SARS-CoV-2 may play a direct role in the pathogenesis of posterior reversible encephalopathy syndrome (PRES) associated with COVID-19: A CARE-compliant case report and literature review.

RATIONALE: During the past 3 years of the corona virus disease 2019 (COVID-19) pandemic, COVID-19 has been recognized to cause various neurological complications, including rare posterior reversible encephalopathy syndrome (PRES). In previously reported cases of PRES associated with COVID-19, the majority of patients had severe COVID-19 infection and known predisposing factors for PRES, such as uncontrolled hypertension, renal dysfunction, and use of immunosuppressants. It remains unclear whether these risk factors or infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contributes to the development of PRES in these patients. Here we report a special case of PRES associated with COVID-19 without any known risk factors for PRES, indicating the SARS-CoV-2's direct role in the pathogenesis of PRES associated with COVID-19. PATIENT CONCERNS: An 18-year-old female patient presented to the emergency department with abdominal pain. Preliminary investigations showed no abnormalities, except for positive results in novel coronavirus nucleic acid tests using oropharyngeal swabs. However, the patient subsequently developed tonic-clonic seizures, headaches, and vomiting on the second day. Extensive investigations have been performed, including brain MRI and lumbar puncture. Brain MRI showed hypointense T1-weighted and hyperintense T2-weighted lesions in the bilateral occipital, frontal, and parietal cortices without enhancement effect. Blood and cerebrospinal fluid analyses yielded negative results. The patient had no hypertension, renal insufficiency, autoimmune disease, or the use of immunosuppressants or cytotoxic drugs. DIAGNOSES: PRES was diagnosed based on the clinical features and typical MRI findings of PRES. INTERVENTIONS: Symptomatic treatments such as anticonvulsants were administered to the patients. OUTCOMES: The patient fully recovered within 1 week. The initial MRI abnormalities also disappeared completely on a second MR examination performed 11 days later, supporting the diagnosis of PRES. The patient was followed up for 6 months and remained in a normal state. LESSONS: The current case had no classical risk factors for PRES, indicating that although the cause of PRES in COVID-19 patients may be multifactorial, the infection of SARS-CoV-2 may play a direct role in the pathogenesis of PRES associated with COVID-19.

Henna plant biomass enhanced azo dye removal: Operating performance, microbial community and machine learning modeling.

The bio-reduction of azo dyes is significantly dependent on the availability of electron donors and external redox mediators. In this study, the natural henna plant biomass was supplemented to promote the biological reduction of an azo dye of Acid Orange 7 (AO7). Besides, the machine learning (ML) approach was applied to decipher the intricate process of henna-assisted azo dye removal. The experimental results indicated that the hydrolysis and fermentation of henna plant biomass provided both electron donors such as volatile fatty acid (VFA) and redox mediator of lawsone to drive the bio-reduction of AO7 to sulfanilic acid (SA). The high henna dosage selectively enriched certain bacteria, such as Firmicutes phylum, Levilinea and Paludibacter genera, functioning in both the henna fermentation and AO7 reduction processes simultaneously. Among the three tested ML algorithms, eXtreme Gradient Boosting (XGBoost) presented exceptional accuracy and generalization ability in predicting the effluent AO7 concentrations with pH, oxidation-reduction potential (ORP), soluble chemical oxygen demand (SCOD), VFA, lawsone, henna dosage, and cumulative henna as input variables. The validating experiments with tailored optimal operating conditions and henna dosage (pH 7.5, henna dosage of 2 g/L, and cumulative henna of 14 g/L) confirmed that XGBoost was an effective ML model to predict the efficient AO7 removal (91.6%), with a negligible calculating error of 3.95%. Overall, henna plant biomass addition was a cost-effective and robust method to improve the bio-reduction of AO7, which had been demonstrated by long-term operation, ML modeling, and experimental validation.

Cell-type-specific optogenetic fMRI on basal forebrain reveals functional network basis of behavioral preference.

