Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with multiple different onset forms of frequent recurrent attacks: A case report and literature review.

INTRODUCTION: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one kind of monogenic hereditary small-vessel disease in the brain caused by mutations in the NOTCH3 gene. However, it is rare for CADASIL to recur with different clinical manifestations in 1 patient, and some atypical clinical manifestations can easily lead to misdiagnosis by clinical physicians. CASE CONCERN: A 34-year-old male presented with transient speech disorder accompanied by weakness in the left side of the body for 1 day in June 2020. Magnetic resonance imaging showed acute ischemic infarction in right centrum semiovale, along with multiple abnormal white matter hyperintensities in the brain. Genetic sequencing identified a heterozygous mutation in the NOTCH3 gene. The patient experienced recurrent episodes in 2021 and 2023, with varying clinical symptoms including visual blurring, abnormal limb sensation, and sudden cognitive dysfunction. DIAGNOSIS: The diagnoses of CADASIL is based on clinical manifestations, imaging results, and genetic reports. INTERVISION AND OUTCOMES: The patient was received symptomatic treatment including antiplatelet aggregation therapy, lipid regulation, and plaque stabilization, resulting in improved symptoms. OUTCOMES: During the course of the disease, after medication treatment and rehabilitation exercise, the patient clinical symptoms have significantly improved. Currently, the patient is closely following up and regularly undergoing relevant examinations. LESSONS: In this rare case, we found that CADASIL can recur multiple times in a patient with different clinical symptoms, which can easily lead to clinical misdiagnosis. Clinicians should consider the possibility of CADASIL in young patients with sudden typical neurological dysfunction.

Mortality from cerebrovascular diseases in China: Exploration of recent and future trends.

BACKGROUND: Cerebrovascular disease (CVD) ranks among the foremost factors responsible for mortality on a global scale. The mortality patterns of CVDs and temporal trends in China need to be well-illustrated and updated. METHODS: We collected mortality data on patients with CVD from Chinese Center for Disease Control and Prevention's Disease Surveillance Points (CDC-DSP) system. The mortality of CVD in 2020 was described by age, sex, residence, and region. The temporal trend from 2013 to 2019 was evaluated using joinpoint regression, and estimated rates of decline were extrapolated until 2030 using time series models. RESULTS: In 2019, the age-standardized mortality in China (ASMRC) per 100,000 individuals was 113.2. The ASMRC for males (137.7/10 5 ) and rural areas (123.0/10 5 ) were both higher when stratified by gender and urban/rural residence. The central region had the highest mortality (126.5/10 5 ), the western region had a slightly lower mortality (123.5/10 5 ), and the eastern region had the lowest mortality (97.3/10 5 ). The age-specific mortality showed an accelerated upward trend from aged 55-59 years, with maximum mortality observed in individuals over 85 years of age. The age-standardized mortality of CVD decreased by 2.43% (95% confidence interval, 1.02-3.81%) annually from 2013 to 2019. Notably, the age-specific mortality of CVD increased from 2013 to 2019 for the age group of over 85 years. In 2020, both the absolute number of CVD cases and the crude mortality of CVD have increased compared to their values in 2019. The estimated total deaths due to CVD were estimated to reach 2.3 million in 2025 and 2.4 million in 2030. CONCLUSION: The heightened focus on the burden of CVD among males, rural areas, the central and western of China, and individuals aged 75 years and above has emerged as a pivotal determinant in further decreasing mortalities, consequently presenting novel challenges to strategies for disease prevention and control.

Long non-coding RNA PCAT5 regulates the progression of Esophageal Squamous Cell Carcinoma via miR-4295/PHF20.

Long non-coding RNAs (lncRNAs) have been discovered through many studies to play a crucial role in tumor progression. LncRNA PCAT5 has been identified as a human cancer-related gene in diverse cancers. However, the specific role of PCAT5 in esophageal squamous cell carcinoma (ESCC) still needs further study. The study aimed to test the PCAT5 expression and find its biological function in ESCC. Functional experiments, including EdU, transwell and TUNEL, were done in the chosen ESCC cell lines under silenced PCAT5. Luciferase reporter and Western blot experiments were implemented to ensure the possible regulatory mechanism involved in ESCC. PCAT5 presented higher expression in ESCC cells in comparison to normal cells. The silence of PCAT5 restrained ESCC cell abilities of proliferation, migration and invasion. On the contrary, it accelerated ESCC cell apoptosis. The results of rescue experiments showed that PCAT5 regulated ESCC cell proliferative, migrated, invasive and apoptotic abilities via sponging miR-4295 to up-regulate PHF20.

