Single-Centre Experience with Endovascular Therapy in Acute Occlusion of ICAS: Preferred Stent Thrombectomy Versus Preferred Angioplasty.

OBJECTIVES: The preferred endovascular therapy (EVT) for large-vessel occlusion in intracranial atherosclerosis (ICAS) is unknown. We compared the efficacy of preferred stent thrombectomy and preferred angioplasty in patients with acute large-vessel occlusion in ICAS. METHODS: Data from consecutive EVT patients (May 2020 to September 2023) with acute middle cerebral artery occlusion in ICAS were retrospectively analyzed. Preferred angioplasty was performed if there was a preoperative "microcatheter first-pass effect;" otherwise, preferred stent thrombectomy was performed. Analyses were grouped according to the two EVT treatments. Clinical data of all patients, including the time from puncture to recanalization, rate of successful reperfusion, early neurological improvement, intracranial hemorrhage, and modified Rankin Scale score at 90 days, were recorded and analyzed. RESULTS: Six-two patients were enrolled in this study (mean age was 60.66±13.21 y, 22.6% female). The preferred angioplasty group had a higher first-pass recanalization rate than the preferred stent thrombectomy group (61.3% vs. 21.9%, P<0.001) and a higher proportion of patients who were functionally independent (defined as a modified Rankin Scale score of 0 to 3) at 90 days [odds ratio,3.681; 95% confidence interval (CI):1.009 to 13.428; P=0.048]. There was no significant difference between the groups in the time from puncture to recanalization, the frequency of successful reperfusion, and early neurological improvement, or intracranial hemorrhage (P>0.05). CONCLUSIONS: This study suggests that for acute middle cerebral artery occlusion in ICAS, preferred angioplasty may be a safe and effective procedure.

Prediction Model for Postoperative Pressure Injury in Patients with Acute Type A Aortic Dissection.

OBJECTIVE: To establish a risk assessment model to predict postoperative National Pressure Injury Advisory Panel stage 2 or higher pressure injury (PI) risk in patients undergoing acute type A aortic dissection surgery. METHODS: This retrospective assessment included consecutive patients undergoing acute type A aortic dissection surgery in the authors' hospital from September 2017 to June 2021. The authors used LASSO (logistic least absolute shrinkage and selection operator) regression analysis to identify the most relevant variables associated with PI by running cyclic coordinate descent with 10-times cross-validation. The variables selected by LASSO regression analysis were subjected to multivariate logistic analysis. A calibration plot, receiver operating characteristic curve, and decision curve analysis were used to validate the model. RESULTS: There were 469 patients in the study, including 94 (27.5%) with postoperative PI. Ten variables were selected from LASSO regression: body mass index, diabetes, Marfan syndrome, stroke, preoperative skin moisture, hemoglobin, albumin, serum creatinine, platelet, and d-dimer. Four risk factors emerged after multivariate logistic regression: Marfan syndrome, preoperative skin moisture, albumin, and serum creatinine. The area under the receiver operating characteristic curve of the model was 0.765. The calibration plot and the decision curve analysis both suggested that the model was suitable for predicting postoperative PI. CONCLUSIONS: This study built an efficient predictive model that could help identify high-risk patients.

Adverse Childhood Experiences Predict Diurnal Cortisol Throughout Gestation.

OBJECTIVE: Adverse childhood experiences (ACEs) are associated with negative prenatal and perinatal health outcomes and may, via these pathways, have intergenerational effects on child health and development. We examine the impact of ACEs on maternal salivary cortisol, a key measure of prenatal biology previously linked with pregnancy-related health outcomes. METHODS: Leveraging assessments across three trimesters, we used linear mixed-effects models to analyze the influence of ACEs on maternal prenatal diurnal cortisol patterns in a diverse cohort of pregnant women (analytic sample, n = 207). Covariates included comorbid prenatal depression, psychiatric medications, and sociodemographic factors. RESULTS: Maternal ACEs were significantly associated with flatter diurnal cortisol slopes (i.e., less steep decline), after adjusting for covariates, with effects consistent across gestation (estimate = 0.15, standard error = 0.06, p = .008). CONCLUSIONS: ACEs experienced before pregnancy may have a robust and lasting influence on maternal prenatal hypothalamic-pituitary-adrenal activity throughout gestation, a key biological marker associated with perinatal and child health outcomes. The findings suggest one route of intergenerational transmission of early adverse experiences and underscore the potential value of assessing prepregnancy adverse experiences for promoting perinatal and maternal and child health.

Closure line-free anastomosis: a modified end-to-end anastomosis technique.

Anastomotic leakage is a severe complication of colorectal surgery. It usually occurs at two areas at risk of ischemia in the anastomotic configuration. We introduce a method that can remove all of the potentially ischemic areas, which is expected to reduce the incidence of anastomotic leakage.

Prenatal diurnal cortisol: Normative patterns and associations with affective symptoms and stress.