The basal forebrain (BF) is a complex structure that plays key roles in regulating various brain functions. However, it remains unclear how cholinergic and non-cholinergic BF neurons modulate large-scale functional networks and their relevance in intrinsic and extrinsic behaviors. With an optimized awake mouse optogenetic fMRI approach, we revealed that optogenetic stimulation of four BF neuron types evoked distinct cell-type-specific whole-brain BOLD activations, which could be attributed to BF-originated low-dimensional structural networks. Additionally, optogenetic activation of VGLUT2, ChAT, and PV neurons in the BF modulated the preference for locomotion, exploration, and grooming, respectively. Furthermore, we uncovered the functional network basis of the above BF-modulated behavioral preference through a decoding model linking the BF-modulated BOLD activation, low-dimensional structural networks, and behavioral preference. To summarize, we decoded the functional network basis of differential behavioral preferences with cell-type-specific optogenetic fMRI on the BF and provided an avenue for investigating mouse behaviors from a whole-brain view.

Electrophysiologic Characteristics of Nitrous-Oxide-Associated Peripheral Neuropathy: A Retrospective Study of 76 Patients.

BACKGROUND AND PURPOSE: The electrophysiologic characteristics of peripheral neuropathy secondary to nitrous oxide (N2O) abuse remain unclear. The paper therefore aimed to summarize the electrophysiologic characteristics of N2O-associated peripheral neuropathy and identify the risk factors of severe nerve injury. METHODS: The electrophysiologic results and clinical data of patients with peripheral neuropathy secondary to N2O abuse at our hospital between 2018 and 2020 were analyzed retrospectively, and their electrophysiologic changes were summarized. RESULTS: Most patients exhibited decreased sensory and motor nerve conduction velocities (75% and 76%), decreased sensory nerve and compound motor action potentials (57% and 59%), and prolonged distal motor latency (59%), while a response was absent in 36%. These findings indicate that N2O abuse can result in generalized injury to sensory and motor nerves. Electrophysiologic results indicated axonal neuropathy in 37 cases (49%), demyelinating peripheral neuropathy in 4 (5%), and mixed neuropathy in 12 (16%). Peripheral nerve injury was more common in the lower limbs (72%) than in the upper limbs (42%, p<0.0001). The upper and lower limbs were primarily affected by sensory nerve demyelination (35%) and motor axonal injury (67%), respectively. Subgroup analysis indicated that longer N2O exposure and longer disease course were associated with more-severe motor axonal injury in the lower limbs. CONCLUSIONS: N2O-associated peripheral neuropathy can lead to sensory and motor nerve injury, with axonal injury being the most common. Injuries were more severe in the lower limbs. Prolonged N2O exposure and disease course increased the severity of motor axonal injury in the lower limbs.

Single-trial motor imagery electroencephalogram intention recognition by optimal discriminant hyperplane and interpretable discriminative rectangle mixture model.

Spatial filtering is widely used in brain-computer interface (BCI) systems to augmented signal characteristics of electroencephalogram (EEG) signals. In this study, a spatial domain filtering based EEG feature extraction method, optimal discriminant hyperplane-common spatial subspace decomposition (ODH-CSSD) is proposed. Specifically, the multi-dimensional EEG features were extracted from the original EEG signals by common space subspace decomposition (CSSD) algorithm, and the optimal feature criterion was established to find the multi-dimensional optimal projection space. A classic method of data dimension optimizing is using the eigenvectors of a lumped covariance matrix corresponding to the maximum eigenvalues. Then, the cost function is defined as the extreme value of the discriminant criterion, and the orthogonal N discriminant vectors corresponding to the N extreme value of the criterion are solved and constructed into the N-dimensional optimal feature space. Finally, the multi-dimensional EEG features are projected into the N-dimensional optimal projection space to obtain the optimal N-dimensional EEG features. Moreover, this study involves the extraction of two-dimensional and three-dimensional optimal EEG features from motor imagery EEG datasets, and the optimal EEG features are identified using the interpretable discriminative rectangular mixture model (DRMM). Experimental results show that the accuracy of DRMM to identify two-dimensional optimal features is more than 0.91, and the highest accuracy even reaches 0.975. Meanwhile, DRMM has the most stable recognition accuracy for two-dimensional optimal features, and its average clustering accuracy reaches 0.942, the gap between the accuracy of the DRMM with the accuracy of the FCM and K-means can reach 0.26. And the optimal three-dimensional features, for most subjects, the clustering accuracy of DRMM is higher than that of FCM and K-means. In general, the decision rectangle obtained by DRMM can clearly explain the difference of each cluster, notably, the optimization of multidimensional EEG features by optimal projection is superior to Fisher's ratio, and this method provides an alternative for the application of BCI. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-021-09768-w.