Herpesvirus latent infection promotes stroke via activating the OTUD1/NF-κB signaling pathway.

OBJECTIVE: Our study aimed to reveal the molecular mechanisms underlying the regulation of cerebral infarction by herpes virus latency infection via the OTUD1/NF-κB signaling pathway using evidence-based medicine Meta-analysis and bioinformatics analysis. METHODS: We conducted a Meta-analysis by searching Pubmed, Embase, and Web of Science databases to evaluate the correlation between herpes virus infection and increased risk of cerebral infarction. We obtained wild-type or mutant herpes virus latent infection-related brain tissue datasets from the GEO database and performed differential analysis to identify differentially expressed genes (DEGs) in the brain tissue after herpes virus latent infection. We further conducted WGCNA co-expression analysis on the cerebral infarction-related datasets from the GEO database to obtain key module genes and intersect them with the DEGs. We used ROC curve analysis to identify the key gene OTUD1 for predicting the occurrence of cerebral infarction and combined correlation and pathway enrichment analyses to identify the downstream pathways regulated by OTUD1. RESULTS: Our meta-analysis revealed that herpes virus infection is associated with an increased risk of cerebral infarction. By integrating the differential analysis and WGCNA co-expression analysis of GEO chip data, we identified three key genes mediating cerebral infarction after herpes virus latent infection. ROC curve analysis identified the key gene OTUD1, and the correlation and pathway enrichment analyses showed that OTUD1 regulates the NF-κB signaling pathway to mediate cerebral infarction. CONCLUSION: Herpes virus latent infection promotes cerebral infarction by activating the OTUD1/NF-κB signaling pathway.

Efficacy and safety of argatroban in treatment of acute ischemic stroke: A meta-analysis.

BACKGROUND: Argatroban is a novel direct thrombin inhibitor that has been used for treatment of acute ischemic stroke (AIS). To our knowledge, no systematic analysis has assessed the efficacy and safety of argatroban for treatment of AIS. AIM: To evaluate the efficacy and safety of argatroban for treatment of AIS. METHODS: Cochrane Library, Medline, PubMed, and Web of Science were searched to retrieve all studies associated with argatroban and AIS. Effective rate, adverse events rate, and 95% confidence intervals were calculated and pooled using meta-analysis methodology. RESULTS: We only found four randomized controlled studies, comprising 354 cases with 213 in the argatroban group and 141 in the control group. Great heterogeneity was found in the four studies (c 2 = 11.44, I 2 = 74%, P = 0.01). Subgroup analysis could not be performed because of the absence of detailed data. The two most recent studies showed acceptable heterogeneity (c 2 = 1.56, I 2 = 36%, P = 0.21). Our analysis showed that argatroban was not more effective than the control therapy in the acute phase of ischemic stroke (Z = 0.01, P = 0.99). Argatroban did not increase the risk of bleeding compared with the control group (c 2 = 0.37, I 2 = 0%, P = 0.54, Z = 0.80, P = 0.42). CONCLUSION: Patients with AIS might not benefit from argatroban and combination therapy with argatroban does not increase bleeding tendency.

Clinical practice: intravenous thrombolysis in a patient with active cancer who experienced wake-up stroke.

After reviewing the diagnosis and treatment process of a patient with active cancer who experienced wake-up stroke, we have summarized the clinical manifestations, laboratory examination results, imaging features, pathological results, and treatment in this report. Patients with active cancer who experience wake-up stroke often have mild neurological deficits at the time of onset. For the patient in this study, laboratory test results were mainly characterized by abnormal coagulation function and elevated tumor markers. The brain magnetic resonance imaging (MRI) images were characterized by involvement of both the arterial and venous systems. Thrombolytic therapy during the window period can improve the symptoms of neurological deficits. Overall, anticoagulation therapy was safe and effective in our patient.

