Evaluating the comprehensive diagnosis efficiency of lung cancer, including measurement of SHOX2 and RASSF1A gene methylation.

Methylation of the promoters of SHOX2 and RASSF1A (LungMe®) exhibits promise as a potential molecular biomarker for diagnosing lung cancer. This study sought to assess the aberrant methylation of SHOX2 and RASSF1A in broncho-exfoliated cells (BEC) and compare it with conventional cytology, histology examination, immunohistochemistry, and serum tumor markers to evaluate the overall diagnostic efficiency for lung cancer. This study recruited 240 patients, including 185 malignant cases and 55 benign cases. In our observation, we noted a slight reduction in the detection sensitivity, however, the ΔCt method exhibited a significant enhancement in specificity when compared to Ct judgment. Consequently, the ΔCt method proves to be a more appropriate approach for interpreting methylation results. The diagnostic sensitivity of cytology and histology was in ranged from 20.0%-35.1% and 42.9%-80%, respectively, while the positive detection rate of LungMe® methylation ranged from 70.0% to 100%. Additionally, our findings indicate a higher prevalence of SHOX2( +) among patients exhibiting medium and high expression of Ki67 (P < 0.01), as opposed to those with low expression of Ki67, but RASSF1A methylation did not show this phenomenon (P = 0.35). Furthermore, CEA, SCCA, and CYFRA21-1 showed positive detection rates of 48.8%, 26.2%, and 55.8%, respectively. Finally, we present a comprehensive lung cancer diagnostic work-up, including LumgMe® methylation. The combined analysis of SHOX2 and RASSF1A methylation serves as a powerful complement and extension to conventional methods, enhancing the accuracy of a lung cancer diagnosis with satisfactory sensitivity and specificity.

Association of the SHOX2 and RASSF1A methylation levels with the pathological evolution of early-stage lung adenocarcinoma.

Background The methylation of SHOX2 and RASSF1A shows promise as a potential biomarker for the early screening of lung cancer, offering a solution to remedy the limitations of morphological diagnosis. The aim of this study is to diagnose lung adenocarcinoma by measuring the methylation levels of SHOX2 and RASSF1A, and provide an accurate pathological diagnosis to predict the invasiveness of lung cancer prior to surgery.Material and methods The methylation levels of SHOX2 and RASSF1A were quantified using a LungMe® test kit through methylation-specific PCR (MS-PCR). The diagnostic efficacy of SHOX2 and RASSF1A and the cutoff values were validated using ROC curve analysis. The hazardous factors influencing the invasiveness of lung adenocarcinoma were calculated using multiple regression.Results: The cutoff values of SHOX2 and RASSF1A were 8.3 and 12.0, respectively. The sensitivities of LungMe® in IA, MIA and AIS patients were 71.3% (122/171), 41.7% (15/36), and 16.1% (5/31) under the specificity of 94.1% (32/34) for benign lesions. Additionally, the methylation level of SHOX2, RASSF1A and LungMe® correlated with the high invasiveness of clinicopathological features, such as age, gender, tumor size, TNM stage, pathological type, pleural invasion and STAS. The tumor size, age, CTR values and LungMe® methylation levels were identified as independent hazardous factors influencing the invasiveness of lung adenocarcinoma.Conclusion: SHOX2 and RASSF1A combined methylation can be used as an early detection indicator of lung adenocarcinoma. SHOX2 and RASSF1A combined (LungMe®) methylation is significantly correlated to age, gender, tumor size, TNM stage, pathological type, pleural invasion and STAS. The SHOX2 and RASSF1A methylation levels, tumor size and CTR values could predict the invasiveness of the tumor prior to surgery, thereby providing guidance for the surgical procedure.

MicroRNA-mediated high expression of PDIA3 was correlated with poor prognosis of patients with LUAD.