Coupled process of in-situ sludge fermentation and riboflavin-mediated nitrogen removal for low carbon wastewater treatment.

Volatile fatty acid recovery from waste activated sludge (WAS) was highly suggested to supplement carbon source for nitrogen removal. However, it was not easy to separate them from the metabolites under the ex-situ fermentation. In this study, in-situ WAS fermentation combined in the denitrification system was established to treat low carbon wastewater (COD/TN = 4), and riboflavin was employed as a redox mediator. This coupled process could simultaneously enhance the WAS fermentation and nitrogen removal, and riboflavin could significantly enrich the fermentative bacteria (Firmicutes phylum), denitrifying bacteria (Denitratisoma genus) and related functional genes (narGHJI, napABC, nirKS, nosZ, norBC), generating more available carbon sources for efficient nitrogen removal. This resulted in the effluent TN (<15 mg/L) satisfying the required discharge standard in China. This study provided new insights into the efficient nitrogen removal from low carbon wastewater, realizing the carbon-neutral operation of new concept wastewater treatment plant in China.

Circ_0000811 acts as a miR-15b sponge and inhibits Prkar2a-mediated JAK2/STAT1 pathway to attenuate cerebral ischemic vertigo.

Circular RNAs (circRNAs) have been noted to express in the brain and thus participate in various diseases related to the central nervous system. However, the potential role of circRNAs in cerebral ischemia (CI)-induced vertigo remains unknown. We initially predicted through bioinformatics analysis the poor expression of circ_0000811 related to CI. A mouse model of CI-induced vertigo was then established, which was validated by measurement of escape latency and medial vestibular nucleus (MVN) blood flow, with NeuN/Annexin counterstaining utilized to detect cell apoptosis in the MVN. An oxygen glucose deprivation (OGD)-exposed neuron-like cell model was further established for in vitro gain- and loss- of function assays, with flow cytometry performed to detect cell apoptosis. The poorly expressed circ_0000811, up-regulated miR-15b expression, and down-regulated Prkar2a expression were observed in both mice with CI-induced vertigo and OGD-exposed cells. Our data then demonstrated that circ_0000811 restoration alleviated CI-induced vertigo in mouse models, and that circ_0000811 acted as a miR-15b sponge to inhibit miR-15b expression. Prkar2a was validated as the target gene of miR-15b. Prkar2a restoration was subsequently revealed to repress OGD-induced neuronal apoptosis through JAK2/STAT1 signaling pathway inactivation. Furthermore, inactivation of the JAK2/STAT1 signaling pathway exerted an anti-apoptotic effect in OGD-induced neurons and an alleviatory effect in mice with CI-induced vertigo with Prkar2a overexpression and circ_0000811 overexpression. Taken together, our work suggests that circ_0000811 is involved in neuronal apoptosis of CI-induced vertigo and may be used as a biomarker for ameliorating CI-induced vertigo.

Analysis of clinical characteristics and prognostic factors in 110 patients with nitrous oxide abuse.

