Ischemic stroke as an initial performance of polycythemia vera in young adults: A case report and literature review.

INTRODUCTION: As the second leading cause of death and disability worldwide, stroke is mainly caused by atherosclerosis and cardiac embolism, particularly in older individuals. Nevertheless, in young and otherwise healthy individuals, the causes of stroke can be more diverse and may include conditions such as patent foramen ovale, vasculitis, coagulopathies, genetic factors, or other undetermined causes. Although these other causes of stroke account for a relatively small proportion compared to ischemic stroke, they are becoming increasingly common in clinical practice and deserve attention. Here, we present a rare female patient with polycythemia vera (PV) who was admitted to the hospital as a stroke patient without any previous medical history. PATIENT CONCERNS: A 40-year-old young woman felt sudden dizziness and slow response. After 4 days of being admitted, she developed blurry vision on the right. DIAGNOSES: Cranial magnetic resonance imaging revealed aberrant signals in the left temporal and parietal lobe, as well as multiple small focal signal abnormalities were observed in the left frontal lobe. Magnetic resonance angiography revealed partial stenosis of the left internal carotid artery. The patient's blood routine examination revealed a significant elevation in complete blood counts, particularly the increase in red blood cells, as well as prolonged clotting time. An abdominal ultrasound and abdomen computed tomography showed splenomegaly. The outcome of the genetic testing was positive for the Janus kinase JAK2 exon V617F mutation (JAK2/V617F). The patient was diagnosed with PV-related stroke. INTERVENTIONS: The patient was treated with phlebotomy, cytoreductive therapy, and low-dose aspirin antiplatelet therapy and was regularly followed up in hematology and neurology clinics after discharge. OUTCOMES: The patient's red blood cell, leukocyte, and thrombocyte counts had fully normalized, with her hemoglobin level measuring at 146 g/L and hematocrit value at 43%. Furthermore, there had been a significant improvement in neurological symptoms. LESSONS: PV, a rare hematological disorder, can present with ischemic stroke as the initial performance, and the diagnosis mainly relies on routine blood tests, bone marrow biopsies, and genetic test. Therefore, clinicians should pay attention to PV, a low-prevalence disease, when encountering stroke in youth.

A Chinese female patient with LGI1 and mGluR5 antibodies: A case report.

RATIONALE: Anti-LGI1 antibody encephalitis and anti-mGluR5 are both uncommon encephalitis, and we report the first case of autoimmune encephalitis (AE) with dual seropositive antibodies of leucine-rich glioma-inactivated 1 (LGI1) and mGluR5. PATIENT CONCERNS: We present a case of AE with dual seropositive antibodies of LGI1 and mGluR5 in a 65-year-old woman who presented with sudden onset left faciobrachial dystonic seizures and unresponsive for 5 hours. DIAGNOSIS: The patient was diagnosed with anti-LGI1 AE and anti-mGluR5 AE mainly based on the clinical symptoms and further test of the antibody in serum and cerebral spinal fluid (CSF). INTERVENTIONS AND OUTCOMES: The patient was treated with glucocorticoid intravenous drip. We also gave her the therapy of immunoglobulin (25 g q.d) for 5 days and anti-epileptic therapy. She had no more convulsions on the left side of the face and limbs. She did not complain of any uncomfort until July 18. LESSONS: Early recognition of AE is crucial. Specific autoantibodies are associated with corresponding syndromes. Our patient was initially diagnosed with acute ischemic stroke. Therefore, we should conduct further study on the related symptoms of AE.

Klebsiella pneumoniae-related brain abscess and meningitis in adults: Case report.

