MS3 Imaging Enables the Simultaneous Analysis of Phospholipid C═C and sn-Position Isomers in Tissues.

Mass spectrometry (MS) imaging of lipids in tissues with high structure specificity is challenging in the effective fragmentation of position-selective structures and the sensitive detection of multiple lipid isomers. Herein, we develop an MS3 imaging method for the simultaneous analysis of phospholipid C═C and sn-position isomers by on-tissue photochemical derivatization, nanospray desorption electrospray ionization (nano-DESI), and a dual-linear ion trap MS system. A novel laser-based sensing probe is developed for the real-time adjustment of the probe-to-surface distance for nano-DESI. This method is validated in mouse brain and kidney sections, showing its capability of sensitive resolving and imaging of the fatty acyl chain composition, the sn-position, and the C═C location of phospholipids in an MS3 scan. MS3 imaging of phospholipids has shown the capability of differentiation of cancerous, fibrosis, and adjacent normal regions in liver cancer tissues.

Ratiometric Fluorescence Aptasensor of Allergen Protein Based on Multivalent Aptamer-Encoded DNA Flowers as Fluorescence Resonance Energy Transfer Platform.

Life-threatening allergic reactions to food allergens, particularly peanut protein Ara h1, are a growing public health concern affecting millions of people worldwide. Thus, accurate and rapid detection is necessary for allergen labeling and dietary guidance and ultimately preventing allergic incidents. Herein, we present a novel ratiometric fluorescence aptasensor based on multivalent aptamer-encoded DNA flowers (Mul-DNFs) for the high-stability and sensitive detection of allergen Ara h1. The flower-shaped Mul-DNFs were spontaneously packaged using ultralong polymeric DNA amplicons driven by a rolling circle amplification reaction, which contains a large number of Ara h1 specific recognition units and has excellent binding properties. Furthermore, dual-color fluorescence-labeled Mul-DNFs probes were developed by hybridizing them with Cy3- and Cy5-labeled complementary DNA (cDNA) to serve as a ratiometric fluorescence aptasensor platform based on fluorescence resonance energy transfer. Benefiting from the combined merits of the extraordinary synergistic multivalent binding ability of Mul-DNFs, the excellent specificity of the aptamer, and the sensitivity of the ratiometric sensor to avoid exogenous interference. The developed ratiometric aptasensor showed excellent linearity (0.05-2000 ng mL-1) with a limit of detection of 0.02 ng mL-1. Additionally, the developed ratiometric fluorescence aptasensor was utilized for quantifying the presence of Ara h1 in milk, infant milk powder, cookies, bread, and chocolate with recoveries of 95.7-106.3%. The proposed ratiometric aptasensor is expected to be a prospective universal aptasensor platform for the rapid, sensitive, and accurate determination of food and environmental hazards.

First pass effect in patients undergoing endovascular treatment for posterior circulation acute ischemic stroke.

OBJECTIVE: This study aims to investigate the impact of first pass effect (FPE) on outcomes in the posterior circulation acute ischemic stroke (PC-AIS) and the independent predictors of FPE. METHODS: This was a multicenter, retrospective study. PC-AIS patients who underwent endovascular treatment were reviewed. The cohort achieving complete or nearly complete reperfusion (defined as expanded treatment in cerebralischemia [eTICI] ≥ 2c) was categorized into the FPE and multiple pass effect (MPE) groups. FPE was defined as achieving eTICI ≥ 2c with a single pass and without the use of rescue therapy. Modified FPE (mFPE) was defined as meeting the criteria for FPE but with eTICI ≥ 2b. The association of FPE with 90-day clinical outcomes and predictors for FPE were both investigated. RESULTS: The study included a total of 328 patients, with 69 patients (21 %) in the FPE group. For primary outcome, FPE had a significant higher favorable outcome (mRS ≤ 3) rate than MPE (65.2 % vs. 44.8 %, p = 0.003). Similar outcomes were observed in the mFPE. Furthermore, FPE was significantly associated with favorable outcome (adjusted OR 2.23, 95 % CI 1.06-4.73, p = 0.036). Positive predictors for FPE included occlusion in the distal basilar artery, the first-line aspiration or combination, and cardioembolic etiology. Negative predictors for FPE included hypertension and general anesthesia. CONCLUSION: For PC-AIS patients due to large or medium vessel occlusion, FPE is associated with favorable clinical outcomes. The first-line techniques of aspiration or combination, as well as avoiding general anesthesia, contribute to a better realization of FPE.

