Association of hemoglobin glycation index with prognosis of coronary artery disease after percutaneous coronary intervention: A retrospective cohort study.

AIMS: To analyze the association between hemoglobin glycation index (HGI) and the long-term prognosis of patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI). METHODS: Predicted glycated hemoglobin (HbA1c) level was calculated using an established formula and HGI represented the difference between laboratory measured HbA1c and predicted HbA1c. A total of 1780 patients were stratified into three subgroups (HGI < -0.4, -0.4 ≦ HGI < 0.12 and HGI ≧ 0.12). The primary endpoints included all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs). RESULTS: ACM occurred in 54 patients: 22 (3.7) in the low-HGI subgroup, 8 (1.3) in the moderate-HGI subgroup and 24 (4.1) in the high-HGI subgroup (p = .012). After adjusting for the traditional clinical prognostic factors, multivariate Cox regression analysis showed that patients in both the low and high HGI subgroups had significantly increased risk of ACM as compared with patients in the moderate HGI subgroup (hazard ratio [HR] = 4.979, 95% confidence interval [CI]: 1.865-13.297, p = .001 and HR = 2.918, 95% CI: 1.075-7.922, p = .036). However, we did not find significant differences in the incidence of CM, MACEs and MACCEs. CONCLUSION: HGI can predicts risk for long-term mortality in patients undergoing PCI. This index could be helpful for the effective clinical management of the CAD population.

Nomogram for Prediction of Postoperative Delirium after Deep Brain Stimulation of Subthalamic Nucleus in Parkinson's Disease under General Anesthesia.

Introduction: Postoperative delirium can increase cognitive impairment and mortality in patients with Parkinson's disease. The purpose of this study was to develop and internally validate a clinical prediction model of delirium after deep brain stimulation of the subthalamic nucleus in Parkinson's disease under general anesthesia. Methods: We conducted a retrospective observational cohort study on the data of 240 patients with Parkinson's disease who underwent deep brain stimulation of the subthalamic nucleus under general anesthesia. Demographic characteristics, clinical evaluation, imaging data, laboratory data, and surgical anesthesia information were collected. Multivariate logistic regression was used to develop the prediction model for postoperative delirium. Results: A total of 159 patients were included in the cohort, of which 38 (23.90%) had postoperative delirium. Smoking (OR 4.51, 95% CI 1.56-13.02, p < 0.01) was the most important risk factor; other independent predictors were orthostatic hypotension (OR 3.42, 95% CI 0.90-13.06, p=0.07), inhibitors of type-B monoamine oxidase (OR 3.07, 95% CI 1.17-8.04, p=0.02), preoperative MRI with silent brain ischemia or infarction (OR 2.36, 95% CI 0.90-6.14, p=0.08), Hamilton anxiety scale score (OR 2.12, 95% CI 1.28-3.50, p < 0.01), and apolipoprotein E level in plasma (OR 1.48, 95% CI 0.95-2.29, p=0.08). The area under the receiver operating characteristic curve (AUC) was 0.76 (95% CI 0.66-0.86). A nomogram was established and showed good calibration and clinical predictive capacity. After bootstrap for internal verification, the AUC was 0.74 (95% CI 0.66-0.83). Conclusion: This study provides evidence for the independent inducing factors of delirium after deep brain stimulation of the subthalamic nucleus in Parkinson's disease under general anesthesia. By predicting the development of delirium, our model may identify high-risk groups that can benefit from early or preventive intervention.

Correlation between metastasis-associated gene 1 expression and tumor-associated macrophages in non-small cell lung cancer.

The role of metastasis-associated gene 1 (MTA1) in the metastasis of non-small cell lung cancer (NSCLC) has been proved, but its role in the tumor microenvironment is still insufficient. The study was performed to explore the correlation between MTA1 and tumor-associated macrophages (TAMs) in NSCLC. The expression profile data of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were downloaded from TCGA database. The tumor-infiltrating immune cells in each LUAD and LUSC patient were estimated using the CIBERSORT method. Then, the online TIMER database containing multiple algorithms was used to analyze the relationship between MTA1 and TAMs. Besides, correlations between MTA1 and TAMs markers were also explored. Additionally, the immunohistochemistry staining of MTA1 protein and CD206 was performed in 75 NSCLC tissue specimens. Associations of MTA1 and CD206 with the clinicopathological characteristics were analyzed, as well as the correlation between MTA1 and CD206. Based on different algorithms, MTA1 expression was correlated with the distribution of infiltrating immune cells in the tumor microenvironment and negatively correlated with tumor immune-stromal score. MTA1 was associated with TAMs markers according to TCGA database. In 75 NSCLC tissue specimens, the positive rate of MTA1 was 60.00% (45/75), which of CD206 was 42.67% (32/75). The MTA1 expression was significantly correlated with T stage, lymph node metastasis, and TNM stage. The CD206 expression was significantly correlated with T stage, lymph node metastasis, TNM stage, and tumor type. Additionally, we found that MTA1 was positively correlated with CD206 in NSCLC and LUSC. In NSCLC, MTA1 expression was correlated with the infiltrations of different types of macrophages and the expression of TAMs markers, as well as the M2-TAMs marker CD206, suggesting that MTA1-promoting tumor metastasis may mediate the infiltration of different types of macrophages in the tumor microenvironment.

