Effects of Argatroban on Hcy, hs-CRP and FIB levels in patients with acute cerebral infarction.

OBJECTIVE: To evaluate the effects of argatroban on the levels of Hcy, hs-CRP and FIB in patients with acute cerebral infarction (ACI). METHODS: A retrospective analysis was performed on 382 patients with ACI who were hospitalized in the Department of Neurology of our hospital from January 2017 to December 2019. Among them, 158 patients received conventional treatment as the control group and 224 patients received combined treatment with argatroban as the study group. NHISS score, mRS score, Hcy, hs-CRP, FIB level, quality of life, adverse reactions were compared between the two groups after treatment. The levels of Hcy and hs-CRP in patients with different mRS scores were compared. RESULTS: A superior clinical efficacy of the study group was observed than the control group (p < 0.05). The study group witnessed a remarkably lower NHISS score, Hcy, hs-CRP and FIB level as compare to the control group (p < 0.05). The ADL and FMA scores in the study group were higher than those in the control group (p < 0.05). The levels of Hcy and hs-CRP in mRS 0-2 patients were lower than those in mRS 3-6 patients (p < 0.05). CONCLUSION: Argatroban in ACI patients can significantly enhance the clinical efficacy and improve the quality of life. It is closely related to the reduction of Hcy and hs-CRP levels, but the mechanism needs to be further studied.

Sublingual Edaravone Dexborneol for the Treatment of Acute Ischemic Stroke: The TASTE-SL Randomized Clinical Trial.

Importance: Sublingual edaravone dexborneol, which can rapidly diffuse and be absorbed through the oral mucosa after sublingual exposure, is a multitarget brain cytoprotection composed of antioxidant and anti-inflammatory ingredients edaravone and dexborneol. Objective: To investigate the efficacy and safety of sublingual edaravone dexborneol on 90-day functional outcome in patients with acute ischemic stroke (AIS). Design, Setting, and Participants: This was a double-blind, placebo-controlled, multicenter, parallel-group, phase 3 randomized clinical trial conducted from June 28, 2021, to August 10, 2022, with 90-day follow-up. Participants were recruited from 33 centers in China. Patients randomly assigned to treatment groups were aged 18 to 80 years and had a National Institutes of Health Stroke Scale score between 6 and 20, a total motor deficit score of the upper and lower limbs of 2 or greater, a clinically diagnosed AIS symptom within 48 hours, and a modified Rankin Scale (mRS) score of 1 or less before stroke. Patients who did not meet the eligibility criteria or declined to participate were excluded. Intervention: Patients were assigned, in a 1:1 ratio, to receive sublingual edaravone dexborneol (edaravone, 30 mg; dexborneol, 6 mg) or placebo (edaravone, 0 mg; dexborneol, 60 µg) twice daily for 14 days and were followed up until 90 days. Main Outcomes and Measures: The primary efficacy outcome was the proportion of patients with mRS score of 1 or less on day 90 after randomization. Results: Of 956 patients, 42 were excluded. A total of 914 patients (median [IQR] age, 64.0 [56.0-70.0] years; 608 male [66.5%]) were randomly allocated to the edaravone dexborneol group (450 [49.2%]) or placebo group (464 [50.8%]). The edaravone dexborneol group showed a significantly higher proportion of patients experiencing good functional outcomes on day 90 after randomization compared with the placebo group (290 [64.4%] vs 254 [54.7%]; risk difference, 9.70%; 95% CI, 3.37%-16.03%; odds ratio, 1.50; 95% CI, 1.15-1.95, P = .003). The rate of adverse events was similar between the 2 groups (89.8% [405 of 450] vs 90.1% [418 of 464]). Conclusion and Relevance: Among patients with AIS within 48 hours, sublingual edaravone dexborneol could improve the proportion of those achieving a favorable functional outcome at 90 days compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT04950920.

Protection roles of serum vitamin D levels in the cardiovascular system.

