Novel mutation in EFEMP1 identified from two Chinese POAG families differentially activated endoplasmic reticulum stress markers and induced glaucoma in mouse.

Primary open-angle glaucoma (POAG) is the most common type of glaucoma. Using whole-exome sequencing, we identified two independent families diagnosed as POAG from the China with a novel EFEMP1 variant (Exon3, c.175A>C p.Met59Leu); Three previously reported variants c.1160G>A p.R387Q, c.1189T>C p.Y397H, and c.1429C>T p.R477C in EFEPM1 from 55 sporadic POAG individuals were also identified. The variant c.175A>C p.Met59Leu co-segregated with the disease phenotype within the families. Immunoprecipitation and western blot assays showed that all three EFEMP1 mutants (p.Met59Leu, pArg140Trp, pArg345Trp) increased intracellular protein aggregations, and pMet59Leu and pArg140Arg also enhanced their extracellular proteins secretion, compared to WT in HEK293T. The differential regulations to endoplasmic reticulum (ER) stress markers ATF4, GPR78/94, and CHOP, and differential phosphorylation activations to CREB at Ser133, AKT at Ser473, p44/42 at Thr202/Tyr204, and STAT3 at Tyr705, were also detected among the mutants and WT. Finally, we revealed a significant increment of intraocular pressure and obvious reduction of RGC cells at the sixth week following intravitreal injection of adenovirus 5 (Ad5) expressing in pMet59Leu compared to WT and GFP controls. Together, variant c.175A>C p.Met59Leu in EFEMP1 is pathogenic and different mutants in EFEMP1 triggered distinct signaling pathways, explaining the reason of mutation-dependent disease phenotypes of EFEMP1.

Identification of two variants in PAX3 and FBN1 in a Chinese family with Waardenburg and Marfan syndrome via whole exome sequencing.

Both Warrensburg (WS) and Marfan syndrome (MFS) can impair the vision. Here, we recruited a Chinese family consisting of two WS affected individuals (II:1 and III:3) and five MFS affected individuals( I:1, II:2, III:1, III:2, and III:5) as well as one suspected MFS individual (II:4). Using whole exome sequencing (WES) and subsequent PCR-Sanger sequencing, we identified one novel heterozygous variant NM_000438 (PAX3) c.208 T > C, (p.Cys70Arg) from individuals with WS and one previous reported variant NM_000138 (FBN1) c.2740 T > A, (p.Cys914Ser) from individuals with MFS and co-segregated with the diseases. Real-time PCR and Western blot assay showed that, compared to their wild-type, both mRNAs and proteins of  PAX3 and FBN1 mutants reduced in HKE293T cells. Together, our study identified two disease-causing variants in a same Chinese family with WS and MFS, and confirmed their damaged effects on their genes' expression. Therefore, those findings expand the mutation spectrum of PAX3 and provide a new perspective for the potential therapy.

Recyclable gold(I)-catalyzed heterocyclization of ynamides with benzyl or indolyl azides towards 2-aminoindoles or 3-amino-ß-carbolines.

A highly efficient heterogeneous gold(I)-catalyzed heterocyclization of ynamides with benzyl or indolyl azides has been achieved in 1,2-dichloroethane under mild conditions via a heterogenized α-imino gold carbene intermediate using 5 mol% of SBA-15-anchored strongly hindered NHC-gold(I) complex [IPr-SBA-15-AuNTf2] as the catalyst, delivering a wide range of valuable 2-aminoindoles or 3-amino-ß-carbolines in mostly good to excellent yields with high regioselectivity. Furthermore, the new heterogenized NHC-gold(I) complex displays the same catalytic activity as IPrAuNTf2 and is facile to recover by centrifugation of the reaction mixture and can be reused at least seven times without any appreciable drop in its catalytic activity.

MiR-122 knockdown regulates vascular smooth muscle cells phenotypic switching through enhanced FOXO3 expression.

Vascular smooth muscle cells (VSMCs) phenotypic switching is identified as enhanced dedifferentiation, proliferation, and migration ability of VSMCs, in which microRNAs have been identified as important regulators of the process. The present study is aimed to explore the pathophysiological effect of miR-122 on VSMC phenotypic modulation. Here, the result showed that the decreased miR-122 expression was found in VSMCs subjected to platelet-derived growth factor-BB (PDGF-BB) treatment. Next, we investigated the response of miR-122 knockdown in VSMCs with PDGF-BB stimulation. MiR-122 silencing showed increased proliferation and migration capability, whereas attenuated the differentiation markers expression. The above results were reversed by miR-122 overexpression. Finally, we further demonstrated that FOXO3 was an important target for miR-122. Collectively, we demonstrated that miR-122 silencing promoted VSMC phenotypic modulation partially through upregulated FOXO3 expression that indicated miR-122 may be a novel therapeutic target for neointimal formation.