Clinical evidence in ischemic stroke: Where we have gone so far and hopes for the future.

OBJECTIVE: Ischemic stroke is a significant cause of disability and death worldwide. Randomized clinical trials (RCTs) are important in changing guidelines and treatment strategies. This study aimed to analyze the progress of RCTs in ischemic stroke and to guide future research directions. METHODS: Ischemic stroke-related RCT articles were identified in six high-impact medical journals using the Web of Science Core Collection database. Google Scholar was used to check whether relevant articles were included in the guidelines. The characteristics of these articles were analyzed and future research hotspots were predicted. RESULTS: 389 relevant articles were included in the analysis. The number of articles increased rapidly from 1972 to 2022, from 5 (1.3%; 1972-1982) to 208 (53.5%; 2013-2022) articles. 338 (86.9%) articles were included in relevant guidelines. According to corresponding author location, Europe was the source of the highest number of publications (183; 47.0%), followed by the Americas (152; 39.1%) and the Western Pacific (54; 13.9%). The number of publications steadily increased over time in the USA, England, Canada, Australia, Germany, and France, and surged in China and Spain, especially in the last 5 years. In recent years, endovascular therapy has accounted for the majority of ischemic stroke-related RCT articles. CONCLUSIONS: Numerous RCTs related to ischemic stroke have been conducted in recent decades, and both the number of articles and their contribution to guideline updates are increasing. Also, a shift in research topics was observed. However, great regional imbalances in this research exist, calling for more research to be conducted in specific regions to promote the generalizability of trial conclusions.

Tandem Mass Spectrometry Imaging Enables High Definition for Mapping Lipids in Tissues.

Mass spectrometry imaging (MSI) of lipids in biological tissues is useful for correlating molecular distribution with pathological results, which could provide useful information for both biological research and disease diagnosis. It is well understood that the lipidome could not be clearly deciphered without tandem mass spectrometry analysis, but this is challenging to achieve in MSI due to the limitation in sample amount at each image spot. Here we develop a multiplexed MS2 imaging (MS2 I) method that can provide MS2 images for 10 lipid species or more for each sampling spot, providing spatial structural lipidomic information. Coupling with on-tissue photochemical derivatization, imaging of 20 phospholipid C=C location isomers is also realized, showing enhanced molecular images with high definition in structure for mouse brain and human liver cancer tissue sections. Spatially mapped t-distributed stochastic neighbor embedding has also been adopted to visualize the tumor margin with enhancement by structural lipidomic information.

Parallel Planar Heterojunction Strategy Enables Sb2 S3 Solar Cells with Efficiency Exceeding 8 .

Solution-processed solar cells based on inorganic heterojunctions provide a potential approach to the efficient, stable and low-cost solar cells required for the terrestrial generation of photovoltaic energy. Antimony trisulfide (Sb2 S3 ) is a promising photovoltaic absorber. Here, an easily solution-processed parallel planar heterojunction (PPHJ) strategy and related principle are developed to prepare efficient multiple planar heterojunction (PHJ) solar cells, and the PPHJ strategy boosts the efficiency of solution-processed Sb2 S3 solar cells up to 8.32 % that is the highest amongst Sb2 S3 devices. The Sb2 S3 -based PPHJ device consists of two kinds of conventional planar heterojunction (PHJ) subcells in a parallel connection: Sb2 S3 -based PHJ subcells dominating the absorption and charge generation and CH3 NH3 PbI3 -based PHJ subcells governing the electron transport towards collection electrode, but it belongs to an Sb2 S3 device in nature. The resulting PPHJ device combines together the distinctive structural features of Sb2 S3 absorbing layer as a main absorber and the duplexity of well-crystallized/oriented CH3 NH3 PbI3 layer in charge transportation as an additional absorber, while the presence of perovskite does not affect device stability. The PPHJ strategy maintains the facile preparation by the conventional sequential depositions of multiple layers, but eliminates the normal complexity in both tandem and parallel tandem PHJ systems.