Protection roles of serum vitamin D levels in the cardiovascular system. This observational study enrolled 286 young ACI patients with type 2 diabetes mellitus in our Hospital from October 2016 to April 2020 as the study group. 127 healthy individuals as the control group. Serum levels of vitamin D and blood pressure indexes of the two groups were measured and the correlation between vitamin D levels and the clinical phenotype of young cerebral infarction was explored. Significantly higher 25-hydroxyvitamin D was observed in the study group vs. control group. During the day, The values of systolic and diastolic blood pressure and mean blood pressure was well-balanced between the two groups. However, at night and within 24 hours, significant differences in systolic and diastolic blood pressure and mean value were observed between the two groups. The higher the vitamin D level, the greater the decrease in blood pressure at night. Serum 25-hydroxyvitamin D was positively correlated with the reduction of night systolic and diastolic blood pressure. Low levels of 25-hydroxyvitamin D led to a small decrease in blood pressure at night, resulting in a vulnerable cardiovascular system and an increased incidence of cerebral infarction in the young population.

Prediction Model between Serum Vitamin D and Neurological Deficit in Cerebral Infarction Patients Based on Machine Learning.

Objective: Vitamin D is associated with neurological deficits in patients with cerebral infarction. This study uses machine learning to evaluate the prediction model's efficacy of the correlation between vitamin D and neurological deficit in patients with cerebral infarction. Methods: A total of 200 patients with cerebral infarction admitted to the Department of Neurology of our hospital from July 2018 to June 2019 were selected. The patients were randomly divided into a training set (n = 140) and a test set (n = 60) in a 7 : 3 ratio. The prediction model is constructed from the training set's data, and the model's prediction effect was evaluated by test set data. The area under the receiver operator characteristic curve was used to assess the prediction efficiency of models. Results: In the training set, the area under the curve (AUC) of the logistic regression model and XGBoost algorithm model was 0.727 (95% CI: 0.601~0.854) and 0.818 (95% CI: 0.734~0.934), respectively. While in the test set, the AUC of the logistic regression model and XGBoost algorithm model was 0.761 (95% CI: 0.640~0.882) and 0.786 (95% CI: 0.670~0.902), respectively. Conclusion: The prediction model of the correlation between vitamin D and neurological deficit in patients with cerebral infarction based on machine learning has a good prediction efficiency.

Complementary Transcriptomic and Proteomic Analysis in the Substantia Nigra of Parkinson's Disease.

Parkinson's disease (PD) is a disease that involves brain damage and is associated with neuroinflammation, mitochondrial damage, and cell aging. However, the pathogenic mechanism of PD is still unknown. Sequencing data and proteomic data can describe the fluctuation of molecular abundance in diseases at the mRNA level and protein level, respectively. In order to explore new targets in the pathogenesis of PD, the study analyzed molecular changes from the database by combining transcriptomic and proteomic analysis. Differentially expressed genes and differentially abundant proteins were summarized and analyzed. Enrichment and cluster analysis emphasized the importance of neurotransmitter release, mitochondrial damage, and vesicle transport. The molecular network revealed a subnetwork of 9 molecules related to SCNA and TH and revealed hub gene with differential expression at both mRNA and protein levels. It found that ACHE and CADPS could be used as new targets in PD, emphasizing that impaired nerve signal transmission and vesicle transport affect the pathogenesis of PD. Our research emphasized that the joint analysis and verification of transcriptomics and proteomics were devoted to understanding the comprehensive views and mechanism of pathogenesis in PD.

Risk factors for cognitive impairment in patients with first-time ischemic stroke.

