Pathological Asymmetry-Guided Progressive Learning for Acute Ischemic Stroke Infarct Segmentation.

Quantitative infarct estimation is crucial for diagnosis, treatment and prognosis in acute ischemic stroke (AIS) patients. As the early changes of ischemic tissue are subtle and easily confounded by normal brain tissue, it remains a very challenging task. However, existing methods often ignore or confuse the contribution of different types of anatomical asymmetry caused by intrinsic and pathological changes to segmentation. Further, inefficient domain knowledge utilization leads to mis-segmentation for AIS infarcts. Inspired by this idea, we propose a pathological asymmetry-guided progressive learning (PAPL) method for AIS infarct segmentation. PAPL mimics the step-by-step learning patterns observed in humans, including three progressive stages: knowledge preparation stage, formal learning stage, and examination improvement stage. First, knowledge preparation stage accumulates the preparatory domain knowledge of the infarct segmentation task, helping to learn domain-specific knowledge representations to enhance the discriminative ability for pathological asymmetries by constructed contrastive learning task. Then, formal learning stage efficiently performs end-to-end training guided by learned knowledge representations, in which the designed feature compensation module (FCM) can leverage the anatomy similarity between adjacent slices from the volumetric medical image to help aggregate rich anatomical context information. Finally, examination improvement stage encourages improving the infarct prediction from the previous stage, where the proposed perception refinement strategy (RPRS) further exploits the bilateral difference comparison to correct the mis-segmentation infarct regions by adaptively regional shrink and expansion. Extensive experiments on public and in-house NCCT datasets demonstrated the superiority of the proposed PAPL, which is promising to help better stroke evaluation and treatment.

Value of Absolute Eosinophil Count in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

Background and Aims: Elevated eosinophils typically indicate hypersensitive inflammation; however, their involvement in cardiovascular events remains incompletely understood. We investigated the association between the absolute eosinophil count (AEC) and major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Additionally, we determine whether the integration of AEC with the SYNTAX II score could improve predictive ability. Methods and Results: The AECs of 1711 patients with ACS undergoing PCI from June 2016 to November 2017 were analyzed on admission. All recruitments were splitted into three groups based on AEC tertiles and 101 participants underwent one or more noteworthy outcomings. The association between AEC and MACCEs (defined as a composite of cardiovascular death, myocardial infarction [MI], and stroke) was tested by Cox proportional-hazards regression analysis. After adjusting for confounders, AEC was independently associated with MACCEs (HR 11.555, 95% CI: 3.318-40.239). Patients in the lowest AEC tertile (T1) as a reference, those in the higher tertiles had an incrementally higher risk of MACCEs (T3: HR 1.848 95% CI: 1.157-2.952; P for trend=0.008). Inclusion of AEC enhanced the predictive accuracy of the SYNTAX II score for MACCEs (AUC: from 0.701 [95% CI: 0.646-0.756] to 0.728 [95% CI: 0.677-0.780]; DeLong's test, P = 0.020). Conclusion: AEC is independently linked to MACCEs in ACS patients who underwent PCI, and adds incremental predictive information to the SYNTAX II score.

Acidification Offset Warming-Induced Increase in N2O Production in Estuarine and Coastal Sediments.

Global warming and acidification, induced by a substantial increase in anthropogenic CO2 emissions, are expected to have profound impacts on biogeochemical cycles. However, underlying mechanisms of nitrous oxide (N2O) production in estuarine and coastal sediments remain rarely constrained under warming and acidification. Here, the responses of sediment N2O production pathways to warming and acidification were examined using a series of anoxic incubation experiments. Denitrification and N2O production were largely stimulated by the warming, while N2O production decreased under the acidification as well as the denitrification rate and electron transfer efficiency. Compared to warming alone, the combination of warming and acidification decreased N2O production by 26 ± 4%, which was mainly attributed to the decline of the N2O yield by fungal denitrification. Fungal denitrification was mainly responsible for N2O production under the warming condition, while bacterial denitrification predominated N2O production under the acidification condition. The reduced site preference of N2O under acidification reflects that the dominant pathways of N2O production were likely shifted from fungal to bacterial denitrification. In addition, acidification decreased the diversity and abundance of nirS-type denitrifiers, which were the keystone taxa mediating the low N2O production. Collectively, acidification can decrease sediment N2O yield through shifting the responsible production pathways, partly counteracting the warming-induced increase in N2O emissions, further reducing the positive climate warming feedback loop.