Lung cancer, especially lung adenocarcinoma (LUAD) as the most common subtype has threatened the health of people. Even though more and more patients diagnosed as LUAD could be treated efficiently or even cured, a spilt of patients still suffer from disease. Here, on the basis of previous research, we firstly performed the mRNA expression of PDIA3 in pan-cancer, and differential expression between tumor and normal groups was followed. We further analyzed the survival difference and ultimately the expression of PDIA3 in LUAD was selected as our current study. Next, we investigated the mRNA and protein expression of PDIA3 from online databases and performed qRT-PCR and western blotting to verify the outcomes. We still analyzed the correlation between the expression of PDIA3 and clinicopathologic parameters and predicted the potential signal pathways as well as the possible upstream molecular of PDIA3. Considering the correlation of PDIA3 and immune infiltration, related analysis of PDIA3 and immune biomarkers along with PD-1/PD-L1, CTLA-4 were made. We clarified the expression of PDIA3 was upregulated in LUAD and its oncogenic role may be played through tumor infiltration. Thus targeting PDIA3 and immune checkpoint could enhance the efficacy of immunotherapy on patients with LUAD.

Evaluation of droplet digital PCR rapid detection method and precise diagnosis and treatment for suspected sepsis (PROGRESS): a study protocol for a multi-center pragmatic randomized controlled trial.

BACKGROUND: Sepsis is still a major public health concern and a medical emergency due to its high morbidity and mortality. Accurate and timely etiology diagnosis is crucial for sepsis management. As an emerging rapid and sensitive pathogen detection tool, digital droplet PCR (ddPCR) has shown promising potential in rapid identification of pathogens and antimicrobial resistance genes. However, the diagnostic value and clinical impact of ddPCR tests remains to be studied in patients with suspected sepsis. PROGRESS trial is aimed to evaluate the clinical effectiveness of a novel ddPCR assay compared with standard practice. METHODS: PROGRESS is a multicenter, open-label, pragmatic randomized controlled trial (pRCT) set in ten hospitals, including departments of infectious disease and intensive care units. In this study, a total of 2292 patients with suspected sepsis will be randomly assigned to two arms: the ddPCR group and the control group with a ratio of 3:1. The primary outcome is the diagnostic efficacy, that is, the sensitivity and specificity of the ddPCR assay compared with the synchronous blood culture. Secondary outcomes include the mortality rates and the mean Sequential Organ Failure Assessment (SOFA) score at follow-up time points, the length of stay in the hospital, the time to directed antimicrobial therapy, duration of broad-spectrum antibiotic use, and the EQ-5D-5L score on day 90. DISCUSSION: It is the first multicenter pragmatic RCT to explore the diagnostic efficacy and clinical impact of the ddPCR assay in patients with suspected sepsis, taking advantage of both RCT's ability to establish causality and the feasibility of pragmatic approaches in real-world studies (RWS). This trial will help us to get a comprehensive view of the assay's capacity for precise diagnosis and treatment of sepsis. It has the potential to monitor the pathogen load change and to guide the antimicrobial therapy, making a beneficial impact on the prognosis of sepsis patients. TRIAL REGISTRATION: ClinicalTrial.gov, NCT05190861. Registered January 13, 2022-'Retrospectively registered', https://clinicaltrials.gov/ct2/show/NCT05190861 .

NEIL3 may act as a potential prognostic biomarker for lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death. This study aimed to develop and validate reliable prognostic biomarkers and signature. METHODS: Differentially expressed genes were identified based on three Gene Expression Omnibus (GEO) datasets. Based on 1052 samples' data from our cohort, GEO and The Cancer Genome Atlas, we explored the relationship of clinicopathological features and NEIL3 expression to determine clinical effect of NEIL3 in LUAD. Western blotting (22 pairs of tumor and normal tissues), Real-time quantitative PCR (19 pairs of tumor and normal tissues), and immunohistochemical analyses (406-tumor tissues subjected to microarray) were conducted. TIMER and ImmuCellAI analyzed relationship between NEIL3 expression and the abundance of tumor-infiltrating immune cells in LUAD. The co-expressed-gene prognostic signature was established based on the Cox regression analysis. RESULTS: This study identified 502 common differentially expressed genes and confirmed that NEIL3 was significantly overexpressed in LUAD samples (P < 0.001). Increased NEIL3 expression was related to advanced stage, larger tumor size and poor overall survival (p < 0.001) in three LUAD cohorts. The proportions of natural T regulatory cells and induced T regulatory cells increased in the high NEIL3 group, whereas those of B cells, Th17 cells and dendritic cells decreased. Gene set enrichment analysis indicated that NEIL3 may activate cell cycle progression and P53 signaling pathway, leading to poor outcomes. We identified nine prognosis-associated hub genes among 370 genes co-expressed with NEIL3. A 10-gene prognostic signature including NEIL3 and nine key co-expressed genes was constructed. Higher risk-score was correlated with more advanced stage, larger tumor size and worse outcome (p < 0.05). Finally, the signature was verified in test cohort (GSE50081) with superior diagnostic accuracy. CONCLUSIONS: This study suggested that NEIL3 has the potential to be an immune-related therapeutic target and an independent predictor of LUAD prognosis. We also developed a prognostic signature for LUAD with a precise diagnostic accuracy.

