Treatment algorithms of relapsing multiple sclerosis: an exploration based on the available disease-modifying therapies in China.

Multiple sclerosis (MS) was defined as a rare disease in China due to its low prevalence. For a long time, interferon ß was the only approved disease-modifying therapy (DMT). Since the first oral DMT was approved in 2018, DMT approval accelerated, and seven DMTs were approved within 5 years. With an increasing number of DMTs being prescribed in clinical practice, it is necessary to discuss the standardized MS treatment algorithms depending on the disease activity and DMT availability. In this review paper, more than 20 Chinese experts in MS have reviewed the therapeutic progress of MS in China and worldwide and discussed algorithms for treating relapsing MS (RMS) based on the available DMTs in China, providing insights for establishing the standardized RMS treatment algorithms in this country.

Treatment algorithms of relapsing multiple sclerosis in China In this review paper, more than 20 Chinese experts in MS have reviewed the therapeutic progress of MS in China and worldwide and discussed algorithms for treating relapsing MS (RMS) based on the available DMTs in China, providing insights for establishing the standardized RMS treatment algorithms in this country: 1) CIS and RRMS account for more than 90% of the MS patients and most of them are mild to moderate; 2) MS patients should initiate DMT treatments as soon as the disease has been diagnosed in order to reduce the risk of disease progression; 3) Patients who have been diagnosed with MS should start treatment with fundamental DMTs unless the disease course has been highly active; 4) MAGNIMS score may be a suitable and simplified assessment tool for measuring treatment response to DMTs; 5) Patients treated with corticosteroids and NSIS should be switched to the standardized DMT treatment during remission in accordance with disease activity.

Metagenomic next-generation sequencing assistance in identifying Mycobacterium avium meningoencephalitis: A case report and literature review.

Nontuberculous mycobacteria associated intracranial infection is a rare disease that mainly occurs in HIV-infected patients. The disease has a poor prognosis. The authors report a case of non-tuberculous mycobacterial meningoencephalitis in a non-AIDS patient, but long history of poorly controlled type 2 diabetes mellitus. A 55-year-old, right-handed, male patient presented with an 8-day history of fever, episodes of severe headache with signs of meningeal irritation. MRI showed hyperintensities/contrast enhancement in the visual pathways, basal ganglia sellar region and leptomeninges. No etiological diagnosis was reached until metagenomic next-generation sequencing (mNGS) was used, showing the presence of Mycobacterium avium. The patient was cured with aggressive antimycobacterial therapy. The authors discuss the clinical manifestations and drug therapy of nontuberculous mycobacteria-related intracranial infections by reviewing relevant literature. As meningoencephalitis by Mycobacterium avium has a high mortality an early diagnosis and appropriate therapeutic interventions are warranted. For this reason, the use of mNGS can be helpful to avoid therapeutic delay.

Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy Is Associated with HLA-A*3303 and HLA-DPB1*0501.

We determined the genetic association between specific human leucocyte antigen (HLA) loci and autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. Our results showed that autoimmune GFAP astrocytopathy was associated with HLA-A*3303 (odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.32-3.06, p = 0.00072, padj. = 0.046) and HLA-DBP1*0501 (OR = 0.51, 95% CI = 0.36-0.71, p = 0.000048, padj. = 0.0062). Moreover, HLA-A*3303 carriers with the disease had a longer hospital stay (p = 0.0005) than non-carriers. This study for the first time provides evidence for a role of genetic factor in the development of autoimmune GFAP astrocytopathy. ANN NEUROL 2024;95:901-906.

Endoplasmic reticulum stress exacerbates microplastics-induced toxicity in animal cells.