Evolution pattern estimated by computed tomography perfusion post-thrombectomy predicts outcome in acute ischemic stroke.

OBJECTIVES: Computed tomography perfusion (CTP) and computed tomography angiography (CTA) have been recommended to select acute ischemic stroke (AIS) patients for endovascular thrombectomy (EVT) but are not widely used for post-treatment evaluation. We aimed to observe abnormalities in CTP and CTA before and after EVT and evaluate post-EVT CTP and CTA as potential tools for improving clinical outcome prediction. METHODS: Patients with AIS who underwent EVT and received CTP and CTA before and after EVT were retrospectively evaluated. The ischemic core was defined as the volume of relative cerebral blood flow <30% and hypoperfusion as the volume of Tmax >6 s. A reduction in hypoperfusion volume >90% between baseline and post-EVT CTP was defined as tissue optimal reperfusion (TOR). The 90-day modified Rankin scale was used to evaluate the clinical outcome. RESULTS: Eighty-three patients were included. Patients with an absent ischemic core or with TOR after EVT had a higher rate of modified Thrombolysis in Cerebral Ischemia score 2c-3 and recanalization of post-treatment vessel condition based on follow-up CTA. Multivariable logistic regression revealed that the baseline ischemic core volume (OR:0.934, p=0.009), TOR (OR:8.322, p=0.029) and immediate NIHSS score after EVT (OR:0.761, p=0.012) were factors significantly associated with good clinical outcome. Combining baseline ischemic core volume and TOR with immediate NIHSS score after EVT showed greatest performance for good outcome prediction after EVT(AUC=0.921). CONCLUSIONS: The addition of pretreatment and post-treatment CTP information to purely clinical NIHSS scores might help to improve the efficacy for good outcome prediction after EVT.

Comparison of percutaneous coronary intervention of native coronary artery versus bypass graft in patients with prior coronary artery bypass grafting.

Background: Large number of patients with prior coronary artery bypass grafting (CABG) need repeat revascularization yearly, and percutaneous coronary intervention (PCI) is the optimal treatment strategy for such patients. However, it is still controversial whether PCI of native coronary artery or bypass graft is more beneficial. The aim of the study was to compare the clinical outcomes between native coronary artery vs. bypass graft PCI in patients with prior CABG. Methods: A total of 1,276 patients with prior CABG who underwent index PCI of native coronary artery (n=1,072) or bypass graft (n=204) were retrospectively examined. Patients were divided into native group and graft group according to the target vessel. The outcomes of the two groups were compared by using inverse probability of treatment weighting (IPTW) and Cox regression analysis. The primary endpoint was the composite of major adverse cardiac and cerebrovascular events (MACCEs), which included all-cause death, non-fatal stroke, non-fatal myocardial infarction (MI), or target vessel revascularization (TVR). Results: Compared with native group, patients in graft group had higher risk of slow-flow/no-reflow phenomenon (1.5% vs. 0.1%, P=0.011 before IPTW, and 2.2% vs. 0.1%, P<0.001 after IPTW) and peri-procedural stroke (0.3% vs. 0, P=0.021 after IPTW). During a median follow-up period of 43 months, there was similar risk of MACCE between two groups. Notably, patients in graft group had a significantly higher incidence of non-fatal MI compared with native group regardless with or without IPTW (7.8% vs. 3.8%, P=0.018 and 8.3% vs. 3.9%, P=0.030, separately). After adjusting for confounding by using Cox regression, bypass graft PCI was associated with a higher risk of non-fatal MI (HR: 2.091, 95% CI: 1.069-4.089; P=0.031), but similar results in MACCE (HR: 1.077, 95% CI: 0.817-1.419; P=0.599) compared with native group. Conclusions: This study found that native coronary artery might be preferred for PCI in patients with prior CABG because of lower rates of slow-flow/no-reflow, peri-procedural stroke, and non-fatal MI at follow-up.

