Bibliometric and visualized analysis of global research on microRNAs in gastric cancer: from 2013 to 2023.

Gastric cancer (GC) imposes a heavy burden on global public health, and microRNAs (miRNAs) play a crucial role in the diagnosis and treatment of GC. Therefore, it is necessary to clarify the hotspots and frontiers in the field of miRNAs in GC to guide future research. A total of 2,051 publications related to miRNAs in GC from January 2013 to December 2023 were searched from the Web of Science Core Collection database. CiteSpace was used to identify research hotspots and delineate developmental trends. In the past decade, China, Nanjing Medical University, and Ba Yi were the most contributing research country, institute, and author in this field, respectively. The role of miRNAs as biomarkers in GC, the mechanism of miRNAs in the progression of GC, and the impact of the mutual effects between miRNAs and Helicobacter pylori on GC have been regarded as the research hotspots. The mechanisms of miRNAs on glucose metabolism and the application of the roles of circular RNAs as miRNA sponges in GC treatment will likely be frontiers. Overall, this study called for strengthened cooperation to identify targets and therapeutic regimes for local specificity and high-risk GC types, and to promote the translation of research results into clinical practice.

The efficacy and safety of intravenous tirofiban in the treatment of acute ischemic stroke patients with early neurological deterioration.

WHAT IS KNOWN AND OBJECTIVE: Many patients with acute ischemic stroke (AIS) develop early neurological deterioration (END), leading to disabilities or death. Thus, this study aimed to investigate the efficacy and safety of intravenous tirofiban in treating patients with AIS and END who missed the thrombolysis time window. METHODS: A total of 123 AIS-END patients participated in the study between January 2021 and December 2021. Patients were randomized into the tirofiban group (n = 63) and the control group (n = 60) based on whether a tirofiban injection was administered. The National Institute of Health Stroke Scale (NIHSS) was used to assess neurological function at the 48th hour and on the 7th day after intervention, and the modified Rankin Scale (mRS) was used to assess neurological recovery 90 days after AIS. Adverse reactions during the intervention were recorded for safety analysis. RESULTS AND DISCUSSION: The 7th day NIHSS and 90th day post-AIS mRS scores of the tirofiban group were significantly lower than those of the control group (p < 0.05), while the 90th day good prognosis (mRS ≤ 2) rate of the tirofiban group was significantly higher (84.13% vs. 65.00%, p < 0.05). Logistic regression demonstrated a protective effect of tirofiban for good prognosis in AIS patients with END (OR = 4.675, 95% CI [1.012-21.605], p < 0.05). No cases of intracranial haemorrhage transformation or death were observed during the treatment in either group. WHAT IS NEW AND CONCLUSION: Tirofiban injection exhibited a high safety profile and significantly improved the prognosis of AIS-END patients who missed the intravenous thrombolysis time window.

Lack of association between serum homocysteine level and middle cerebral artery stenosis.

OBJECTIVES: Lowering homocysteine (HCY) has beneficial effects on vascular events in primary prevention but not in secondary prevention. Research on serum HCY level and middle cerebral artery (MCA) stenosis is lacking. The purpose of the study was to determine the association between these factors and provide more evidence for the prevention of ischemic stroke. METHODS: A total of 412 patients (35-93 years old) in the Neurology Department were recruited. Data of clinical and biochemical vascular risk factors were collected. MCA stenosis, including M1, M2, and M3, was determined by brain magnetic resonance angiography (MRA) and classified into stenosis or no stenosis. The differences and associations were analyzed by relevant statistical methods. RESULTS: There was no significant difference (p = 0.325) in HCY levels between the MCA stenosis and no stenosis groups at baseline. Logistic regression analysis demonstrated that there was no significant association between HCY levels and MCA stenosis (p = 0.447). After the two groups were matched for age and sex, there was still no difference (p = 0.540 for males and 0.061 for females) or association (p = 0.709 for males and 0.098 for females). In addition, we found that ischemic stroke was more prevalent in the MCA stenosis group and uric acid was higher in males with MCA stenosis. CONCLUSIONS: The study indicates a lack of association between serum HCY level and MCA stenosis, which may partially explain the negative results of secondary prevention clinical trials focused on lowering serum HCY level. Future studies on HCY reduction should focus more on primary prevention of ischemic stroke.