Human and animal exposure to microplastics (MPs) contained in food is inevitable because of their widespread existence in the environment. Nevertheless, MPs toxicity studies in ruminants often lack attention. Here, we assessed the cytotoxicity of polystyrene microplastics (PS MPs) on goat mammary epithelial cells (GMECs). Compared to controls, PS MPs treatment significantly reduced cell viability, altered cell morphology and disrupted organelle integrity. Detection of membrane potential and reactive oxygen species (ROS) suggested that PS MPs induced mitochondrial dysfunction and oxidative stress. Further transcriptome analysis also confirmed alterations in these pathways. In addition, several genes related to endoplasmic reticulum (ER) homeostasis were significantly regulated in the transcriptional profile. Subsequent experiments confirmed that PS MPs induce ER stress via the PERK/eIF2α/CHOP pathway, accompanied by intracellular Ca2+ overload. Meanwhile, downstream activation of the Bax/Bcl-2 pathway and caspase cascade released apoptotic signals, which led to apoptosis in GMECs. Interestingly, the addition of PERK inhibitor (ISRIB) attenuated PS MPs-induced ER stress and apoptosis, which suggests that ER stress may exacerbate PS MPs-induced cytotoxicity. This work reveals the impact of MPs on mammalian cytotoxicity, enriches the mechanisms for the toxicity of MPs, and provides insight for further assessment of the risk of MPs in food.

Enhanced sludge solubilization by a fluidized electrode: Granular activated carbon promoted electrochemical oxidation.

Electrochemical sludge pretreatment is receiving increasing attention because of its small footprint and higher environmental compatibility. However, the limited effective area of electrode plates and the low conductivity of sludge hinder the widespread application of electrochemical pretreatment. In this study, granular activated carbon (GAC) was employed to construct a fluidized electrode electrochemical system (FEE) to promote electrochemical pretreatment. Under the optimal operating parameters, the FEE system could effectively facilitate sludge decomposition, indicated by 126% increase in soluble chemical oxygen demand (SCOD) and 23.1% reduction in sludge volume. Mechanism study revealed that the addition of GAC significantly enhanced the conductivity of sludge, thereby promoting the oxidation capacity of FEE system. Furthermore, continuously generated H2O2 in FEE further promoted sludge solubilization. GAC offered an effectively, green and sustainable enhancement approach for sludge electrochemical pretreatment.

Development and validation of a machine learning model to predict prognosis in HIV-negative cryptococcal meningitis patients: a multicenter study.

PURPOSE: To predict prognosis in HIV-negative cryptococcal meningitis (CM) patients by developing and validating a machine learning (ML) model. METHODS: This study involved 523 HIV-negative CM patients diagnosed between January 1, 1998, and August 31, 2022, by neurologists from 3 tertiary Chinese centers. Prognosis was evaluated at 10 weeks after the initiation of antifungal therapy. RESULTS: The final prediction model for HIV-negative CM patients comprised 8 variables: Cerebrospinal fluid (CSF) cryptococcal count, CSF white blood cell (WBC), altered mental status, hearing impairment, CSF chloride levels, CSF opening pressure (OP), aspartate aminotransferase levels at admission, and decreased rate of CSF cryptococcal count within 2 weeks after admission. The areas under the curve (AUCs) in the internal, temporal, and external validation sets were 0.87 (95% CI 0.794-0.944), 0.92 (95% CI 0.795-1.000), and 0.86 (95% CI 0.744-0.975), respectively. An artificial intelligence (AI) model was trained to detect and count cryptococci, and the mean average precision (mAP) was 0.993. CONCLUSION: A ML model for predicting prognosis in HIV-negative CM patients was built and validated, and the model might provide a reference for personalized treatment of HIV-negative CM patients. The change in the CSF cryptococcal count in the early phase of HIV-negative CM treatment can reflect the prognosis of the disease. In addition, utilizing AI to detect and count CSF cryptococci in HIV-negative CM patients can eliminate the interference of human factors in detecting cryptococci in CSF samples and reduce the workload of the examiner.

miR-486 Responds to Apoptosis and Autophagy by Repressing SRSF3 Expression in Ovarian Granulosa Cells of Dairy Goats.