The hypothalamic-pituitary-adrenal (HPA) axis in pregnancy has attracted considerable research attention, in part, because it may be a mechanism by which diverse prenatal exposures alter perinatal and child health outcomes. Symptoms of affective disturbance and stress are among the most-studied prenatal factors associated with HPA axis alterations, but there remains uncertainty about the nature of the association because of the limitations to, and variability in, data collection and analytic approaches. The current study capitalized on a prospective, longitudinal pregnancy cohort that examined salivary diurnal cortisol, collected at 5 time points across the day, at each trimester in a diverse sample of women. Detailed data on affective symptoms and major life events were collected at each trimester, as were data on health behaviors, medication, and socio-demographics. Results indicated modest stability of individual differences in diurnal cortisol across pregnancy, which was evident for diurnal slope (ICC = .20) and measures of total output (area under the curve, ICC = .25); substantial gestation-related increases in total cortisol output across pregnancy was also observed (p < .001). Adjusting for health behaviors, medication, and socio-demographic covariates, elevated levels of depressive symptoms and major life events were significantly (p < .05) associated with a higher morning awakening value and flatter diurnal slope, which was evident across all trimesters. In addition to the normative gestation-related changes in cortisol production, our results demonstrate selective but robust associations between psychological symptoms, stressors, and the HPA axis across gestation, and suggest both methodological and mechanistic strategies for future study.

Remnant Cholesterol and Common Carotid Artery Intima-Media Thickness in Patients With Ischemic Stroke.

BACKGROUND: Remnant cholesterol makes great contribution to residual risk of cardiovascular disease, but population-based evidence on the relationship between remnant cholesterol and atherosclerosis is rare. Common carotid artery intima-media thickness (cIMT) is an imaging marker of subclinical atherosclerosis. We aimed to explore the association between remnant cholesterol levels and cIMT in patients with ischemic stroke. METHODS: One thousand four hundred ninety-six ischemic stroke patients with baseline serum lipids and carotid artery imaging data were included in this analysis. Fasting remnant cholesterol was calculated as total cholesterol minus HDL (high-density lipoprotein) cholesterol minus LDL (low-density lipoprotein) cholesterol. Abnormal cIMT was defined as mean cIMT and maximum cIMT value ≥1 mm. Logistic regression and restricted cubic spline models were used to assess the relationships between remnant cholesterol levels and abnormal cIMT. RESULTS: The multivariable-adjusted odds ratios (95% CIs) for the highest versus lowest quartile of remnant cholesterol were 2.06 (1.46-2.91) for abnormal mean cIMT and 1.70 (1.23-2.35) for abnormal maximum cIMT. There were linear associations between remnant cholesterol levels and both abnormal mean cIMT (P for linearity, <0.001) and abnormal maximum cIMT (P for linearity, 0.003). Moreover, the remnant cholesterol-cIMT association remained significant in the subsample of patients with optimal LDL cholesterol levels (n=179). CONCLUSIONS: Elevated fasting remnant cholesterol levels were positively associated with mean cIMT and maximum cIMT in patients with ischemic stroke, even in patients with optimal LDL cholesterol levels. Future prospective studies are needed to verify our findings and to assess the effect of remnant cholesterol-lowering interventions in patients with ischemic stroke.

A "building block" approach to the new influenza A virus entry inhibitors with reduced cellular toxicities.

Influenza A virus (IAV) is a severe worldwide threat to public health and economic development that results in the emergence of drug-resistant or highly virulent strains. Therefore, it is imperative to develop potent anti-IAV drugs with different modes of action to currently available drugs. Herein, we show a new class of antiviral peptides generated by conjugating two known short antiviral peptides: part-1 (named Jp with the sequence of ARLPR) and part-2 (named Hp with the sequence of KKWK). The new peptides were thus created by hybridization of these two domains at C- and N- termini, respectively. The anti-IAV screening results identified that C20-Jp-Hp was the most potent peptide with IC50 value of 0.53 µM against A/Puerto Rico/8/34 (H1N1) strain. Interestingly, these new peptides display lower toxicities toward mammalian cells and higher therapeutic indices than their prototypes. In addition, the mechanism of action of C20-Jp-Hp was extensively investigated.

A facile and dynamic assay for the detection of peptide aggregation.

We report on a facile method to detect the aggregation and co-aggregation of peptides by tryptophan fluorescence spectroscopy. Peptide aggregates (PAs) play a pivotal role in neurodegenerative diseases, such as Alzheimer's and Parkinson's. The detection of the formation of aggregates, especially in the early stage, will facilitate the diagnosis and treatment of the associated disease. In this study, by choosing a tryptophan-containing peptide of EP2, we investigated its fluorescence spectroscopic characteristics in the process of PAs. The results showed that the intensity of emission spectra was significantly enhanced with the formation of PAs within 48 h. In addition, by employing EP2 as a fluorescence probe, we found that EP2 was able to effectively monitor the aggregation of other peptides/proteins that are otherwise difficult to detect with conventional approach. Thus, these preliminary data provide a promising diagnostic tool to detect the formation of PAs.