Comorbidity among inpatients with dementia: a preliminary cross-sectional study in West China.

OBJECTIVE: To investigate comorbidities among hospitalized patients with dementia. METHOD: Data were extracted from the discharge records in our hospital. Comorbidities based on ICD-10 were selected from the Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI). The distributions of these comorbidities were described in dementia inpatients and age- and sex-matched nondementia controls, as well as in inpatients with Alzheimer's disease and vascular dementia. A logistic regression model was applied to identify dementia-specific morbid conditions. RESULTS: A total of 3355 patients with dementia were included, with a majority of 1503 (44.8%) having Alzheimer's disease, 395 (11.8%) with vascular dementia, and 441 (13.1%) with mixed dementia. The mean number of comorbidities was 3.8 in dementia patients (vs. 2.9 in controls). The most prevalent comorbidities in inpatients with dementia compared with those without dementia were cerebral vascular disease (73.0% vs. 35.9%), hypertension (62.8% vs. 56.2%), and peripheral vascular disease (53.7% vs. 31.2%). Comorbidities associated with dementia included epilepsy (OR 4.8, 95% CI 3.5-6.8), cerebral vascular disease (OR 4.1, 95% CI 3.7-4.5), depression (OR 4.0, 95% CI 3.2-5.0), uncomplicated diabetes (OR 1.5, 95% CI 1.4-1.7), peripheral vascular disease (OR 1.8, 95% CI 1.6-2.0), rheumatoid arthritis collagen vascular disease (OR 1.7, 95% CI 1.3-2.3), and anemia (OR 1.2, 95% CI 1.04-1.3). Some comorbidities suggested a protective effect against dementia. They were hypertension (OR 0.8, 95% CI 0.7-0.9), COPD (OR 0.6, 95% CI 0.5-0.6), and solid tumor without metastasis (OR 0.4, 95% CI 0.3-0.4). Vascular dementia has more cardiovascular and cerebrovascular comorbidities than Alzheimer's disease. CONCLUSION: Patients with dementia coexisted with more comorbidities than those without dementia. Comorbidities (esp. cardio-cerebral vascular risks) in patients with vascular dementia were more than those in patients with AD. Specifically, vascular and circulatory diseases, epilepsy, diabetes and depression increased the risk of dementia.

PRPF31 interacts with PRPH2 confirmed by co-immunoprecipitation and co-localization.

Both PRPF31 and PRPH2 are the causative genes for retinitis pigmentosa. And both of them are associated with the balance of rhodopsin. In this study, we aim to investigate the co-expression and interaction of PRPF31 and PRPH2. We used PRPF31-eGFP, PRPF31-3xFlag and PRPH2-mCherry vectors were transfected into HEK293T and APRE-19 cells. Immunoblotting and co-immunoprecipitation (Co-IP) were used for gene expression validation and protein interaction. Immunofluorescence staining assay was used to test the co-localization analysis of PRPF31 and PRPH2. Co-IP experiments showed that PRPF31 could be pulled down with an anti-PRPH2 antibody. There was co-localization between PRPF31 and PRPH2 in HEK293T, APRE-19 and mouse retina. The Co-IP and co-localization experiments suggest that PRPF31 interacted with PRPH2.

Recyclable Gold Catalyst for the Stereoselective Thioallylation of Alkynes.

The heterogeneous gold(I)-catalyzed stereoselective thioallylation of electron-deficient alkynes with allyl sulfides has been achieved by using an MCM-41-immobilized sterically demanding NHC-gold(I) complex [MCM-41-IPrAuNTf2] as the catalyst under mild conditions, delivering a wide variety of stereodefined tri- and tetrasubstituted functionalized vinyl sulfides in good to excellent yields. The new heterogeneous MCM-41-IPrAuNTf2 catalyst exhibits an activity comparable to a homogeneous IPrAuNTf2 complex and can be recovered via a simple filtration process and reused for at least seven consecutive cycles without any apparent loss of its catalytic activity and selectivity.