Tumor metastasis has a significant relationship with the development of acute ischemic stroke in Chinese cancer patients: a retrospective study.

OBJECTIVE: This study was designed to analyze the relationship between tumor metastasis and acute ischemic stroke (AIS) in Chinese cancer patients. METHODS: This retrospective study included 119 cancer patients with AIS and 152 cancer patients without AIS. Basic information was collected and tumor metastasis status was determined for all patients. RESULTS: The whole cohort had a median age of 59 (49-69) years with 150 men (55.4%). There were 98 patients (36.2%) with tumor metastasis. Patients with AIS had significantly more males, tumor metastasis, lung cancer, hypertension, diabetes mellitus, higher age, D-dimer, international normalized ratio, prothrombin time, prothrombin activity, and thrombin time, while they had significantly lower levels of hemoglobin, red blood cells, and hematocrit. In multivariate logistic regression analysis, AIS was significantly and positively associated with age, tumor metastasis, D-dimer, and thrombin time. In multivariate Cox regression analysis, tumor metastasis, AIS, D-dimer, thrombin time, and fibrinogen were significantly and positively associated with worse prognosis. CONCLUSIONS: This study demonstrates that tumor metastasis was positively and independently associated with AIS in Chinese cancer patients, suggesting that tumor metastasis has a significant relationship with the development of AIS. Additionally, tumor metastasis and AIS had negative independent effects on the prognosis of patients.

Cerebrospinal fluid tumor markers predict treatment response in a patient with carcinomatous meningitis.

We report on a 56-year-old female patient diagnosed with carcinomatous meningitis caused by lung cancer. The diagnosis was confirmed by lung computed tomography, enhanced brain magnetic resonance imaging, histopathology, cerebrospinal fluid (CSF) cytology, and serum and CSF tumor markers. Genetic testing detected an epidermal growth factor receptor gene exon 19 deletion. The patient survived for 29 months after systemic treatment with gefitinib, radiotherapy, and chemotherapy. Dynamic monitoring of CSF and serum tumor markers was carried out during the treatment process. We considered that CSF tumor marker levels may have allowed the early diagnosis of meningeal carcinomatosis, and that systemic therapy in the early stage of the disease may prolong survival.

Clinical Characteristics and Risk Factors of Lung Cancer-Associated Acute Ischemic Stroke.

OBJECTIVE: To research the clinical characteristics and risk factors of lung cancer-associated acute ischemic stroke (LCA-AIS). METHODS: Patients diagnosed with LCA-AIS, simple lung cancer, and simple AIS were enrolled. The primary information, laboratory results, tumor histopathology, neurological deficits, and survival time of the patients were collected and analyzed. RESULTS: (1) In the LCA-AIS group, the pathology of 69.56% patients were adenocarcinoma, and the proportion of poorly differentiated patients was significantly more than that in moderately differentiated or highly differentiated. The number of stage IV lung cancer patients in the LCA-AIS group was significantly more common than in other stages. (2) 56.52% of patients with lung cancer were diagnosed before AIS, and the peak of AIS attack was 1-6 months after the diagnosis of lung cancer. (3) The independent risk factors of LCA-AIS were CYFRA-211 (OR 1.070; 95% confidence interval 1.005, 1.139; p = 0.035), TT (OR 1.275; 95% confidence interval 1.089, 1.493; p = 0.003), and Hct (OR 0.878; 95% confidence interval 0.779, 0.990; p = 0.034), making ROC curve, suggesting the area under the curve is 0.871. (4) The neurological deficit of patients in the LCA-AIS group was similar to the simple AIS group and could not be identified by the severity of neurological deficits. (5) The median survival time of LCA-AIS group patients was five months (95% confidence interval 3.796, 6.204). There were statistical differences in survival time between LCA-AIS group and simple AIS group patients (p < 0.001). CONCLUSIONS: The interaction between lung cancer and AIS may shorten patients' life expectancy and worsen their quality of life.