PURPOSE: To review the clinical symptoms, auxiliary examination findings, and outcomes of patients with nitrous oxide (N2 O) abuse, and analyze the factors that affect outcomes. METHODS: Patients with N2 O abuse treated in the Department of Neurology between January 2018 and December 2020 were included. The clinical data of these patients were collected, and follow-up was conducted to determine the outcomes. RESULTS: The average age of the 110 patients with N2 O abuse was 21.4 ± 4.2 years (range: 14-33 years). Clinical presentation primarily included neurological symptoms, such as limb numbness and/or weakness (97%), psychiatric symptoms, changes in appetite, and skin hyperpigmentation. Laboratory test results were characterized by vitamin B12 deficiency (60%, 34 out of 57 cases) and high homocysteine level (69%, 31 out of 45 cases). Electromyography indicated mixed axonal and demyelination injury (92%, 80 out of 87 cases). Motor and sensory nerves were simultaneously involved, and injury primarily involved the lower limbs. One hundred and seven (97%) patients were clinically diagnosed with peripheral neuropathy, of whom 26 (24%) exhibited spinal abnormalities on magnetic resonance imaging, supporting a diagnosis of subacute combined degeneration. Treatment included N2 O withdrawal and vitamin B12 supplementation. Reexamination of six patients indicated that treatment was effective. Follow-up was completed for 51 patients. Thirty-four patients (67%) recovered completely, 17 patients (33%) had residual limb numbness, and only one patient experienced relapse. Sex was an independent prognostic factor; the outcomes of female patients were better than that of male patients. CONCLUSION: The recreational use of N2 O has largely expanded among youth in recent decades, which has become a growing public health concern in China. It highlights the importance of the recognition of various clinical symptoms, particularly limb numbness and/or weakness related to the cases of N2 O abuse. The therapeutic administration of vitamin B12 supplementation and N2 O withdrawal can make the overall prognosis good, especially for female patients.

Overexpressing circ_0000831 is sufficient to inhibit neuroinflammation and vertigo in cerebral ischemia through a miR-16-5p-dependent mechanism.

Circular RNAs (circRNAs) hold potential as stroke-related biomarkers due to involvement in various pathophysiological processes associated with cerebral ischemia and stability in peripheral blood. Differentially expressed circulating circRNAs were identified by preliminary sequencing analysis, through which we identified underexpressed circ_0000831 in ischemic stroke (IS). Validation was performed in peripheral blood of IS patients by quantitative polymerase chain reaction. Microglia was exposed to oxygen-glucose deprivation (OGD), where polarization phenotypes and inflammation were assessed. Middle cerebral artery occlusion was performed in mice to mimic ischemic stroke-induced vertigo, where cerebral blood flow, neurological deficits, vertigo degree, infarct area, inflammation and cell apoptosis were assayed in response to ectopic expression and knockdown of circ_0000831, miR-16-5p, and AdipoR2. Mechanically, circ_0000831 bound to miR-16-5p and downregulated miR-16-5p, and AdipoR2 was targeted by miR-16-5p and increased PPARγ expression in microglia. Furthermore, circ_0000831, AdipoR2, or PPARγ overexpression or miR-16-5p inhibition alleviated neuroinflammation, vertigo, neurological deficit, and cell apoptosis in MCAO mice. Consistently, circ_0000831, AdipoR2, or PPARγ upregulation or miR-16-5p downregulation diminished apoptosis and inflammation of OGD-induced microglia. Consequently, these findings pinpoint the circ_0000831/miR-16-5p/AdipoR2 axis as an essential signaling pathway during ischemia stroke. Thus, the circRNA circ_0000831 may work as a possible target for novel treatment in patients with ischemic stroke.

Clinical and MRI Differences Between Patients With Subacute Combined Degeneration of the Spinal Cord Related vs. Unrelated to Recreational Nitrous Oxide Use: A Retrospective Study.