Prognostic Nutritional Index as a Novel Predictor of Long-Term Prognosis in Patients with Coronary Artery Disease After Percutaneous Coronary Intervention.

BACKGROUND: The Prognostic Nutritional Index (PNI) has been reported to be correlated with long-term outcomes after gastrointestinal tumor surgery. However, to our knowledge, only a few studies have shown that the PNI is related to cardiovascular diseases. Therefore, we aimed to assess the association between the PNI and long-term outcomes in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). METHODS: This was retrospective observational study. A total of 3561 patients with CAD after PCI were retrospectively enrolled in the CORFCHD-ZZ study from January 2013 to December 2017. The patients (3519) were divided into three groups according to PNI tertiles: the first tertile (PNI < 47.12, n = 1173), the second tertile (47.12 ≤ PNI < 51.50, n = 1185), and the third tertile (PNI ≥ 51.50, n = 1161). The mean follow-up time was 37.59 ± 22.24 months. The primary endpoint long-term mortality, including all-cause mortality (ACM) and cardiac mortality (CM).Secondary endpoints were major adverse cardiovascular events (MACEs) and major adverse cardiovascular and cerebrovascular events (MACCEs). RESULT: In our study, the incidences of ACM in the first, second, and third tertiles were 3.8%, 1.8% and 1.4%, respectively (P < 0.001). The incidences of CM occurring in the first, second, and third tertiles were 1.7%, 3.1% and 2.1%, respectively (P < 0.001).There was statistically significant different in primary endpoints incidence. MACEs occurred in 139 patients (11.8%) in the first tertile, 121 patients(11.1%) in the second tertile and 123 patients(10.8%) in the third tertile(P = 0.691). MACCEs occurred in 183 patients (15.6%) in the first tertile, 174 patients(14.7%) in the second tertile and 160 patients(13.85%) in the third tertile(P = 0.463).There was no statistically significant different in secondary endpoints incidence. Kaplan-Meier analyses showed that elevated PNI was significantly related to long-term CM (log rank, P < 0.001) and long-term ACM (log-rank, P < 0.001). Cox regression analyses suggested that compared with the patients in the first tertile, the risk of ACM was decreased to 60.9% (HR = 0.609, 95% CI: 0.398-0.932, P = 0.029) in the second tertile and 40.3%(HR = 0.403, 95% CI: 0.279-0.766, P = 0.003) in the third tertile, while the risk of CM was decreased to 58.8%(HR = 0.588, 95% CI: 0.321-0.969, P = 0.038) in the second tertile and 46.6%(HR = 0.466, 95% CI: 0.250-0.870, P = 0.017) in the third tertile. Multivariate Cox regression analyses showed that the PNI was an independent predictor of long-term ACM and CM. CONCLUSION: Our finding shown that PNI is an independent predictor in CAD patients after PCI，the higher the PNI, the less occurring adverse event. Therefore，PNI may be an new biomarker to predict long-term outcome of CAD patients after PCI.

The age, NT-proBNP, and Ejection Fraction Score as a Novel Predictor of Clinical Outcomes in CAD Patients After PCI.

