prognostic value compared with the previous reference methods.

Identification of Fangchinoline as a novel autophagy inhibitor with an adjuvant of chemotherapy against lung cancer.

Autophagy is a fundamental recycling pathway that enhances cellular resilience, promoting survival. However, this survival mechanism can impede anti-cancer treatment strategies designed to induce cell death. In this study, we identified a novel autophagy inhibitor, Fangchinoline (Fan) isolated from the traditional Chinese medicine Stephania tetrandra. We speculated that when Fan blocks autophagy, cancer cells lose substantial self-preservation abilities during treatment. Firstly, we examined in detail the mechanism through which Fan inhibits autophagy. Specifically, Fan induced a significant increase in autophagosomes, as indicated by GFP-LC3 labeling, confirmed by the up-regulation of LC3-II. The autophagy receptor protein p62 was also up-regulated, suggesting a potential inhibition of autophagy flux. We further ruled out the possibility of fusion barriers between lysosomes and autophagosomes, as confirmed by their co-localization in double fluorescence staining. However, the lysosomal acid environment might be compromised, as suggested by the diminished fluorescence of acidity-sensitive dyes in the lysosomes and the corresponding decrease in mature forms of lysosomal cathepsin. To test the anti-cancer potential of Fan, we combined it with Cisplatin (Cis) or Paclitaxel (PTX) for lung cancer cell treatment. This combined treatment demonstrated a synergistically enhanced killing effect. These promising anti-tumor results were also replicated in a xenografted tumor model. The significance of this research lies in the identification of Fan as a potent autophagy inhibitor and its potential to enhance the efficacy of existing anti-cancer drugs. By unraveling the mechanisms of Fan's action on autophagy and demonstrating its synergistic effect in combination therapies, our study provides valuable insights for developing novel strategies to overcome autophagy-mediated resistance in cancer treatment.

Identification of Fangjihuangqi Decoction as a late-stage autophagy inhibitor with an adjuvant anti-tumor effect against non-small cell lung cancer.

BACKGROUND: Clinically, although chemotherapy is one of the most commonly used methods of treating tumors, chemotherapeutic drugs can induce autophagic flux and increase tumor cell resistance, leading to drug tolerance. Therefore, theoretically, inhibiting autophagy may improve the efficacy of chemotherapy. The discovery of autophagy regulators and their potential application as adjuvant anti-cancer drugs is of substantial importance. In this study, we clarified that Fangjihuangqi Decoction (FJHQ, traditional Chinese medicine) is an autophagy inhibitor, which can synergistically enhance the effect of cisplatin and paclitaxel on non-small cell lung cancer (NSCLC) cells. METHODS: We observed the changes of autophagy level in NSCLC cells under the effect of FJHQ, and verified the level of the autophagy marker protein and cathepsin. Apoptosis was detected after the combination of FJHQ with cisplatin or paclitaxel, and NAC (ROS scavenger) was further used to verify the activation of ROS-MAPK pathway by FJHQ. RESULTS: We observed that FJHQ induced autophagosomes in NSCLC cells and increased the levels of P62 and LC3-II protein expression in a concentration- and time-gradient-dependent manner, indicating that autophagic flux was inhibited. Co-localization experiments further showed that while FJHQ did not inhibit autophagosome and lysosome fusion, it affected the maturation of cathepsin and thus inhibited the autophagic pathway. Finally, we found that the combination of FJHQ with cisplatin or paclitaxel increased the apoptosis rate of NSCLC cells, due to increased ROS accumulation and further activation of the ROS-MAPK pathway. This synergistic effect could be reversed by NAC. CONCLUSION: Collectively, these results demonstrate that FJHQ is a novel late-stage autophagy inhibitor that can amplify the anti-tumor effect of cisplatin and paclitaxel against NSCLC cells.

Analysis of ecological quality changes and influencing factors in Xiangjiang River Basin.