Effects of microplastics on denitrification and associated N2O emission in estuarine and coastal sediments: insights from interactions between sulfate reducers and denitrifiers.

Global estuarine and coastal zones are facing severe microplastics (MPs) pollution. Sulfate reducers (SRB) and denitrifiers (DNB) are two key functional microorganisms in these zones, exhibiting intricate interactions. However, whether and how MPs modulate the interactions between SRB and DNB, with implications for denitrification and associated N2O emissions, remains poorly understood. Here, we simultaneously investigated the spatial response patterns of SRB-DNB interactions and denitrification and associated N2O emissions to different MPs exposure along an estuarine gradient in the Yangtze Estuary. Spatial responses of denitrification to polyvinyl chloride (PVC) and polyadipate/butylene terephthalate (PBAT) MPs exposure were heterogeneous, while those of N2O emissions were not. Gradient-boosted regression tree and multiple regression model analyses showed that sulfide, followed by nitrate (NO3-), controlled the response patterns of denitrification to MPs exposure. Further mechanistic investigation revealed that exposure to MPs resulted in a competitive and toxic (sulfide accumulation) inhibition of SRB on DNB, ultimately inhibiting denitrification at upstream zones with high sulfide but low NO3- levels. Conversely, MPs exposure induced a competitive inhibition of DNB on SRB, generally promoting denitrification at downstream zones with low sulfide but high NO3- levels. These findings advance the current understanding of the impacts of MPs on nitrogen cycle in estuarine and coastal zones, and provide a novel insight for future studies exploring the response of biogeochemical cycles to MPs in various ecosystems.

Association of human telomerase reverse transcriptase promoter mutation with unfavorable prognosis in glioma: A systematic review and meta-analysis.

Background: Glioma is one of the most malignant and aggressive tumors, with an extremely poor prognosis. Human telomerase reverse transcriptase (hTERT) promoter mutation is regarded as a risk factor in tumor growth. Although the prevalence of hTERT promoter (pTERT) mutation in gliomas has been investigated, the results are inconsistent. This meta-analysis aims to investigate the prognostic value of hTERT in glioma patients and its interaction with other biomarkers. Materials and Methods: We searched 244 citations from four databases: PubMed (2000-2021), Web of Science (2000-2021), Embase (2010-2021), and Cochrane Library (2000-2021) with 28 articles included. Results: We calculated hazard ratios (HRs) using the random effect model and the pooled result suggested that TERT promoter mutation predicted poorer overall survival (HR: 1.53, 95% confidence interval [CI]: 1.34-1.75, P < 0.001, I2: 49.9%, pheterogeneity:0.002) and progression-free survival (HR: 1.55, 95% CI: 1.27-1.88, P < 0.001, I2: 0.0%, pheterogeneity: 0.473). For subgroup analysis, we analyzed multiple factors including iso-citrate dehydrogenase (IDH) genotype, age, diagnosis, pTERT region, so as to locate the sources of heterogeneity. Interestingly, in IDH mutant subgroup, pTERT mutation became a beneficial prognostic factor (HR: 0.73, 95% CI: 0.57-0.93, I2: 22.3%, pheterogeneity: 0.277), which is contrary to the results in pooled analysis. Conclusion: In general, pTERT mutation may result in shorter survival time in glioma patients, but longer survival time when glioma patients are combined with IDH mutation.