The accumulation of ovarian granulosa cell (GC) apoptosis underlies follicular atresia. By comparing the previous sequencing results, miR-486 was found to be differentially expressed at higher levels in the monotocous goat than in the polytocous goat. Unfortunately, the miRNA-mediated mechanisms by which the GC fate is regulated are unknown in Guanzhong dairy goats. Therefore, we investigated miR-486 expression in small and large follicles, as well as its impact on normal GC survival, apoptosis and autophagy in vitro. Here, we identified and characterized miR-486 interaction with Ser/Arg-rich splicing factor 3 (SRSF3) using luciferase reporter analysis, detecting its role in GC survival, apoptosis and autophagy regulation through qRT-PCR, Western blot, CCK-8, EdU, flow cytometry, mitochondrial membrane potential and monodansylcadaverine, etc. Our findings revealed prominent effects of miR-486 in the regulation of GC survival, apoptosis and autophagy by targeting SRSF3, which might explain the high differential expression of miR-486 in the ovaries of monotocous dairy goats. In summary, this study aimed to reveal the underlying molecular mechanism of miR-486 regulation on GC function and its effect on ovarian follicle atresia in dairy goats, as well as the functional interpretation of the downstream target gene SRSF3.

Early autoimmunity and outcome in virus encephalitis: a retrospective study based on tissue-based assay.

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.

Toxic effects of zinc oxide nanoparticles as a food additive in goat mammary epithelial cells.

Zinc oxide nanoparticles (ZnO NPs) have recently been used as food preservatives and additives because of their good antibacterial and nutritional functions. This study performed RNA-seq analyses to evaluate the potential toxicity of ZnO NPs on goat mammary epithelial cells (GMECs) in vitro. Our results suggested that the ZnO NP treatment significantly reduced GMEC viability in a time- and dose-dependent manner. Transcriptomic analysis showed that ZnO NP exposure changed the expression levels of more than 500 genes in GMECs, including various biological pathways. We observed that decreased mitochondrial membrane potential caused mitochondrial dysfunction. Further study indicated that the treatment of cells with ZnO NPs resulted in the accumulation of reactive oxygen species (ROS), which led to oxidative stress. Meanwhile, the expression of genes (TNFα, TNFR1, FADD, Caspase 8 and Caspase 6) associated with the death receptor pathway was upregulated, which indicated the death receptor-mediated extrinsic apoptosis pathway was activated. Moreover, the expression levels of Bax, Cytc, Caspase 3 and Caspase 9 were upregulated, while the expression levels of Bcl2 were downregulated, which indicated mitochondria-mediated intrinsic apoptosis pathway was activated. More notably, ZnO NP exposure increased the expression levels of ER stress-related genes (PERK, ATF4, eIF2α and CHOP) and proteins (p-PERK, p-eIF2α, PERK and CHOP). Furthermore, gene ontology (GO) terms and genes related to autophagy were altered, suggesting that exposure to ZnO NPs might activate autophagy in GMECs. In summary, our findings showed that ZnO NPs could exert significant toxic effects on GMECs through multiple mechanisms. These pathways are related to each other and influence each other to participate in ZnO NPs-induced the damage of GMECs. Thus, their safe use in the feed and food industry should be considered. Meanwhile, RNA-seq might represent a new method of assessing the toxicity mechanisms of nanomaterials.

Meningoencephalitis associated with GAD65 autoimmunity.