The Xiangjiang River Basin is an important part of the Yangtze River Basin and an important area in Hunan Province. Thus, taking steps to protect the ecological sustainability of the Xiangjiang River Basin, such as the construction of the protection of ecological security in Hunan Province and the Yangtze River Protection Law, is important for national projects However, research on the ecological quality of the Xiangjiang River Basin is mostly biased toward the evaluation of ecosystem services or an individual ecological index. Furthermore, a long-term evaluation of multiple indicators is lacking. Therefore, based on Google Earth Engine and geographic detectors, the remote sensing ecological index was used to evaluate this area. The year-by-year research on the Xiangjiang River Basin from 2001 to 2020 clarified its past ecological quality change trend, explored the reasons for the ecological quality change, and provided a basis for protecting its ecological quality. The following results are presented. (1) Regarding spatial distribution, areas with poor ecological environments are mainly distributed at the centers of Chang-Zhu-Tan, Hengyang, and various districts and counties. (2) Regarding the time variation, the ecological quality of the Xiangjiang River Basin from 2001 to 2020 showed a slight downward trend, with a downward slope of approximately - 0.0000357143; a rapid increase, with a growth rate of approximately 0.00395; And an overall improvement over 20 years. The areas with declining ecological quality are mainly located in the Chang-Zhu-Tan urban agglomeration, the city center of Hengyang, and the county centers of various county towns. (3) The factor detection results show that human factors play a key role in population density and land use, with average q values of 0.429 and 0.353, respectively. Among natural factors, elevation and slope play a key role, with average q values of 0.230 and 0.351, respectively; hence, Land use directly affect on the ecological quality in a location. These findings will provide important information for managers to formulate ecological restoration measures for the Xiangjiang River.

Cancer-associated fibroblasts potentiate colorectal cancer progression by crosstalk of the IGF2-IGF1R and Hippo-YAP1 signaling pathways.

Colorectal cancer (CRC) is one of the most common cancers worldwide. The tumor microenvironment exerts crucial effects in driving CRC progression. Cancer-associated fibroblasts (CAFs) serve as one of the most important tumor microenvironment components promoting CRC progression. This study aimed to elucidate the novel molecular mechanisms of CAF-secreted insulin-like growth factor (IGF) 2 in colorectal carcinogenesis. Our results indicated that IGF2 was a prominent factor upregulated in CAFs compared with normal fibroblasts. CAF-derived conditioned media (CM) promoted tumor growth, migration, and invasion of HCT 116 and DLD-1 cells. IGF1R expression is significantly increased in CRC, serving as a potent receptor in response to IGF2 stimulation and predicting unfavorable outcomes for CRC patients. Apart from the PI3K-AKT pathway, RNA-seq analysis revealed that the YAP1-target signature serves as a prominent downstream effector to mediate the oncogenic signaling of IGF2-IGF1R. By single-cell RNA sequencing (scRNA-seq) and immunohistochemical validation, IGF2 was found to be predominantly secreted by CAFs, whereas IGF1R was expressed mainly by cancer cells. IGF2 triggers the nuclear accumulation of YAP1 and upregulates YAP1 target signatures; however, these effects were abolished by either IGF1R knockdown or inhibition with picropodophyllin (PPP), an IGF1R inhibitor. Using CRC organoid and in vivo studies, we found that cotargeting IGF1R and YAP1 with PPP and verteporfin (VP), a YAP1 inhibitor, enhanced antitumor effects compared with PPP treatment alone. In conclusion, this study revealed a novel molecular mechanism by which CAFs promote CRC progression. The findings highlight the translational potential of the IGF2-IGF1R-YAP1 axis as a prognostic biomarker and therapeutic target for CRC. © 2022 The Pathological Society of Great Britain and Ireland.

A five-parameter score for predicting saphenous vein graft degenerative and/or occlusive disease in recurring ischemic symptoms after one year post coronary artery bypass grafting.