Optimising epilepsy management with a smartphone application: a randomised controlled trial.

OBJECTIVE: To assess whether a practical intervention based upon a smartphone application (app) would improve self-management and seizure control in adults with epilepsy. DESIGN, SETTING: Randomised, controlled trial in western China, December 2017 to August 2018. PARTICIPANTS: 380 eligible people with epilepsy were recruited; 327 completed the 6-month follow-up (176 in the app group, 151 in the control group). MAIN OUTCOME MEASURES: Self-management of epilepsy (measured with the validated Chinese Epilepsy Self-Management Scale, C-ESMS) and self-reported seizure frequency. RESULTS: In the intention-to-treat analysis, the mean C-ESMS score increased significantly in the app group between baseline and the 6-month evaluation (from 121.7 [SD, 12.1] to 144.4 [SD, 10.0]; P < 0.001); improvements on the information management, medication management, and safety management subscales were also statistically significant. At 6 months, the mean overall C-ESMS score for the app group was significantly higher than that for the control group (125.4 [SD, 1.5];  P < 0.001). The proportion of patients who were seizure-free at the 6-month follow-up was larger for the app than the control group (54 of 190, 28% v 22 of 190, 12%), as was the proportion with reductions in frequency of between 75 and 100% (22 of 190, 12% v 8 of 190, 4%). Changes in C-ESMS score were not statistically associated with seizure frequency. CONCLUSIONS: Using a smartphone app improved epilepsy self-management scores in people in western China. It should be further tested in larger populations in other areas. Our preliminary investigation of building digital communities for people with epilepsy should encourage similar approaches to managing other chronic diseases. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900026864, 24 October 2019.

Whole exome sequencing reveals novel EYS mutations in Chinese patients with autosomal recessive retinitis pigmentosa.

Purpose: Retinitis pigmentosa (RP) belongs to a group of inherited retinal diseases with high genetic heterogeneity. This study aimed at identifying the disease-causing variants in patients with autosomal recessive RP. Methods: Three RP families with autosomal recessive inheritance and 139 sporadic RP patients were included. Complete ophthalmic examinations were conducted in all the study subjects. DNA samples were extracted from patients' peripheral blood for whole exome sequencing (WES) analysis. Direct Sanger sequencing was conducted for validating the identified mutations and cosegregation pattern in the RP families. Results: One novel (c.7492G>C:p.Ala2498Pro and c.8422C>T:p.Ala2808Thr) and one reported (c.8012T>A:p.Leu2671X and 6416G>A:p.Cys2139Tyr) pair of compound heterozygous mutations, as well as one reported compound homozygous mutation (c.6416G>A:p.Cys2139Tyr/c.8012T>A:p.Leu2671X), were identified in the EYS gene from three families with autosomal recessive RP. All the mutations were cosegregated with the RP phenotype in the RP families. For the sporadic RP patients, seven novel and seven reported EYS variants were identified in 19 patients, including two novel frameshift (c.8301dupT:p.Asp2767fs and c.9437_9440del:p.Glu3146fs), three novel missense (c.8297G>C:p.Gly2766Ala, c.9052T>C:p.Trp3018Arg, and c.8907T>G:p.Cys2969Trp), and one nonsense (c.490C>T:p.Arg164X) variants. All the novel mutations were confirmed by Sanger sequencing. Most of the variants were located at the C-terminus of the EYS protein. Bioinformatics analyses indicated that all detected variants were damaging or possibly damaging. Conclusions: This study identified eight novel EYS variants and expanded the spectrum of EYS mutations in Chinese RP patients.

Mortality-specific comorbidity among inpatients with ischemic stroke in West China.

OBJECTIVE: This study aimed to investigate the current condition of mortality-specific comorbidity among hospitalized patients with ischemic stroke. METHODS: Five-year data of inpatients with ischemic stroke (IS) were extracted from the hospital medical database. A retrospective review of eighteen mortality-specific comorbidities in extensively validated Charlson Comorbidity Index (CCI) was carried out for each patient. In addition, the distribution of the CCI-based prognostic score was calculated. RESULTS: A total of 10 331 (male 57.6%) cases with IS were recruited in the present study. The most prevalent mortality-specific comorbidities from high to low were as follows: peripheral vascular disease (35.1%), diabetes uncomplicated (25.2%),mild liver disease (18.3%), chronic pulmonary disease (14.7%), congestive heart failure (10.8%), atrial fibrillation or flutter (10.3%), diabetes complicated (9.1%), moderate or severe renal disease (7.5%), and dementia (7.1%). High prevalence of comorbidities in the elderly was also noted (31.1% patients with score ≥3). Spearman correlation analysis with a rho of 0.25 (P < 0.001) showed a mild correlation between the age- and the CCI-based prognostic score. CONCLUSION: High prevalence of peripheral vascular disease, diabetes, liver disease, chronic pulmonary disease, congestive heart failure, atrial fibrillation, or flutter as major contributors to mortality was presented in in-hospital patients with IS in our area. One-third of old patients with IS expose high mortality risk with the CCI score ≥3. Early prevention and management of the potential comorbidities are necessary to reduce the mortality.