INTRODUCTION: Klebsiella pneumoniae is once thought to be a less common cause of brain abscess in adults and is mainly hospital-acquired. Community-acquired CNS infection (brain abscess and meningitis) caused by K pneumoniae without other metastatic septic abscesses is exceedingly rare. Therefore, we present a rare adult patient with invasive cerebral abscess and meningitis without other invasive abscesses related to K pneumoniae. PATIENT CONCERNS: A 64-year-old woman experienced a sudden onset of severe continuous headache accompanied by intermittent nausea, vomiting, and fever. Meanwhile, she experienced tinnitus and had a feeling of swelling in the right ear. DIAGNOSIS: Cranial magnetic resonance imaging revealed abnormal hyperintensity signals in the left head of the caudate nucleus. The next generation sequencing of cerebral spinal fluid showed infection with K pneumoniae. The patient was diagnosed with K pneumoniae-related brain abscesses and meningitis. INTERVENTIONS: Antibacterial treatment was carried out for 2 months. OUTCOMES: The patient recovered well. CONCLUSION: Despite the progress of modern neurosurgical techniques, new antibiotics, and modern imaging techniques, brain abscesses are still a potentially fatal infection. Streptococci are common organisms that result in brain abscesses. Nevertheless, Klebsiella species, once thought to be a less common cause of brain abscess in adults, has become an increasingly important cause of brain abscess, especially in Asia.

Past Exposure to Cigarette Smoke Aggravates Cognitive Impairment in a Rat Model of Vascular Dementia via Neuroinflammation.

Smoking is a risk factor for dementia. Cognitive function can be partially restored after quitting smoking, but still lower than never smoked group. The underlying mechanisms still remain unclear. The effects of smoking cessation combined with cerebral chronic hypoperfusion (CCH) on cognitive function have never been described. Here, we established a cigarette smoking cessation model, a CCH model, and a cigarette smoking cessation plus CCH model. We investigated cognitive function in these models and the mechanisms of the neuroinflammation, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3)/cysteine aspartate-specific proteinase (caspase-1)/interleukin- 1ß (IL-1ß) pathway, and eucaryotic initiation factor 2α (eIF2α) /autophagy pathway. We used morris water maze (MWM) and novel object recognition (NOR) test to evaluate cognitive function in rats. Nissl staining was performed to observe cell morphology in the hippocampal CA1 area. A neuroinflammatory marker (glial fibrillary acidic protein, GFAP) was assessed by Western blot analysis and immunohistochemistry staining. IL-1ß levels were detected by ELISA. The protein levels of NLRP3/caspase-1/ IL-1ß and eIF2α/autophagy pathway were evaluated by Western blot analysis. LC3 was assessed by immunofluorescence staining. CCH can affect cognitive function by influencing neuroinflammation, NLRP3/caspase-1/IL-1ß pathway, and eIF2α/autophagy pathway. Past exposure to cigarette smoke can also affect cognitive function by influencing neuroinflammation and NLRP3/caspase-1/IL-1ß pathway, which may be induced by smoking and may not be alleviated after smoking cessation. Past exposure to cigarette smoke does not influence autophagy, which may be increased by smoking and then decrease to normal levels after smoking cessation. Past exposure to smoking can further aggravate cognitive impairment and neuroinflammation in VaD animals: cognitive impairment induced by CCH via neuroinflammation, NLRP3/caspase-1/IL-1ß, and eIF2α/autophagy pathway and cognitive impairment induced by past exposure to cigarette smoke via neuroinflammation and NLRP3/caspase-1/IL-1ß pathway. The combined group had the worst cognitive impairment because of harmful reasons.

Sacubitril/valsartan inhibits ox­LDL­induced MALAT1 expression, inflammation and apoptosis by suppressing the TLR4/NF­κB signaling pathway in HUVECs.

The therapeutic effect of sacubitril/valsartan (S/V) on heart failure has been confirmed, while its role in atherosclerosis remains largely unexplored. The present study aimed to investigate the effects of S/V on the expression of metastasis­associated lung adenocarcinoma transcript 1 (MALAT1), inflammation and apoptosis in human umbilical vein endothelial cells (HUVECs) induced by oxidized low­density lipoprotein (ox­LDL) and to elucidate its possible mechanism. Cell Counting Kit­8 assay was used to detect cell viability. Reverse transcription­quantitative PCR was performed to detect the MALAT1 expression. ELISA was performed to detect the levels of IL­1ß, IL­6 and TNF­α. Flow cytometry was conducted to detect the apoptotic rate of cells. A nitric oxide (NO) detection kit was used to determine the concentration of NO. Western blotting analysis was performed to determine the levels of intercellular cell adhesion molecule (ICAM)­1, vascular cell adhesion molecule (VCAM)­1, endothelin­1, caspase­3, Bax, Bcl­2, Toll­like receptor 4 (TLR4), p65 and p­p65. Compared with the ox­LDL group, S/V treatment significantly increased the cell viability, NO concentration and Bcl­2 expression, decreased the levels of IL­1ß, IL­6 and TNF­α and reduced the expressions of MALAT1, ICAM­1, VCAM­1, cleaved­caspase­3, Bax, TLR4 and p­p65. Overall, the findings suggested that S/V could downregulate the expression of MALAT1, inhibit inflammation and apoptosis and improve endothelial function in ox­LDL­induced HUVECs via inactivating the TLR4/NF­κB signaling pathway. Therefore, S/V might be utilized as a promising therapeutic strategy for the prevention and treatment of atherosclerosis.