BACKGROUND: The recurrence rate of ischemic symptoms after coronary artery bypass grafting (CABG) is increasing in recent years. How to prevent and treat saphenous vein graft disease (SVGD [symptomatic ⩾50% stenosis in at least one Saphenous vein graft]) has been a clinical challenge to date. Different pathogenesis may exist in SVGD of different periods. There are currently few available scores for estimating the risk of SVGD after one year post CABG. OBJECTIVE: We sought to develop and validate a simple predictive clinical risk score for SVGD with recurring ischemia after one year post CABG. METHODS AND RESULTS: This was a cross-sectional study and the results were validated using bootstrap resampling on a separate cohort. A nomogram and risk scoring system were developed based on retrospective data from a training cohort of 606 consecutive patients with recurring ischemia >1 year after CABG. Logistic regression model was used to find the predictive factors and to build a nomogram. To assess the generalization, models were validated using bootstrap resampling and an external cross-sectional study of 187 consecutive patients in four other hospitals. In multivariable analysis of the primary cohort, native lesion vessel number, SVG age, recurring ischemia type, very low-density lipoprotein level, and left ventricular end-diastolic diameter were independent predictors. A summary risk score was derived from nomogram, with a cut-off value of 15. In internal and external validation, the C-index was 0.86 and 0.82, indicating good discrimination. The calibration curve for probability of SVGD showed optimal agreement between actual observations and risk score prediction. CONCLUSION: A simple-to-use risk scoring system based on five easily variables was developed and validated to predict the risk of SVGD among patients who recurring ischemia after one year post CABG. This score may be useful for providing patients with individualized estimates of SVGD risk.

Berbamine Hydrochloride inhibits lysosomal acidification by activating Nox2 to potentiate chemotherapy-induced apoptosis via the ROS-MAPK pathway in human lung carcinoma cells.

Autophagy is typically activated in cancer cells as a rescue strategy in response to cellular stress (e.g., chemotherapy). Herein, we found that Berbamine Hydrochloride (Ber) can act as an effective inhibitor of the late stage of autophagic flux, thereby potentiating the killing effect of chemotherapy agents. Lung carcinoma cells exposed to Ber exhibited increased autophagosomes, marked by LC3-II upregulation. The increased level of p62 after Ber treatment indicated that the autophagic flux was blocked at the late stage. The lysosome staining assay and cathepsin maturation detection indicated impaired lysosomal acidification. We found that Nox2 exhibited intensified co-localization with lysosomes in Ber-treated cells. Nox2 is a key enzyme for superoxide anion production capable of transferring electrons into the lysosomal lumen, thereby neutralizing the inner protons; this might explain the aberrant acidification. This hypothesis is further supported by the observed reversal of lysosomal cathepsin maturation by Nox2 inhibitors. Finally, Ber combined with cisplatin exhibited a synergistic killing effect on lung carcinoma cells. Further data suggested that lung carcinoma cells co-treated with Ber and cisplatin accumulated excessive reactive oxygen species (ROS), which typically activated MAPK-mediated mitochondria-dependent apoptosis. The enhanced anti-cancer effect of Ber combined with cisplatin was also confirmed in an in vivo xenograft mouse model. These findings indicate that Ber might be a promising adjuvant for enhancing the cancer cell killing effect of chemotherapy via the inhibition of autophagy. In this process, Nox2 might be a significant mediator of Ber-induced aberrant lysosomal acidification.

Prognostic Value of Metabolic Syndrome in Patients With Non-ST Elevated Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

Objective: We aim to investigate the prognostic effects of metabolic syndrome (MS) on patients with non-ST elevated myocardial infarction (NSTEMI) after percutaneous coronary intervention (PCI). Methods: Patients with NSTEMI undergoing PCI were consecutively collected. According to the presence or absence of MS, they were divided into two groups and followed up for 1 year. The endpoint was major adverse cardiovascular events (MACE), including all-cause death, unstable angina hospitalization, heart failure (HF) hospitalization, non-fatal recurrent myocardial infarction (MI), and target lesion revascularization. Also, six subgroups were made according to gender, age, left ventricular ejection fraction (LVEF), Global Registry of Acute Coronary Events (GRACE) score, hypersensitive troponin (hsTNT), and several diseased vessels. Cox proportional hazard model was adopted to analyze the effect of MS on MACE in all the patients and different subgroups. Results: A total of 1,295 patients were included in the current analysis and 660 (50.97%) of them had MS. About 88 patients were lost to follow-up, and the overall average follow-up was 315 days. MS was an independent risk factor for MACE (HR 1.714, CI 1.265-2.322, p = 0.001), all-cause death, heart failure (HF) hospitalization, and non-fatal recurrent MI. In the MS component, BMI ≥28 kg/m2 was positively associated with MACE. Subgroup analysis indicated the prognostic value of MS was more striking for patients with the following: age of >60, LVEF of ≤40%, GRACE of >140, multivessel disease, or hsTNT of >0.1 ng/ml. Conclusions: The MS was a robust adverse prognostic factor in patients diagnosed with NSTEMI, especially among those of older age and at higher ischemic risk. A BMI of ≥28 kg/m2 independently predicted the occurrence of MACE. Prognosis may be improved by controlling abdominal obesity.