Cerebral amyloid angiopathy-related inflammation: a case report presenting with a rare variant in SORL1 gene.

BACKGROUND: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare clinical entity, characterized by headaches, seizures, rapidly progressive cognitive decline, behavioral changes and magnetic resonance imaging (MRI) findings underlying the autoimmune and inflammatory reaction at the level of CAA-affected vessel. CAA-ri is likely responsive to corticosteroid. MRI shows asymmetric and multifocal white matter hyperintensity (WMH) lesions and multiple cerebral microbleeds. Apolipoprotein E (ApoE) ε4 homozygosity is associated with CAA-ri strongly [Neurology 68(17):1411-1416, 2007, Ann Neurol 73(4):449-458, 2013, J Alzheimers Dis 44(4):1069-1074, 2015]. SORL1 processes a causal involvement in Alzheimer's disease (AD) as a proposed modulator of the amyloid precursor protein (APP). It is unclear whether SORL1 is involved with CAA-ri or not. CASE PRESENTATION: A 48-year-old woman suffered from a one-day history of a headache, nausea, and vomiting. Neurological examination revealed normal. We diagnosed this case as probable CAA-ri according to the clinic manifestations and MRI. Gene detection indicated a rare variant in SORL1 and ApoE ε4 homozygosity. When treated with corticosteroid, the patient's clinical symptoms and MRI manifestations were almost relieved. However, when keeping the corticosteroid withdrawal for three months, the patient relapsed with a headache and typical images on MRI emerged. Corticosteroid therapy was effective again. Unfortunately, susceptibility weighted imaging (SWI) showed increased microbleeds. With tapering corticosteroid slowly, no recurrence was found on this patient with four-month follow-up. CONCLUSION: A variant of SORL1 may be associated with CAA-ri, recurrence of disease could be detected with MRI by an increased microbleeds. Our case report suggests that corticosteroid therapy might be effective for CAA-ri.

lncRNA ZEB1-AS1 Mediates Oxidative Low-Density Lipoprotein-Mediated Endothelial Cells Injury by Post-transcriptional Stabilization of NOD2.

Oxidized-low density lipoprotein (ox-LDL) can induce injury of endothelial cells, causing atherosclerosis, which is an important initial event in several cardiovascular diseases. Long non-coding RNAs (lncRNAs) have emerged as regulators of diverse biological processes, but their specific biological functions and biochemical mechanisms in ox-LDL-induced endothelial cell injury have not been well investigated. Here, we describe the initial functional analysis of a poorly characterized human lncRNA ZEB1 antisense 1 (ZEB1-AS1). We found that ox-LDL treatment could induce a decreased cell viability and an increased cell apoptosis in endothelial cells, and knockdown of ZEB1-AS1 significantly reversed this effect. Mechanistically, ox-LDL treatment could sequester p53 from binding to ZEB1-AS1 promoter region, causing transcriptional activation and upregulation of ZEB1-AS1. Moreover, enhanced ZEB1-AS1 could upregulate Nucleotide-Binding Oligomerization Domain 2 (NOD2) expression through recruiting leucine-rich pentatricopeptide repeat motif-containing protein (LRPPRC) to stabilize NOD2 mRNA. Experimental data showed that knockdown of NOD2 or LRPPRC dramatically abrogated the functional role of ZEB1-AS1 in ox-LDL-induced endothelial cell injury. In summary, we demonstrated that lncRNA ZEB1-AS1 regulates the ox-LDL-induced endothelial cell injury via an LRPPRC-dependent mRNA stabilization mechanism. Therefore, ZEB1-AS1 may serve as a multi-potency target to overcome endothelial cell injury, atherosclerosis and other cardiovascular diseases.

Effect of Berberine on Angiogenesis and HIF-1α / VEGF Signal Transduction Pathway in Rats with Cerebral Ischemia - Reperfusion Injury.