Profiling and characterization of microRNAs responding to sodium butyrate treatment in A549 cells.

Butyrate inhibits growth of lung cancer. However, the molecular mechanism is still unclear. Here we profiled miRNAs that responded to sodium butyrate(NaB) stimulation in A549 cells, a non-small cell lung cancer cell line, using microarray. We found 33 up-regulated microRNAs and 22 down-regulated microRNAs (log2 ≥1.5 folds, P-value <0.05). The expression of miR-3935, miR-574-3p, and miR-494-3p was confirmed by realtime qPCR. Then,we explored their potential targets of miR-3935 and miR-494-3p using long noncoding RNA(LncRNA) microarray. Using cell expressing negative microRNA as control, we found 103 up-regulated transcripts (including 69 mRNA and 34 LncRNA), and 36 down-regulated transcripts (including 34 mRNAs and 2 LncRNA), in miR-3935 over-expressing A549 cells; 128 up-regulated transcripts (121 mRNAs, 7 LncRNAs) and 180 down-regulated transcripts (169 mRNAs, 11 LncRNAs) in mir-494-3p, respectively (log2 Fold change ≥ 1 & P < 0.05). The expression of RNF115, NTRK3, SLC39A6, and USB1 was confirmed with qPCR. Immunoblotting was adopted to detect RNF115 expression in miR-3935 overexpressed A549 cells. Then, using a luciferase reporter assay system, we found that miR-3935 overexpression significantly decreased 3UTR of RNF115 mediated luciferase expression .In addition, we also observed that the proliferation and migration of A549 cells was obviously prevented by miR-3935 overexpression. Finally, we showed miR-3935 and miR-494-3p induced interferon stimulated gene 15(ISG15) expression through activating its promoter transcription. Together, we profiled microRNAs that responded to NaB treatment and characterized their biological functions in A549 cells. Those results provided new clue for the future treatment of non small cell lung cancer.

Mortality-specific comorbidity among inpatients with epilepsy: A preliminary cross-sectional study in West China.

PURPOSE: The purpose of this study was to investigate the current condition of mortality-specific comorbidity among hospitalized patients with epilepsy (PWE). METHODS: The discharge abstract records of PWE from over 730,000 admissions were extracted from the hospital medical database. Fourteen mortality-related comorbidities from an epilepsy-specific index (ESI) were selected for the present assessment. The hospital-based prevalence of these comorbidities was estimated. The distributions of PWE with an ESI-based prognostic score were calculated. RESULTS: A cohort of 11,422 PWE (male 58.5%) was included in the present study. The order of comorbidities in terms of high to low prevalence ranking was as follows: hypertension (19.6%), peripheral vascular disease (8.1%), cardiac arrhythmias (5.8%), dementia (4.6%), renal disease (4.1%), congestive heart failure (3.8%), metastatic cancer (3.4%), brain tumor (2.4%), paraplegia and hemiplegia (2.0%), solid tumor without metastasis (1.7%), anoxic brain injury (1.4%), pulmonary circulation disorders (1.3%), moderate or severe liver disease (1.1%), and aspiration pneumonia (0.2%). High rates of comorbidities in the elderly were also noted. Spearman correlation analysis showed a moderate correlation between the changes in ages and prognostic score with a rho of 0.6 (p<0.001). The percentage of females with a score of 0 was higher than that of males (p<0.001), indicating that the prognostic survival of the majority of females was relatively longer than that of males. CONCLUSION: Our study demonstrated that the comorbidity burden of female PWE was relatively lower than that of male PWE. High prevalence of cardiac and vascular diseases was found in PWE, thereby affecting the long-term survival rate. Considering that the propensity of increased comorbidity was prevalent with age, we should implement early preventive measures to manage the potential comorbidities associated with mortality, reduce disease burden, and prolong the survival of PWE.