BACKGROUND: Previous evidences have been proved that age, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and ejection fraction are tightly associated with the long-term outcomes in patients suffered from coronary artery disease (CAD). Therefore, the present study aimed to assess the prognosis value of age, NT-proBNP, and ejection fraction (ABEF) score in CAD patients who underwent percutaneous coronary intervention (PCI). METHODS: Observational cohort methodology was used in this study which enrolled totally 3561 patients. And the patients were followed up regularly for 37.59 ± 22.24 months. Patients were classed into three groups based on the tertiles of ABEF sore: first tertile (<5.06, n = 831), second tertile (5.06-6.25, n = 839), and third tertile (≥ 6.25, n = 834). The ABEF score was calculated as follows: age (years)/ejection fraction (%) + NT-proBNP (NT-proBNP<177pg/mL was 1, 177≤NT-proBNP≥524pg/mL was 2 and NT-proBNP > 524pg/mL is 3). The association between ABEF score and adverse prognosis, including all-cause death (ACD), cardiac death (CD), major adverse cardiovascular events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs), in patients who underwent PCI was analyzed. RESULTS: According to the risk category of ABEF score, the incidences of ACD (P < .001), CD (P < .001) and MACCEs (P = .021) among the three groups showed significant differences. Multivariate Cox regression analysis suggested that the respective risks of ACD and CD were increased 3.013 folds (hazard risk [HR] = 4.013 [95% confidence interval [CI]: 1.922-8.378], P < .001) and 4.922 folds ([HR] = 5.922 [95% [CI]: 2.253-15.566], P < .001) in the third tertile compared with those in the first tertile. Kaplan-Meier survival analyses showed that the cumulative risks of ACD,CD and MACCEs in patients with the high ABEF score tended to increase. CONCLUSION: The present study indicated ABEF score was a novel biomarker suitable for predicting adverse prognosis in patients after PCI, which may be used for early recognition and risk stratification.

Pre-operative breathing training based on video learning reduces emergence delirium in preschool children: A randomized clinical trial.

STUDY OBJECTIVE: Emergence delirium is a common complication in preschool children after general anesthesia and may result in undesirable complications. This study aimed to determine whether breathing training after watching an informative video during the pre-operative visit could reduce the incidence of emergence delirium in preschool children after otorhinolaryngologic surgery under general anesthesia. DESIGN: A single-center, double-blinded, randomized controlled trial. SETTING: Perioperative care. PATIENTS: A total of 170 children undergoing otorhinolaryngologic surgery, aged 3-7 years, ASA physical status I or II were involved. INTERVENTIONS: Patients were randomized to receive breathing training during the pre-operative visit (Training group) or to receive pre-operative visit only (Control group) the day before surgery. MEASUREMENTS: Emergence delirium was measured by the Pediatric Anesthesia Emergence Delirium score during the anesthesia recovery time. Data regarding extubation time and post-anesthesia care unit stay time were collected. MAIN RESULTS: Children who received breathing training during the pre-operative visit had a significantly lower incidence of emergence delirium than those who only underwent the pre-operative visit (10.4% vs. 35.1%, P < 0.001). The awakening time score and the maximum score in the post-anesthesia care unit were significantly lower in the training group compared with the control group [4.4 ± 3.4 vs. 6.9 ± 4.2, P < 0.001 and 5.0 (5.0) vs 7.0 (7.0), P = 0.001, respectively]. We found no differences in the extubation time and post-anesthesia care unit stay time between groups. CONCLUSIONS: We concluded that breathing training based on video learning during the pre-operative visit in preschool children undergoing otorhinolaryngologic surgery could significantly decrease the incidence of emergence delirium. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Reference number: ChiCTR1900026162); registered on September 24, 2019.

High-resolution quantitative trait locus mapping for rice grain quality traits using genotyping by sequencing.

Rice is a major food crop that sustains approximately half of the world population. Recent worldwide improvements in the standard of living have increased the demand for high-quality rice. Accurate identification of quantitative trait loci (QTLs) for rice grain quality traits will facilitate rice quality breeding and improvement. In the present study, we performed high-resolution QTL mapping for rice grain quality traits using a genotyping-by-sequencing approach. An F2 population derived from a cross between an elite japonica variety, Koshihikari, and an indica variety, Nona Bokra, was used to construct a high-density genetic map. A total of 3,830 single nucleotide polymorphism markers were mapped to 12 linkage groups spanning a total length of 2,456.4 cM, with an average genetic distance of 0.82 cM. Seven grain quality traits-the percentage of whole grain, percentage of head rice, percentage of area of head rice, transparency, percentage of chalky rice, percentage of chalkiness area, and degree of chalkiness-of the F2 population were investigated. In total, 15 QTLs with logarithm of the odds (LOD) scores >4 were identified, which mapped to chromosomes 6, 7, and 9. These loci include four QTLs for transparency, four for percentage of chalky rice, four for percentage of chalkiness area, and three for degree of chalkiness, accounting for 0.01%-61.64% of the total phenotypic variation. Of these QTLs, only one overlapped with previously reported QTLs, and the others were novel. By comparing the major QTL regions in the rice genome, several key candidate genes reported to play crucial roles in grain quality traits were identified. These findings will expedite the fine mapping of these QTLs and QTL pyramiding, which will facilitate the genetic improvement of rice grain quality.