Prognostic biomarker TUBA1C is correlated to immune cell infiltration in the tumor microenvironment of lung adenocarcinoma.

BACKGROUND: TUBA1C is a microtubule component that is involved in a variety of cancers. Our main objective was to investigate TUBA1C expression, its prognostic value, its potential biological functions, and its impact on the immune system of patients with lung adenocarcinoma (LUAD). METHODS: The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA) and Immunohistochemistry Analysis were used to analyze TUBA1C expression, its clinicopathology, overall survival (OS), and disease-free survival (DFS) in LUAD patients. We also determined the correlation between TUBA1C and tumor-infiltrating immune cells (TIICs) by using CIBERSORT and GEPIA databases. To determine the expression of TUBA1C in LUAD, we analyzed a collection of immune infiltration levels and cumulative survival of LUAD tissues in TIMER database. By using UALCAN, STRING, and GeneMANIA databases, we investigated the protein-coding genes related to TUBA1C and its co-expression genes in LUAD tissues. Gene set enrichment analysis (GSEA) was performed by using the TCGA dataset. RESULTS: The mRNA and the protein expression of TUBA1C were found to be up-regulated in LUAD tissues. The univariate analysis indicated that an increased expression of TUBA1C was significantly correlated to the following parameters: age, stage, and lymph node metastasis. An over-expression of TUBA1C was associated with a poor prognosis of LUAD. In TIMER and CIBERSORT databases, we found that TUBA1C is correlated with 13 types of TIICs: activated B cell, activated CD4 T cell, central memory CD4 T cell, effector memory CD8 T cell, eosinophils, immature B cell, gamma-delta T cell, immature dendritic cell, mast cell, memory B cell, natural killer T cell, regulatory T cell, and type 2T helper cell. By performing GSEA, we found that TUBA1C is closely correlated to cell cycle, p53 signaling pathway, glycolysis, and gluconeogenesis. CONCLUSIONS: Our findings indicate that TUBA1C is associated with TIICs in tumor microenvironment. Therefore, it serves as a novel prognostic biomarker and a target for future treatment methods of LUAD.

CLEC5A promotes the proliferation of gastric cancer cells by activating the PI3K/AKT/mTOR pathway.

Gastric cancer (GC), as one of the most prevalent malignancies, contributes to the high morbidity and mortality worldwide. By analyzing the bioinformatics, qRT-PCR and IHC assays, we found that CLEC5A is overexpressed in GC and associated with poorer prognosis. CLEC5A silencing inhibits cell growth and DNA replication and induces cell cycle arrest and cell apoptosis. Bioinformatics analyses and Western blotting revealed that CLEC5A depletion led to the dysregulation of the PI3K/AKT/mTOR pathway. CLEC5A-mediated GC proliferation and anti-apoptosis were impaired by blocking the PI3K/AKT/mTOR pathway with LY294002. We hypothesize that CLEC5A is of vital importance to GC initiation and progression via the PI3K/AKT/mTOR pathway, and that our results might represent promising therapeutic strategies for GC patients.

miR-335 inhibited cell proliferation of lung cancer cells by target Tra2ß.