Development of a Miniature Mass Spectrometry System for Point-of-Care Analysis of Lipid Isomers Based on Ozone-Induced Dissociation.

Disorder of lipid homeostasis is closely associated with a variety of diseases. Although mass spectrometry (MS) approaches have been well developed for the characterization of lipids, it still lacks an integrated and compact MS system that is capable of rapid and detailed lipid structural characterization and can be conveniently transferred into different laboratories. In this work, we describe a novel miniature MS system with the capability of both ozone-induced dissociation (OzID) and collision-induced dissociation (CID) for the assignment of sites of unsaturation and sn-positions in glycerolipids. A miniature ozone generator was developed, which can be operated at a relatively high pressure. By maintaining high-concentration ozone inside the linear ion trap, OzID efficiency was significantly improved for the identification of C═C locations in unsaturated lipids, with reaction times as short as 10 ms. Finally, the miniature OzID MS system was applied to the analysis of C═C locations and sn-positions of lipids from biological samples. Direct sampling and fast detection of changes in phospholipid isomers were demonstrated for the rapid discrimination of breast cancer tissue samples, showing the potential of the miniature OzID MS system for point-of-care analysis of lipid isomer biomarkers in complex samples.

Visible-Light-Driven [2 + 2] Photocycloadditions between Benzophenone and C═C Bonds in Unsaturated Lipids.

The [2 + 2] photocycloaddition of alkenes and carbonyls is of fundamental interest and practical importance, as this process is extensively involved in oxetane-ring constructions. Although individual carbonyl group or alkene moiety has been utilized as photoactive species for oxetane formations upon ultraviolet photoexcitation, direct excitation of the entire noncovalent complex involving alkene and carbonyl substrates to achieve [2 + 2] photocycloadditions is rarely addressed. Herein, complexes with noncovalent interactions between benzophenone and C═C bonds in unsaturated lipids have been successfully characterized, and for the first time a [2 + 2] cycloaddition leading to the formation of oxetanes has been identified under visible-light irradiation. The mechanism of this reaction is distinctly different from the well-studied Paternò-Büchi reaction. The entire complexes characterized as dimeric proton-bonded alkene and carbonyl substrates can be excited under visible light, leading to electron transfer from the alkene moiety in fatty acyls to the carbonyl group within the complex. These results provide new insight into utilizing noncovalent complexes for the synthesis of oxetanes in which the excitation wavelength becomes independent of each individual substrate.

Point-of-Care Tissue Analysis Using Miniature Mass Spectrometer.

The combination of direct sampling ionization and miniature mass spectrometer presents a promising technical pathway of point-of-care analysis in clinical applications. In this work, a miniature mass spectrometry system was used for analysis of tissue samples. Direct tissue sampling coupled with extraction spray ionization was used with a home-built miniature mass spectrometer, Mini 12. Lipid species in tissue samples were well profiled in rat brain, kidney, and liver in a couple of minutes. By incorporating a photochemical (Paternò-Büchi) reaction, fast identification of lipid C═C location was realized. Relative quantitation of the lipid C═C isomer was performed by calculating the intensity ratio C═C diagnostic product ions, by which FA 18:1 (Δ9)/FA 18:1 (Δ11) was found to change significantly in mouse cancerous breast tissue samples. Accumulation of 2-hydroxylglutarate in human glioma samples, not in normal brains, can also be easily identified for rapid diagnosis.