Emerging role of m6A methylation modification in ovarian cancer.

m6A (N6-methyladenosine) methylation, a well-known modification in tumour epigenetics, dynamically and reversibly fine tunes the entire process of RNA metabolism. Aberrant levels of m6A and its regulators, which can predict the survival and outcomes of cancer patients, are involved in tumorigenesis, metastasis and resistance. Ovarian cancer (OC) ranks first among gynaecological tumours in the causes of death. At first diagnosis, patients with OC are usually at advanced stages owing to a lack of early biomarkers and effective targets. After treatment, patients with OC often develop drug resistance. This article reviews the recent experimental advances in understanding the role of m6A modification in OC, raising the possibility to treat m6A modification and its regulators as promising diagnostic markers and therapeutic targets for OC.

ADS Score as a Novel Predictor of Outcomes in Patients Who Underwent Percutaneous Coronary Intervention.

Objectives: A novel AFR- albumin-derived neutrophil to lymphocyte ratio (dNLR) score (ADS) were reported to associate with clinical outcome in various malignancies, However, the relation between the ADS score and outcomes in coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) has not been investigated. Methods: Three thousand five hundred and sixty-one patients were divided into two groups according to ADS score: low group (ADS score <2; n = 2,682) and high group (ADS score ≥ 2; n = 879). Overall, there were 133 all-cause mortality (ACM) during the following up. The incidence of ACM in the low group is 2.7% (72/2,682) and high group is 6.9% (61/879). The ACM incidence was significantly higher in high group compared to that in the low group (P < 0.001). Cardiac mortality (CM) occurred in 82 patients: 44(1.6%) in the low group and 38 (4.3%) in the high group. There was significant difference in the CM incidence between the low group and high group (P < 0.001). Major adverse cardiac and cerebrovascular events (MACCE) occurred in 520 patients: 366 (13.6%) in the low group and 154 (17.5%) in the high group. There was significant difference in the MACCE incidence between the low group and high group (P = 0.005). Major adverse cardiac and events (MACE) occurred in 395 patients: 281(10.5%) in the low group and 114 (13.0%) in the high group. There was significant difference in the MACE incidence between the low group and high group (P = 0.041). The multivariate Cox proportional hazards model showed that ADS score was independently correlated with the ACM [adjusted HR = 2.031 (1.357-3.039), P = 0.001]; CM [adjusted HR = 1.883 (1.127-3.147), P = 0.016]; MACCE [adjusted HR = 1.352 (1.096-1.668), P = 0.005], and MACE [adjusted HR = 1.260 (0.987-1.608), P = 0.063]. Conclusion: The present study indicated that the ADS score was associated with long-term mortality, the MACCE, and the MACE in CAD patients underwent PCI.

Association of Derived Neutrophil-To-Lymphocyte Ratio With Prognosis of Coronary Heart Disease After PCI.

Aims: The present study aimed to investigate the prognostic role of derived neutrophil-to-lymphocyte ratio (dNLR) in patients with coronary heart disease (CHD) after PCI. Methods: A total of 3,561 post-PCI patients with CHD were retrospectively enrolled in the CORFCHD-ZZ study from January 2013 to December 2017. The patients (3,462) were divided into three groups according to dNLR tertiles: the first tertile (dNLR < 1.36; n = 1,139), second tertile (1.36 ≥ dNLR < 1.96; n = 1,166), and third tertile(dNLR ≥ 1.96; n = 1,157). The mean follow-up time was 37.59 ± 22.24 months. The primary endpoint was defined as mortality (including all-cause death and cardiac death), and the secondary endpoint was major adverse cardiovascular events (MACEs) and major adverse cardiovascular and cerebrovascular events (MACCEs). Results: There were 2,644 patients with acute coronary syndrome (ACS) and 838 patients with chronic coronary syndrome (CCS) in the present study. In the total population, the all-cause mortality (ACM) and cardiac mortality (CM) incidence was significantly higher in the third tertile than in the first tertile [hazard risk (HR) = 1.8 (95% CI: 1.2-2.8), p = 0.006 and HR = 2.1 (95% CI: 1.23-3.8), p = 0.009, respectively]. Multivariate Cox regression analyses suggested that compared with the patients in the first tertile than those in the third tertile, the risk of ACM was increased 1.763 times (HR = 1.763, 95% CI: 1.133-2.743, p = 0.012), and the risk of CM was increased 1.763 times (HR = 1.961, 95% CI: 1.083-3.550, p = 0.026) in the higher dNLR group during the long-term follow-up. In both ACS patients and CCS patients, there were significant differences among the three groups in the incidence of ACM in univariate analysis. We also found that the incidence of CM was significantly different among the three groups in CCS patients in both univariate analysis (HR = 3.541, 95% CI: 1.154-10.863, p = 0.027) and multivariate analysis (HR = 3.136, 95% CI: 1.015-9.690, p = 0.047). Conclusion: The present study suggested that dNLR is an independent and novel predictor of mortality in CHD patients who underwent PCI.