OBJECTIVE: To determine the risk factors for cognitive impairment (CI) in patients with first-time ischemic stroke. METHODS: The clinical data of 180 patients with ischemic stroke who were admitted to our hospital from January 2018 to December 2019 was retrospectively analyzed. Patients with MMSE score ≤24 were included into the CI group and the rest of the patients were placed into the normal group. Multivariate logistic regression was applied to describe risk factors for CI in patients with first-time ischemic stroke. RESULTS: Among the patients with first-time ischemic stroke, 96 cases (53%) developed CI, 84 cases (47%) were normal. In different subtypes of TOAST classifications, patients with large-artery atherosclerosis had the highest CI incidence (66.96%). For different infarction sites, the highest CI incidence occurred in the frontal lobe (82.35%), and the lowest was from cerebellar infarction (37.50%). The difference of CI incidences in the frontal lobe, parietal lobe, temporal lobe and occipital lobe was significant between the two groups (P<0.05). Logistic regression analysis indicated that independent risk factors for CI in patients with first ischemic stroke include age ≥60 years old, diabetes history, CRP >6.53 mg/L, Hcy >13.84 µmol/L, NIHSS score >4.37, VD <45.16 nmol/L, and the difference was statistically significant (P<0.05). CONCLUSION: The study showed a high CI incidence in patients with preexisting ischemic stroke. Age ≥60 years old, history of diabetes mellitus, CRP >6.53 mg/L, Hcy >13.84 µmol/L, NIHSS score >4.37 score, VD <45.16 nmol/L are independent risk factors for CI in patients with first-time ischemic stroke.

Dysregulation of lncRNA SNHG1/miR-145 axis affects the biological function of human carotid artery smooth muscle cells as a mechanism of carotid artery restenosis.

Carotid angioplasty and stenting have developed into reliable options for patients with carotid stenosis. However, postoperative restenosis remains a serious and unresolved problem. Restenosis is partly caused by the proliferation of vascular smooth muscle cells. As certain long non-coding RNAs (lncRNAs) affect cell proliferation and migration, the present study aimed to investigate them as novel biomarkers for restenosis development and to further reveal the potential underlying mechanisms. The expression of lncRNA small nucleolar RNA host gene 1 (SNHG1) and microRNA145 (miR-145) in human carotid artery smooth muscle cells (hHCtASMCs) was analyzed using reverse transcription-quantitative PCR. In addition, a luciferase reporter assay was performed to investigate the interaction between SNHG1 and miR-145. The effects of the SNHG1/miR-145 axis on the proliferation and migration of hHCtASMCs were evaluated by Cell Counting Kit-8 and Transwell assays. Serum SNHG1 and miR-145 expression levels were increased and decreased, respectively, in patients with restenosis (all P<0.001). High SNHG1 and low miR-145 were identified as risk factors for restenosis onset (all P<0.01). Furthermore, decreasing SNHG1 expression levels in hHCtASMCs inhibited cell proliferation and migration. The luciferase reporter assay and expression results demonstrated that miR-145 may be a target of SNHG1 and mediated the effects of SNHG1 on hHCtASMC proliferation and migration. The results obtained suggested that abnormal expression of SNHG1 and miR-145 may be risk factors for restenosis. The present study revealed that the SNHG1/miR-145 axis regulates hHCtASMC proliferation and migration, indicating its potential for restenosis prevention and treatment.

Edaravone Dexborneol Versus Edaravone Alone for the Treatment of Acute Ischemic Stroke: A Phase III, Randomized, Double-Blind, Comparative Trial.