Long-term outcomes of 316 patients with STEMI following coronary stent implantation.

BACKGROUND: Stent thrombosis (ST)-related ST-segment elevation myocardial infarction (STEMI) has very high mortality and poor prognosis. With the extensive construction of the chest pain center in China, the question arises as to whether these special patients will benefit. METHODS: From January 2015 to February 2018, 316 patients with STEMI admitted to the coronary care unit (CCU) of Tianjin Chest Hospital after coronary stent implantation were enrolled in this retrospective study. All patients underwent coronary angiography. According to whether STEMI was due to ST, these patients were divided into either a ST group (n=247) or a non-ST group (n=69). The in-hospital mortality and major adverse cardiac events (MACEs), including all-cause mortality, re-ST, target vessel revascularization (TVR), and acute myocardial infarction (AMI) within the 1-year follow-up were compared between the two groups. RESULTS: 78% of cases of STEMI following coronary stent implantation were caused by ST. The in-hospital mortality of the ST group was 0.8% and that of the non-ST group was 1.4% (P>0.05). Forty-two cases had MACEs in the 1-year follow-up, with a higher incidence in the ST group compared to the non-ST group (15.4% vs. 5.8%, P=0.038). The Kaplan-Meier survival analysis showed a lower 1-year event free survival (EFS) in the ST group compared to the non-ST group (84.6% vs. 94.2%, P=0.035). Age over 80-years-old, hypertension, diabetes, hypercholesterolemia, and family history of coronary artery disease (CAD) were all independent risk factors for MACE. CONCLUSION: ST is the leading cause of STEMI in patients following coronary stent implantation. There was no significant difference in mortality between the ST group and the non-ST group during hospitalization, with a worse prognosis in the ST group during the 1-year follow-up.

Integrated analysis reveals the pivotal interactions between immune cells in the melanoma tumor microenvironment.

Melanoma is the most lethal type of skin cancer. Despite the breakthroughs in the clinical treatment of melanoma using tumor immunotherapy, many patients do not benefit from these immunotherapies because of multiple immunosuppressive mechanisms. Therefore, there is an urgent need to determine the mechanisms of tumor-immune system interactions and their molecular determinants to improve cancer immunotherapy. In this study, combined analysis of microarray data and single-cell RNA sequencing data revealed the key interactions between immune cells in the melanoma microenvironment. First, differentially expressed genes (DEGs) between normal and malignant tissues were obtained using GEO2R. The DEGs were then subjected to downstream analyses, including enrichment analysis and protein-protein interaction analysis, indicating that these genes were associated with the immune response of melanoma. Then, the GEPIA and TIMER databases were used to verify the differential expression and prognostic significance of hub genes, and the relationship between the hub genes and immune infiltration. In addition, we combined single cell analysis from GSE123139 to identify immune cell types, and validated the expression of the hub genes in these immune cells. Finally, cell-to-cell communication analysis of the proteins encoded by the hub genes and their interactions was performed using CellChat. We found that the CCL5-CCR1, SELPLG-SELL, CXCL10-CXCR3, and CXCL9-CXCR3 pathways might play important roles in the communication between the immune cells in tumor microenvironment. This discovery may reveal the communication basis of immune cells in the tumor microenvironment and provide a new idea for melanoma immunotherapy.

Fangchinoline inhibits non-small cell lung cancer metastasis by reversing epithelial-mesenchymal transition and suppressing the cytosolic ROS-related Akt-mTOR signaling pathway.