CRF-CRFR1 system within the dorsal medial prefrontal cortex are involved in consolation deficits under acute restraint stress in mandarin voles.

Consolation is a complex empathic behavior that has recently been observed in some socially living rodents. Despite the growing body of literature suggesting that stress affects some simple form of empathy, the relationship between stress and consolation remains largely understudied. Using monogamous mandarin voles, we found that an acute restraint stress exposure significantly reduced consolation-like behaviors and induced anxiety-like behaviors. Along with these behavioral changes, corticotropin-releasing factor (CRF) and CRF receptor 1 (CRFR1) neurons were activated within the anterior cingulate cortex (ACC) and prelimbic cortex (PrL) but not within the infralimbic cortex (IL). Chemogenetic activation of CRF neurons in the ACC and PrL, recaptured acute stress-induced behavioral dysfunctions. We further observed that intracellular PKA and PKC signaling pathways mediate CRF-induced behavioral dysfunctions, but they work in a regional-specific, sex-biased manner. Together, these results suggest that the local CRF-CRFR1 system within the ACC and PrL is involved in the consolation deficits and anxiety induced by acute stress.

Optimized Propofol Anesthesia Increases Power of Subthalamic Neuronal Activity in Patients with Parkinson's Disease Undergoing Deep Brain Stimulation.

INTRODUCTION: Propofol is a general anesthetic option for deep brain stimulation (DBS) of the subthalamic nucleus (STN) of patients with Parkinson's disease (PD). However, its effects on STN activity and neuropsychological outcomes are controversial. The optimal propofol anesthesia for asleep DBS is unknown. This study investigated the safety and effectiveness of an optimized propofol anesthesia regimen in asleep DBS. METHODS: This retrospective study enrolled 68 PD patients undergoing bilateral STN-DBS surgery. All patients received local scalp anesthesia, with (asleep group, n = 35) or without (awake group, n = 33) propofol-remifentanil general anesthesia by target-controlled infusion under electroencephalogram monitoring. The primary outcome was subthalamic neuronal spiking characterization during microelectrode recording. The secondary outcomes were clinical outcomes including motor, cognition, mind, sleep, and quality of life at 6 months. RESULTS: Significantly increased delta and theta power were obtained under propofol anesthesia (awake vs. asleep group, mean ± standard deviation; delta: 31.97 ± 9.87 vs. 39.77 ± 10.56, p < 0.01; theta: 21.09 ± 5.55 vs. 24.82 ± 6.63, p = 0.01). After excluding the influence of confounding factors of age and preoperative motor scores, there was a statistically significant influence on the delta, theta, and alpha power of STN neuronal activity under different anesthesia regimens (delta: ß = 2.64, p < 0.01; theta: ß = 2.11, p < 0.01; alpha: ß = 1.42, p = 0.01). There were no differences in modified burst index, firing rate, tract numbers of microelectrode recording, and other clinical outcomes between the two groups. CONCLUSION: Optimized propofol anesthesia enhanced the delta, theta, and alpha power in STN compared with the awake technique and likely contributed to target recognition under propofol anesthesia. These results demonstrate that propofol is suitable, but needs to be optimized, for asleep STN-DBS. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identification number: ChiCTR2100045942. Registered 29 April 2021-Retrospectively registered.

Monocyte-to-albumin ratio as a novel predictor of long-term adverse outcomes in patients after percutaneous coronary intervention.