BACKGROUND AND PURPOSE: Edaravone dexborneol, comprised of 2 active ingredients, edaravone and (+)-borneol, has been developed as a novel neuroprotective agent with synergistic effects of antioxidant and anti-inflammatory in animal models. The present clinical trial aimed at testing the effects of edaravone dexborneol versus edaravone on 90-day functional outcome in patients with acute ischemic stroke (AIS). METHODS: A multicenter, randomized, double-blind, comparative, phase III clinical trial was conducted at 48 hospitals in China between May 2015 and December 2016. Inclusion criteria included patients diagnosed as AIS, 35 to 80 years of age, National Institutes of Health Stroke Scale Score between 4 and 24, and within 48 hours of AIS onset. AIS patients were randomized in 1:1 ratio into 2 treatment arms: 14-day infusion of edaravone dexborneol or edaravone injection. The primary end point was the proportion of patients with modified Rankin Scale score ≤1 on day 90 after randomization. RESULTS: One thousand one hundred sixty-five AIS patients were randomly allocated to the edaravone dexborneol group (n=585) or the edaravone group (n=580). The edaravone dexborneol group showed significantly higher proportion of patients experiencing good functional outcomes on day 90 after randomization, compared with the edaravone group (modified Rankin Scale score ≤1, 67.18% versus 58.97%; odds ratio, 1.42 [95% CI, 1.12-1.81]; P=0.004). The prespecified subgroup analyses indicated that a greater benefit was observed in female patients than their male counterparts (2.26, 1.49-3.43 versus 1.14, 0.85-1.52). CONCLUSIONS: When edaravone dexborneol versus edaravone was administered within 48 hours after AIS, 90-day good functional outcomes favored the edaravone dexborneol group, especially in female patients. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02430350.

Long non-coding RNA cyclin-dependent kinase inhibitor 2B antisense ribonucleic acid 1 is associated with in-stent restenosis and promotes human carotid artery smooth muscle cell proliferation and migration by sponging miR-143-3p.

Carotid angioplasty and stenting (CAS) is an efficient therapeutic approach for carotid stenosis. However, in-stent restenosis (ISR) frequently occurs and seriously affects the therapeutic efficacy of CAS. Certain non-coding (nc)RNAs serve potential roles in ISR development and progression. Thus, the goals of the present study were to investigate novel biomarkers for ISR development and to further uncover the mechanisms underlying the progression of ISR. The expression of long ncRNA cyclin-dependent kinase inhibitor (CDKN)2B-antisense 1 (AS1) and microRNA (miR)-143-3p in patients with ISR and human carotid artery smooth muscle cells (hHCtASMCs) was analyzed using reverse transcription-quantitative PCR. A luciferase reporter assay was performed to examine the interaction between CDKN2B-AS1 and miR-143-3p. The effects of the CDKN2B/miR-143-3p axis on hHCtASMC proliferation and migration were assessed using Cell Counting Kit-8 and Transwell assays. The results indicated that serum CDKN2B-AS1 was increased and miR-143-3p was decreased in patients with ISR as compared with that in patients with no ISR (all P<0.001). CDKN2B-AS1 and miR-143-3p were identified as risk factors for ISR onset (all P<0.05) and knockdown of CDKN2B-AS1 in hHCtASMCs led to inhibited cell proliferation and migration. Furthermore, the luciferase reporter assay and expression analysis indicated that miR-143-3p is a target of CDKN2B-AS1 and may mediate the effects of CDKN2B-AS1 on hHCtASMC proliferation and migration. In conclusion, dysregulation of CDKN2B-AS1 and miR-143-3p may represent risk factors for the occurrence of ISR. The in vitro results suggested that the CDKN2B-AS1/miR-143-3p axis may regulate the proliferation and migration of hHCtASMCs, indicating its potential to be developed as a target for preventative measures and therapies for ISR.

Long non-coding RNA LINC01194 promotes the proliferation, migration and invasion of lung adenocarcinoma cells by targeting miR-641/SETD7 axis.