Accumulating evidence has suggested that the dysregulation of miRNA is an important factor in the pathogenesis of lung cancer. Here, we demonstrate that miR-335 expression is reduced in non-small cell lung cancer (NSCLC) tumors relative to non-cancerous adjacent tissues, while the expression of Tra2ß is increased. In addition, clinical data revealed that the increased Tra2ß and decreased miR-335 expression observed in NSCLC cells was associated with poor patient survival rates. In vitro experimentation showed that the overexpression of miR-335 inhibited the growth, invasion and migration capabilities of A459 lung cancer cells, by targeting Tra2ß. In contrast, inhibition of miR-335 or overexpression of the Tra2ß target gene stimulated the growth, invasion and migratory capabilities of A459 lung cancer cells in vitro. Furthermore, overexpression of miR-335 or inhibition of Tra2ß decreased the phosphorylation of Rb-S780 and Rb-AKT. Overall, these findings suggest that the downregulation of miR-335 in A459 lung cancer cells promoted cell proliferation through upregulation of Tra2ß, mediated via activation of the AKT/mTOR signaling pathway, and suggest that miR-335 may have potential as a novel therapeutic target for NSCLC.

Inflammation is correlated with severity and outcome of cerebral venous thrombosis.

BACKGROUND: Few studies have suggested a relationship between inflammation and cerebral venous thrombosis (CVT). This retrospective study aimed to explore the changes in inflammation in different CVT stages and the correlation between inflammation and severity and outcome of CVT. METHODS: In total, 95 suitable patients with CVT and 41 controls were compared. Patients with CVT were divided into three groups. The inflammatory factors studied included hypersensitive C-reactive protein (Hs-CRP), interleukin-6 (IL-6), and neutrophil-to-lymphocyte ratio (NLR) in the peripheral blood and immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) in the cerebrospinal fluid (CSF). The severity of CVT was evaluated with the modified Rankin Scale (mRS), the National Institutes of Health Stroke Scale (NIHSS), fundus condition, intracranial pressure (ICP), and complications on admission. The short-term outcome was evaluated with the mRS at discharge. RESULTS: The following results were obtained: (1) Inflammatory factor levels in patients with CVT were higher than those in the controls. (2) Inflammatory factor levels in the acute and subacute stages were significantly higher than those in the chronic stage (all P < 0.05). (3) Serum NLR and CSF IgM levels were positively related to baseline degree of disability (odds ratio [OR], 1.279, 95% confidence interval [CI] 1.009-1.621, P = 0.042; OR 1.402, 95% CI 1.036-1.896, P = 0.028). The Hs-CRP level was positively correlated with the baseline occurrence of seizure (OR 1.040, 95% CI 1.001-1.080, P = 0.043). The baseline serum NLR (r = 0.244, P = 0.017), CSF IgA (r = 0.615, P < 0.001), CSF IgM (r = 0.752, P < 0.001), and CSF IgG (r = 0.248, P = 0.015) levels were positively associated with NIHSS. (4) The baseline NLR was significantly associated with high risk of poor outcome at discharge (OR 1.339, 95% CI 1.097-1.784, P = 0.007). Moreover, the ROC showed that NLR ≥ 4.205 could better predict the poor outcome at discharge. The data were analyzed using SPSS. CONCLUSIONS: Inflammation may develop after CVT and gradually decrease during the course. Inflammation was significantly correlated with severity on admission and short-term poor outcome at discharge in CVT.

Toxic effect of the novel chiral insecticide IPP and its biodegradation intermediate in nematode Caenorhabditis elegans.

Caenorhabditis elegans, a kind of model organism, was used to investigate biodegradation pathway of IPP and M1 in nematodes, in vivo toxicity from IPP and M1 and the possible underlying molecular mechanism. The results showed that both IPP and M1 could decrease lifespan, locomotion behavior, reproductive ability and AChE activity. During IPP biodegradation process, three intermediates (M1-M3) were monitored and identified. Based on the identified metabolites and their biodegradation courses, a possible biodegradation pathway was proposed. IPP was probably transformed to different three metabolites in nematodes through oxidation and elimination of methyl and propyl etc. Under the same concentration, IPP had more severe toxicity than M1 on nematodes. IPP and M1 might reduce lifespan and decrease reproductive ability through influencing insulin/IGF signaling pathway and TOR signaling pathway. They could decrease expression levels of daf-16, sgk-1, aak-2, daf-15 and rict-1 genes, which involved in IGF and TOR signaling pathway.

miR-1236-3p suppresses the migration and invasion by targeting KLF8 in lung adenocarcinoma A549 cells.