BACKGROUND: Monocyte count and serum albumin (Alb) have been proven to be involved in the process of systemic inflammation. Therefore, we investigated the prognostic value of monocyte-to-albumin ratio (MAR) in patients who underwent percutaneous coronary intervention (PCI). METHODS: We enrolled a total of 3561 patients in the present study from January 2013 to December 2017. They were divided into two groups according to MAR cut-off value (MAR < 0.014, n=2220; MAR ≥ 0.014, n=1119) as evaluated by receiver operating characteristic (ROC) curve. The average follow-up time was 37.59 ± 22.24 months. RESULTS: The two groups differed significantly in the incidences of all-cause mortality (ACM; P<0.001), cardiac mortality (CM; P<0.001), major adverse cardiovascular events (MACEs; P=0.038), and major adverse cardiovascular and cerebrovascular events (MACCEs; P=0.037). Multivariate Cox regression analyses revealed MAR as an independent prognostic factor for ACM and CM. The incidence of ACM increased by 56.5% (hazard ratio [HR] = 1.565; 95% confidence interval [CI], 1.086-2.256; P=0.016) and that of CM increased by 76.3% (HR = 1.763; 95% CI, 1.106-2.810; P=0.017) in patients in the higher-MAR group. Kaplan-Meier survival analysis suggested that patients with higher MAR tended to have an increased accumulated risk of ACM (Log-rank P<0.001) and CM (Log-rank P<0.001). CONCLUSION: The findings of the present study suggested that MAR was a novel independent predictor of long-term mortality in patients who underwent PCI.

Alkaline phosphatase-to-albumin ratio as a novel predictor of long-term adverse outcomes in coronary artery disease patients who underwent PCI.

BACKGROUND: Alkaline phosphatase (ALP) and albumin (ALB) have been shown to be associated with coronary artery disease (CAD), and it has been reported that alkaline phosphatase-to-albumin ratio (AAR) is associated with the liver damage and poorer prognosis of patients with digestive system malignancy. Moreover, several previous studies showed that there was a higher incidence of malignancy in CAD patients. However, to our knowledge, the relationship between AAR and long-term adverse outcomes in CAD patients after undergoing percutaneous coronary intervention (PCI) has not been investigated. Therefore, we aim to access the relation between AAR and long-term adverse outcomes in post-PCI patients with CAD. METHODS: A total of 3378 post-PCI patients with CAD were enrolled in the retrospective Clinical Outcomes and Risk Factors of Patients with Coronary Heart Disease after PCI (CORFCHD-ZZ) study from January 2013 to December 2017. The median duration of follow-up was 37.59 ± 22.24 months. The primary end point was long-term mortality including all-cause mortality (ACM) and cardiac mortality (CM). The secondary end points were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs). RESULTS: Kaplan-Meier analyses showed that an increased AAR was positively correlated with incidences of long-term ACM (log-rank, P=0.014), CM (log-rank, P=0.011), MACEs (log-rank, P=0.013) and MACCEs (log-rank, P=0.006). Multivariate Cox regression analyses showed that the elevated AAR was an independent predictor of long-term ACM (adjusted HR = 1.488 [1.031-2.149], P=0.034), CM (adjusted HR = 1.837 [1.141-2.959], P=0.012), MACEs (adjusted HR = 1.257 [1.018-1.551], P=0.033) and MACCEs (adjusted HR = 1.237 [1.029-1.486], P=0.024). CONCLUSION: An elevated AAR is a novel independent predictor of long-term adverse outcomes in CAD patients following PCI.

Long-term dual antiplatelet-induced intestinal injury resulting in translocation of intestinal bacteria into blood circulation increased the incidence of adverse events after PCI in patients with coronary artery disease.

BACKGROUND AND AIMS: The present study aimed to investigate the efficacy and safety of long-term (>18 months) dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). METHODS: A total of 3205 coronary artery disease (CAD) patients after PCI from CORFCHD-PCI, a retrospective cohort study (Identifier: ChiCTR-ORC-16010153), were divided into two groups: monotherapy of aspirin or clopidogrel group (SAPT group, n = 2188 and DAPT group, n = 1017) according to whether to discontinue DAPT 18 months after PCI. After propensity matching analysis (PSM), we included 1017 patients in the DAPT group and 1017 patients in the SAPT group. All the patients were followed-up for at least 18 months and the longest follow-up time is 120 months. The primary endpoint was the incidence of major adverse cardiac events (MACEs). The secondary endpoints were the incidence of major adverse cardiovascular and cerebrovascular events (MACEEs) and bleeding events. We also selected 178 patients for detection of claudin-3 and intestinal fatty acid-binding protein and 58 patients for 16s RNA sequencing of whole blood. RESULTS: The incidences of MACEs (13.9% vs. 9.0%, p = 0.001) and MACCEs (16.3% vs.10.0%, p < 0.001) were significantly increased in the DAPT group compared to the SAPT group. We also found DAPT increased the bleeding events compared to SAPT (4.6% vs. 2.9%, p = 0.048). Multivariate Cox regression analyses showed that in the DAPT group, cumulative risk of MACCEs increased 1.797 times (HR = 1.797, 95%CI: 1.429-2.226, p < 0.001), MACEs increased 1.737 times (HR = 1.737, 95%CI: 1.360-2.218, p < 0.001) and the bleeding events increased 2.129 times (HR = 2.129, 95%CI: 1.388-3.266, p = 0.001) compared to the SAPT group. We also found the plasma concentrations of claudin-3 and intestinal fatty acid-binding protein (I-FABP) were significantly higher in patients in the DAPT group compared with patients in the SAPT group (both p < 0.001). Correspondingly, the abundance of blood intestinal bacteria in the DAPT group was significantly increased compared to that in the SAPT group (p < 0.001). Furthermore, high-throughput metabolomics analysis suggested that serum level of ceramide (d18:1/16:0) and Neu5Ac was significantly increased in the DAPT group compared to the SAPT group (both p < 0.001). CONCLUSIONS: The present study suggests that long-term dual antiplatelet therapy longer than 18 months significantly increases the incidence of both ischemic events and bleeding events after PCI. This preliminary study also indicates that long-term DAPT causes intestinal injury, which induces translocation of intestinal bacteria into the bloodstream.

