Sex differences in the correlation between white matter hyperintensity and 3-month outcome in acute stroke patients.

Background: The severity of white matter hyperintensities (WMH) has been shown to be an independent predictor of poor stroke outcome, but the effect of sex on this correlation has not been investigated further. Therefore, the purpose of our study was to assess whether there was a sex difference between the severity of WMH and poor stroke outcome. Methods: This retrospective study included 449 patients with acute ischemic stroke (AIS) who received intravenous thrombolysis. WMH severity was graded based on the Fazekas scale. The association between WMH severity and stroke outcome was explored through multivariable regression analyses in men and women. Results: Among women, when dividing WMH severity into tertiles, T3 (Fazekas scale >3) had a 5.334 times higher risk for unfavorable outcomes than T1 (Fazekas scale <2) (p-trend = 0.026) in the adjusted model. In addition, moderate-severe WMH (Fazekas scale 3-6) had a 3.391 (1.151-9.991) times higher risk than none-mild WMH (Fazekas scale 0-2) (p = 0.027). Conclusions: The risk of unfavorable outcomes increased proportionally with the enlargement of the WMH severity in females, suggesting the sex-specific value of the WMH severity in optimizing the risk stratification of stroke.

The Therapeutic Target of IBD and the Mechanism of Dipyridamole in Treating IBD Explored by Geo Gene Chips, Network Pharmacology, and Molecular Docking.

BACKGROUND AND AIMS: Inflammatory Bowel Disease (IBD) is a refractory disease with repeated attacks, and there is no accurate treatment target at present. Dipyridamole, a phosphodiesterase (PDE) inhibitor, has been proven to be an effective treatment for IBD in a pilot study. This study explored the therapeutic target of IBD and the pharmacological mechanism of dipyridamole for the treatment of IBD. MATERIALS AND METHODS: The candidate targets of dipyridamole were obtained by searching the pharmMapper online server and Swiss Target Prediction Database. The IBD-related targets were selected from four GEO chips and three databases, including Genecards, DisGeNET, and TTD database. A protein-protein interaction (PPI) network was constructed, and the core targets were identified according to the topological structure. KEGG and GO enrichment analysis and BioGPS location were performed. Finally, molecular docking was used to verify dipyridamole and the hub targets. RESULTS: We obtained 112 up-regulated genes and 157 down-regulated genes, as well as 105 composite targets of Dipyridamole-IBD. Through the PPI network analysis, we obtained the 7 hub targets, including SRC, EGFR, MAPK1, MAPK14, MAPK8, PTPN11, and LCK. The BioGPS showed that these genes were highly expressed in the immune system, digestive system, and endocrine system. In addition, the 7 hub targets had good intermolecular interactions with dipyridamole. The therapeutic effect of dipyridamole on IBD may involve immune system activation and regulation of inflammatory reactions involved in the regulation of extracellular matrix, perinuclear region of cytoplasm, protein kinase binding, and positive regulation of programmed cell death through cancer pathway (proteoglycans in cancer), lipid metabolism, Ras signaling pathway, MAPK signaling pathway, PI3K-AKT signaling pathway, Th17 cell differentiation, and other cellular and innate immune signaling pathways. CONCLUSION: This study predicted the therapeutic target of IBD and the molecular mechanism of dipyridamole in treating IBD, providing a new direction for the treatment of IBD and a theoretical basis for further research.

Predictive value of neutrophil to apolipoprotein A1 ratio in patients with acute ischaemic stroke.

