Efficacy of antiplatelet drugs combined with Argatroban in treating acute ischemic stroke and its impact on patients' coagulation function and neurological function: a preliminary trial.

This retrospective study analyzed the efficacy of combined antiplatelet therapy with Argatroban in treating acute ischemic stroke (AIS) and its impact on patients' coagulation and neurological functions. Clinical data of 113 AIS patients admitted between January 2021 and January 2023 were retrospectively analyzed. Patients were divided into control (n = 56) and observation (n = 57) groups based on treatment interventions. The control group patients were treated with antiplatelet drugs, while the observation group patients received combination therapy with apatinib on the basis of the control group treatment. Compared to the control group, the observation group demonstrated higher clinical efficacy, improved coagulation parameters, reduced stroke severity (measured by NIHSS), enhanced daily living abilities (BI scores), and lowered inflammatory and neural injury markers post-treatment. Adverse reaction incidence was similar between groups. Combining Argatroban with antiplatelet drugs in AIS management showed superior efficacy without increasing adverse effects, suggesting its potential for clinical application.

Analysis of risk factors for the efficacy of tirofiban in the treatment of acute ischemic stroke.

OBJECTIVE: To analyse the risk factors for tirofiban efficacy in the early treatment of acute ischemic stroke. METHODS: The clinical data of 204 patients with acute ischemic stroke treated with tirofiban were retrospectively analysed. The early efficacy of tirofiban was assessed by a ≥ 4-point decline in the National Institutes of Health Stroke Scale (NIHSS) score or via the complete disappearance of neurological deficits at the end of ischemic stroke treatment, and patients were divided into an effective groupand an ineffective group. Univariate and multivariate logistic regression analyses were used to compare the differences in clinical data between the two groups. RESULTS: Multivariate logistic regression analysis showed that heavy drinking (OR 0.477, 95% CI 0.249-0.899, P = 0.023), elevated total cholesterol (OR 0.331, 95% CI 0.141-0.734, P = 0.008), NIHSS score at initiation of treatment (OR 1.130, 95% CI 1.026-1.253, P = 0.016) and time from onset to treatment (OR 0.839, 95% CI 0.700-0.979, P = 0.038) were independent risk factors affecting the early efficacy of tirofiban. CONCLUSION: The early curative effect of tirofiban in acute ischemic stroke patients with a heavy drinking history and elevated total cholesterol was poor. In patients with acute ischemic stroke, the higher the NIHSS score was within a certain range (8 < NIHSS ≤15 and the Org 10,172 Trial in the Treatment of Acute Stroke (TOAST) belongs to small-artery occlusion lacunar) at the initiation of treatment and the shorter the time from onset to treatment, the better the early curative effect was.

Safety and efficacy of low-dose and long-course tirofiban in large hemispheric infarction.

Background: The clinical efficacy and safety of tirofiban in the treatment of large hemispheric infarction (LHI) remain controversial. Methods: This study prospectively enrolled patients with acute LHI who were admitted to Putuo Hospital affiliated with Shanghai University of Traditional Chinese Medicine from June 2021 to December 2021. The patients were randomly assigned to the tirofiban group [3-4 µg/(kg·h)] or control group (clopidogrel 75 mg/d). Results: A total of 71 patients with acute LHI were selected: 36 in the tirofiban group and 35 in the control group. The reduction of the NIHSS score in the tirofiban group was 2.92 ± 9.31 at discharge, and that of the control group was -3.23 ± 12.06 (p = 0.021, OR, 0.006; 95% CI, 0.004-0.008). Six patients (16.7%) in tirofiban group and 14 patients (40%) in control group died during hospitalization (p = 0.029, OR, 0.300; 95% CI, 0.099-0.908). There was significant difference in Modified Rankin Scale (mRS) 5-6 scores at 90 days between the two groups (p = 0.023, OR, 0.327; 95% CI, 0.124-0.867). However, there was no significant difference in mRS 0-1 (p = 0.321, OR, 0.972; 95% CI, 0.920-1.027), mRS 2 (p = 0.572, OR, 2.00; 95% CI, 0.173-23.109), mRS 3 (p = 0.225, OR, 2.214; 95% CI, 0.601-8.161), or mRS 4(p = 0.284, OR, 1.859; 95% CI, 0.593-5.825) scores between the two groups. There was no difference in symptomatic intracranial hemorrhage (p = 0.29, OR, 0.305; 95% CI, 0.030-3.081), asymptomatic intracranial hemorrhage (p = 0.123, OR, 0.284; 95% CI, 0.053-1.518). There was a significant difference in systemic bleeding events during hospitalization (p = 0.044, OR, 0.309; 95% CI, 0.096-1.000). Conclusions: Low-dose and long-course tirofiban treatment may significantly improve the early neurological function and reduce the in-hospital mortality in LHI patients. Meanwhile, tirofiban does not increase the risk of any type of bleeding events.

LINC00173 Interacts With DNMT1 to Regulate LINC00173 Expression via Promoter Methylation in Hydroquinone-Induced Malignantly Transformed TK6 Cells and Benzene-Exposed Workers.