Effects of CircRNA-ITCH on proliferation and apoptosis of hepatocellular carcinoma cells through inhibiting Wnt/ß-catenin signaling pathway.

PURPOSE: To explore the effects of circular ribonucleic acid (circRNA)-E3 ubiquitin protein ligase (ITCH) on the proliferation and apoptosis of hepatocellular carcinoma (HCC) cells and its possible molecular mechanism. METHODS: To study the role of circRNA-ITCH in the occurrence and development of HCC. The relative expression level of circRNA-ITCH was detected via quantitative polymerase chain reaction (qPCR) in four kinds of HCC Huh-7, U251, HB611 and SMMC-7721 cell lines, and human normal liver L-02 cell line. Moreover, the effect of overexpression of circRNA-ITCH on the TCF luciferase activity was detected using ß-catenin/TCF-responsive luciferase reporter assay. Finally, the influences of overexpression of circRNA-ITCH on the protein levels of ß-catenin and Wnt3α and the mRNA levels of c-myc and cyclinD1 were determined using Western blotting and qPCR, respectively. RESULTS: Compared with that in human normal liver L-02 cell line, the expression of circRNA-ITCH was significantly down-regulated in HCC Huh-7, U251, HB611 and SMMC-7721 cell lines (p<0.05). According to the results of CCK-8 assay, colony formation assay and flow cytometry, the overexpression of circRNA-ITCH could obviously inhibit cell proliferation, suppress colony formation ability and induce apoptosis (p<0.05). The results of dual-luciferase reporter assay revealed that there was a significant interaction between circRNA-ITCH and miR-7 or miR-214 (p<0.05). CircRNA-ITCH was involved in the regulating of Wnt/ß-catenin signal transduction pathway and inhibited the expressions of c-myc and cyclinD1. CONCLUSIONS: CircRNA-ITCH affects the proliferation and apoptosis of HCC cells through inhibiting the Wnt/ß-catenin signal transduction pathway, thereby exerting a carcinogenic effect in the occurrence and development of HCC. The research results provide a new therapeutic target for HCC.

Iron dysregulation in vascular dementia: Focused on the AMPK/autophagy pathway.

Recent researches suggested that iron dysregulation play an important role in the pathogenesis of vascular dementia (VD). Iron deposition had been found in hippocampus in vascular dementia model in recent research. Nevertheless, the underlying mechanisms of iron deposition and its neurotoxicity in vascular dementia was still unclear. Thus, our research was aimed at whether the neurotoxicity of iron was associated with autophagy regulation. We established a chronic cerebral hypoperfusion model in the rat brain in order to mimic the vascular dementia using permanent bilateral common carotid artery occlusion (2VO). The preparation of iron overloaded rats model by intraperitoneal injection of iron dextran. Following, we tested the learning and memory function of each group using Morris Water Maze. Consequently, we analyzed the iron content and iron transport related molecules (TFR1, DMT1) in hippocampus. Furthermore, we examined the effect of iron deposition on autophagy-related molecules including AMPK, Beclin1 and LC3 and the number of autophagosomes in hippocampus. Last, we tested the apoptosis of neurons in hippocampus. We found that iron deposition in hippocampus in model groups which accompanied the decline of learning and memory function. And the expression of TFR1 and DMT1 were up-regulated in model groups. Moreover, iron deposition up-regulated the expression of AMPK, Beclin1 and LC3 and increase the number of autophagosomes in hippocampus. And the expression of Bax was up-regulated and Bcl-2 was down-regulated in iron deposition groups. To sum up, our data suggested that iron deposition increased AMPK/autophagy pathway associated molecules in the hippocampus and promoted neuronal apoptosis, which might be a new pathogenesis in vascular dementia.