Objective: To explore the clinical and imaging characteristics of subacute combined degeneration of the spinal cord (SCD) related to recreational nitrous oxide (N2O) use. Methods: Clinical and imaging data were retrospectively collected from patients with SCD related to recreational N2O use who were diagnosed and treated at Shengjing Hospital of China Medical University from January 2016 to June 2020. The clinical and imaging features of patients with recreational N2O-related SCD were compared with those of patients with N2O-unrelated SCD, who were diagnosed and treated during the same period of time. Results: The study enrolled 50 patients (male/female: 22/28, age: 21.4 ± 4.7 years) with N2O-related SCD and 48 patients (male/female: 27/21, age: 62.0 ± 11.4 years) with SCD unrelated to N2O use. The most common signs/symptoms of the patients in both groups were limb numbness and weakness and unsteady gait, but the incidence of limb weakness, unsteady gait, disorders of urination and defecation, anorexia, reduced deep sensation in lower limbs, ataxia, and positive Babinski sign were lower in the N2O-related SCD group than those in the N2O-unrelated SCD group (P < 0.05). The functional disability rating score of patients in the N2O-related SCD group (median: 3, IQR: 2-5) was also significantly lower than the score in the N2O-unrelated SCD group (median: 5, IQR: 4-7) (P < 0.05). The serum vitamin B12 level was significantly lower in the N2O-unrelated SCD group (median: 96 pg/mL, IQR: 50-170 pg/mL) than the level in the N2O-related SCD group (median: 218 pg/mL, IQR:121-350 pg/mL) (P < 0.05), while both groups had similarly increased levels of homocysteine (P > 0.05). Compared with the N2O-unrelated SCD patients, more patients with N2O-related SCD had abnormal spinal magnetic resonance imaging (MRI) scans (80.0 vs. 64.2%). The patients with N2O-related SCD also had wider spinal lesions on sagittal MRI (5.3 ± 0.8 mm vs. 4.2 ± 1.0 mm), fewer spinal segments with lesions (median: 5, IQR: 4-6 segments vs. median: 6, IQR: 5-7.5 segments), and a higher incidence of the inverted V sign on axial MRI (72.0 vs. 31.2%) (all P < 0.05). Conclusion: The recreational use of N2O has become an important cause of SCD in young patients. Compared with the N2O-unrelated SCD patients, the N2O-related SCD patients had less severe clinical presentations, less obvious decrease in serum VB12 levels, and more obvious MRI changes.

SQSTM1 variant in disorders of the frontotemporal dementia-amyotrophic lateral sclerosis spectrum: identification of a novel heterozygous variant and a review of the literature.

INTRODUCTION: Accumulating evidence shows that SQSTM1 plays a vital role in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), which represent a neurodegenerative disease continuum. Here, we report a novel SQSTM1 variant in a patient presenting with progressive nonfluent aphasia (PNFA) and progressive bulbar palsy (PBP). Relevant literature about FTD and FTD-ALS caused by SQSTM1 mutation was reviewed to better understand its clinical features. METHODS: We collected data from a 66-year-old male patient with a novel heterozygous variant (c.995C > G, p.S332X) in the SQSTM1 gene who was diagnosed with PNFA and PBP and performed a PubMed literature search using the advanced research criteria: [("frontotemporal lobar degeneration") OR ("frontotemporal dementia") OR ("amyotrophic lateral sclerosis") OR ("motor neuron disease")] AND ("SQSTM1"). The clinical features of FTD and FTD-ALS related to SQSTM1 mutation were summarized based on previous cases and our new case. RESULTS: The initial symptom of the current patient was progressive verb finding difficulties and effortful speech output, which developed into dysarthria and dysphagia in subsequent months. The results, including tongue atrophy, fasciculations, neurogenic changes, and mild left dominant hypometabolism of 18F-fluorodeoxyglucose PET in the frontal cortex, suggest the possibility of PNFA and PBP. A novel likely pathogenic heterozygous variant (c.995C > G, p.S332X) in the SQSTM1 gene was identified. The literature search revealed a total of 33 FTD and FTD-ALS cases related to the SQSTM1 mutation with detailed clinical information. The mean age of onset (including our patient) was 63.5 ± 9.7 years. bvFTD was the most common clinical phenotype. The missense mutation in the SQSTM1 gene coding region and the UBA domain involvement are its main genetic characteristics. CONCLUSION: Although rare, mutations in SQSTM1 can lead to various clinical subtypes of FTD and FTD-ALS, including the rare combination of PNFA and PBP. Exon missense mutation is the main type of mutation, which is common in the UBA domain.

Skin hyperpigmentation: a rare presenting symptom of nitrous oxide abuse.