Mortality of Escalation and Modulation Antithrombotic Therapy in Coronary Artery Disease Patients: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: The net clinical benefit of antithrombotic therapy (ATT) reflects the concomitant effects of bleeding and ischemic events. OBJECTIVES: We sought to assess the overall effect of the modulation or escalation of ATT on all-cause mortality as well as ischemic and bleeding events. METHODS: We performed a meta-analysis of randomized controlled trials comparing escalation or modulation of ATT versus standard ATT in patients with coronary artery disease. A total of 32 studies with 160,659 subjects were enrolled in this analysis. RESULTS: Neither escalation nor modulation of ATT has significant effect on all-cause mortality (escalation: relative risk [RR]: 0.94, 95% confidence interval [CI]: 0.85-1.04; modulation: RR: 0.90; 95% CI: 0.81-1.01). Compared with standard ATT therapy, escalation of ATT was associated with lower risk of myocardial infarction (MI; RR: 0.84, 95% CI: 0.76-0.94), but had a higher risk of major or minor bleeding (RR: 1.38, 95% CI: 1.15-1.66). Modulation of ATT was associated with a similar risk of MI (RR: 1.07, 95% CI: 0.96-1.19), but a reduced risk for major or minor bleeding (RR: 0.58, 95% CI: 0.51-0.66). Meta-regression combining both escalation and modulation studies found that the heterogeneity of all-cause mortality was mainly attributed to the heterogeneity of major or minor bleeding (adjusted R-squared = 100.00%, p = 0.004), but not to MI. CONCLUSION: Either escalation or modulation of ATT has little benefit in all-cause mortality. The variability of the treatment effects on all-cause mortality was mainly attributed to the variability of major or minor bleeding, but not to MI.

Efficacy and Safety of Direct Oral Anticoagulants in the Treatment of Left Ventricular Thrombus After Acute Anterior Myocardial Infarction in Patients Who Underwent Percutaneous Coronary Intervention.

AIMS: To explore treatment with Direct Oral Anticoagulants (DOACs) in left ventricular thrombus (LVT) after ST-segment elevation myocardial infarction (STEMI) in patients who underwent percutaneous coronary intervention (PCI). BACKGROUND: Contemporary data regarding using DOACs for LVT after STEMI patients who underwent PCI is limited. OBJECTIVES: To investigate the efficacy and safety of DOACs on the treatment of LVT post STEMI and PCI. METHODS: This retrospective study enrolled patients with LVT post STEMI and PCI within 1month from onset who received warfarin or DOACs at discharge. The primary endpoint was LVT resolution. Secondary endpoints were major adverse cardiovascular events (MACEs), including death, stroke, systemic embolism (SE), myocardial infarction (MI) and major or minor bleeding. RESULTS: A total of 128 consecutive patients were recruited, of which 72 received warfarin and 56 DOACs [48 on rivaroxaban and 8 on dabigatran]. The rate of LVT resolution was higher within 1 month in the DOACs group than warfarin (26.8% vs. 11.1%; p = 0.022) (Kaplan-Meier estimates, p = 0.002). No significant differences were found at 3 months (p = 0.246), 6 months (p = 0.201), 9 months (p = 0.171) and 12 months (p = 0.442). No patients treated with DOACs had major bleeding, while two patients with warfarin had upper gastrointestinal bleeding (0 vs. 2 (2.8%); p = 0.209). No death or SE occurred. No significant differences on secondary endpoints were found in both the groups, including stroke, MI, minor bleeding and all bleeding events. CONCLUSION: DOACs appear to be a suitable alternative to warfarin for the management of LVT post STEMI, especially in patients who are intolerant to warfarin.

Prognostic significance of multiple triglycerides-derived metabolic indices in patients with acute coronary syndrome.