BACKGROUND: It is increasingly evidenced that long non-coding RNAs (lncRNAs) play an important role in various diseases. LncRNA LINC01194 acts as an oncogene in several cancer types. Nevertheless, the role of LINC01194 in lung adenocarcinoma (LUAD) has not yet been revealed. METHODS: qRT-PCR was used to detect the expression of LINC01194, miR-641 and SETD7 mRNA, while western blot was exploited to examine SETD7 protein level. Cell proliferation was detected by colony formation and EdU assays. Transwell assays detected cell migration and invasion. TUNEL assay and flow cytometry analysis were used to detect cell apoptosis. RIP, RNA pull down and luciferase reporter assays detected the binding among LINC01194, miR-641 and SETD7. RESULTS: LINC01194 was significantly upregulated in LUAD tissues and cell lines. Knockdown of LINC01194 resulted in decreased cell proliferation, migration and invasion, and increased apoptosis. Mechanistic experiments unveiled that LINC01194 augmented SETD7 expression in LUAD cells by competitively interacting with miR-641. Rescue experiments showed that miR-641 inhibition and SETD7 overexpression rescued the repressing impacts on LUAD cell proliferation, migration and invasion caused by LINC01194 knockdown. CONCLUSION: LINC01194 promotes the progression of LUAD by enhancing miR-641-targeted SETD7. The LINC01194/miR-641/SETD7 axis might provide new molecular targets for treating LUAD.

Relevance of dissolved organic matter generated from green manuring of Chinese milk vetch in relation to water-soluble cadmium.

Dissolved organic matter (DOM) can become a carrier of soil contaminants. Therefore, an understanding of the evolution and characteristics of DOM produced by Chinese milk vetch during green manuring is crucial. In this study, DOM solutions from 28 days' manuring with three different organic materials were characterized using three-dimensional fluorescence excitation-emission matrix (3D-EEM) with parallel factor (PARAFAC) analysis, and ultraviolet-visible spectroscopy. With the green manuring milk vetch at flowering period (MVFP), the DOC and water-soluble cadmium (WS-Cd) in soil solution reached 1875 mg/l and 2.64 µg/l, respectively, on day 6 after manuring. The PARAFAC analysis modeled three components: protein-like (tryptophan) and two humic-like components (humic acid and fulvic acid); DOM produced by MVFP was primarily protein-like during the early stage of decomposition. The aromaticity and molecular weight of DOM in the MVFP treatment was lower than in the other treatments, which could promote the release of soil particle-adsorbed Cd to soil solution. Principal components analysis showed that aromaticity was the main factor affecting Cd solubility, and the negative linear correlation of aromaticity with WS-Cd reached 0.4827. The results of this study supported the idea that manuring with MVFP might accelerate Cd infiltration to deep soil with water under gravity.

Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis.

AIM: To explore the correlation between serum vitamin B12 level and peripheral neuropathy in patients with chronic atrophic gastritis (CAG). METHODS: A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination from September 2013 to September 2016 were selected for this study. The age of these patients ranged within 18- to 75-years-old. Blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori (H. pylori) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12 deficiency risk factors, and to analyze the relationship between vitamin B12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin B12, patients with peripheral neuropathy were observed. RESULTS: Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were risk factors for the occurrence of peripheral nerve degeneration. Furthermore, CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve (R = 0.463). After vitamin B12 supplementation, patients with peripheral neuropathy improved. CONCLUSION: Serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin B12 deficiency and peripheral neuropathy. When treating CAG, vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy associated with vitamin B12 deficiency may be considered in patients with CAG. Furthermore, the timely supplementation of vitamin B12 during the clinical treatment of CAG can reduce or prevent peripheral nervous system lesions.

Study of the effects of nesfatin-1 on gastric function in obese rats.

AIM: To investigate the effects of nesfatin-1 on gastric function in obese rats. METHODS: The obese rat model was induced by a high-fat diet. The gastric emptying rate and gastric acid secretory capacity of the rats were determined after treatment with different drug concentrations of nesfatin-1 and administration routes. Based on this, the expression of H+/K+-ATPase was measured using RT-PCR and western blot to preliminarily explore the mechanism of gastric acid secretion changes. RESULTS: Body weight, body length, and Lee's index of the rats significantly increased in the high-fat diet-induced obese rat model. Two hours after lateral intracerebroventricular injection of nesfatin-1, the gastric emptying rate and gastric acid secretory capacity of rats decreased. Four hours after injection, both were restored to normal levels. In addition, the expression of H+/K+-ATPase decreased and moved in line with changes in gastric acid secretory capacity. This in vivo experiment revealed that intracerebroventricular injection of nesfatin-1, rather than intravenous injection, could suppress gastric function in obese rats. Moreover, its effect on the gastric emptying and gastric acid secretory capacity of rats is dose-dependent within a certain period of time. CONCLUSION: Through this research, we provide a theoretical basis for further studies on nesfatin-1, a potential anti-obesity drug.