Risk assessment of in-hospital mortality of patients with epilepsy: A large cohort study.

PURPOSE: This study aimed to explore the mortality risks of hospitalized patients with epilepsy (PWE). METHODS: Our data source was extracted from discharge abstracts in a hospital medical database. Various clinical variables, including demographical characteristics, natural features of epilepsy, and comprehensive set of comorbidities, were screened to investigate the risk. Comorbidities were defined using a validated ICD-10-based classification. The distributions of comorbid conditions and demographics were presented. In-hospital mortality rates of groups with epilepsy and without epilepsy were compared. Logistic regression was applied to explore the important predictors of in-hospital mortality. RESULTS: A cohort of 11,422 PWE (male: 58.5%, mean age: 40.2 years) was recruited for the study. The most common comorbidities were cerebrovascular disease, hypertension, and peripheral vascular disease, which accounted for 23.5%, 18.8%, and 8.0% of the study cohort, respectively. In-hospital mortality rates were 2.9% and 1.1% in the epilepsy and nonepilepsy cohort, respectively. Male patients exhibited an increased risk of death (odds ratio (OR) = 1.2; 95% confidence interval (CI) = 1.0-1.6). Patients aged over 65 years were more likely to die than those below 18 years (OR = 18.2; 95% CI = 8.8-31.0). Patients with comorbidities, including central nervous system (CNS) infections, renal disease, traumatic brain and head injuries, anoxic brain injury, metastatic cancer, pulmonary circulation disorders, encephalopathy, solid tumor without metastasis, cardiac arrhythmias, and diabetes without complication, had a higher risk of in-hospital death than patients without comorbidities (OR = 6.1, 5.2, 5.1, 4.4, 3.7, 2.5, 2.4, 2.0, 1.5, 1.4, respectively; 95% CI = 4.1-9.1, 3.8-7.0, 2.8-9.5, 2.4-8.3, 2.2-6.3, 1.5-4.3, 1.4-4.2, 1.1-3.7, 1.1-2.1, 1.0-1.9, respectively). CONCLUSION: The in-hospital mortality of PWE increased remarkably with age, and this parameter was predominant in male patients. Central nervous system infection, renal disease, traumatic brain and head injuries, anoxic brain injury, metastatic cancer, pulmonary circulation disorders, encephalopathy, solid tumor without metastasis, cardiac arrhythmias, and diabetes without complication were the most important comorbidities associated with in-hospital death.

Lysosomal storage disease in the brain: mutations of the ß-mannosidase gene identified in autosomal dominant nystagmus.

PURPOSE: Genetic etiology of congenital/infantile nystagmus remains largely unknown. This study aimed to identify genomic mutations in patients with infantile nystagmus and an associated disease network. METHODS: Patients with inherited and sporadic infantile nystagmus were recruited for whole-exome and Sanger sequencing. ß-Mannosidase activities were measured. Gene expression, protein-protein interaction, and nystagmus-associated lysosomal storage disease (LSD) genes were analyzed. RESULTS: A novel heterozygous mutation (c.2013G>A; p.R638H) of MANBA, which encodes lysosomal ß-mannosidase, was identified in patients with autosomal-dominant nystagmus. An additional mutation (c.2346T>A; p.L749H) in MANBA was found by screening patients with sporadic nystagmus. MANBA was expressed in the pretectal nucleus of the developing midbrain, known to be involved in oculomotor and optokinetic nystagmus. Functional validation of these mutations demonstrated a significant decrease of ß-mannosidase activities in the patients as well as in mutant-transfected HEK293T cells. Further analysis revealed that nystagmus is present in at least 24 different LSDs involving the brain. CONCLUSION: This is the first identification of MANBA mutations in patients with autosomal-dominant nystagmus, suggesting a new clinical entity. Because ß-mannosidase activities are required for development of the oculomotor nervous system, our findings shed new light on the role of LSD-associated genes in the pathogenesis of infantile nystagmus.

Oxygen-enriched pitch-derived hierarchically porous carbon toward boosted zinc-ion storage performance.