BACKGROUND: Triglyceride (TG) and its related metabolic indices, all recognized as surrogates of insulin resistance, have been demonstrated to be relevant to clinical prognosis. However, the relative value of these TG-related indices for predicting cardiovascular events among patients with acute coronary syndrome (ACS) has not been examined. METHODS: The TG, the triglyceride-glucose (TyG) index, the atherogenic index of plasma, TG to high-density lipoprotein cholesterol ratio, and the lipoprotein combine index were assessed in 1694 ACS patients undergoing percutaneous coronary intervention. The primary endpoint was major adverse cardiovascular event (MACE), which was the composite of all-cause mortality, stroke, myocardial infarction, or unplanned repeat revascularization. RESULTS: During a median follow-up of 31 months, 345 patients (20.4%) had MACE. The risk of the MACE was increased with higher TG and the four TG-derived metabolic indices [TG-adjusted hazard ratio (HR) = 1.002, 95% CI: 1.001-1.003; TyG index-adjusted HR = 1.736, 95% CI: 1.398-2.156; atherogenic index of plasma-adjusted HR = 2.513, 95% CI: 1.562-4.043; TG to high-density lipoprotein cholesterol ratio-adjusted HR = 1.148, 95% CI: 1.048-1.258; and lipoprotein combine index-adjusted HR = 1.009, 95% CI: 1.004-1.014; P < 0.001 for all indices]. TG and all the four indices significantly improved the predictive ability for MACE in addition to the baseline model. Among them, TyG index showed the best ability for predicting MACE compared with the other three indices from all the three measurements ( P < 0.05 for all comparison). CONCLUSIONS: TG and TG-derived metabolic indices were all strongly associated with MACE among ACS patients undergoing percutaneous coronary intervention. Among all the indices, TyG index showed the best ability to predict the risk of MACE.

Prognostic Impact of Multiple Lymphocyte-Based Inflammatory Indices in Acute Coronary Syndrome Patients.

Background: The aim of this study was to evaluate the prognostic values of five lymphocyte-based inflammatory indices (platelet-lymphocyte ratio [PLR], neutrophil-lymphocyte ratio [NLR], monocyte-lymphocyte ratio [MLR], systemic immune inflammation index [SII], and system inflammation response index [SIRI]) in patients with acute coronary syndrome (ACS). Methods: A total of 1,701 ACS patients who underwent percutaneous coronary intervention (PCI) were included in this study and followed up for major adverse cardiovascular events (MACE) including all-cause death, non-fatal ischemic stroke, and non-fatal myocardial infarction. The five indices were stratified by the optimal cutoff value for comparison. The association between each of the lymphocyte-based inflammatory indices and MACE was assessed by the Cox proportional hazards regression analysis. Results: During the median follow-up of 30 months, 107 (6.3%) MACE were identified. The multivariate COX analysis showed that all five indices were independent predictors of MACE, and SIRI seemingly performed best (Hazard ratio [HR]: 3.847; 95% confidence interval [CI]: [2.623-5.641]; p < 0.001; C-statistic: 0.794 [0.731-0.856]). The addition of NLR, MLR, SII, or SIRI to the Global Registry of Acute Coronary Events (GRACE) risk score, especially SIRI (C-statistic: 0.699 [0.646-0.753], p < 0.001; net reclassification improvement [NRI]: 0.311 [0.209-0.407], p < 0.001; integrated discrimination improvement [IDI]: 0.024 [0.010-0.046], p < 0.001), outperformed the GRACE risk score alone in the risk predictive performance. Conclusion: Lymphocyte-based inflammatory indices were significantly and independently associated with MACE in ACS patients who underwent PCI. SIRI seemed to be better than the other four indices in predicting MACE, and the combination of SIRI with the GRACE risk score could predict MACE more accurately.

Elevated Remnant Cholesterol is Associated with Adverse Cardiovascular Outcomes in Patients with Acute Coronary Syndrome.