Few drugs alleviate non-small cell lung cancer (NSCLC) metastasis effectively. Small molecular screening demonstrated that fangchinoline (Fan) reversed epithelial-mesenchymal transition (EMT) in NSCLC cells, inhibiting cell invasion and migration. RNA sequencing (RNA-seq) of Fan-treated NSCLC cells revealed that Fan potently quenched the NADP+ metabolic process. Molecular docking analysis revealed that Fan directly and specifically targeted NOX4. NOX4 was associated with poor prognosis in NSCLC in both The Cancer Genome Atlas (TCGA) and Hong Kong cohorts. In mitochondrial DNA-depleted ρ0 NSCLC cells, Fan decreased cytosolic reactive oxygen species (ROS) to inhibit the Akt-mTOR signaling pathway by directly promoting NOX4 degradation. In TCGA and Hong Kong cohorts, NOX4 upregulation acted as a driver event as it positively correlated with metastasis and oxidative stress. Single-cell RNA-seq indicated that NOX4 was overexpressed, especially in cancer cells, cancer stem cells, and endothelial cells. In mice, Fan significantly impeded subcutaneous xenograft formation and reduced metastatic nodule numbers in mouse lung and liver. Drug sensitivity testing demonstrated that Fan suppressed patient-derived organoid growth dose-dependently. Fan is a potent small molecule for alleviating NSCLC metastasis by directly targeting NOX4 and is a potential novel therapeutic agent.

Latent class cluster analysis of knowledge on acute myocardial infarction in community residents: a cross-sectional study in Tianjin, China.

OBJECTIVE: Public knowledge of early onset symptoms and risk factors (RF) of acute myocardial infarction (AMI) is very important for prevention, recurrence and guide medical seeking behaviours. This study aimed to identify clusters of knowledge on symptoms and RFs of AMI, compare characteristics and the awareness of the need for prompt treatment. DESIGN: Multistage stratified sampling was used in this cross-sectional study. Latent GOLD Statistical Package was used to identify and classify the respondent subtypes of the knowledge on AMI symptoms or modifiable RFs. Multivariable logistic regression was performed to identify factors that predicted high knowledge membership. PARTICIPANTS: A structured questionnaire was used to interview 4200 community residents aged over 35 in China. 4122 valid questionnaires were recovered. RESULTS: For AMI symptoms and RFs, the knowledge levels were classified into two or three distinct clusters, respectively. 62.7% (Symptom High Knowledge Cluster) and 39.5% (RF High Knowledge Cluster) of the respondents were able to identify most of the symptoms and modifiable RFs. Respondents who were highly educated, had higher monthly household income, were insured, had regular physical examinations, had a disease history of AMI RFs, had AMI history in immediate family member or acquaintance or had received public education on AMI were observed to have higher probability of knowledge on symptoms and RFs. There was significant difference in awareness of the prompt treatment in case of AMI occurs among different clusters. 'Calling an ambulance' was the most popular option in response of seeing others presenting symptoms of AMI. CONCLUSIONS: A moderate or relatively low knowledge on AMI symptoms and modifiable RFs was observed in our study. Identification of Knowledge Clusters could be a way to detect specific targeted groups with low knowledge of AMI, which may facilitate health education, further reduce the prehospital delay in China and improve patient outcomes.

The Relevance of Interventional Time and Clinical Outcomes in Patients with NSTEMI Based on the GRACE Score.

Objective: To investigate the relevance between interventional time and clinical outcomes in non-ST-elevation myocardial infarction (NSTEMI) patients of different risk stratifications, which were divided into different groups according to GRACE scores and the time from admission to percutaneous coronary intervention (PCI). Method: Patients were grouped according to the GRACE score and the time from admission to intervention therapy. The Cox multivariate risk regression model was used to analyze the correlation between the GRACE score and the time from admission to intervention therapy with major adverse cardiovascular events (MACEs). Cox interactive item regression was also used to investigate the correlation between the time of intervention therapy and GRACE risk stratification with clinical outcomes and to evaluate the efficacy of intervention therapy in different risk stratifications of patients with NSTEMI. Results: Interactive item Cox regression analysis and subgroup analysis show that high-risk NSTEMI patients with a GRACE score > 140 points and the time from admission to intervention < 24 h (p = 0.0004) and 24-72 h (p = 0.0143) have interactive effects on the impact of the MACE event with the reference of intervention time > 72 h and GRACE score < 108 points. The time from admission to intervention < 24 h is an independent protective factor for the occurrence of MACE events (HR = 0.166, 95% CI 0.052-0.532, p = 0.0025). Middle-risk patients with NSTEMI with a GRACE score of 109-140 points and the time from admission to intervention < 24 h (p = 0.0370) and 24-72 h (p = 0.0471) have an interactive effect on the impact of MACE. The time from admission to intervention > 72 h is an independent protective factor for the occurrence of MACE (HR = 0.201, 95% CI 0.045-0.897, p = 0.0355). Conclusion: The time from admission to intervention < 24 h could effectively reduce the risk of MACE events within 1 year in high-risk patients with NSTEMI (GRACE score > 140 points); the time from admission to intervention > 72 h can reduce the risk of MACE events within 1 year in low-risk patients with NSTEMI (GRACE score ≤ 108 points).