The neutrophil to apolipoprotein A1 ratio has emerged as a possible prognostic biomarker in different medical conditions. Nonetheless, the predictive potential of neutrophil to apolipoprotein A1 ratio in determining the 3-month prognosis of acute ischaemic stroke patients who undergo intravenous thrombolysis has yet to be fully acknowledged. In this study, 196 acute ischaemic stroke patients with recombinant tissue plasminogen activator and 133 healthy controls were included. Meanwhile, we incorporated a total of 386 non-thrombolytic acute ischaemic stroke patients. The acute ischaemic stroke patients with recombinant tissue plasminogen activator were divided into four groups based on quartiles of neutrophil to apolipoprotein A1 ratio. The association between neutrophil to apolipoprotein A1 ratio and the 3-month prognosis was evaluated through univariate and multivariate regression analyses. Additionally, subgroup analyses were conducted to investigate the predictive value of neutrophil to apolipoprotein A1 ratio in different patient populations. Adverse outcomes were defined as a modified Rankin Scale score of 3-6. The study findings revealed a significant association between elevated neutrophil to apolipoprotein A1 ratio levels and poor prognosis in acute ischaemic stroke patients. In the highest quartile of neutrophil to apolipoprotein A1 ratio levels (Q4), after controlling for age, gender, admission National Institutes of Health Stroke Scale score, blood urea nitrogen and stroke subtypes, the odds ratio for adverse outcomes at 3 months was 13.314 (95% confidence interval: 2.878-61.596, P = 0.001). An elevated neutrophil to apolipoprotein A1 ratio value was found to be associated with a poor prognosis in acute ischaemic stroke patients, regardless of whether they received recombinant tissue plasminogen activator treatment or not. The new model, which incorporating neutrophil to apolipoprotein A1 ratio into the conventional model, demonstrated a statistically significant improvement in discriminatory power and risk reclassification for 3-month poor outcomes in acute ischaemic stroke patients treated with recombinant tissue plasminogen activator. The new model exhibited a categorical net reclassification index (P = 0.035) of 12.9% and an integrated discrimination improvement (P = 0.013) of 5.2%. Subgroup analyses indicated that the predictive value of neutrophil to apolipoprotein A1 ratio differed across stroke subtypes. Neutrophil to apolipoprotein A1 ratio is a potential biomarker for predicting the prognosis of acute ischaemic stroke patients. The clinical implications of our findings are significant, as early identification and intervention in high-risk patients can improve their outcomes. However, further studies are required to validate our results and elucidate the underlying mechanisms of the association between neutrophil to apolipoprotein A1 ratio and poor prognosis in acute ischaemic stroke patients.

Towards low carbon demand and highly efficient nutrient removal: Establishing denitrifying phosphorus removal in anaerobic/anoxic/oxic + nitrification system.

A two-sludge anaerobic/anoxic/oxic + nitrification system with simultaneous nitrogen and phosphorus removal was studied for enhanced low-strength wastewater treatment. After 158 days of operation, excellent NH4+-N, chemical oxygen demand (COD) and PO43--P removal (99.0 %, 90.0 % and 92.0 %, respectively) were attained under a low carbon/nitrogen ratio of 5, resulting in effluent NH4+-N, COD and PO43--P concentrations of 0.3, 30.0 and 0.5 mg/L, respectively. The results demonstrate that the anaerobic/anoxic/oxic sequencing batch reactor (A2-SBR) and nitrification sequencing batch reactor (N-SBR) had favorable denitrifying phosphorus removal and nitrification performance, respectively. High-throughput sequencing results indicate that the phosphate-accumulating organisms Dechloromonas (1.1 %) and Tetrasphaera (1.2 %) were enriched in the A2-SBR, while the ammonia-oxidizing bacteria Nitrosomonas (7.8 %) and the nitrite-oxidizing bacteria Nitrospira (18.1 %) showed excellent accumulation in the N-SBR. Further analysis via functional prediction revealed that denitrification is the primary pathway of nitrogen metabolism throughout the system. Overall, the system achieved low carbon and high efficiency nutrient removal.

Is There an Association Between Parkinson's Disease and Periodontitis? A Systematic Review and Meta-Analysis.

BACKGROUND: Multiple observational studies have yielded controversial results regarding the association between Parkinson's disease (PD) and periodontitis. OBJECTIVE: This systematic review and meta-analysis was conducted to ascertain their bidirectional relationship. METHODS: A literature search for relevant studies was performed in PubMed, EMBASE, the Cochrane Library, and Web of Science databases from inception to December 19, 2022. Effect sizes (ES) with 95% confidence intervals were pooled under the random-effects model. Then, leave-one-out sensitivity analysis and contour-enhanced funnel plot were applied to assess the stability of the results. RESULTS: A total of 34 studies and 24 studies were included for systematic review and quantitative meta-analysis, respectively. Pooled ES indicated that periodontitis was not significantly associated with PD risk (HR = 1.13, 95% CI 0.88-1.45, n = 3; OR = 1.94, 95% CI 0.55-6.90, n = 7), while the Mendelian randomization study revealed no association between PD and periodontitis risk (coefficient [B] = -0.0001, standard error = 0.0001, p = 0.19). Furthermore, PD patients exhibited higher levels of periodontal pocket depth (SMD = 1.10, 95% CI 0.53-1.67), clinical attachment level (SMD = 1.40, 95% CI 0.55-2.26), plaque index (SMD = 0.81, 95% CI 0.22-1.39), and Oral Health Impact Profile-14 score (SMD = 0.91, 95% CI 0.33-1.49) compared to healthy controls. CONCLUSIONS: Our meta-analysis identified no bidirectional association between PD risk and periodontitis risk, though the prevalence of periodontitis and poorer oral status was higher in PD patients.