AIMS: This study aimed to investigate the association of elevated RC levels with adverse cardiovascular outcomes in acute coronary syndrome (ACS) patients with and without diabetes. METHODS: We analyzed data from 1716 patients with ACS undergoing percutaneous coronary intervention. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol. RC ＞75th percentile of the cohort (＞0.79 mmol/L) was defined as abnormally elevated RC. Cox-regression models and Kaplan-Meier analyses were used to assess the relationship between RC ＞0.79 mmol/L and major adverse cardiovascular events (MACE). RESULTS: During a median follow-up of 927 days, a total of 354 patients had at least one event. In the overall population, compared with those with RC ≤ 0.79 mmol/L, patients with RC ＞0.79 mmol/L had a significantly higher risk of MACE after adjustment for potential confounders (hazard ratio: 1.572, 95% confidence interval: 1.251-1.975, P＜0.001). In addition, RC ＞0.79 mmol/L was associated with an increased risk of MACE of 66.7% (P=0.001) and 50.1% (P=0.022) in the diabetic and non-diabetic subgroups (P for interaction=0.073), respectively. The addition of RC significantly improved the predictive ability of baseline models for MACE in diabetic patients (all P＜0.05), but not in non-diabetic patients (all P＞0.05). CONCLUSION: Abnormally elevated RC was significantly associated with worse prognosis in both diabetic and non-diabetic patients with ACS; however, the prognostic value of RC might be superior among diabetic patients.

Monoterpenoid indole alkaloids with potential neuroprotective activities from the stems and leaves of Melodinus cochinchinensis.

A chemical study on the stems and leaves of Melodinus cochinchinensis resulted in the isolation and identification of a new monoterpenoid indole alkaloid, melodicochine A (1), together with seven known monoterpenoid indole alkaloids (2-8). The chemical structure of 1 was elucidated on the basis of extensive spectral data analyses and the known compounds were identified by comparing their experimental spectral data with the reported data in the literature. All isolated indole alkaloids were evaluated for their neuroprotective effects against 6-hydroxydopamine induced cell death in human neuroblastoma SH-SY5Y cells in vitro. Monoterpenoid indole alkaloids 1-8 exhibited notable neuroprotective effects with EC50 values in range of 0.72 ± 0.06 to 17.89 ± 0.16 µM.[Formula: see text].

Association of serum complement C1q with cardiovascular outcomes among patients with acute coronary syndrome undergoing percutaneous coronary intervention.

OBJECTIVE: To determine the association of serum complement C1q levels with cardiovascular outcomes among patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), and evaluate the value of C1q modified by high-sensitivity C-reactive protein (hs-CRP) levels as an independent predictor. METHODS: As a single-center prospective observational study, we analyzed 1701 patients who had received primary or elective PCI for ACS at Beijing Anzhen Hospital, Capital Medical University, Beijing, China between June 1, 2016 and November 30, 2017. The associations of C1q modified by hs-CRP with major adverse cardiovascular events (MACE) were determined in survival analysis. RESULTS: Patients with the lowest C1q tertile had the highest cumulative risk of MACE (log-rank P = 0.007). In fully adjusted Cox regression models, stratifying the total population according to hs-CRP dichotomy, C1q was significantly associated with MACE in patients with hs-CRP levels less than 2 mg/L but not in those with 2 mg/L or more (P interaction = 0.02). In patients with hs-CRP levels less than 2 mg/L, with the lowest C1q tertile as reference, the risk of MACE was reduced by 40.0% in the middle C1q tertile [hazard ratio (HR) = 0.600, 95% CI: 0.423-0.852, P = 0.004] and by 43.9% in the highest C1q tertile (HR = 0.561, 95% CI: 0.375-0.840, P = 0.005). CONCLUSIONS: Serum complement C1q is significantly associated with cardiovascular outcomes in patients with ACS undergoing PCI, only when hs-CRP levels are less than 2 mg/L. This finding implicates the usefulness of C1q for the risk stratification in ACS patients with reduced systemic inflammation.

Pathogenicity of Seneca Valley virus in pigs and detection in Culicoides from an infected pig farm.