Long-term exposure to benzene or its metabolite, hydroquinone (HQ), can causally contribute to acute myeloid leukemia. Long-noncoding RNAs are essential epigenetic regulators with critical roles in tumor initiation and malignant progression; however, the mechanism by which aberrantly expressed LINC00173 (long intergenic nonprotein coding RNA 173) regulates the pathogenesis of acute myeloid leukemia is not fully understood. Here, we found that the expression of LINC00173 decreased while the expression of DNA methyltransferase 1 (DNMT1) increased, and the methylation of LINC00173 promoter was negatively correlated with LINC00173 expression in GEPIA, CCLE databases, benzene-exposed workers, B-cell non-Hodgkin's lymphoma, K562, U937, or HQ-induced malignantly transformed TK6 (HQ-MT cells). Furthermore, in 5-aza-2'-deoxycytidine (DNA methyltransferase inhibitor) or trichostatin A (histone deacetylation inhibitor)-treated HQ-MT cells, the expression of LINC00173 was restored by reduced DNA promoter methylation levels. HQ-MT cells with DNMT1 knockout by CRISPR/Cas9 restored the expression of LINC00173 and inhibited the DNA methylation of its promoter as well as enrichment of DNMT1 to promoter. Overexpression of LINC00173 inhibited the expression of DNMT1, cell proliferation, tumor growth, enhanced chemosensitivity to cisplatin, and apoptosis in HQ-MT cells. LINC00173 interacts with DNMT1 to regulate the methylation of LINC00173 promoter. Overall, this study provides evidence that interaction between DNMT1 and LINC00173 regulates the expression of LINC00173 by regulating its promoter methylation level, thus regulating the function of HQ-MT cells in vitro and in vivo, providing a new therapeutic target for benzene-induced tumor.

Regulatory loop between lncRNA FAS-AS1 and DNMT3b controls FAS expression in hydroquinone-treated TK6 cells and benzene-exposed workers.

Hydroquinone (HQ), one of the main metabolites of benzene, is a well-known human leukemogen. However, the specific mechanism of how benzene or HQ contributes to the development of leukemia is unknown. In a previous study, we demonstrated the upregulation of DNA methyltransferase (DNMT) expression in HQ-induced malignant transformed TK6 (HQ-TK6) cells. Here, we investigated whether a regulatory loop between the long noncoding RNA FAS-AS1 and DNMT3b exists in HQ-TK6 cells and benzene-exposed workers. We found that the expression of FAS-AS1 was downregulated in HQ-TK6 cells and workers exposed to benzene longer than 1.5 years via histone acetylation, and FAS-AS1 expression was negatively correlated with the time of benzene exposure. Restoration of FAS-AS1 in HQ-TK6 cells promoted apoptosis and inhibited tumorigenicity in female nude mice. Interestingly, treatment with a DNMT inhibitor (5-aza-2-deoxycytidine), histone deacetylase inhibitor (trichostatin A), or DNMT3b knockout led to increased FAS-AS1 through increased H3K27ac protein expression in HQ-TK6 cells, and DNMT3b knockout decreased H3K27ac and DNMT3b enrichment to the FAS-AS1 promoter region, which suggested that DNMT3b and/or histone acetylation involve FAS-AS1 expression. Importantly, restoration of FAS-AS1 resulted in reduced expression of DNMT3b and SIRT1 and increased expression of FAS in both HQ-TK6 cells and xenograft tissues. Moreover, the average DNMT3b expression in 17 paired workers exposed to benzene within 1.5 years was decreased, but that of the remaining 103 paired workers with longer exposure times was increased. Conversely, DNMT3b was negatively correlated with FAS-AS1 expression. Both FAS-AS1 and DNMT3b influenced the enrichment of H3K27ac in the FAS promoter region by regulating the expression of SIRT1, consequently upregulating FAS expression. Taken together, these observations demonstrate crosstalk between FAS-AS1 and DNMT3b via a mutual inhibition loop and indicate a new mechanism by which FAS-AS1 regulates the expression of FAS in benzene-related carcinogenesis.

[Effects of hindlimb unloading on bone histomorphometry and bone mass in rats].

OBJECTIVE: To study the effects of hindlimb unloading on bone histomorphometry, bone local growth factor, bone biomechanical properties and bone contents in rats. METHOD: Male SD rats were arranged into free active control group (CON) and tail-suspended group (TS) with 9 rats in each group. The experiment lasted for 3 weeks. Bone histomorphometry, bone local growth factor, biomechanical properties and bone contents were measured before and after tail suspension. RESULT: Structure of the trabecular bone was disorganized. Compared with CON, trabecular bone volume (% Tb. Ar), mean trabecular plate thickness (Tb. Th), osteoblast surface (Ob. S) were significantly reduced in TS. The eroded surface (Oc. N/BS) tended to be higher, though not significant at this stage of tail suspension; alkaline phosphatase (ALP) activity in the tibia were significantly reduced, but NO content in the femoral trunk was significantly decreased; bone biomechanical properties, bone mineral content (BMC), bone density (BD) and bone collagen density (BCD) in the femur were significantly reduced. CONCLUSION: Hindlimb unloading may lead to regression of bone microstructure, change of bone local growth factor content, reduction of bone biomechanical properties and bone content.