MicroRNAs (miRNAs) have a great effect on regulating tumor cell migration, invasion, proliferation and prognosis. However, the mechanism of miR-1236-3p on regulating carcinogenesis is still unknown. In this study, the expression of miR-1236-3p was lower in lung adenocarcinoma tissues than that in adjacent normal tissue. In lung adenocarcinoma A549 cell line, miR-1236-3p decreased ability of cell invasion and migration, furthermore, we show that KLF8 is targeted by miR-1236-3p, and expression of miR-1236-3p is negatively correlated with KLF8. Additionally, miR-1236-3p suppressed the expression of KLF8 and EMT (epithelial mesenchymal transition)-related genes. Overexpression of KLF8 can promote EMT-related genes at protein level. In conclusion, our results support the fact that miR-1236-3p acts as a tumor inhibitor in lung adenocarcinoma by suppressing the activity of KLF8, and it may play a critical role in the diagnosis and treatment of lung cancer.

Relationship between Post-Thrombolysis Blood Pressure and Outcome in Acute Ischemic Stroke Patients Undergoing Thrombolysis Therapy.

BACKGROUND: The management of blood pressure (BP) for acute ischemic stroke (AIS) patients undergoing thrombolysis is still under debate. The purpose of this study was (1) to explore the association between post-thrombolysis BP and functional outcome and (2) to examine whether post-thrombolysis BP can predict functional outcome in Chinese AIS patients undergoing thrombolysis therapy. METHODS: From December 2012 to November 2016, AIS patients undergoing thrombolysis were reviewed retrospectively in the Department of Neurology at Xuanwu Hospital. The BP levels were measured before and immediately after thrombolysis. Clinical outcomes, which comprised favorable outcome (modified Rankin Scale score 0-2) and unfavorable outcome (modified Rankin Scale score 3-6) at 3 months, were analyzed by logistic regression model. A receiver operating characteristic curve was used to evaluate the predictive value of post-thrombolysis BP. RESULTS: Patients with unfavorable outcome at 3 months had a higher post-thrombolysis systolic BP than those with favorable outcome (P = .015). Multivariate analysis showed that post-thrombolysis systolic BP below 159.5 mm Hg was associated with favorable outcome. According to the receiver operating characteristic curve, post-thrombolysis systolic BP was a predictor of functional outcome with an area under the curve of .573 (95% confidence interval = .504-.642). CONCLUSIONS: Our study indicated that post-thrombolysis systolic BP is a predictor of functional outcome for Chinese AIS patients undergoing thrombolysis therapy. It is reasonable for AIS patients to keep post-thrombolysis systolic BP below 159.5 mm Hg to obtain a favorable outcome.

Study on the interaction of plasma protein binding rate between edaravone and taurine in human plasma based on HPLC analysis coupled with ultrafiltration technique.

In this work, two high-performance liquid chromatography (HPLC) assays were developed and validated for the independent determination of edaravone and taurine using 3-methyl-1-p-tolyl-5-pyrazolone and L-glutamine as internal standards. In in vitro experiments, human plasma was separately spiked with a mixture of edaravone and taurine, edaravone or taurine alone. Plasma was precipitated with acetonitrile containing 0.1% formic acid. Ultrafiltration was employed to obtain the unbound ingredients of the two drugs. The factors that might influence the ultrafiltration effiency were elaborately optimized. Plasma supernatant and ultrafiltrate containing taurine were derivated with o-phthalaldehyde and ethanethiol in the presence of 40 mmol/L sodium borate buffer (pH 10.2) at room temperature within 1 min. Chromatographic separations were achieved on an InertSustain C18 column (250 × 4.6 mm, 5 µm). Isocratic 50 mmol/L ammonium acetate-acetonitrile and gradient 50 mmol/L sodium acetate (pH 5.3)-methanol were respectively selected as the mobile phase for the determination of edaravone and taurine. All of the validation data including linearity, extraction recovery, precision, accuracy and stability conformed to the requirements. Results showed that there were no significant alterations in the plasma protein binding rate of taurine and edaravone, implying that the proposed combination therapy was pharmacologically feasible.