A Correlation Between Monocyte to Lymphocyte Ratio and Long-Term Prognosis in Patients With Coronary Artery Disease After PCI.

Monocyte to lymphocyte ratio (MLR) has been confirmed as a novel marker of poor prognosis in patients with coronary heart disease (CAD). However, the prognosis value of MLR for patients with CAD after percutaneous coronary intervention (PCI) needs further studies. In present study, we aimed to investigate the correlation between MLR and long-term prognosis in patients with CAD after PCI. A total of 3,461 patients with CAD after PCI at the First Affiliated Hospital of Zhengzhou University were included in the analysis. According to the cutoff value of MLR, all of the patients were divided into 2 groups: the low-MLR group (<0.34, n = 2338) and the high-MLR group (≥0.34, n = 1123). Kaplan-Meier curve was performed to compare the long-term outcome. Multivariate COX regression analysis was used to assess the independent predictors for all-cause mortality, cardiac mortality and MACCEs. Multivariate COX regression analysis showed that the high MLR group had significantly increased all-cause mortality (ACM) [hazard ratio (HR) = 1.366, 95% confidence interval (CI): 1.366-3.650, p = 0.001] and cardiac mortality (CM) (HR = 2.379, 95%CI: 1.611-3,511, p < 0.001) compared to the low MLR group. And high MLR was also found to be highly associated with major adverse cardiovascular and cerebrovascular events (MACCEs) (HR = 1.227, 95%CI: 1.003-1.500, p = 0.047) in patients with CAD undergoing PCI. MLR was an independent predictor of ACM, CM and MACCEs in CAD patients who underwent PCI.

Different baseline physical activity predicts susceptibility and resilience to chronic social defeat stress in mice: Involvement of dopamine neurons.

Physical inactivity, the fourth leading mortality risk factor worldwide, is associated with chronic mental illness. Identifying the mechanisms underlying different levels of baseline physical activity and the effects of these levels on the susceptibility to stress is very important. However, whether different levels of baseline physical activity influence the susceptibility and resilience to chronic social defeat stress (CSDS), and the underlying mechanisms in the brain remain unclear. The present study segregated wild-type mice into low baseline physical activity (LBPA) and high baseline physical activity (HBPA) groups based on short term voluntary wheel running (VWR). LBPA mice showed obvious susceptibility to CSDS, while HBPA mice were resilient to CSDS. In addition, the expression of tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) was lower in LBPA mice than in HBPA mice. Furthermore, activation of TH neurons in the VTA of LBPA mice by chemogenetic methods increased the levels of VWR and resilience to CSDS. In contrast, inhibiting TH neurons in the VTA of HBPA mice lowered the levels of VWR and increased their susceptibility to CSDS. Thus, this study suggests that different baseline physical activities might be mediated by the dopamine system. This system also affects the susceptibility and resilience to CSDS, possibly via alteration of the baseline physical activity. This perspective on the neural control and impacts on VWR may aid the development of strategies to motivate and sustain voluntary physical activity. Furthermore, this can maximize the impacts of regular physical activity toward stress-reduction and health promotion.

C-reactive protein-to-serum albumin ratio as a novel predictor of long-term outcomes in coronary artery disease patients who have undergone percutaneous coronary intervention: analysis of a real-world retrospective cohort study.