Initial dosage optimisation of cyclosporine in Chinese paediatric patients undergoing allogeneic haematopoietic stem cell transplantation based on population pharmacokinetics: a retrospective study.

OBJECTIVE: Improved understanding of cyclosporine A (CsA) pharmacokinetics in children undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT) is crucial for effective prevention of acute graft-versus-host disease and medication safety. The aim of this study was to establish a population pharmacokinetic (Pop-PK) model that could be used for individualised therapy to paediatric patients undergoing allo-HSCT in China. DESIGN, SETTING AND PARTICIPANTS: A retrospective analysis of 251 paediatric HSCT patients who received CsA intravenously in the early post transplantation period at Women and Children's Medical Center in Guangzhou was conducted. ANALYSIS MEASURES: The model building dataset from 176 children was used to develop and analyse the CsA Pop-Pk model by using the nonlinear mixed effect model method. The basic information was collected by the electronic medical record system. Genotype was analysed by matrix-assisted time-of-flight mass spectrometry. The stability and predictability of the final model were verified internally, and a validation dataset of 75 children was used for external validation. Monte Carlo simulation is used to adjust and optimise the initial dose of CsA in paediatric allo-HSCT patients. RESULTS: The typical values for clearance (CL) and volume of distribution ([Formula: see text]) were 14.47 L/hour and 2033.53 L, respectively. The body weight and haematocrit were identified as significant variables for V, while only body weight had an impact on CL. The simulation based on the final model suggests that paediatrics with HSCT required an appropriate intravenous dose of 5 mg/kg/day to reach the therapeutic trough concentration. CONCLUSIONS: The CsA Pop-PK model established in this study can quantitatively describe the factors influencing pharmacokinetic parameters and precisely predict the intrinsic exposure to CsA in children. In addition, our dosage simulation results can provide evidence for the personalised medications TRIAL REGISTRATION NUMBER: ChiCTR2000040561.

Elevated Albumin to Globulin Ratio on Day 7 is Associated with Improved Function Outcomes in Acute Ischemic Stroke Patients with Intravenous Thrombolysis.

Background and Purpose: Albumin to globulin ratio (A/G) has been established as a representative biomarker for assessing inflammation and nutritional status. However, the prognostic value of A/G has rarely been reported in acute ischemic stroke (AIS) patients with intravenous thrombolysis (IVT). Methods: A total of 311 AIS patients who had undergone IVT and completed 3-month follow-up were retrospectively recruited in this study. Albumin (Alb), globulin (Glb) and A/G on admission, within 24 hours after IVT and on day 7 were recorded. Poor outcome was defined as death or major disability (modified Rankin Scale, 3-6) at 3 months. Results: Among the 311 cases, 260 patients had admission blood samples, 296 cases had blood samples within 24 hours after IVT and 126 cases had blood samples on day 7. The patients with and without available blood samples were well-balanced. During the first 24 h, we observed A/G to increase significantly compared with baseline whereas at day 7 it was almost back to baseline in patients with a poor outcome. Receiver operating characteristic (ROC) curves analysis showed that A/G had a better performance in discriminating patients at high risk and low risk of a poor outcome than either Alb or Glb alone and carried the highest predictive ability on day 7 (AUC = 0.807). Lower 7-day A/G was independently associated with a poor outcome (per-SD increase, OR = 0.182, 95% CI: 0.074-0.446). Conclusion: A/G is an important prognostic indicator for AIS outcomes and merits dynamic monitoring.

Predictive Value of Globulin to Prealbumin Ratio for 3-Month Functional Outcomes in Acute Ischemic Stroke Patients.