Enhancement of photocatalytic activity of g-C3N4 by hydrochloric acid treatment of melamine.

Modified g-C3N4 samples (g-X, where X corresponds to the number of hours of acid treatment of the melamine) with outstanding photocatalytic performance were prepared by using hydrochloric acid-treated melamine as a precursor and calcining at 550 °C for 2 h. An x-ray diffractometer, field-emission scanning electron microscope, infrared spectrometer, N2 adsorption-desorption test, x-ray photoelectron spectroscopy, and ultraviolet-visible diffuse-reflectance spectroscopy analysis were carried out to characterize the phase composition, microstructure, chemical structure, specific surface area (SSA), chemical states, elemental composition and optical properties of the samples, respectively. The photocatalytic performance of the samples was evaluated by degrading the Rhodamine B (RhB) aqueous solution. The results showed that the crystal structure and vibration bands of melamine changed due to the reaction with hydrochloric acid. The crystallinity and grain size of g-C3N4 in g-X (X = 1, 2, 4, 6, 8, 10) reduced, and the SSA values of g-X increased compared to that of the g-0 sample, which was synthesized from pristine melamine. The g-X samples exhibited excellent photocatalytic activity towards degradation of RhB compared to g-0. The photocatalytic activity of the g-X samples increased gradually as the acid treatment time of the melamine increased from 1 h to 2 h, and then decreased gradually with the extension of the acid treatment time. The rate constant (k) values of g-X are higher than that of g-0. g-2 presented the highest rate constant (k = 0.052 min-1), which was 5.5 times higher than that of g-0. The improved photocatalytic activity of the g-X samples was attributed to the higher SSA value, the appearance of surface defects, the outstanding photo-carrier separation efficiency and stronger light harvesting ability of g-X, with the last two factors being more significant. Acid treatment of melamine is helpful in the preparation of high performance g-C3N4 photocatalyst, and the microstructure and photocatalytic performance of g-C3N4 were affected significantly by the acid treatment time.

Locating Carbon-Carbon Double Bonds in Unsaturated Phospholipids by Epoxidation Reaction and Tandem Mass Spectrometry.

The presence of carbon-carbon double bonds (C═Cs) in unsaturated phospholipids is closely related to lipid conformations and physiochemical activities. Previously, we have demonstrated that epoxidation reaction facilitated by low-temperature plasma (LTP) enabled the structural analysis of unsaturated fatty acids (FAs). Epoxidation of the C═C leads to the production of an epoxide, which can be easily cleaved via collision-induced dissociation (CID) to produce diagnostic ions indicative of the C═C bond locations in FAs. In this work, we further developed this method for analysis of phospholipids. Tandem mass spectrometry analysis with epoxidation reaction was performed in both positive and negative ion mode to analyze phosphatidylcholines (PCs), phosphatidic acids (PAs), phosphatidylethanolamines (PEs), phosphatidylglycerols (PGs), and phosphatidylinositols (PIs). The developed method was applied in a shotgun lipidomics approach to characterize phospholipids in a bovine liver extract.

Caveolin-1 affects tumor drug resistance in esophageal squamous cell carcinoma by regulating expressions of P-gp and MRP1.