Early extremity MRI findings and pathological synovial changes in antigen-induced arthritis rabbit model.

PURPOSE: To investigate the association between early extremity MRI (E-MRI) findings and synovial pathological changes in antigen-induced arthritis (AIA) rabbit model. MATERIALS AND METHODS: AIA was successfully induced in the right knee of 32 sensitized Japanese white rabbits, which were then divided into four groups according to the time of killing after AIA induction: 1-week (Group A), 2-weeks (Group B), 3-weeks (Group C), and 4-weeks (Group D); the left knee served as control in each rabbit. RESULTS: There were varying degrees of joint effusion in all AIA groups. E-MRI scan showed low signal in T1-weighted images (T1Wi) and high signal in T2-weighted images (T2Wi). Enhanced E-MRI revealed elevated synovial signal at the right knee in the three-dimensional spoiled gradient T1WI, showing linear and band-shaped, diffuse hyperintensity. Histological examination of right knees found scattered inflammatory cell infiltration, swelling, and proliferation of the synovial cells at 7 days after AIA induction and dispersed and disordered proliferation of synovial cells up to 3 layers at 28 days postinduction. The synovial enhancement of right knee E-MRI was consistent with a synovial pathology score for all rabbits (Kappa = 0.965, P < 0.01). CONCLUSION: E-MRI can reveal the degree of changes in the joints and synovium at different periods of the AIA model.

LC-MS/MS methods for the determination of edaravone and/or taurine in rat plasma and its application to a pharmacokinetic study.

Three liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were respectively developed and validated for the simultaneous or independent determination of taurine and edaravone in rat plasma using 3-methyl-1-p-tolyl-5-pyrazolone and sulfanilic acid as the internal standards (IS). Chromatographic separations were achieved on an Agilent Zorbax SB-Aq (100 × 2.1 mm, 3.5 µm) column. Gradient 0.03% formic acid-methanol, isocratic 0.1% formic acid-methanol (90:10) and 0.02% formic acid-methanol (40:60) were respectively selected as the mobile phase for the simultaneous determination of two analytes, taurine or edaravone alone. The MS acquisition was performed in multiple reaction monitoring mode with a positive and negative electrospray ionization source. The mass transitions monitored were m/z [M + H](+) 175.1 → 133.0 and [M + H](+) 189.2 → 147.0 for edaravone and its IS, m/z [M - H](-) 124.1 → 80.0 and [M - H](-) 172.0 → 80.0 for taurine and its IS, respectively. The validated methods were successfully applied to study the pharmacokinetic interaction of taurine and edaravone in rats after independent intravenous administration and co-administration with a single dose. Our collective results showed that there were no significant alterations on the main pharmacokinetic parameters (area under concentration-time curve, mean residence time, half-life and clearance) of taurine and edaravone, implying that the proposed combination therapy was pharmacologically feasible.

Dabigatran etexilate versus warfarin in cerebral venous thrombosis in Chinese patients (CHOICE-CVT): An open-label, randomized controlled trial.