Background: Encephalitis has been recognized in patients with autoimmunity related to the 65-kDa isoform of glutamic acid decarboxylase (GAD65) antibodies; however, patients with meningoencephalitis associated with those antibodies have been rarely identified in the medical literature. We aimed to define the frequency, clinical features, response to therapy, and functional outcomes of patients with meningoencephalitis associated with GAD antibodies. Methods: We retrospectively studied consecutive patients attending a tertiary care center for evaluation of an autoimmune neurological disorder from January 2018 to June 2022. The modified Rankin Scale (mRS) was used to assess the functional outcome at the last follow-up. Results: We evaluated 482 patients with confirmed autoimmune encephalitis during the study period. Four among the 25 patients with encephalitis related to GAD65 antibodies were identified. One patient was excluded owing to the coexistence of NMDAR antibodies. Three male patients aged 36, 24, and 16 years had an acute (n = 1) or subacute (n = 2) onset of confusion, psychosis, cognitive symptoms, seizures, or tremor. No patient had fever or clinical signs of meningeal irritation. Mild pleocytosis (<100 leukocytes/106) was identified in two patients, whereas one patient had normal CSF. Following immunotherapy with corticosteroids (n = 3) or intravenous immunoglobulin (n = 1), significant improvement was observed in all three cases, achieving a good outcome (mRS 1) in all cases. Conclusion: Meningoencephalitis is an uncommon presentation of GAD65 autoimmunity. Patients present with signs of encephalitis but with meningeal enhancement and have good outcomes.

Prevalence of multiple sclerosis in Guangzhou, China: A population-based case-finding prospective study.

BACKGROUND: Multiple sclerosis (MS) is rare in China, and the prevalence previously reported may be biased. Currently, few studies that have investigated the prevalence of MS in China based on the latest diagnostic criteria. METHODS: Through a population-based survey from August 8, 2021 to December 31, 2021, we calculated the prevalence of multiple sclerosis in 18,676,605 residents of Guangzhou, China. MS patients were identified through the health insurance system of the Guangzhou Health Insurance Bureau, and we surveyed 17 large tertiary hospitals using a case-finding approach. All MS patients were diagnosed according to the 2017 McDonald criteria. RESULTS: A total of 143 patients in the resident population of Guangzhou were diagnosed with MS, with a crude prevalence of 0.77 per 100,000 (95% confidence interval (CI): 0.65-0.90), and the prevalence was higher in in females (1.14/100,000) than in males (0.44/100,000). The age-adjusted prevalence was 0.92 per 100,000 (95% CI: 0.77-1.10). The prevalence peaked at the age of 25-29 years (2.86/100,000) for both males and females (1.44/100,000 and 4.42/100,000, respectively). CONCLUSIONS: This is the first study to report the prevalence of MS in Guangzhou, China, according to the criteria. Our study shows that the prevalence of MS in Guangzhou is lower than that in other cities in China.

Anti-homer-3 Antibody Encephalitis in a 10-Year-Old Child: Case Report and Review of the Literature.

Objective: We present a rare case with anti-Homer-3 antibodies positive encephalitis in the youngest patient ever identified and reviewed the literature. Case Report: A 10-year-old, Chinese boy came for evaluation of a 2-week history of cognitive impairment, irritability, dysarthria, and cautious gait. The neurological examination was consistent with the pan-cerebellar syndrome and encephalopathy. Cerebrospinal fluid (CSF) was inflammatory with increased leukocytes. Magnetic resonance imaging of the brain showed hyperintensities in both cerebellar hemispheres and vermis in Fluid-attenuated inversion recovery (FLAIR) and T2- weighted sequences. Infectious disorders were ruled out, but positivity for anti-Homer-3 antibodies was detected in the CSF, but not in the serum. Additionally, low titers of voltage-gated calcium channel (VGCC) antibodies were found in the serum. Treatment with intravenous (IV) corticosteroids did not provide meaningful clinical improvement; however, the patient achieved almost complete recovery (modified Ranking Scale score: 1) following IV immunoglobulin. Conclusion: Anti-Homer-3 cerebellar ataxia with encephalopathy should be considered within the differential diagnosis of acute inflammatory cerebellar disease in children and it may coexist with VGCC antibodies.

PITX2 regulates steroidogenesis in granulosa cells of dairy goat by the WNT/ß-catenin pathway.