Esophageal squamous cell carcinoma (ESCC) is the most common cancer in China, and multidrug resistance (MDR) remains one of the biggest problems in ESCC chemotherapy. In this study, we aimed to investigate the mechanism of Caveolin-1, an integral membrane protein, on regulating ESCC MDR. First, immunohistochemistry was used to check the protein expression of Caveolin-1, MDR-related protein of P-glycoprotein (P-gp), and multidrug resistance protein 1 (MRP1) in 84 pathologically characterized ESCC tissues, matched adjacent tumor, and adjacent normal-looking tissues. The results showed that Caveolin-1 expression level was elevated in ESCC tissues than that of matched adjacent tumor and adjacent normal-looking tissues (P < 0.05), and the expression of Caveolin-1 has close correlation with P-gp and MRP1 during tumor genesis of ESCC (P = 0.034, P = 0.009, respectively). Then, Caveolin-1 overexpression and knockdown were used to investigate its effect on expressions of P-gp and MRP1 in ESCC cell line Ec9706. The messenger RNA (mRNA) and protein expression levels of P-gp and MRP1 were checked by real-time quantitative reverse transcription-PCR (qRT-PCR) and Western blot (WB). The results showed that Caveolin-1 overexpression significantly promotes the mRNA and protein expression of MRP1 (P < 0.05), while almost has no effect on the mRNA and protein expression of P-gp (P > 0.05); Cavoelin-1 knockdown inhibits the mRNA and protein expressions of both P-gp and MRP1 (P < 0.05). The similar result was found in another ESCC cell line Eca109. So, it is concluded that Caveolin-1 affects ESCC MDR by regulating the expressions of P-gp and MRP1; therefore, it can be taken as a significant marker and target in tumor therapy.

Drinking water: a risk factor for high incidence of esophageal cancer in Anyang, China.

Anyang is known to be a high-incidence area of esophageal cancer (EC) in China. Among a long list of risk factors, the quality of drinking water was evaluated. We have selected 3806 individuals and collected 550 drinking water samples correspondent with this not-matched case-control survey. There are 531 EC patients included based on Population Cancer Registry from 92 townships, of which 3275 controls with long-lived aged over 90 years and free from EC are used as controls in the same regions. Our result suggests that the quality of drinking water is a highly associated risk factor for EC. The residential ecological environment and the quality of water resource positively link with each other. The analysis of water samples also demonstrated that the concentrations of methyl ethylamine, morpholine, N-methylbenzylamine, nitrate and chloride in water from springs and rivers are higher than those in well and tap water (P = 0.001). Micronuclei formation tests show that well water and tap water in these regions have no mutagenicity.

A novel di-functional fluorescent probe for ONOO- and Zn2+ imaging in cells.

Peroxynitrite (ONOO-) is one of the most significant reactive oxygen species (ROS) in living cells. Zn2+ in living cells plays an essential part in different physiological processes. The abnormal concentration of ONOO- and Zn2+ in living cells are related to many kinds of diseases, such as anemia, epilepsy, diarrhea, Alzheimer's disease, and so on. The relationship of ONOO- and Zn2+ in living cells when the relative disease occurs remains unknown. So we develop the first probe H-1 for detecting ONOO- and Zn2+ at the same time. The probe H-1 shows high selectivity, good anti-interference capability, low detection limit and short response time to ONOO- and Zn2+. When the probe was applied to detect ONOO- and Zn2+ in HeLa cells, we could observe the fluorescence changing in the green and blue channels separately without interference in real time. It has the potential to employ the relation of ONOO- and Zn2+ in some disease mechanism research.

The BDNF Val66Met polymorphism serves as a potential marker of body weight in patients with psychiatric disorders.

Brain-derived neurotrophic factor (BDNF) is a predominant neurotrophic factor in the brain, indispensable for neuronal growth, synaptic development, neuronal repair, and hippocampal neuroplasticity. Among its genetic variants, the BDNF Val66Met polymorphism is widespread in the population and has been associated with the onset and aggravation of diverse pathologies, including metabolic conditions like obesity and diabetes, cardiovascular ailments, cancer, and an array of psychiatric disorders. Psychiatric disorders constitute a broad category of mental health issues that influence mood, cognition, and behavior. Despite advances in research and treatment, challenges persist that hinder our understanding and effective intervention of these multifaceted conditions. Achieving and maintaining stable body weight is pivotal for overall health and well-being, and the relationship between psychiatric conditions and body weight is notably intricate and reciprocal. Both weight gain and loss have been linked to varying mental health challenges, making the disentanglement of this relationship critical for crafting holistic treatment strategies. The BDNF Val66Met polymorphism's connection to weight fluctuation in psychiatric patients has garnered attention. This review investigated the effects and underlying mechanisms by which the BDNF Val66Met polymorphism moderates body weight among individuals with psychiatric disorders. It posits the polymorphism as a potential biomarker, offering prospects for improved monitoring and therapeutic approaches for mental illnesses.