Objective: We aimed to evaluate and compare the association between globulin to albumin ratio (GAR) and globulin to prealbumin ratio (GPR) and 3-month functional prognosis of acute ischemic stroke (AIS) patients receiving intravenous thrombolysis therapy. Methods: 234 AIS patients undergoing intravenous thrombolysis were retrospectively enrolled with acute ischemic stroke from February 2016 to October 2019. Blood sample was collected within 24 h after admission. Poor outcome was defined as the modified Rankin Scale (mRS) ≥ 3 and a favorable outcome as mRS < 3. Severe stroke was defined as the National Institutes of Health Stroke Scale (NIHSS) score > 10 on admission. Student's t-test, Mann-Whitney U test, Chi-square test, logistics' regression analysis, and receiver operating characteristic (ROC) analysis were performed. Results: Patients with poor functional outcome had higher GAR and GPR levels compared with favorable functional group (p = 0.001, p < 0.001, respectively). Severe stroke was also associated with these two increasing variables. After adjustment for confounding factors, multivariate logistic regression analysis indicated that GPR was an independent indicator predictor of AIS. Conclusions: The 24 h GPR level can predict the 3-month functional outcome in AIS patients accepting recombinant tissue plasminogen activator (r-tPA) intravenous thrombosis.

Dynamic Neutrophil-Lymphocyte Ratios Predict Short-term Prognostic Outcome of Thrombolysis in Patients with Acute Ischemic Stroke.

AIM: The main purpose of this study was to investigate the dynamic changes of neutrophils-lymphocytes ratios (NLRs) in patients with acute ischemic stroke (AIS) and their relationships with 3-month prognostic outcomes. METHODS: Two hundred ninety-one patients with AIS were included in this study, followed up for 3 months. At admission, 1 and 7 days after recombinant tissue plasminogen activator (r-tPA) injection, blood samples were obtained. Outcome events included excellent outcome, good outcome, and death defined as modified Rankin Scale (mRS) scores of 0-1, 0-2, and 6 respectively. RESULTS: NLRs measured in admission and 7 days after r-tPA treatment were associated with prognosis outcome after 3 months. Twenty-four-hour NLR is an excellent indicator in forecasting (excellent outcome's the areas under the curve (AUC) = 0.725; good outcome AUC = 0.742; death AUC = 0.759). In addition, we were surprised to find that dynamic increase in NLR within 24 h is significantly related to excellent and good outcomes. CONCLUSIONS: Twenty-four-hour NLR is related to the severity of AIS and poor prognosis, which can help early risk stratification. SIGNIFICANCE: We can predict the prognosis of AIS more accurately. Compared with previous studies, our study has shown the dynamic changes of NLR and its relationship with NIHSS and multiple prognostic.

Systemic Immune-Inflammation Index Predicts 3-Month Functional Outcome in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis.

BACKGROUND AND PURPOSE: Systemic immune-inflammation index (SII), a novel inflammation index derived from counts of circulating platelets, neutrophils and lymphocytes, has been studied in developing incident cancer. However, the clinical value of SII in acute ischemic stroke (AIS) patients had not been further investigated. Therefore, we aimed to explore the association between SII and severity of stroke as well as 3-month outcome of AIS patients. METHODS: A total of 216 AIS patients receiving intravenous thrombolysis (IVT) and 875 healthy controls (HCs) were retrospectively recruited. Blood samples were collected within 24h after admission. Severity of stroke was assessed by the National Institute of Health stroke scale (NIHSS) scores on admission and poor 3-month functional outcome was defined as Modified Rankin Scale (mRS) > 2. RESULTS: SII levels in AIS patients were higher than in HCs. The cut-off value of SII is 545.14×109/L. Patients with SII > 545.14×109/L had higher NIHSS scores (median: 5 vs 9, p < 0.001), a positive correlation between SII and NIHSS was observed (rs = 0.305, p < 0.001). Multivariate logistic regression analyses showed that high SII was one of the independent risk factors for poor prognosis at 3 months of AIS patients (OR = 3.953, 95% CI = 1.702-9.179, p = 0.001). The addition of SII to the conventional prognostic model improved the reclassification (but not discrimination) of the functional outcome (net reclassification index 39.3%, p = 0.007). CONCLUSION: SII is correlated with stroke severity at admission and can be a novel prognostic biomarker for AIS patients treated with IVT.