The lack of cathode materials with satisfactory Zn2+ storage capability substantially hinders the realization of high-performance aqueous zinc-ion hybrid capacitors (ZHCs). Herein, we propose a facile KMnO4 template-assisted KOH activation strategy to prepare a novel oxygen-enriched hierarchically porous carbon (HPC-1-4). This strategy efficiently converts coal tar pitch (CTP) into a well-tuned carbon material with a large specific surface area of 3019 m2 g-1 and a high oxygen content of 9.20 at%, which is conducive to providing rich active sites, rapid charge transport, and appreciable pseudocapacitance for Zn-ion storage. Thus, the as-fabricated HPC-1-4-based aqueous ZHC exhibits prominent performance, including a high gravimetric capacity (206.7 mAh g-1 at 0.25 A g-1), a remarkable energy density (153.4 Wh kg-1 at 184.2 W kg-1), and an impressive power output (15240 W kg-1 at 63.5 Wh kg-1). In-depth ex-situ characterizations indicate that the excellent electrochemical properties of ZHCs are due to the synergistic effect of the Zn2+ adsorption mechanism and reversible chemisorption. In addition, the assembled quasi-solid-state device demonstrates excellent electrochemical stability of up to 100% capacity retention over 50000 cycles, accompanied with a desirable energy density of 115.6 Wh kg-1. The facile preparation method of converting CTP into carbonaceous functional materials has advanced the development of efficient and eco-friendly energy storage technologies.

Circadian aspects of mortality in hospitalized patients: A retrospective observation from a large cohort.

AIM: This study aimed to describe the circadian characteristics of hospitalized mortality in order to provide nursing guidance for preventing in-hospital mortality. DESIGN: A retrospective analysis on inpatient information was implemented. METHODS: Harmonic Analysis of Time Series was applied to quantify the periodic structure of the frequency of the occurrence of death. RESULTS: A total of 3300 cases were included in the present study (male, 63.4% and median age 73 years), including 1540 (46.7%) ICU patients. Incidence of overall hospitalized death exhibited a circadian pattern, presenting peaks from 07:00 to 12:00 and 15:00 to 20:00 P.M., with 21.5% and 13.1% increase above the average at those peak points, respectively. Similarly, the incidence of sudden cardiac death (SCD) showed peaks between 06:00-12:00 and 15:00-20:00, with a 34.7% and 28.0% increase above the average at peak time, respectively. The distribution of death incidence revealed no statistical difference between SCD and non-SCD (p = 0.525).

Anti-contactin-associated protein-like 2 antibody autoimmune encephalitis with rapidly progressive parkinsonism: a case report and literature review.

OBJECTIVE: Anti-contactin-associated protein-like 2 (CASPR2) antibody encephalitis is a rare autoimmune encephalitis (AE) that often presents with epilepsy, cognitive dysfunction, peripheral neuropathy, autonomic nerve damage, and ataxia. Parkinsonism is often observed in neurodegenerative diseases but progresses slowly, and rapidly progressive parkinsonism is rare. Given that it is a curable parkinsonism, identifying and providing early immunotherapy is crucial. METHODS: We reported a patient initially presenting with anxiety and depression, whose symptoms were relieved following mood regulation treatment. After discontinuation of the mood-regulating drugs, mood disorders recurred, accompanied by parkinsonism. The onset of parkinsonism was subacute (< 3-month disease course), and progression was rapid. After immunotherapy, all symptoms disappeared completely. We reviewed all relevant literature on anti-CASPR2 antibody encephalitis with parkinsonism. RESULTS: Our literature review revealed three cases (including our patient): two male and one female, ranging in age from 48 to 72 years. All patients had parkinsonism, generalized tonic-clonic seizures, and hyponatremia. Three patients had anti-CASPR2 antibody positivity in the serum, and one patient had anti-CASPR2 antibody positivity in the CSF. All three patients were treated with anti-epileptic drugs and intravenous steroid pulse therapy, followed by oral steroid therapy, symptoms improved. CONCLUSION: Parkinsonism can be easily misdiagnosed as a neurodegenerative disease, especially during the early stages. In patients with parkinsonism, treatable diseases should be considered in addition to neurodegenerative diseases. In clinical practice, anti-CASPR2 antibody encephalitis should be considered if rapidly progressing parkinsonism is encountered after ruling out common etiologies.

MicroRNA-183 as a Novel Regulator Protects Against Cardiomyocytes Hypertrophy via Targeting TIAM1.