Context: Recreational nitrogen oxide (N2O) abuse can cause nervous system damage. There was a sharp increase in the number of patients with neurological disorders associated with recreational N2O use in China, as recreational N2O use became popular in young people nationwide. Among cases with neurological disorders caused by N2O abuse, a few showed skin hyperpigmentation, which has rarely been reported. We explored the characteristics of hyperpigmentation in N2O abusers to draw the attention of clinicians to this rare cutaneous symptom related to N2O abuse.Methods: We retrospectively collected data of patients with neurological disorders related to recreational N2O abuse in Shengjing Hospital of China Medical University from January 2014 to June 2019. Detailed clinical data were gathered from patients who manifested skin pigmentation, including the history of N2O abuse and characteristics of neurological lesions and skin pigmentation.Results: In total, 66 patients (average age: 22.7 ± 4.5 years, 36 males) with neurological disorders due to N2O abuse were included; four of them (17-23 years old, 1 male) manifested skin hyperpigmentation. The duration of N2O abuse of the four patients ranged from 2 to 24 months, and they all had peripheral neuropathy; the two patients also had subacute combined degeneration of the spinal cord. One patient exhibited significant hyperpigmentation throughout the body (trunk, limbs, and face), with no abnormalities in cortisol and other biochemical tests. One patient presented with punctuate pigmentation throughout the trunk. Two patients presented with finger skin pigmentation, especially in the distal phalanxes. Pigmentation after N2O use remitted slowly with vitamin B12 supplementation.Conclusion: Skin hyperpigmentation is a rare symptom in N2O abusers, which can distribute locally in hands or diffusely throughout the body. Therefore, attention should be paid to a history of N2O abuse and serum vitamin B12 level should be tested.

Mechanical thrombectomy with second-generation devices for acute cerebral middle artery M2 segment occlusion: A meta-analysis.

BACKGROUND: The benefit of mechanical thrombectomy for an acute ischemic stroke involving M2 segment occlusion is not clear, especially when performed with second-generation thrombectomy devices. METHOD: We reviewed the literature to investigate clinical outcomes and the rates of recanalization, symptomatic intracerebral hematoma, and mortality in mechanical thrombectomy performed using second-generation thrombectomy devices. We compared the outcomes between patients treated for M2 and M1 occlusions. RESULTS: Seven studies involving 805 patients with M2 thrombectomy were included in this meta-analysis. The functional independence rate 90 days after thrombectomy (modified Rankin Scale 0-2) was 59.3% (OR 1.81, 95% CI 1.74-1.88). The recanalization rate (thrombolysis in cerebral infarction 0-2) was 84.16% (OR 2.32, 95% CI 2.08-2.29). The symptomatic intracerebral hematoma rate was 4.9% (OR 1.05, 95% CI 1.03-1.09). The mortality was 7.7% (OR 1.08, 95% CI 1.03-1.13). The outcomes were better in patients with M2 occlusion than in those with M1 occlusion. In a subgroup analysis, we found that among patients with hypertension, mechanical thrombectomy achieved better functional outcomes and recanalization in M2 occlusion than M1 occlusion. CONCLUSION: Mechanical thrombectomy performed with second-generation thrombectomy devices for M2 occlusion can provide a good functional outcome as well as satisfying recanalization. Moreover, there was no significant difference in the symptomatic intracerebral hematoma and mortality rates, suggesting this procedure is as safe in M2 occlusion as in M1 occlusion.

The sharp rise of neurological disorders associated with recreational nitrous oxide use in China: a single-center experience and a brief review of Chinese literature.

INTRODUCTION: In recent years, there has been a sharp increase in the number of patients with neurological disorders associated with recreational use of nitrous oxide (N2O) in China. Here, we summarize the clinical characteristics of patients with neurological disorders associated with N2O abuse diagnosed in our Hospital. Further, we conducted a literature search on recent cases reported in mainland China to improve the awareness of the outbreak of neurological disorders associated with N2O abuse. METHODS: We retrospectively collected data of patients diagnosed with neurological disorders associated with recreational use of N2O in Shengjing Hospital of China Medical University from January 2018 to June 2019, and performed a literature search using the "nitrous oxide" and "neurological disorder" as keywords in the Chinese literature databases of WANFANG and CNKI and the English literature databases of Pubmed and Web of Science RESULTS: We enrolled 43 patients (average age: 21.9 ± 3.3 years). The main clinical manifestations were weakness and paresthesia in the four extremities and unsteady gait. Further, most patients showed significantly lower levels of serum vitamin B12 (169.4 ± 79.1 pg/mL) and increased homocysteine levels (78.1 ± 32.2 µmol/L). MRI of the spinal cord showed longitudinal high T2 signal lesions in the dorsal spinal cord in some patients. Moreover, electromyography showed sensory and motor nerve axonal damage combined with demyelination, which was relatively more severe in the lower limbs. There was rapid improvement of the symptoms after treatment with intramuscular injections of vitamin B12 and the overall prognosis was good. The literature search indicated that the number of published papers and related patients showed a rapid annual increase since the first Chinese case reported in 2016 CONCLUSION: Recreational use of N2O is an emerging public health problem in China that needs prompt action from the society and government. Early diagnosis and treatment allow a good overall prognosis.