The effectiveness and safety of dual antiplatelet therapy in ischemic cerebrovascular disease with intracranial and extracranial arteriostenosis in Chinese patients: A randomized and controlled trail.

BACKGROUND: There are limited data on the effect of dual antiplatelet treatment with clopidogrel plus aspirin in patients with ischemic cerebrovascular disease and intracranial and extracranial arteriostenosis. The aim of our study was to evaluate the efficacy and safety of aspirin plus clopidogrel in the treatment of ischemic cerebrovascular disease with intracranial and extracranial arteriostenosis. METHODS: Patients with clinically evident acute cerebral infarction or transient ischemic attack combined with intracranial and extracranial arteriostenosis (greater than 50%) who were unsuitable or reluctance to perform stent implantation were enrolled in this study. We randomly assigned these patients to receive clopidogrel (75 or 50 mg) plus aspirin (100 mg) or aspirin (100 mg) once daily through 90 days, and followed them for 90 days. We examined the main endpoints including the recurrence of stroke, death from cardiovascular causes, and bleeding events. RESULTS: In all, 200 patients were recruited and followed for 90 days. Ischemic stroke occurred in 6 patients (9.1%) treated with 50 mg clopidogrel and aspirin, 6 patients (9.1%) receiving 75 mg clopidogrel and aspirin, whereas 19 patients (27.9%) in the aspirin group (aspirin alone vs copidogrel 50 mg plus aspirin; 95% confidence intervals 1.704-23.779, P < 0.05; aspirin alone vs copidogrel 75 mg plus aspirin; 95% confidence intervals 1.190-13.240, P < 0.05). There were more hemorrhagic events among recipients (3 patients [2.3%]) in the copidogrel plus aspirin group than aspirin recipients (0 patient [0%]), including 1 subcutaneous hemorrhage in the group of 50 mg clopidogrel and aspirin, doubling the number of nasal and gum bleeding in the group of 75 mg clopidogrel and aspirin (P > 0.05). No intracranial hemorrhage and gastro-intestinal hemorrhage occurred in these 3 groups. CONCLUSION: Accordingly, 50 mg clopidogrel plus aspirin, and 75 mg clopidogrel plus aspirin were all superior to aspirin alone as stroke prevention in patients with cerebral infarction or transient ischemic attack combined with intracranial and extracranial arteriostenosis. The effect of secondary stroke prevention was similar between 50 mg clopidogrel plus aspirin and 75 mg clopidogrel plus aspirin. The therapy of 75 mg clopidogrel plus aspirin resulted in a worrisome tread in bleeding events.

A novel method for amino starch preparation and its adsorption for Cu(II) and Cr(VI).

A novel method was proposed to prepare amino starch by reacting ethylenediamine with previously synthesized dialdehyde starch. Different factors affecting the preparation, i.e., ethylenediamine concentration, ethylenediamine:dialdehyde starch molar ratio, pH, duration and temperature have been studied. The modified starch was characterized by IR spectroscopy, elemental analysis, X-ray diffraction and differential scanning calorimetry. The amino starch derivatives were evaluated as adsorbents. The adsorption activity for heavy metals such as Cu(II) and Cr(VI) by crosslinked amino starch was studied in terms of adsorption amount, kinetics and isotherm; and adsorbent reuse were also studied. Adsorption processes for Cu(II) and Cr(VI) on crosslinked amino starch fit a Langmuir isotherm, and adsorption for Cu(II) and Cr(VI) from aqueous solution was endothermic reactions. Crosslinked amino starch was very effective for the adsorption of Cu(II) and Cr(VI), and efficient in capacity, recycled.