Paired-like homeodomain transcription factor 2 (PITX2), a major driver of multiple tissue development, is a transcription factor that regulates gene expression in organisms. However, it is unknown if PITX2 regulates goat granulosa cell (GC) steroidogenesis. Therefore, we investigated the role and mechanism of PITX2 in GC steroidogenesis. In our study, PITX2 significantly facilitated the secretion level of estrogen and progesterone through increasing CYP11A1, CYP19A1, and STAR mRNA and protein expressions in GCs. Furthermore, PITX2 participated in the WNT pathway, enhancing the production of E2 and P4 in GCs. PITX2 in GCs increased the DVL-1 and CTNNB1 expression, involved in the WNT/ß-catenin signaling pathway related to steroidogenesis. Moreover, GC steroidogenesis-related gene translation was decreased by CTNNB1-siRNA but enhanced when transfected with PITX2. PITX2 regulates secretion of E2 and P4 from GCs via the WNT/ß-catenin pathway and alters GC proliferation and steroidogenesis. These findings will help understand the role of PITX2 in goat ovarian follicular development and oocyte maturation.

TMEM151A Variants Cause Paroxysmal Kinesigenic Dyskinesia: A Large-Sample Study.

BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesias. Only one-third of PKD patients are attributed to proline-rich transmembrane protein 2 (PRRT2) mutations. OBJECTIVE: We aimed to explore the potential causative gene for PKD. METHODS: A cohort of 196 PRRT2-negative PKD probands were enrolled for whole-exome sequencing (WES). Gene Ranking, Identification and Prediction Tool, a method of case-control analysis, was applied to identify the candidate genes. Another 325 PRRT2-negative PKD probands were subsequently screened with Sanger sequencing. RESULTS: Transmembrane Protein 151 (TMEM151A) variants were mainly clustered in PKD patients compared with the control groups. 24 heterozygous variants were detected in 25 of 521 probands (frequency = 4.80%), including 18 missense and 6 nonsense mutations. In 29 patients with TMEM151A variants, the ratio of male to female was 2.63:1 and the mean age of onset was 12.93 ± 3.15 years. Compared with PRRT2 mutation carriers, TMEM151A-related PKD were more common in sporadic PKD patients with pure phenotype. There was no significant difference in types of attack and treatment outcome between TMEM151A-positive and PRRT2-positive groups. CONCLUSIONS: We consolidated mutations in TMEM151A causing PKD with the aid of case-control analysis of a large-scale WES data, which broadens the genotypic spectrum of PKD. TMEM151A-related PKD were more common in sporadic cases and tended to present as pure phenotype with a late onset. Extensive functional studies are needed to enhance our understanding of the pathogenesis of TMEM151A-related PKD. © 2021 International Parkinson and Movement Disorder Society.

Therapeutic Response and Possible Biomarkers in Acute Attacks of Neuromyelitis Optica Spectrum Disorders: A Prospective Observational Study.

Objective: To explore the outcomes of NMOSD attacks and investigate serum biomarkers for prognosis and severity. Method: Patients with NMOSD attacks were prospectively and observationally enrolled from January 2019 to December 2020 at four hospitals in Guangzhou, southern China. Data were collected at attack, discharge and 1/3/6 months after acute treatment. Serum cytokine/chemokine and neurofilament light chain (NfL) levels were examined at the onset stage. Results: One hundred patients with NMOSD attacks were included. The treatment comprised intravenous methylprednisolone pulse therapy alone (IVMP, 71%), IVMP combined with apheresis (8%), IVMP combined with intravenous immunoglobulin (18%) and other therapies (3%). EDSS scores decreased significantly from a medium of 4 (interquartile range 3.0-5.5) at attack to 3.5 (3.0-4.5) at discharge, 3.5 (2.0-4.0) at the 1-month visit and 3.0 (2.0-4.0) at the 3-month visit (p<0.01 in all comparisons). The remission rate was 38.0% at discharge and 63.3% at the 1-month visit. Notably, relapse occurred in 12.2% of 74 patients by the 6-month follow-up. Higher levels of T helper cell 2 (Th2)-related cytokines, including interleukin (IL)-4, IL-10, IL-13, and IL-1 receptor antagonist, predicted remission at the 1-month visit (OR=9.33, p=0.04). Serum NfL levels correlated positively with onset EDSS scores in acute-phase NMOSD (p<0.001, R2 = 0.487). Conclusions: Outcomes of NMOSD attacks were generally moderate. A high level of serum Th2-related cytokines predicted remission at the 1-month visit, and serum NfL may serve as a biomarker of disease severity at attack. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04101058, identifier NCT04101058.