BACKGROUND: Porcine vesicular disease is caused by the Seneca Valley virus (SVV), it is a novel Picornaviridae, which is prevalent in several countries. However, the pathogenicity of SVV on 5-6 week old pigs and the transmission routes of SVV remain unknown. METHODS: This research mainly focuses on the pathogenicity of the CH-GX-01-2019 strain and the possible vector of SVV. In this study, 5-6 week old pigs infected with SVV (CH-GX-01-2019) and its clinical symptoms (including rectal temperatures and other clinical symptoms) were monitored, qRT-PCR were used to detect the viremia and virus distribution. Neutralization antibody assay was set up during this research. Mosquitoes and Culicoides were collected from pigsties after pigs challenge with SVV, and SVV detection within mosquitoes and Culicoides was done via RT-PCR. RESULTS: The challenged pigs presented with low fevers and mild lethargy on 5-8 days post infection. The viremia lasted more than 14 days. SVV was detected in almost all tissues on the 14th day following the challenge, and it was significantly higher in the hoofs (vesicles) and lymph nodes in comparison with other tissues. Neutralizing antibodies were also detected and could persist for more than 28 days, in addition neutralizing antibody titers ranged from 1:128 to 1:512. Mosquitoes and Culicoides were collected from the pigsty environments following SVV infection. Although SVV was not detected in the mosquitoes, it was present in the Culicoides, however SVV could not be isolated from the positive Culicoides. CONCLUSIONS: Our work has enriched the knowledge relating to SVV pathogenicity and possible transmission routes, which may lay the foundation for further research into the prevention and control of this virus.

GLP-1 and Underlying Beneficial Actions in Alzheimer's Disease, Hypertension, and NASH.

GLP-1 is derived from intestinal L cells, which takes effect through binding to GLP-1R and is inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4). Since its discovery, GLP-1 has emerged as an incretin hormone for its facilitation in insulin release and reduction of insulin resistance (IR). However, GLP-1 possesses broader pharmacological effects including anti-inflammation, neuro-protection, regulating blood pressure (BP), and reducing lipotoxicity. These effects are interconnected to the physiological and pathological processes of Alzheimer's disease (AD), hypertension, and non-alcoholic steatohepatitis (NASH). Currently, the underlying mechanism of these effects is still not fully illustrated and a better understanding of them may help identify promising therapeutic targets of AD, hypertension, and NASH. Therefore, we focus on the biological characteristics of GLP-1, render an overview of the mechanism of GLP-1 effects in diseases, and investigate the potential of GLP-1 analogues for the treatment of related diseases in this review.

Mental Health Multimorbidity among Caregivers of Older Adults During the COVID-19 Epidemic.

OBJECTIVE: To investigate mental health status and associated factors among caregivers of older adults during the COVID-19 epidemic in China. METHODS: From March 1 to 31, 2020, 916 caregivers of older adults participated in an online cross-sectional survey on the prevalence of anxiety, depression, and sleep problems. The seven-item Generalized Anxiety Disorder Scale (GAD-7) was administered to measure anxiety symptoms, the two-item Patient Health Questionnaire (PHQ-2) was used to assess depressive symptoms, and a self-developed questionnaire was used to assess sleep quality and duration. Six questions about COVID-19-related experiences were used to assess community-level infection contact and the level of exposure to media information. The prevalence rates of anxiety, depression and sleep problems were computed. The Wald χ2 were applied to compare the differences between subgroups. Multiple logistic regression analyses were performed to investigate factors associated with anxiety, depression, sleep problems, and multimorbidity. RESULTS: The prevalence rates of anxiety, depression, and sleep problems were 46.8%, 29.8%, and 10.8%, respectively. Approximately 263 participants (28.7%) presented with two or more mental health problems. Being female (OR, 2.254; 95% CI, 1.510-3.363), having community-level COVID-19 contact (OR, 1.856; 95% CI, 1.189-2.898), and having a mental disorder (OR, 3.610; 95% CI, 1.644-7.930) were associated with increased risk of multimorbidity among caregivers. Caregivers who preferred positive information (OR, 0.652; 95% CI, 0.472-0.899) had reduced risk of multimorbidity. CONCLUSION: Anxiety and depression were common among caregivers of older adults during the COVID-19 epidemic. Being female and having community-level COVID-19 contact were independent risk factors for experiencing multiple mental health problems. Preexisting mental disorders increased the risk of multimorbidity among caregivers, while enhanced access to positive media information decreased the risk of multimorbidity.

