Clinical Characteristics and Short-Term Prognosis of Autoimmune Encephalitis: A Single-Center Cohort Study in Changsha, China

Background and Purpose: The incidence and prevalence of autoimmune encephalitis is gradually increasing. This retrospective observational study primarily aimed to analyze the clinical characteristics of autoimmune encephalitis patients in the Second Xiangya Hospital and report patient prognoses after immunotherapy.Methods: The clinical data of 86 patients who were diagnosed with autoimmune encephalitis from October 2014 to September 2018 were collected, and their corresponding clinical characteristics, laboratory examination, treatment, and outcome data analyzed.Results: In our study, 72 patients (83.7%) were positive for anti-NMDAR (N-methyl-D-aspartate receptor) antibody; 5 patients (6%) for anti-GABABR (γ-aminobutyric acid receptor-A); 4 patients (4.7%) for anti-LGI1 (leucine-rich, glioma inactivated 1); 3 patients (3.5%) for anti-Caspr2 (contactin-associated protein-like 2) (1 patient was positive for both anti-LGI1 and anti-Caspr2 antibodies); and 3 patients (3.5%) for onconeural antibodies. Among the 86 patients diagnosed as having autoimmune encephalitis, 50% showed acute disease onset (≤2 weeks). The most common inducing factor was fever or cold (17/86, 19.8%). The main clinical symptoms included, among others, psychiatric disturbances (82.5%), epilepsy (60.5%), autonomic dysfunction (58.1%), sleep disorders (45.3%), consciousness disorders (45.3%), and speech disorders (46.5%). No significant correlation between ICU admission rates and CSF or serum antibody scores was observed. However, CSF antibody scores of (+ + +) and (++) were associated with longer lengths of hospitalization (p < 0.05) and a higher CSF WBC count when compared with CSF antibody scores of (+) in patients with anti-NMDAR encephalitis (p < 0.05). Additionally, there was no significant correlation between mRS score difference on admission and discharge (after immunotherapy) and age, sex, and choice of immune treatment, while immune therapy taken within 15 days from onset was more inclined to be associated with an mRS score difference ≥2 after immunotherapy in patients with anti-NMDAR encephalitis (p = 0.006).Conclusions: Autoimmune encephalitis has an acute or sub-acute onset and presents with psychotic symptoms, epilepsy, and autonomic dysfunction. The sex ratio in anti-NMDAR encephalitis was nearly balanced. Infection was a major factor inducing anti-NMDAR encephalitis, and the CSF antibody scores could be helpful in determining its prognosis since these scores showed associations with hospitalization duration and CSF WBC counts

Caffeine regulates both osteoclast and osteoblast differentiation via the AKT, NF-κB, and MAPK pathways

Background: Although caffeine generally offers benefits to human health, its impact on bone metabolism remains unclear.Aim and Methods: This study aimed to systematically evaluate the long-term effects of caffeine administration on osteoclasts, osteoblasts, and ovariectomy-induced postmenopausal osteoporosis (OP).Results: Our in vitro findings revealed that 3.125 and 12.5 μg/mL caffeine inhibited RANKL-mediated osteoclastogenesis in RAW 264.7 cells through the MAPK and NF-κB pathways, accompanied by the inactivation of nuclear translocation of nuclear factor NFATc1. Similarly, 3.125 and 12.5 μg/mL of caffeine modulated MC3T3-E1 osteogenesis via the AKT, MAPK, and NF-κB pathways. However, 50 μg/mL of caffeine promoted the phosphorylation of IκBα, P65, JNK, P38, and AKT, followed by the activation of NFATc1 and the inactivation of Runx2 and Osterix, ultimately disrupting the balance between osteoblastogenesis and osteoclastogenesis. In vivo studies showed that gavage with 55.44 mg/kg caffeine inhibited osteoclastogenesis, promoted osteogenesis, and ameliorated bone loss in ovariectomized mice.Conclusion: Conversely, long-term intake of high-dose caffeine (110.88 mg/kg) disrupted osteogenesis activity and promoted osteoclastogenesis, thereby disturbing bone homeostasis. Collectively, these findings suggest that a moderate caffeine intake (approximately 400 mg in humans) can regulate bone homeostasis by influencing both osteoclasts and osteoblasts. However, long-term high-dose caffeine consumption (approximately 800 mg in humans) could have detrimental effects on the skeletal system