Lateral flow assay for simultaneous detection of multiple mycotoxins using nanozyme to amplify signals.

Co-contamination of multiple mycotoxins produces synergistic toxic effects, leading to more serious hazards. Therefore, the simple, rapid and accurate simultaneous detection of multiple mycotoxins is crucial. Herein, a three-channel aptamer-based lateral flow assay (Apt-LFA) was established for the detection of aflatoxin M1 (AFM1), aflatoxin B1 (AFB1) and ochratoxin A (OTA). The multi-channel Apt-LFA utilized gold­iridium nanozyme to catalyze the chromogenic substrate, which effectively achieved signal amplification. Moreover, the positions and lengths of the complementary sequences were screened by changes in fluorescence intensity. After grayscale analysis, the semi-quantitative results showed that the detection limits of AFM1, AFB1 and OTA were 0.39 ng/mL, 0.36 ng/mL and 0.82 ng/mL. The recoveries of the multiplexed competitive sensors in complex matrices of real samples were 93.33%-97.01%, 95.72%-102.67%, and 106.88%-109.33%, respectively. In conclusion, the assembly principle of the three-channel Apt-LFA is simple, which can provide a new idea for the simultaneous detection of small molecule targets.

MicroRNAs: A novel signature in the metastasis of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a malignant epithelial tumor, characterized by squamous cell differentiation, it is the sixth leading cause of cancer-related deaths globally. The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered, coupled with higher risk of metastasis, which is an exceedingly malignant characteristic of cancer, frequently leading to a high mortality rate. Unfortunately, there is currently no specific and effective marker to predict and treat metastasis in ESCC. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules, approximately 22 nucleotides in length. miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence, progression, and prognosis of cancer. Here, we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis, and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors. This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis, with the ultimate aim of reducing the mortality rate among patients with ESCC.

Early venous filling after mechanical thrombectomy in acute ischemic stroke due to large vessel occlusion in anterior circulation.

BACKGROUND: The significance of early venous filling (EVF) after mechanical thrombectomy (MT) in acute ischemic stroke (AIS) is not fully understood. In this study, we aimed to investigate the impact of EVF after MT. METHODS: From January 2019 to May 2022, AIS patients with successful recanalization (modified Thrombolysis in Cerebral Infarction score (mTICI) ≥2b) after MT were retrospectively reviewed. EVF was evaluated on final digital subtraction angiography runs after successful recanalization and was categorized into phase subgroups (arterial phase and capillary phase) and pathway subgroups (cortical veins subgroup and thalamostriate veins subgroup), respectively. The impact of EVF subgroups on functional outcomes after successful recanalization were both investigated. RESULTS: A total of 349 patients achieving successful recanalization after MT were included, including 45 patients in the EVF group and 304 patients in the non-EVF group. Multivariable logistic regression analysis showed the EVF group had a higher rate of intracranial hemorrhage (ICH; 66.7% vs 22%, adjusted odds ratio (aOR) 6.805, 95% CI 3.389 to 13.662, P<0.001), symptomatic ICH (sICH; 28.9% vs 4.9%, aOR 6.011, 95% CI 2.493 to 14.494, P<0.001) and malignant cerebral edema (MCE; 20% vs 6.9%, aOR 2.682, 95% CI 1.086 to 6.624, P=0.032) than the non-EVF group. Furthermore, the cortical veins subgroup of EVF had a higher rate of mortality than the thalamostriate veins subgroup (37.5% vs 10.3%, P=0.029). CONCLUSIONS: EVF is independently associated with ICH, sICH and MCE after successful recanalization of MT, but not with favorable outcome and mortality.

Systemic-inflammatory indices and clinical outcomes in patients with anterior circulation acute ischemic stroke undergoing successful endovascular thrombectomy.