MicroRNA-217-5p ameliorates endothelial cell apoptosis induced by ox-LDL by targeting CLIC4.

BACKGROUND AND AIMS: Endothelial cell apoptosis plays an essential role in the pathogenesis of atherosclerosis. MicroRNAs and chloride intracellular channels (CLICs) have been verified to participate in the endothelial cell apoptosis process, however, the underlying molecular mechanisms are still unclear. The main aim of this study was to investigate the biological effects of microRNA-217-5p (miR-217-5p) and CLIC4 on endothelial cell apoptosis in atherosclerosis. METHODS AND RESULTS: An atherosclerotic mouse model (n = 18) was constructed by feeding apolipo protein E knockout ApoE(-/-) mice with high-fat diet for 12 weeks. An atherosclerotic cell model was established by treating human aortic endothelial cells with oxidized low-density lipoprotein (ox-LDL; 50 µg/mL) for 24 h. Quantitative real-time polymerase chain reaction and immunofluorescent staining confirmed the downregulation of miR-217-5p and upregulation of CLIC4 in atherosclerotic endothelial cells. Combined with western blot, flow cytometry assay and Hoechst staining, we demonstrated that miR-217-5p upregulation or CLIC4 knockdown regulated the apoptosis-related genes, ameliorated mitochondrial membrane permeability and therefore inhibited the apoptosis of aortic endothelial cells induced by ox-LDL. We further confirmed that miR-217-5p inhibited apoptosis of endothelial cells through targeting CLIC4 using luciferase report assay and rescue experiments. CONCLUSION: We revealed for the first time that miR-217-5p inhibited apoptosis of endothelial cells in atherosclerosis and identified CLIC4 as a novel target of miR-217-5p. Our work provides a potential therapeutic approach for the treatment of atherosclerosis.

Clinical characteristics and short-term prognosis of LGI1 antibody encephalitis: a retrospective case study.

BACKGROUND: Recently, most reports of Leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis are from Europe and the US, while the short term outcome and clinical characteristics of Chinese patients are rarely reported,we study the clinical manifestations, laboratory results and brain magnetic resonance images (MRI) of eight patients who were recently diagnosed with LGI1 antibody encephalitis in our hospital to improve the awareness and knowledge of this disease. METHODS: Eight patients (five males and three females; mean age, 63.4) with LGI1 antibody encephalitis who were diagnosed and treated in the Department of Neurology of Shengjing Hospital of China Medical University from September 2016 to June 2017 were recruited for the current study. Their general information, clinical manifestations, treatment regimens, and short-term prognoses were retrospectively analyzed, as were the results from MRI and laboratory findings. RESULTS: Overall, patient symptoms included cognitive impairment, which manifested primarily as memory deficits (8/8), seizures (including faciobrachial dystonic seizure, (FBDS)) (8/8), psychiatric and behavioral disorders (7/8), sleep disorders (4/8), and autonomic abnormalities (3/8). Five patients also had abnormal findings on brain MRI, mainly involving the hippocampus, basal ganglia and insula. Hyponatremia occurred in six cases. All patients tested positive for LGI1 antibodies in their serum/cerebrospinal fluid (CSF)and patients were negative for tumors. Symptoms rapidly improved after treatment with immunoglobulin and/or steroid therapy. The patients were followed up for 4-13 months after discharge, and two patients relapsed. CONCLUSION: Primary symptoms of LGI1 antibody encephalitis include memory impairments, seizures, FBDS, and mental and behavioral abnormalities. Increased titers of LGI1 antibodies are also present in the serum/CSF of patients. Patients often have hyponatremia, and MRIs show abnormalities in various brain regions. Finally, immunotherapy shows good efficacy and positive benefits, although patients may relapse in the short-term.