Metabolic health phenotype better predicts subclinical atherosclerosis than body mass index-based obesity phenotype in the non-alcoholic fatty liver disease population

BackgroundNon-alcoholic fatty liver disease (NAFLD), especially lean NAFLD is associated with an increased risk of atherosclerotic cardiovascular disease (CVD). It is not currently known which clinical phenotypes of NAFLD contribute most to individual subclinical atherosclerosis risk. We examined the relationship between body mass index (BMI), the metabolically healthy status, and subclinical atherosclerosis in the NAFLD population.MethodsData from asymptomatic NAFLD subjects who participated in a routine health check-up examination were collected. Participants were stratified by BMI (cutoff values: 24.0–27.9 kg/m2 for overweight and ≥28.0 kg/m2 for obesity) and metabolic status, which was defined by Adult Treatment Panel III criteria. Subclinical atherosclerosis was evaluated by brachial-ankle pulse wave velocity (baPWV) in 27,738 participants and by carotid plaque in 14,323 participants.ResultsWithin each BMI strata, metabolically unhealthy subjects had a significantly higher prevalence of subclinical atherosclerosis than metabolically healthy subjects, whereas fewer differences were observed across subjects within the same metabolic category. When BMI and metabolic status were assessed together, a metabolically unhealthy status was the main contributor to the association of clinical phenotypes with the subclinical atherosclerosis burden (all p < 0.001). When BMI and metabolic abnormalities were assessed separately, the incidence of subclinical disease did not increase across BMI categories; however, it increased with an increase in the number of metabolic abnormalities (0, 1, 2 and ≥3).ConclusionA metabolically healthy status in NAFLD patients was closely correlated with subclinical atherosclerosis, beyond that of the BMI-based obesity phenotype. The application of metabolic phenotyping strategies could enable more precise classification in evaluating cardiovascular risk in NAFLD

The gut metabolite indole-3-propionic acid activates ERK1 to restore social function and hippocampal inhibitory synaptic transmission in a 16p11.2 microdeletion mouse model

Background: Microdeletion of the human chromosomal region 16p11.2 (16p11.2+/−) is a prevalent genetic factor associated with autism spectrum disorder (ASD) and other neurodevelopmental disorders. However its pathogenic mechanism remains unclear, and efective treatments for 16p11.2+/− syndrome are lacking. Emerging evidence suggests that the gut microbiota and its metabolites are inextricably linked to host behavior through the gut-brain axis and are therefore implicated in ASD development. Despite this, the functional roles of microbial metabo‑ lites in the context of 16p11.2+/− are yet to be elucidated. This study aims to investigate the therapeutic potential of indole-3-propionic acid (IPA), a gut microbiota metabolite, in addressing behavioral and neural defcits associated with 16p11.2+/−, as well as the underlying molecular mechanisms. // Results: Mice with the 16p11.2+/− showed dysbiosis of the gut microbiota and a signifcant decrease in IPA levels in feces and blood circulation. Further, these mice exhibited signifcant social and cognitive memory impairments, along with hyperactivation of hippocampal dentate gyrus neurons and reduced inhibitory synaptic transmission in this region. However, oral administration of IPA efectively mitigated the histological and electrophysiological alterations, thereby ameliorating the social and cognitive defcits of the mice. Remarkably, IPA treatment signifcantly increased the phosphorylation level of ERK1, a protein encoded by the Mapk3 gene in the 16p11.2 region, with‑ out afecting the transcription and translation of the Mapk3 gene. // Conclusions: Our study reveals that 16p11.2+/− leads to a decline in gut metabolite IPA levels; however, IPA supple‑ mentation notably reverses the behavioral and neural phenotypes of 16p11.2+/− mice. These fndings provide new insights into the critical role of gut microbial metabolites in ASD pathogenesis and present a promising treatment strategy for social and cognitive memory defcit disorders, such as 16p11.2 microdeletion syndrome