BACKGROUND: C-reactive protein (CRP) has been proposed as a contributor to the pathogenesis of coronary artery disease (CAD) and inflammatory reactions, which are associated with a decrease in serum albumin, and it has been reported that the CRP-to-serum albumin ratio (CAR) can predict CAD severity in inpatient ischemic cardiomyopathy (ICM) patients. However, the relationship between the CAR and long-term adverse outcomes in CAD patients after percutaneous coronary intervention (PCI) is still unknown. METHODS: A total of 3561 CAD patients enrolled in the Outcomes and Risk Factors of Patients with Coronary Heart Disease after PCI: an investigation based on case records and follow-up (CORFCHD-ZZ), a retrospective cohort study conducted from January 2013 to December 2017, and 1630 patients meeting the study inclusion criteria were divided into two groups based on the CAR (CAR < 0.186; n = 1301 and CAR ≥ 0.186; n = 329). The primary outcome was long-term mortality, including all-cause mortality (ACM) and cardiac mortality. The average follow-up time was 37.59 months. RESULTS: We found that there were significant differences between the two groups in the incidences of ACM (P < 0.001) and cardiac mortality (P = 0.003). Cox multivariate regression analyses demonstrated that CAR was an independent predictor of ACM [hazard ratio, 2.678; (95% confidence interval (CI), 1.568-4.576); P < 0.001] and cardiac mortality (hazard ratio, 2.055; 95% CI, 1.056-3.998; P = 0.034) in CAD patients after PCI. CONCLUSION: This study revealed that the CAR is an independent and novel predictor of long-term adverse outcomes in CAD patients who have undergone PCI.

A Novel ABC Score Predicts Mortality in Non-ST-Segment Elevation Acute Coronary Syndrome Patients Who underwent Percutaneous Coronary Intervention.

OBJECTIVE: In the present study, we aimed to establish a novel score to predict long-term mortality of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients who underwent percutaneous coronary intervention (PCI). METHODS: A total of 2,174 NSTE-ACS patients from the CORFCHD-ZZ study were enrolled as the derivation cohort. The validation cohort including 1,808 NSTE-ACS patients were from the CORFCHD-PCI study. Receiver operating characteristic analysis and area under the curve (AUC) evaluation were used to select the candidate variables. The model performance was validated internally and externally. The primary outcome was cardiac mortality (CM). We also explored the model performance for all-cause mortality (ACM). RESULTS: Initially, 28 risk factors were selected and ranked according to their AUC values. Finally, we selected age, N-terminal pro-B-type natriuretic peptide, and creatinine to develop a novel prediction model named "ABC" model. The ABC model had a high discriminatory ability for both CM (C-index: 0.774, p < 0.001) and ACM (C-index: 0.758, p < 0.001) in the derivation cohort. In the validation cohort, the C-index of CM was 0.802 (p < 0.001) and that of ACM was 0.797 (p < 0.001), which suggested good discrimination. In addition, this model had adequate calibration in both the derivation and validation cohorts. Furthermore, the ABC score outperformed the GRACE score to predict mortality in NSTE-ACS patients who underwent PCI. CONCLUSION: In the present study, we developed and validated a novel model to predict mortality in patients with NSTE-ACS who underwent PCI. This model can be used as a credible tool for risk assessment and management of NSTE-ACS after PCI.

Fasting blood glucose to HDL-C ratio as a novel predictor of clinical outcomes in non-diabetic patients after PCI.

Background The present study was to assess the prognostic value of fasting blood glucose to high-density lipoprotein cholesterol ratio (GHR) in non-diabetic patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). Methods and results A total of 6645 non-diabetic patients from two independent cohorts, the CORFCHD-PCI study (n=4282) and the CORFCHD-ZZ (n=2363) study, were enrolled in Clinical Outcomes and Risk Factors of Patients with Coronary Heart Disease after PCI. Patients were divided into two groups according to the GHR value. The primary outcome included all-cause mortality (ACM) and cardiac mortality (CM). The average follow-up time was 36.51 ± 22.50 months. We found that there were significant differences between the two groups in the incidences of ACM (P=0.013) and CM (P=0.038). Multivariate Cox regression analysis revealed GHR as an independent prognostic factor for ACM. The incidence of ACM increased 1.284-times in patients in the higher GHR group (hazard ratio [HR]: 1.284 [95% confidence interval [CI]: 1.010-1.631], P<0.05). Kaplan-Meier survival analysis suggested that patients with high GHR value tended to have an increased accumulated risk of ACM. However, we did not find significant differences in the incidence of major adverse cardiac events, main/major adverse cardiovascular and cerebrovascular events (MACCE), stroke, recurrent myocardial infarction (MI) and bleeding events. Conclusions The present study indicates that GHR index is an independent and novel predictor of ACM in non-diabetic CAD patients who underwent PCI.