High Level of Serum and Cerebrospinal Fluid of Heparan Sulfate and Hyaluronic Acid Might Be a Biomarker of Severity of Neuromyelitis Optica.

Background: Neuromyelitis optica (NMO), multiple sclerosis (MS) and autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy are idiopathic inflammatory demyelinating diseases (IIDDs) that mainly present as encephalomyelitis. Heparan sulfate (HS) and hyaluronic acid (HA) are two components of glycocalyx, a carbohydrate-rich layer on the surface of blood vessels that mediates interaction with blood. Degradation of glycocalyx in NMO is poorly understood. Purpose: To detect the serum and cerebrospinal fluid (CSF) levels of shed HS and HA and to correlate these levels with disease severity to determine their diagnostic value. Methods: We obtained serum and CSF samples from 24 NMO patients, 15 MS patients, 10 autoimmune GFAP astrocytopathy patients, and 18 controls without non-inflammatory neurological diseases. Soluble HS and HA, and IFNγ, IL17A, and matrix metalloproteinase (MMP) 1 were detected via ELISA. Results: Serum and CSF levels of HS, HA and related cytokines but not of plasma MMP1 were significantly elevated in these diseases. Notably, HS and HA levels were positively correlated with Expanded Disability Status Scale scores. Conclusions: Our results indicate glycocalyx degradation and inflammation in NMO, MS and autoimmune GFAP astrocytopathy. Moreover, increased shedding of HS or HA may indicate a worse clinical situation. Furthermore, therapeutic strategies that protect glycocalyx may be effective in these diseases.

High Level of Soluble CD146 In Cerebrospinal Fluid Might be a Biomarker of Severity of Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

Background: Disruption of the blood-brain barrier (BBB) is an important pathophysiological process of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. A recent multi-center study showed that soluble (s) CD146 is a potential biomarker for monitoring early BBB damage and central nervous system inflammation, but little is known about sCD146 in anti-NMDAR encephalitis. Method: Twenty-three anti-NMDAR encephalitis patients and seventeen controls with non-inflammatory neurological diseases were recruited. sCD146 and inflammatory cytokines in cerebrospinal fluid (CSF) and serum were detected by ELISA. Modified Rankin scale (mRS) scores were used to assess the neurological status of each patient. A follow-up review was completed three months after discharge. Results: sCD146 levels in the CSF of patients with the acute stage anti-NMDAR encephalitis were significantly increased compared with controls and accompanied by increases in TNF-α, IL-6 and IL-10. CSF sCD146 was positively correlated with neuroinflammatory factors in the CSF and with mRS score. Three months after effective treatment, CSF sCD146 in patients was significantly decreased but remained significantly different compared with the controls. Conclusion: Our data suggested that higher expression of CSF sCD146 correlated with more serious neurological damage. Therefore, levels of CSF sCD146 may represent a promising indicator for monitoring disease and optimizing clinical treatment decisions in the early stages of anti-NMDAR encephalitis.

Whole Transcriptome Analysis: Implication to Estrous Cycle Regulation.