Non-targeted Metabolomic Study on Anti-aging Effect of Ripe Pu-erh Tea on D-Galactose-Induced Aging Mice

Delaying aging has become a hot spot of social concern and research. Our previous studies have shown that ripe Pu-erh tea can delay aging in mice by regulating the intestinal flora, but the metabolites in response to endogenous substances in mice are not clear. In this paper, the Morris water maze test was used to detect learning and memory capacity in control, D-galactose-induced aging, and ripe Pu-erh tea-treated mice. Non-targeted metabolomics was used to detect metabolites in the brain tissue and serum of mice from each group for the purpose of exploring the anti-aging effect of ripe Pu-erh tea on D-galactose-induced aging mice, screening differential metabolites among the three groups and analyzing the related metabolic pathways. The results showed that ripe Pu-erh tea improved learning capacity, and regulated 26 differential metabolites in the brain tissue of aging mice, mainly involved in the glycerophospholipid metabolism, vitamin B6 metabolism, histidine metabolism and purine metabolism pathways, among which the glycerophospholipid metabolism and histidine metabolism pathway were the most significant. A total of 11 differential metabolites were identified in serum, mainly involved in the metabolism of vitamin B6 and arachidonic acid, among which vitamin B6 metab olism pathway was the most significant. After the intervention with ripe Pu-erh tea, the contents of glycerophospholipid metabolites including phosphatidylcholine [PC (20:5/20:4)], phosphatidyl ethanlamine [PE (22:2/14:0)], phosphatidylserine [PS (20:5/18:1)] and lysophosphatidylcholine [LysoPC (18:2)], the histidine metabolite carnosine, and the vitamin B6 metabolite pyridoxal 5’-phosphate were significantly increased in aging mice. These results suggest that ripe Pu-erh tea can delay aging by regulating lipid and amino acid metabolism

Efficacy and safety of Lianhua Qingwen granule in the treatment of non-influenza viral pneumonia: a randomized, double-blind, placebo-controlled, multicenter clinical study

ObjectiveTo observe the effectiveness and safety of Lianhua Qingwen granule in the treatment of non-influenza viral pneumonia.MethodsThis study was a multicenter, randomized, double-blind, placebo-controlled trial. Subjects who met the inclusion and exclusion criteria and were clinically diagnosed with viral pneumonia (negative for influenza virus) were randomly divided into the Lianhua Qingwen granule trial group and placebo control group. Patients in the trial group was given Lianhua Qingwen granule, 2 bags at a time, 3 times a day, and the controls were given placebo, with a treatment course of 7 days. Patients’ clinical symptoms and signs, and treatment-associated adverse events were observed. Subjects should be included in the full analysis set (FAS) as long as they were all given the medication and had an effectiveness test performed after randomization. Subjects should be included in the Per Protocol Set (PPS),a subset of the total analysis set, which should contain those with strong compliance, no protocol violations, and complete baseline values for the primary indicators.ResultsA total of 169 subjects were enrolled in 12 subcenters, including 151 (76 in the trial group and 75 in the control group) in the FAS and 140 (68 in the trial group and 72 in the control group) in the PPS. After 7 days of treatment, the clinical symptom relief rates were 82.98% (FAS) and 87.12% (PPS) in the trial group, and 75.11% (FAS) and 76.02% (PPS) in the control group, respectively. The clinical symptom relief rates in the trial group were significantly higher than those in the control group (p < 0.001). Significant improvements in single symptoms of cough and expectoration in the trial group were observed compared with the control group (p < 0.05). There were no statistical differences in fever, sputum color change, chest pain, muscle pain, dyspnea, chills, and thirst between the two groups (p > 0.05).SafetyThere were no significant differences in body weight, vital signs, blood routine, urine routine, stool routine, and blood biochemical indicators (CK, AST, ALT, Cr, and Bun) between the two groups before and after treatment (p > 0.05). During treatment, there were no significant differences in the incidence of adverse events and serious adverse events between the two groups (p > 0.05).ConclusionLianhua Qingwen granules improved the clinical symptoms of patients with non-influenza virus pneumonia, especially ameliorating cough and expectoration. Lianhua Qingwen granules were associated with good safety