BACKGROUND: The efficacy and safety of dabigatran etexilate for Chinese patients with cerebral venous thrombosis (CVT) has not been well established. METHODS: CHOICE-CVT was an exploratory, single-center, randomized, open-label study in the National Center for Neurological Disorders involving Chinese patients with CVT aged 18 to 80 years who were randomly assigned (1:1) to either dabigatran etexilate or warfarin. Oral anticoagulants were initiated after 10-15 days of LMWH. The primary efficacy and safety endpoints included the number of patients with recurrent CVT and/or deep venous thrombosis (DVT) and major clinical bleeding within 180 days. Secondary efficacy endpoints included venous recanalization and change in papilledema at day 180. Secondary safety outcomes comprised death, clinical nonmajor bleeding, and any bleeding. The study was registered with ClinicalTrials.gov under NCT03930940. RESULTS: Between October 2017 and February 2023, a total of 89 patients were enrolled and randomly assigned to receive either dabigatran etexilate (n = 44) or warfarin (n = 45). At day 180, the dabigatran etexilate group showed a statistically nonsignificant but likely clinically significant number of patients with recurrent CVT and/or DVT (8 (18.2%; 95% CI, 6.3-30.0) vs 3 (6.7%; 95% CI, 0.0-14.2), p = 0.099, with a power (1-ß) of 38.401%) compared with the warfarin group. The dabigatran etexilate group showed a comparable number of patients with clinical major bleeding (0 (0) vs 0 (0) p = 1.000), and clinical nonmajor bleeding (1 (2.3%; 95% CI, 0.0-6.9) vs 1 (2.2%; 95% CI, 0.0-6.7)) but demonstrated a lower risk of any bleeding (1 (2.3%; 95% CI, 0.0-6.9) vs 9 (20.0%; 95% CI, 7.8-32.2)) compared with the warfarin group. Most patients in both groups achieved venous recanalization according to the Modified Qureshi scale (27 (75%; 95% CI, 60.1-89.9) in the dabigatran etexilate group vs 34 (82.9%; 95% CI, 70.9-95.0) in the warfarin group) and exhibited improvement in papilledema as per the Frisén classification (35 (97.2%; 95% CI, 91.6-100.0) in the dabigatran etexilate group vs 37 (88.1%, 95% CI, 77.9-98.3) in the warfarin group). CONCLUSIONS: These findings regarding efficacy and safety support the consideration of dabigatran etexilate therapy as a viable treatment option for Chinese patients with CVT.

Prognostic value of poly-microorganisms detected by droplet digital PCR and pathogen load kinetics in sepsis patients: a multi-center prospective cohort study.

This study aimed to investigate the prognostic value of a novel droplet digital polymerase chain reaction (DDPCR) assay in sepsis patients. In this prospective cohort study, univariable and multivariable Cox regressions were used to assess risk factors for 28-day mortality. We also monitored pathogen load together with clinical indicators in a subgroup of the cohort. A total of 107 sepsis patients with positive baseline DDPCR results were included. Detection of poly-microorganisms [adjusted hazard ratio (HR) = 3.19; 95% confidence interval (CI) = 1.34-7.62; P = 0.009], high Charlson Comorbidity Index (CCI) score (adjusted HR = 1.14; 95% CI = 1.01-1.29; P = 0.041), and Sequential Organ Failure Assessment (SOFA) score (adjusted HR = 1.18; 95% CI = 1.05-1.32; P = 0.005) at baseline were independent risk factors for 28-day mortality while initial pathogen load was not associated (adjusted HR = 1.17; 95% CI = 0.82-1.66; P = 0.385). Among 63 patients with serial DDPCR results, an increase in pathogen load at days 6-8 compared to baseline was a risk factor for 28-day mortality (P = 0.008). Also, pathogen load kinetics were significantly different between day-28 survivors and nonsurvivors (P = 0.022), with a decline overtime only in survivors and an increase from days 3 and 4 to days 6-8 in nonsurvivors. Using DDPCR technique, we found that poly-microorganisms detected and increased pathogen load a week after sepsis diagnosis were associated with poor prognosis.IMPORTANCEThis prospective study was initiated to explore the prognostic implications of a novel multiplex PCR assay in sepsis. Notably, our study was the largest cohort of sepsis with droplet digital polymerase chain reaction pathogen monitoring to date, allowing for a comprehensive evaluation of the prognostic significance of both pathogen species and load. We found that detection of poly-microorganisms was an independent risk factors for 28-day mortality. Also, pathogen load increase 1 week after sepsis diagnosis was a risk factor for 28-day mortality, and differential pathogen load kinetics were identified between day-28 survivors and nonsurvivors. Overall, this study demonstrated that pathogen species and load were highly correlated with sepsis prognosis. Patients exhibiting conditions mentioned above face a more adverse prognosis, suggesting the potential need for an escalation of antimicrobial therapy.Registered at ClinicalTrials.gov (NCT05190861).

Development and application of a LC-MS/MS assay for the simultaneous quantification of edaravone and taurine in beagle plasma.