Electrocardiographic patterns predict the presence of collateral circulation and in-hospital mortality in acute total left main occlusion.

BACKGROUND: Data on the clinical characteristics, electrocardiogram (ECG) findings and outcomes of patients with acute myocardial infarction (AMI) due to total unprotected left main (ULM) artery occlusion is limited. METHODS: Between 2009 and 2021, 44 patients with AMI due to total ULM occlusion underwent primary percutaneous coronary intervention (PCI) at our institution. The ECG, collateral circulation, clinical and procedural characteristics, and in-hospital mortality were retrospectively evaluated. RESULTS: Twenty five patients presented with shock and 18 patients had in-hospital mortality. Nineteen patients presented with ST-segment elevation myocardial infarction (STEMI), while 25 presented with non-ST-segment elevation myocardial infarction (NSTEMI). ST-segment elevation (STE) in I and STEMI were associated with the absence of collateral circulation, while STE in aVR was associated with its presence. In the NSTEMI group, patients with STE in both aVR and aVL showed more collateral filling of the left anterior descending coronary artery (LAD) territory, while patients with STE in aVR showed more collateral filling of the LAD and the left circumflex artery territory. Compared with total ULM occlusion, patients with partial ULM obstruction presented with more STE in aVR, less STE in aVR and aVL, and less STEMI. Shock, post-PCI TIMI 0-2 flow, non-STE in aVR, STEMI, and STE in I predicted in-hospital mortality. STEMI and the absence of collateral flow were significantly associated with shock. CONCLUSIONS: STE in the precordial leads predicted the absence of collateral circulation while STE in aVR and STE in both aVR and aVL predicted different collateral filling territories in ULM occlusion. STE in I, non-STE in aVR, and STEMI predicted in-hospital mortality in these patients.

Anti-Diabetic Effects of Ethanol Extract from Sanghuangporous vaninii in High-Fat/Sucrose Diet and Streptozotocin-Induced Diabetic Mice by Modulating Gut Microbiota.

Type 2 diabetes mellitus (T2DM) may lead to abnormally elevated blood glucose, lipid metabolism disorder, and low-grade inflammation. Besides, the development of T2DM is always accompanied by gut microbiota dysbiosis and metabolic dysfunction. In this study, the T2DM mice model was established by feeding a high-fat/sucrose diet combined with injecting a low dose of streptozotocin. Additionally, the effects of oral administration of ethanol extract from Sanghuangporous vaninii (SVE) on T2DM and its complications (including hypoglycemia, hyperlipidemia, inflammation, and gut microbiota dysbiosis) were investigated. The results showed SVE could improve body weight, glycolipid metabolism, and inflammation-related parameters. Besides, SVE intervention effectively ameliorated the diabetes-induced pancreas and jejunum injury. Furthermore, SVE intervention significantly increased the relative abundances of Akkermansia, Dubosiella, Bacteroides, and Parabacteroides, and decreased the levels of Lactobacillus, Flavonifractor, Odoribacter, and Desulfovibrio compared to the model group (LDA > 3.0, p < 0.05). Metabolic function prediction of the intestinal microbiota by PICRUSt revealed that glycerolipid metabolism, insulin signaling pathway, PI3K-Akt signaling pathway, and fatty acid degradation were enriched in the diabetic mice treated with SVE. Moreover, the integrative analysis indicated that the key intestinal microbial phylotypes in response to SVE intervention were strongly correlated with glucose and lipid metabolism-associated biochemical parameters. These findings demonstrated that SVE has the potential to alleviate T2DM and its complications by modulating the gut microbiota imbalance.

Prognostic value of PCSK9 levels in patients with non-ST elevation myocardial infarction undergoing percutaneous coronary intervention (PCI).