Background: There is a lack of comprehensive profile assessment on complete blood count (CBC)-derived systemic-inflammatory indices, and their correlations with clinical outcome in patients with anterior circulation acute ischemic stroke (AIS) who achieved successful recanalization by endovascular thrombectomy (EVT). Methods: Patients with anterior circulation AIS caused by large vessel occlusion (AIS-LVO) were retrospectively screened from December 2018 to December 2022. Systemic-inflammatory indices including ratios of neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte (PLR), and platelet-to-neutrophil (PNR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate inflammation systemic index (AISI) on admission and the first day post-EVT were calculated. Their correlations with symptomatic intracranial hemorrhage (sICH) and unfavorable 90-day functional outcome (modified Rankin Scale score of 3-6) were analyzed. Results: A total of 482 patients [65 (IQR, 56-72) years; 33 % female] were enrolled, of which 231 (47.9 %) had unfavorable 90-day outcome and 50 (10.4 %) developed sICH. Day 1 neutrophil and monocyte counts, NLR, MLR, PLR, SII, SIRI, and AISI were increased, while lymphocyte and PNR were decreased compared to their admission levels. In multivariate analyses, neutrophil count, NLR, SII, and AISI on day 1 were independently associated with 90-day functional outcome. Moreover, day 1 neutrophil count, NLR, MLR, PLR, PNR, SII, and SIRI were independently linked to the occurrence of sICH. No admission variables were identified as independent risk factors for patient outcomes. Conclusion: CBC-derived systemic-inflammatory indices measured on the first day after successful EVT are predictive of 90-day functional outcome and the sICH occurrence in patients with anterior circulation AIS-LVO.

Alterations of Hemostatic Molecular Markers During Acute Large Vessel Occlusion Stroke.

BACKGROUND: This study aimed to investigate regional levels of TAT (thrombin-antithrombin complex), PIC (plasmin-α2 plasmin inhibitor complex), t-PAIC (tissue plasminogen activator-plasminogen activator inhibitor complex), sTM (soluble thrombomodulin), and D-dimer, along with their associations with clinical and procedural characteristics in patients with acute ischemic stroke undergoing endovascular thrombectomy. METHODS AND RESULTS: We retrospectively analyzed 166 consecutive patients with acute ischemic stroke (62±11.54 years of age, 34.3% women) using prospectively maintained clinical databases and blood samples from local ischemic (proximal to thrombus) and systemic (femoral artery, self-control) arterial compartments. Levels of TAT, PIC, t-PAIC, and D-dimer were significantly elevated, whereas sTM was significantly reduced, in local ischemic regions compared with their systemic levels. Each 1-unit increase in ischemic TAT (adjusted odds ratio [aOR], 1.086 [95% CI, 1.03-1.145]; P=0.002; area under the curve [AUC], 0.833) and PIC (aOR, 1.337 [95% CI, 1.087-1.644]; P=0.006; AUC, 0.771) correlated significantly with higher symptomatic intracranial hemorrhage risk. Additionally, each 1-unit increase in ischemic TAT (aOR, 1.076 [95% CI, 1.016-1.139]; P=0.013; AUC, 0.797), PIC (aOR, 1.554 [95% CI, 1.194-2.022]; P=0.001; AUC, 0.798), and sTM (aOR, 0.769 [95% CI, 0.615-0.961]; P=0.021; AUC, 0.756) was significantly associated with an increased risk of an unfavorable 90-day outcome (modified Rankin scale of 3-6). These hemostatic molecules, individually or combined, significantly improved the predictive power of conventional risk factors, as evidenced by significant increases in net reclassification improvement and integrated discrimination improvement (all P<0.01). CONCLUSIONS: We observed a hyperactive state of the coagulation-fibrinolysis system within the local ischemic region during hyperacute stroke. Rapid automated measurement of hemostatic molecular markers, particularly TAT, PIC, and sTM, during intra-arterial procedures may provide additional information for stroke risk stratification and therapeutic decision-making, and warrants further investigation.