An LC-MS/MS method was developed and validated for the simultaneous quantification of edaravone and taurine in beagle plasma. The plasma sample was deproteinized using acetonitrile containing formic acid. Chromatographic separations were achieved on an Agilent Zorbax SB-Aq (100 × 2.1 mm, 3.5 µm) column, with a gradient of water (containing 0.03% formic acid) and methanol as the mobile phase at a flow rate of 0.3 mL/min. The analyte detection was carried out in multiple reaction monitoring mode and the optimized precursor-to-product transitions of m/z [M+H](+) 175.1 → 133.0 (edaravone), m/z [M+H](+) 189.1 → 147.0 (3-methyl-1-p-tolyl-5-pyrazolone, internal standard, IS), m/z [M-H](-) 124.1→80.0 (taurine), and m/z [M-H](-) 172.0 → 80.0 (sulfanilic acid, IS) were employed to quantify edaravone, taurine, and their corresponding ISs, respectively. The LOD and the lower LOQ were 0.01 and 0.05 µg/mL for edaravone and 0.66 and 2 µg/mL for taurine, respectively. The calibration curves of these two analytes demonstrated good linearity (r ＞ 0.99). All the validation data including the specificity, precision, recovery, and stability conformed to the acceptable requirements. This validated method has successfully been applied in the pharmacokinetic study of edaravone and taurine mixture in beagle dogs.

Association between admission systemic immune-inflammation index and mortality in critically ill patients with sepsis: a retrospective cohort study based on MIMIC-IV database.

Systemic immune-inflammation index (SII) has been identified as a prognostic biomarker for various diseases. Our study aimed to investigate the association between SII and mortality risk in critically ill patients with sepsis, thus exploring possible tools for rapid screening. This retrospective cohort study was conducted using clinical data extracted from the Medical Information Mart for Intensive Care Database. The study included only patients diagnosed with sepsis admitted to the intensive care unit for the first time. We used the restricted cubic splines to explore the relationship between SII and 28-day mortality. Kaplan-Meier curve and Cox regression models were performed to evaluate the association between SII and mortality. Subgroup analysis was performed to explore the stability of the primary results. A total of 16,007 patients with sepsis were eligible in the final analysis. We found a J-shaped relationship between SII and mortality risk. The SII level associated with the lowest mortality risk was 774.46*109/L. Compared with the reference group (second SII quartile), the 28-day mortality was increased in the highest quartile and third quartile groups of SII levels; fully adjusted HRs were 1.16 (1.02 to 1.32) and 1.40 (1.23 to 1.58), respectively. However, although the lower SII (Q1 group) also showed a trend toward a higher hazard of 28-day mortality, there was no statistical difference, with a fully adjusted HR of 1.05 (0.92 to 1.21). In the population of critically ill patients with sepsis, low and high SII levels were associated with an increased risk of short-term mortality. The 28-day mortality risk was lowest at SII levels of 774.46*109/L.

A case report of autoimmune glial fibrillary acidic protein astrocytopathy presenting as an isolated spinal cord lesion.

INTRODUCTION: Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a group of neurological syndromes involving the meninges, brain, spinal cord, and optic nerves and is characterized by sensitivity to steroid therapy. Due to the diverse clinical presentation and lack of uniform diagnostic criteria, GFAP-A can easily be overlooked or diagnosed as another disease. It is even rarer when presenting as an isolated spinal cord lesion. CASE REPORT: We report the case of a 70-year-old man with initial symptoms of numbness and weakness in both lower limbs, followed by difficulty in urination and defecation, and progression of numbness upward to the hands. Magnetic resonance imaging (MRI) showed a lesion in the spinal cord from cervical level 2 to thoracic 7 in a T2-weighted image. T1-weighted image showed a punctate, lamellar strengthening lesion with significant spinal strengthening. GFAP immunoglobulin G (IgG) was detected in the cerebrospinal fluid and blood. After treatment with intravenous gamma globulin (IVIG), the patient symptoms improved and spinal cord enhancement was reduced. CONCLUSION: Long segment cases with punctate and patchy enhancement of the spinal cord are difficult to distinguish from CLAPPERS, so GFAP-A antibody detection is very important. This atypical case also increases neurologists' understanding of GFAP-A.