BACKGROUND: MicroRNAs serve as important regulators of the pathogenesis of cardiac hypertrophy. Among them, miR-183 is well documented as a novel tumor suppressor in previous studies, whereas it exhibits a downregulated expression in cardiac hypertrophy recently. The present study was aimed to examine the effect of miR-183 on cardiomyocytes hypertrophy. METHODS: Angiotensin II (Ang II) was used for establishment of cardiac hypertrophy model in vitro. Neonatal rat ventricular cardiomyocytes transfected with miR-183 mimic or negative control were further utilized for the phenotype analysis. Moreover, the bioinformatics analysis and luciferase reporter assays were used for exploring the potential target of miR-183 in cardiomyocytes. RESULTS: We observed a significant decreased expression of miR-183 in hypertrophic cardiomyocytes. Overexpression of miR-183 significantly attenuated the cardiomyocytes size morphologically and prohypertrophic genes expression. Moreover, we demonstrated that TIAM1 was a direct target gene of miR-183 verified by bioinformatics analysis and luciferase reporter assays, which showed a decreased mRNA and protein expression in the cardiomyocytes transfected with miR-183 upon Ang II stimulation. Additionally, the downregulated TIAM1 expression was required for the attenuated effect of miR-183 on cardiomyocytes hypertrophy. CONCLUSIONS: Taken together, these evidences indicated that miR-183 acted as a cardioprotective regulator for the development of cardiomyocytes hypertrophy via directly regulation of TIAM1.

Autoimmune Encephalitis With Psychotic Manifestations and Cognitive Impairment Presenting as Schizophrenia: Case Report and Literature Review.

Autoimmune encephalitis is characterized by mental and behavioral symptoms, seizures, and cognitive impairment. The presence of schizophrenia needs to be distinguished from that of autoimmune encephalitis. Herein, we describe the case of a woman who exhibited abnormal mental behavior and cognitive impairment. The patient had experienced similar symptoms more than 20 years previously and had been diagnosed with schizophrenia. The patient's psychotic symptoms improved after treatment with antipsychotic drugs; however, cognitive impairment persisted. She was diagnosed with anti-N-methyl-D-aspartate (NMDA)-receptor concurrent with anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor encephalitis. She showed improvement after treatment with steroids and intravenous immunoglobulins (IVIgs). Furthermore, we reviewed the literature and found that, including the present case, 10 patients have been diagnosed with anti-NMDA concurrent with anti-AMPA-receptor encephalitis. Three of these patients were men and seven were women, and their ages ranged from 21 to 71 years. Moreover, seven (70%) patients had a history of tumors. Symptoms of these patients included psychotic symptoms, varying degrees of consciousness disturbance, seizures, dyskinesia, dystonia, autonomic dysfunction, agitation, and verbal reduction. Brain magnetic resonance imaging findings showed scattered fluid-attenuated inversion recovery hyperintensity in subcortical white matter and/or medial temporal lobe in seven (70%) patients. After combination treatment, including tumor removal and administration of steroids, IVIg, plasma exchange, or immunity inhibitors, the symptoms improved in part of the patients. It is necessary to exclude autoimmune encephalitis for patients with psychiatric manifestations and cognitive impairment. Timely combination therapy is important in anti-NMDA-receptor concurrent with anti-AMPA-receptor encephalitis.

RIP2 Knockdown Attenuates Vascular Smooth Muscle Cells Activation via Negative Regulating Myocardin Expression.

BACKGROUND: RIP2 is an adaptor protein contributing to the activation of nuclear factor-κB induced by TNF receptor-associated factor (TRAF) and nucleotide oligomerization domain (NOD)-dependent signaling implicated in innate and adaptive immune response. Beyond regulation of immunity, we aimed to elucidate the role of RIP2 in vascular smooth muscle cell (VSMC) phenotypic modulation. METHODS AND RESULTS: In the current study, we observed that RIP2 showed an increased expression in VSMCs with PDGF-BB stimulation in a dose-dependent manner. Knockdown of RIP2 expression mediated by adenovirus dramatically accelerated the expression of VSMC-specific differentiation genes induced by PDGF-BB. Silencing of RIP2 inhibited proliferative and migratory ability of VSMCs. Additionally, we demonstrated that RIP2 knockdown can promoted myocardin expression. Furthermore, RIP2 inhibition also can attenuate the formation of intimal hyperplasia. CONCLUSIONS: These findings suggested that RIP2 played an important role in regulation of VSMCs differentiation, migration, and proliferation that may due to affect myocardin expression. Our results indicated that RIP2 may be a novel therapeutic target for intimal hyperplasia.