BACKGROUND: The role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in predicting major adverse cardiovascular events (MACEs) in Non-ST elevation myocardial infarction (NSTEMI) patients is still an open question, and the PCSK9 concentration of clinical usefulness remains unknown in guiding treatment. METHODS AND RESULTS: A total of 272 patients with NSTEMI were included in our prospective observational cohort study. Patients were followed up for 1 year. Their baseline plasma PCSK9 levels were determined by enzyme-linked immunosorbent assay. Patients were divided into high, medium, and low PCSK9 groups. All patients followed up for the occurrence of MACEs and received PCI therapy after admission. The associations of PCSK9 with MACEs were evaluated. The results showed that the incidence of composite MACEs was greater at higher concentrations of PCSK9. PCSK9 level was related to the level of lipoproteins, high-sensitivity C-reactive protein (hs-CRP), platelet volume distribution width, and D-Dimer. There was also a statistically significant correlation between PCSK9 concentrations and the GRACE score. The Kaplan-Meier curves showed that patients with high PCSK9 level had lower event-free survival rate. The survival analysis indicated high level of PCSK9-predicted MACEs independently. Subgroup analysis demonstrated that the prognostic value of high PCSK9 level was greater for patients classified by the GRACE score as high risk. CONCLUSION: In an NSTEMI setting, the concentration of PCSK9 is associated with hypercoagulability and hyperinflammation. High levels of PCSK9 independently predict future MACEs in patients with NSTEMI, particularly those classified by the GRACE score as high risk.

Effects of Evolocumab Added to Moderate-Intensity Statin Therapy in Chinese Patients With Acute Coronary Syndrome: The EMSIACS Trial Study Protocol.

Background: Several studies have demonstrated that using a higher dose of statin can easily induce liver injury and myopathy. Low-density lipoprotein cholesterol (LDL-C) is a well-established modifiable risk factor for cardiovascular disease; however, the large majority of Chinese patients cannot meet the target level of LDL-C recommended by the Chinese expert consensus. Evolocumab has been demonstrated to reduce LDL-C by approximately 60% in many studies. Nevertheless, whether combined evolocumab and moderate-intensity statin is as effective in lowering LDL-C and decreasing incidence of MACE in Chinese patients presenting with the acute phase of acute coronary syndrome (ACS) remains unknown. Therefore, the "Evolocumab added to Moderate-Intensity Statin therapy on LDL-C lowering and cardiovascular adverse events in patients with Acute Coronary Syndrome" (EMSIACS) is conducted. Methods: The EMSIACS is a prospective, randomized, open-label, parallel-group, multicenter study involving analyzing the feasibility and efficacy of evolocumab added to moderate-intensity statin therapy on lowering LDL-C levels in adult Chinese patients hospitalized for acute phase ACS. The sample size calculation is based on the primary outcome, and 500 patients will be planned to recruit. Patients are randomized in evolocumab arm (evolocumab 140mg every 2weeks plus rosuvastatin 10mg/day or atorvastatin 20mg/day) and statin-only arm (rosuvastatin 10mg/day or atorvastatin 20mg/day). The primary outcome is the percentage change in LDL-C in weeks 4 and week 12 after treatment. The secondary outcome is the occurrence of MACE after 12weeks and 1year of treatment. Discussion: If the EMSIACS trial endpoints prove statistically significant, the evolocumab added to moderate-intensity statin therapy will have the potential to effectively lower subjects' LDL-C levels, especially for the Chinese patients with acute phase ACS. However, if the risk of MACE is not significantly different between the two groups, we may extend follow-up time for secondary outcome when the clinical trial is over. Clinical trial registration: The study is registered to ClinicalTrials.gov (NCT04100434), which retrospectively registered on November 24, 2020.

Assessment of soil erosion in the Dongting Lake Basin, China: Patterns, drivers, and implications.