OBJECTIVE: To investigate the effect of berberine on angiogenesis and signal transduction pathway of hypoxia-inducible growth factor-1α (HIF-1α) / vascular endothelial growth factor (VEGF) in rats with cerebral ischemia-reperfusion injury. STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Luoyang Central Hospital Affiliated with Zhengzhou University, China, from 2016 to 2017. METHODOLOGY: Forty-five rats were randomly divided into control group, model group and berberine group, 15 rats in each group. The model of rat with cerebral ischemia-reperfusion injury was duplicated by suture method. Neurological score was evaluated before, after operation, and 7 days after administration. Microvessel density (MVD) of cerebral ischemia- reperfusion cortex was detected by immunohistochemistry. HIF-1α mRNA and VEGF mRNA of cerebral ischemia- reperfusion cortex were detected by RT-PCR. HIF-1α, and VEGF protein expression of cerebral ischemia-reperfusion cortex was detected by Western Blotting. RESULTS: After operation and 7 days of administration, the neurological scores of the control group, model group, and berberine group were different (all p<0.001). After 7 days of administration, neurological score of berberine group was lower than that of model group (p <0.001), MVD, HIF-1α mRNA and VEGF mRNA expression. HIF-1α and VEGF protein expression levels were lower in model group than berberine group (all p <0.001). CONCLUSION: Berberine can promote angiogenesis in the rat with cerebral ischemia-reperfusion injury. Its mechanism may be activation of HIF-1α / VEGF signal transduction pathway.

Knockdown of long noncoding RNA XIST alleviates oxidative low-density lipoprotein-mediated endothelial cells injury through modulation of miR-320/NOD2 axis.

Atherosclerosis remains to be one of the most common vascular disorders resulting in morbidity and mortality in the world. Recent studies suggested that endothelial cells (ECs) injury caused by oxidative low-density lipoprotein (ox-LDL) is an early marker for atherosclerosis. Nevertheless, the mechanisms of ox-LDL-induced ECs injury are complicated and largely unknown. Here, we found lncRNA XIST (X-inactive specific transcript) was upregulated in human umbilical vein endothelial cells (HUVECs) stimulated by ox-LDL. Knockdown of XIST boosted the cell viability and suppressed cell apoptosis under ox-LDL stimuli. Further experiments identified XIST regulated the expression of Nucleotide-Binding Oligomerization Domain 2 (NOD2) by sponging miR-320. XIST silencing exerted a protective effect on ox-LDL-induced HUVECs injury via miR-320/NOD2 regulatory network. Our data provide insight into the role of the lncRNA XIST in ox-LDL mediated ECs injury, which can aid in developing new therapeutic strategies for the treatment of atherosclerosis.

Morphological parameters and anatomical locations associated with rupture status of small intracranial aneurysms.

Characterization of the rupture risk factors for small intracranial aneurysms (SIAs, ≤5 mm) is clinically valuable. The present study aims to identify image-based morphological parameters and anatomical locations associated with the rupture status of SIAs. Two hundred and sixty-three patients with single SIAs (128 ruptured, 135 unruptured) were included, and six morphological parameters, including size, aspect ratio (AR), size ratio (SR), height-width ratio (H/W), flow angle (FA) and aneurysm width-parent artery diameter ratio, and the aneurysm locations were evaluated using three-dimensional geometry, and were used to identify a correlation with aneurysm rupture. Statistically significant differences were observed between ruptured and unruptured groups for AR, SR, H/W, FA, and aneurysm locations, from univariate analyses. Logistic regression analysis further revealed that AR (p = 0.034), SR (p = 0.004), H/W (p = 0.003), and FA (p < 0.001) had the strongest independent correlation with ruptured SIAs after adjustment for age, gender and other clinical risk factors. A future study on a larger SIA cohort need to establish to what extent the AR, SR, H/W and FA increase the risk of rupture in patients with unruptured SIAs in terms of absolute risks.

Transorbital Doppler with carotid siphon monitoring detects right-to-left shunt effectively.