Estrous cycle is one of the placental mammal characteristics after sexual maturity, including estrus stage (ES) and diestrus stage (DS). Estrous cycle is important in female physiology and its disorder may lead to diseases, such as polycystic ovary syndrome, ovarian carcinoma, anxiety, and epilepsy. In the latest years, effects of non-coding RNAs and messenger RNA (mRNA) on estrous cycle have started to arouse much concern, however, a whole transcriptome analysis among non-coding RNAs and mRNA has not been reported. Here, we report a whole transcriptome analysis of goat ovary in estrus and diestrus periods. Estrus synchronization was conducted to induce the estrus phase and on day 32, the goats shifted into the diestrus stage. The ovary RNA of estrus and diestrus stages was respectively collected to perform RNA-sequencing. Then, the circular RNA (circRNA), microRNA (miRNA), long non-coding RNA (lncRNA), and mRNA databases of goat ovary were acquired, and the differential expressions between estrus and diestrus stages were screened to construct circRNA-miRNA-mRNA/lncRNA and lncRNA-miRNA/mRNA networks, thus providing potential pathways that are involved in the regulation of estrous cycle. Differentially expressed mRNAs, such as MMP9, TIMP1, 3BHSD, and PTGIS, and differentially expressed miRNAs that play key roles in the regulation of estrous cycle, such as miR-21-3p, miR-202-3p, and miR-223-3p, were extracted from the network. Our data provided the miRNA, circRNA, lncRNA, and mRNA databases of goat ovary and each differentially expressed profile between ES and DS. Networks among differentially expressed miRNAs, circRNAs, lncRNAs, and mRNAs were constructed to provide valuable resources for the study of estrous cycle and related diseases.

Hypothalamic lesions in neuromyelitis optica spectrum disorders: exploring a scoring system based on magnetic resonance imaging.

PURPOSE: We propose a scoring system for early diagnosis of sleep abnormalities in neuromyelitis optica spectrum disorders (NMOSD) with hypothalamic lesions based on magnetic resonance imaging (MRI). MATERIALS AND METHODS: We evaluated MRI features of 45 patients with hypothalamic lesions identified from two cohorts. Univariate logistic regression analysis identified factors associated with sleepiness, which were subsequently used to develop a scoring system. Interrater reliability was determined using intraclass correlation coefficient (ICC). Correlations between scores and clinical features were analyzed. RESULTS: In total, 48.9% of 45 patients with hypothalamic lesions exhibited sleepiness. The number of involved slices, maximum width/length of hypothalamic lesions, and boundaries extending beyond the hypothalamus were associated with sleepiness (all p < 0.05). The sensitivity and specificity of the scoring system were 68.2% and 87.0%, respectively. The ICC values for the maximum width and length measurement of hypothalamic lesions were 0.82 and 0.81, respectively. Daily sleep time and Epworth sleepiness scale scores were positively correlated with MRI-based scores (p < 0.05, 95% confidence interval (CI) 0.69-0.93 and p < 0.05, 95% CI 0.55-0.88, respectively). CONCLUSION: A scoring system based on MRI features was developed to provide diagnosis of sleepiness in NMOSD with hypothalamic lesions earlier than other measures.

Association of Polymorphisms in Inflammatory Cytokines Encoding Genes With Anti-N-methyl-D-Aspartate Receptor Encephalitis in the Southern Han Chinese.

Background: Single nucleotide polymorphisms (SNPs) that occur within genes encoding inflammatory cytokines can result in quantitative or qualitative changes in their expression or functionality, potentially leading to the development of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. This study sought to evaluate the relationship between SNPs in inflammatory cytokines genes and the incidence of anti-NMDAR encephalitis in the Southern Han Chinese. Methods: In total, we enrolled 107 patients with anti-NMDAR encephalitis as well as 202 inpatient controls who had no first-degree relative with autoimmune diseases. Genotyping determination of all 309 patients was conducted for the IL-1ß rs16944, IL-4 rs2243250, IL-4 rs2070874, IL-6 rs1800796, IL-10 rs1800872, and IL-17 rs2275913 gene SNPs. Results: We observed statistically significant differences in the frequencies of G allele in IL-1ß rs16944 between anti-NMDAR encephalitis and controls (p = 0.017). Also, IL-1ß, IL-4, IL-6, IL-10, and IL-17 SNPs were not associated with the disease (p > 0.05). Conclusions: We found that patients with anti-NMDAR encephalitis exhibit a distinct immunological profile, and we found that the decreased frequency of G allele in IL-1ß rs16944 showed a protective role for anti-NMDAR encephalitis in the Southern Han Chinese.