Soil loss caused by erosion is a global problem. Therefore, the assessment of soil erosion and the its driving mechanism are of great significance to soil conservation. However, soil erosion is affected by both climate change and human activities, which have not been quantified, and few researchers studied the differences in the driving mechanisms of soil erosion depending on the land use type. Therefore, the spatiotemporal characteristics and changing trends of soil erosion in the Dongting Lake Basin were analyzed in this study. Geographic detectors were used to identify the dominant factors affecting soil erosion in different land use types. In this study, a sensitivity experiment was conducted to clarify the relative contributions of climate change and human activities to soil erosion changes. In addition, we studied the effects of different land use types and vegetation cover restoration on soil erosion. The results show that soil erosion in the Dongting Lake Basin decreased from 2000 to 2018. Human activities represented by land use types and vegetation coverage significantly contributed to the alleviation of soil erosion in the Dongting Lake Basin, whereas climate change represented by rainfall slightly aggravated soil erosion in the study area. The restoration of grassland vegetation and transfer of cultivated land to woodlands in the study area improved the soil erosion. The slope steepness is the key factor affecting the intensity of soil erosion in dry land, paddy fields, and unused land, whereas the vegetation coverage is the key factor affecting the intensity of soil erosion in woodland, garden land, and grassland. Detailed spatiotemporally mapping of soil erosion was used to determine the connections between soil erosion and potential drivers, which have important implications for vegetation restoration and the optimization of land use planning.

Phillyrin for COVID-19 and Influenza Co-infection: A Potential Therapeutic Strategy Targeting Host Based on Bioinformatics Analysis.

Background: The risk of co-epidemic between COVID-19 and influenza is very high, so it is urgent to find a treatment strategy for the co-infection. Previous studies have shown that phillyrin can not only inhibit the replication of the two viruses, but also has a good anti-inflammatory effect, which is expected to become a candidate compound against COVID-19 and influenza. Objective: To explore the possibility of phillyrin as a candidate compound for the treatment of COVID-19 and influenza co-infection and to speculate its potential regulatory mechanism. Methods: We used a series of bioinformatics network pharmacology methods to understand and characterize the pharmacological targets, biological functions, and therapeutic mechanisms of phillyrin in COVID-19 and influenza co-infection and discover its therapeutic potential. Results: We revealed potential targets, biological processes, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and upstream pathway activity of phillyrin against COVID-19 and influenza co-infection. We constructed protein-protein interaction (PPI) network and identified 50 hub genes, such as MMP9, IL-2, VEGFA, AKT, and HIF-1A. Furthermore, our findings indicated that the treatment of phillyrin for COVID-19 and influenza co-infection was associated with immune balance and regulation of hypoxia-cytokine storm, including HIF-1 signaling pathway, PI3K-Akt signaling pathway, Ras signaling pathway, and T cell receptor signaling pathway. Conclusion: For the first time, we uncovered the potential targets and biological pathways of phillyrin for COVID-19 and influenza co-infection. These findings should solve the urgent problem of co-infection of COVID-19 and influenza that the world will face in the future, but clinical drug trials are needed for verification in the future.

The clinical features and prognosis of type 4C myocardial infarction in patients with non-ST-segment elevation myocardial infarction.

BACKGROUND: Type 4C myocardial infarction (MI) is a special type of myocardial infarction related to restenosis without thrombosis. There is a lack of relevant data on this new classification of acute MI (AMI). This study set out to examine the prognosis and treatment of type 4C MI in patients with non-ST-segment elevation MI (NSTEMI). METHODS: With reference to the NSTEMI cohort study database, we enrolled 1,032 cases of type 1 MI and 42 cases of type 4C MI from the period January 01, 2018 to August 31, 2018. All cases were followed up for 1 year. The outcome was major cardiovascular adverse events (including all-cause deaths, nonfatal MI, heart failure necessitating hospitalization, uncontrollable angina pectoris, and revascularization of the target vessels). Risk ratios (RR) were calculated using the generalized linear model. Cox multivariate analysis was performed to analyze the prognostic effects of drug-coated balloon (DCB) angioplasty or drug-eluting stent (DES) implantation in patients with type 4C MI. RESULTS: Compared with type 1 MI, type 4C MI was associated with a higher incidence of major adverse cardiovascular events (MACEs) [21.43% vs. 5.14%; adjusted RR: 3.725, 95% confidence interval (CI): 1.937-7.164]. Type 4C MI also showed a higher 1-year mortality rate than type 1 MI (7.14% vs. 1.55%; unadjusted RR: 4.607, 95% CI: 1.395-15.212). However, after adjusting for covariates, no statistical difference was noted (adjusted RR: 2.515, 95% CI: 0.768-8.233). Multiple adjustments to the Cox multivariate models revealed that neither DCB nor DES affected the clinical outcomes. CONCLUSIONS: Type 4C MI has a poorer prognosis than type 1 MI. DCB angioplasty and DES implantation show similar efficacy in the treatment of type 4C MI.