Interleukin-17 Contributes to the Pathogenesis of Autoimmune Hepatitis through Inducing Hepatic Interleukin-6 Expression

T helper cells that produce IL-17 (Th17 cells) have recently been identified as the third distinct subset of effector T cells. Emerging data suggests that Th17 cells play an important role in the pathogenesis of many liver diseases by regulating innate immunity, adaptive immunity, and autoimmunity. In this study, we examine the role and mechanism of Th17 cells in the pathogenesis of autoimmune hepatitis (AIH). The serum levels of IL-17 and IL-23, as well as the frequency of IL-17+ cells in the liver, were significantly elevated in patients with AIH, compared to other chronic hepatitis and healthy controls. The hepatic expressions of IL-17, IL-23, ROR-γt, IL-6 and IL-1β in patients with AIH were also significantly increased and were associated with increased inflammation and fibrosis. IL-17 induces IL-6 expression via the MAPK signaling pathway in hepatocytes, which, in turn, may further stimulate Th17 cells and forms a positive feedback loop. In conclusion, Th17 cells are key effector T cells that regulate the pathogenesis of AIH, via induction of MAPK dependent hepatic IL-6 expression. Blocking the signaling pathway and interrupting the positive feedback loop are potential therapeutic targets for autoimmune hepatitis

Analysis of Gradient Change of Landscape Characteristics in Farm-Forest Ecotone-A Case Study on Mudanjiang in Heilongjiang Province

Farm-forest ecotone is proven to be ecologically sensitive areas, where there is obvious change from environmental gradient. The landscape characteristic is mainly influenced by elevation, slope and human activities. Taking Mudanjiang in Heilongjiang Province as example, this paper analyzes spatial-temporal distribution of landscape characteristics in elevation and slope by using the technology of GIS and RS, and the method of trend surface analysis and landscape pattern analysis. The results show that dynamic process of land for agriculture and forestry has a direct influence on the changing rate and direction of landscape characteristics in Mudanjiang. Landscape patch number, fragmentation and diversity index have a peak value in elevation gradient, and the value appears in those whose elevation is less than 800 meters; other indices gradually decrease with the slope increasing except patch number, which has a lesser peak value. Trend surface Analysis of ecological potential power can conclude that gradient change of landscape was concentrated in low-altitude and high-slope region from 1976 to 1988; on the contrary, mainly concentrated in the high-altitude and low-slope region from 1988 to 2000. Thus, the prominence of landscape gradient change is distributed in the regions where there are frequent human activities

Impact of Different Double-Moment Microphysical Schemes on Simulations of a Bow-Shaped Squall Line in East China

Four typical double-moment cloud microphysical schemes (Milbrandt, Morrison, NSSL and WDM6) in WRF (Weather Research and Forecasting) are used to investigate the impact of the different schemes on the simulation of a straight squall line evolving into a bow-shaped one in East China on 15 April 2016. Although simulations with Milbrandt, Morrison and WDM6 schemes can produce bow-shaped squall lines, only the WDM6 scheme can simulate the evolution process of the straight squall line to a bow-shaped one well. The simulation results with the NSSL scheme produce a broken straight squall line. The possible reason is that the range and intensity of cold pools and the rear inflows are different among the four schemes when the observed squall line evolves into a standard bow-shaped squall line. The mixing ratio and number concentration of rain water with the WDM6 scheme is largest in strong convective areas, and the cold pool and rear inflow are also strongest among the four schemes. Compared with the WDM6 scheme, the mixing ratio and number concentration of rain water are less with the Milbrandt and Morrison schemes. Also, the cold pool and rear inflow with the Milbrandt scheme are weaker than for the WDM6 scheme but stronger than those with the Morrison scheme. The rainwater mixing ratio is very low and no obvious cold pool and rear inflow exist with the NSSL scheme