Background Transtemporal Doppler (TTD) with middle cerebral artery (MCA) is widely used for right-to-left shunt (RLS) detection. However, an alternative method for patients without suitable temporal bone windows should be established. The present study prospectively evaluated the effectiveness of transorbital Doppler (TOD) with carotid siphon (CS) monitoring in detecting RLS. Methods A total of 357 subjects with sufficient temporal bone windows underwent simultaneous TTD with MCA and TOD with CS. After injection of microbubbles, the numbers of artificial high-intensity signals were recorded at rest and after Valsalva maneuver. Results TOD with CS detected RLS in 146 patients. Sensitivity was 97.1%, specificity 95%, positive predictive value 92.5%, and negative predictive value 98.1%. The total positive rates for RLS detection by CS (40.9%) and MCA (37.8%) monitoring were comparable without significant difference, but TOD with CS detected significantly more grade 2 and 3 RLS than TTD with MCA (p = 0.001). The RLS rates of cryptogenic stroke patients was significantly higher than that of healthy controls, and RLS in cryptogenic stroke was remarkably higher than that in transient ischemia attack patients (p < 0.05). TOD with CS examined significantly more grade 2 and 3 RLSs than the MCA approach in the cryptogenic stroke patients (p = 0.037). Conclusion TOD with CS monitoring is able to detect RLS effectively in different populations including healthy subjects, cryptogenic stroke, transient ischemia attack, and migraine patients. In comparing to the TTD with MCA approach, TOD with CS monitoring could detect comparable rate of RLS, but more high grades of RLS.

Nanog attenuates lipopolysaccharide-induced inflammatory responses by blocking nuclear factor-κB transcriptional activity in BV-2 cells.

Nanog, a unique homeobox transcription factor, maintains self-renewal and pluripotency of embryonic stem cells by binding to nuclear factor κB proteins in order to inhibit their transcriptional and prodifferentiation activities. We previously reported that Nanog attenuated inflammatory responses in rat primary microglia cells stimulated by lipopolysaccharide. However, the effects of Nanog on another microglia cell type, BV-2 cells, are still unknown. In this study, we investigated whether Nanog attenuated inflammatory responses in lipopolysaccharide-stimulated BV-2 cells and found that Nanog significantly decreased the release of nitric oxide and the expression of inducible nitric oxide synthase at the mRNA and protein levels. The production of proinflammatory cytokines including tumor necrosis factor-α and interleukin-1ß was also significantly inhibited by Nanog. Further, we observed that the transcriptional activity of nuclear factor κB was dramatically reduced by Nanog. These results suggest that Nanog may be a potential anti-inflammatory therapy for neurological diseases caused by persistent microglia activation.

[Serum levels of homocysteine and folate in neonates with asphyxia].

OBJECTIVE: To determine whether serum homocysteine and folate levels are correlated with the occurrence of neonatal asphyxia and to study the effects of gender and gestational age on serum homocysteine and folate levels. METHODS: Thirty-five neonates with mild asphyxia (19 males and 16 females) and 40 normal neonates (control group,18 males and 22 females) were enrolled in this study. The asphyxia and the control groups consisted of 10 and 11 cases of preterm infants respectively. Serum homocysteine levels were measured using ELASA. Serum folate levels were measured using radioimmunity assay. RESULTS: Serum homocysteine level (14.66+/-2.61 micromol/L vs 7.55+/-0.50 mumol/L; P<0.05) was significantly higher and serum folate level (2.47+/-0.24 ng/mL vs 3.28+/-0.28 ng/mL; P<0.05) was significantly lower in the asphyxia group than that in the control group. There were no significant differences in serum levels of homocysteine and folate between males and females either in the asphyxia group or the control group. The asphyxiated neonates born at premature showed increased serum homocysteine level compared with the full-term neonates with asphyxia (21.25+/-5.01 micromol/L vs 12.34+/-2. 01 micromol/L; P<0.05). CONCLUSIONS: The increased serum homocysteine level and decreased serum folate level are correlated with the occurrence of neonatal asphyxia. Serum homocysteine and folate levels are not associated with the gender. A more significantly increased serum homocysteine level may be found in asphyxiated neonates born at premature.