Adjustment of the GRACE Risk Score by Monocyte to High-Density Lipoprotein Ratio Improves Prediction of Adverse Cardiovascular Outcomes in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

BACKGROUND AND AIMS: The monocyte to high-density lipoprotein cholesterol ratio (MHR), a novel marker for inflammation and lipid metabolism, has been demonstrated to be associated with poor prognosis in many patient populations. However, the prognostic influence of MHR in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) is poorly understood. Here, we sought to investigate the relationship between MHR and adverse cardiovascular (CV) outcomes in such patients and determine whether MHR could improve the GRACE risk score based prognostic models. METHODS AND RESULTS: MHR was applied to 1,720 patients with ACS undergoing PCI who were admitted to our CV center from June 2016 to November 2017. These patients were stratified into three groups according to MHR tertiles. The relationship between MHR and the primary endpoint (overall death, non-fatal stroke, non-fatal myocardial infarction, or unplanned repeat revascularization) was examined by Cox proportional hazards regression analysis. During a median follow-up of 31 months, 353 patients had at least one primary endpoint event. Compared with those in the lowest MHR tertile, patients in the middle and highest tertiles [adjusted HR: 1.541 (95% CI: 1.152-2.060) and 1.800 (95%CI: 1.333-2.432), respectively], had a higher risk of the primary endpoint. The addition of MHR has an incremental effect on the predictive ability of the GRACE risk score for the primary endpoint (cNRI: 0.136, P < 0.001; IDI: 0.006, P < 0.001). CONCLUSION: MHR was independently and significantly associated with adverse CV outcomes in ACS patients who underwent PCI and improved the predictive ability of the GRACE risk score based prognostic models. REGISTRATION NUMBER: http://www.chictr.org.cn/hvshowproject.aspx?id=21397; ChiCTR1800017417.

Nutritional Risk Index Improves the GRACE Score Prediction of Clinical Outcomes in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

Background: Malnutrition has been shown to be associated with adverse cardiovascular outcomes in many patient populations. Aims: To investigate the prognostic significance of malnutrition as defined by nutritional risk index (NRI) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) and whether NRI could improve the GRACE score based prognostic models. Methods: This study applied NRI among 1,718 patients with ACS undergoing PCI. Patients were divided into three nutritional risk groups according to their baseline NRI: no nutritional risk (NRI ≥ 100), mild nutritional risk (97.5 ≤ NRI <100), and moderate-to-severe nutritional risk (NRI <97.5). The primary endpoint was the composite of major adverse cardiovascular events (MACE), including all-cause death, non-fatal stroke, non-fatal myocardial infarction, or unplanned repeat revascularization. Results: During a median follow-up of 927 days, 354 patients developed MACE. In the overall population, compared with normal nutritional status, malnutrition was associated with increased risk for MACE [adjusted HR for mild and moderate-to-severe nutritional risk, respectively: 1.368 (95%CI 1.004-1.871) and 1.473 (95%CI 1.064-2.041)], and NRI significantly improved the predictive ability of the GRACE score for MACE (cNRI: 0.070, P = 0.010; IDI: 0.005, P < 0.001). In the diabetes subgroup, malnutrition was associated with nearly 2-fold high adjusted risk of MACE, and the GRACE score combined with NRI appeared to have better predictive ability than that in the overall population. Conclusion: Malnutrition as defined by NRI was independently associated with MACE in ACS patients who underwent PCI, especially in individuals with diabetes, and improved the predictive ability of the GRACE score based prognostic models.