Super short membrane-active lipopeptides inhibiting the entry of influenza A virus.

Influenza A viruses (IAV) are significant pathogens that result in millions of human infections and impose a substantial health and economic burdens worldwide. Due to the limited anti-influenza A therapeutics available and the emergence of drug resistant viral strains, it is imperative to develop potent anti-IAV agents with different mode of action. In this study, by applying a pseudovirus based screening approach, two super short membrane-active lipopeptides of C12-KKWK and C12-OOWO were identified as effective anti-IAV agents with IC50 value of 7.30±1.57 and 8.48±0.74 mg/L against A/Puerto Rico/8/34 strain, and 6.14±1.45 and 7.22±0.67 mg/L against A/Aichi/2/68 strain, respectively. The mechanism study indicated that the anti-IAV activity of these peptides would result from the inhibition of virus entry by interacting with HA2 subunit of hemagglutinin (HA). Thus, these peptides may have potentials as lead peptides for the development of new anti-IAV therapeutics to block the entry of virus into host cells.

The protective effects of urocortin1 against intracerebral hemorrhage by activating JNK1/2 and p38 phosphorylation and further increasing VEGF via corticotropin-releasing factor receptor 2.

Urocortin (UCN) has exhibited antiinflammatory and neuroprotective effects on intracerebral hemorrhage (ICH). However, the underlying mechanisms are still not clear. Therefore, this study was aimed to investigate effects of UCN1 on ICH in vitro and in vivo and further explore the possible mechanism. ICH was induced by an infusion of autologous blood into the unilateral striatum of anesthetized male Sprague-Dawley rats. The rats were randomly divided into three groups (8 rats per group): sham ICH control group, ICH saline group and ICH UCN1 group. UCN1 was infused into the lateral ventricle after 1h post-ICH. Neurological deficits were evaluated by modified neurological severity score (mNSS). Brain edema was assessed using the dry/wet method. The neurological cell metabolic activity of N2a and SH-SY5Y was detected by CCK-8. The level of VEGF, JNK and p38 were determined by enzyme-linked immunosorbent assay and western blot. Post-treatment with UCN1 could improve neurological deficits and reduce brain edema. Moreover, UCN1 could increase the metabolic activity of neuron cells dose-dependently and these effects could be abolished by corticotropin-releasing factor receptor 2 (CRFR2) antagonist anti-Svg-30. Furthermore, the level of VEGF, JNK and p38 were up-regulated by post-treatment with UCN1 via CRFR2. The protective effects of UCN1 against ICH are possibly mediated by activating the phosphorylation of JNK and p38 and further increasing the level of VEGF via CRFR2.

Oral fibrinogen-depleting agent lumbrokinase for secondary ischemic stroke prevention: results from a multicenter, randomized, parallel-group and controlled clinical trial.

BACKGROUND: Elevated fibrinogen (Fg) level is a known risk factor for ischemic stroke. There are few clinical trials on oral fibrinogen-depleting therapies for secondary ischemic stroke prevention. We aimed to assess the effects of one-year therapy with oral lumbrokinase enteric-coated capsules on secondary ischemic stroke prevention. METHODS: This is a multicenter, randomized, parallel group and controlled study that began treatment in hospitalized patients with ischemic stroke and continued for 12 months. Patients were randomized to either the control group that received the standard stroke treatment or the fibrinogen-depleting group that received the standard stroke treatment plus enteric-coated lumbrokinase capsules. The NIH Stroke Scale scores (NIHSSs) and plasma Fg level were recorded. The carotid artery intima-media thickness (IMT) and status of plaques were examined through carotid ultrasound examination. Primary outcomes included all-cause mortality, any event of recurrent ischemic stroke/transient ischemic attack (TIA), hemorrhagic stroke, myocardial infarction and angina, and other noncerebral ischemia or hemorrhage. Kaplan-Meier survival analysis and the Long-rank test were used to compare total vascular end point incidence between the two groups. Comparison of median values between two groups was done by the Student t test, one-way analysis of variance (ANOVA), or non-parametric rank sum test. RESULTS: A total of 310 patients were enrolled, 192 patients in the treatment group and 118 patients in the control group. Compared to the control group, the treatment group showed favorable outcomes in the Fg level, carotid IMT, the detection rate of vulnerable plaques, the volume of carotid plaques, NIHSS scores, and incidence of total vascular (6.78% and 2.08%, respectively) and cerebral vascular events (5.93% and 1.04%, respectively) (P < 0.05). In the treatment group, the volume of carotid plaques was significantly related to the carotid IMT, the plaque diameter, width and number (P = 0.000, 0.000, 0.000, 0.022; F = 13.51, 2.52, 11.33, -3.29, but there was a weak correlation with the Fg level (P = 0.056). After 1-year therapy, the incidence of overall vascular end points was reduced by 4.7%. CONCLUSION: Long-term oral fibrinogen-depleting therapy may be beneficial for secondary ischemic stroke prevention.