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Objective To evaluate the efficacy and safety of low-dose rituximab (RTX) strategy in patients with neuromyelitis optica spectrum disorder (NMOSD) over a period exceeding 5 years and to investigate the impact of treatment compliance on clinical outcomes. Methods We conducted a retrospective analysis of 81 NMOSD patients who received low-dose RTX at Tangdu Hospital from January 2014 to December 2019. The treatment protocol involved an induction phase of 100 mg weekly for three weeks, followed by maintenance doses of 100 mg every six months. Demographic characteristics, the expanded disability status scale (EDSS) scores, annualized relapse rates (ARR), number and date of attacks, and adverse events were collected. The influence of compliance on treatment efficacy was assessed using multivariable Cox regression and propensity score-weighted analysis. Results Over the follow-up period, 32.1% of patients experienced relapses, with the ARR significantly reduced from a median of 1.5 before treatment to 0 after RTX therapy ( p  < 0.001). EDSS scores improved significantly from a median of 3.5 to 1.5 ( p  < 0.001). The relapse rate was significantly lower in the good compliance group compared to the poor compliance group (9.5% vs. 56.4%, p  < 0.001), and good compliance was associated with a reduced risk of relapse (HR 0.07; 95% CI 0.02–0.25, p  < 0.001). A total of 19 patients (23.5%) experienced mild adverse events, with no serious adverse events reported. Conclusion Our findings support the long-term efficacy and safety of low-dose RTX strategy in treating NMOSD, highlighting the crucial role of treatment compliance in achieving favorable clinical outcomes.

Multivariate statistical analysis approaches are extensively employed in process monitoring because they can effectively detect abnormal conditions in industrial processes. However, both Gaussian and non-Gaussian variables are often present in industrial processes. A single multivariate statistical process monitoring method often has difficulty simultaneously dealing with variable information of mixed distribution characteristics. This paper proposes a multivariate quality-related process monitoring method based on a Bayesian classifier to address this issue. The proposed method separates the variables into Gaussian and non-Gaussian parts using a Jarque–Bera test. Then, Gaussian and non-Gaussian properties are extracted through modified kernel partial least squares and kernel independent component analysis. After feature extraction, a Bayesian-based classifier relevance vector machine is constructed to monitor quality-related information of the process, which avoids the construction of a threshold in conventional methods and offsets the drawbacks of insufficient single statistic information. A numerical simulation and the Tennessee-Eastman process verify the effectiveness of the method.

Human brucellosis, caused by Brucella , is an infectious disease with specific endemic regions, especially in pastoral areas, and may affect multiple organ systems. Neurological involvement, namely neurobrucellosis, occurs in very few of these patients. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most frequent type of autoimmune encephalitis and is usually associated with tumors or herpes simplex virus infections. However, the link between the two disease entities is unknown. In this report, we present a rare case of a 29-year-old Chinese man with anti-NMDAR encephalitis associated with neurobrucellosis, with the detection of anti-NMDAR antibodies by cell-based assay and Brucella melitensis by metagenomic next-generation sequencing in his cerebrospinal fluid sample. The patient improved after antimicrobial treatment and immunotherapies, including steroids and intravenous immunoglobulin. This case implicates Brucella infection as a possible trigger for the production of anti-NMDAR antibodies, and prospective studies should reveal whether there is a casual relationship between brucellosis and anti-NMDAR antibodies.

ObjectiveTo address a novel lower-dose rituximab (RTX) therapy strategy based on our clinical experience and assess its efficacy and safety in neuromyelitis optica spectrum disorder (NMOSD).MethodsA multicenter, open-label, self-controlled, prospective follow-up study. Totally, 108 NMOSD patients were enrolled and a lower-dose RTX strategy was applied including 100 mg weekly for 3 weeks and then reinfusions every 6 months. Annualized relapse rate (ARR), the expanded disability status scale (EDSS) score and length of spinal cord lesions were included to evaluate the efficacy. Side effects were recorded to assess the safety profile.ResultsOf 108 patients, 80 (74.1%) initiated low-dose RTX therapy immediately after acute attack treatment and 33 (30.6%) initiated it after the first attack. During a median treatment period of 35.5 (22.0–48.8) months, significant decreases were observed in median ARR (1.1 [0.8–2.0] versus 0 [0–0.2], p < 0.001), EDSS score (3.5 [2.5–4.0] versus 2.0 [1.0–3.0], p < 0.001) and spinal cord lesion segments (5.0 [4.0–8.0] versus 3.0 [1.0–6.0], p < 0.001). The cumulative risk of relapses significantly decreased during the post- versus pre-RTX period (HR 0.238, 95%CI 0.160–0.356, p < 0.001) and on early therapy initiated within 24 months after disease onset versus delayed therapy (HR 0.506, 95%CI 0.258–0.994, p = 0.041). No serious side effects were recorded and all the subjects did not discontinue treatment due to RTX-related side effects.ConclusionOur research provided evidence supporting the lower-dose RTX strategy in treating NMOSD and reopened the issues of optimal dosage and therapy initiation timing.

Background It is well demonstrated that immunosuppressants can reduce, but not eliminate the risk of generalized development in ocular myasthenia gravis (OMG). In this study, we aimed to explore the predictive factors of generalized conversion of OMG patients who received immunosuppressive treatments. Methods OMG patients under immunosuppressive treatments in Tangdu Hospital from June 2008 to June 2012 were retrospectively reviewed. Baseline clinical characteristics were documented. Patients were followed up regularly by face-to-face interview and the main outcome measure was generalized conversion. The logistic regression analysis was performed to determine the predictive factors of generalization of OMG. Results Two hundred twenty-three eligible OMG patients completed the final follow-up visit and 38 (17.0%) progressed to generalized MG (GMG) at a median time to generalization of 0.9 year. Patients with adult onset and positive repetitive nerve stimulation (RNS) of facial or axillary nerve had higher conversion rate than those with juvenile onset and negative RNS ( p  = 0.001; p  = 0.019; p  = 0.015, respectively). Adult-onset patients converted earlier than juvenile-onset OMG patients ( p  = 0.014). Upon multivariate logistic regression analysis, age of onset (Odds ratio [OR] 1.023, 95% confidence interval [CI] 1.006–1.041, p  = 0.007) and positive facial nerve RNS (OR 2.826, 95%CI 1.045–5.460, p  = 0.038) were found to be positively associated with generalized development. Moreover, an obviously negative association was found for disease duration (OR 0.603, 95%CI 0.365–0.850, p  = 0.019). Conclusions Age of onset, disease duration and facial nerve RNS test can predict generalized conversion of OMG under immunosuppressive therapy. Adult-onset, shorter disease duration and facial nerve RNS-positive OMG patients have a higher risk of generalized development.

Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) have been proved to be T cell-mediated autoimmune diseases. Recent researches indicate that humoral immunity is also involved in the pathogenesis of these disorders. T follicular helper (Tfh) cells are critical for B cell differentiation and antibody production. However, the role of Tfh cells in MS and EAE remains unclear. Here, we found elevated frequencies of CD4 CXCR5 PD-1 Tfh-like cells in both MS patients and EAE. In EAE mice, Tfh-like cells, together with B cells, were found in the ectopic lymphoid structures in spinal cords. Moreover, Tfh-like cells promoted the antibody production IL-21/IL-21R and CD40 ligand/CD40 interaction and the synergy effect of STAT3 and non-canonical NF-κB signaling pathway inside B cells. Moreover, adoptive transfer of Tfh-like cells could increase the severity and delay the remission of EAE. In conclusion, our data indicate that Tfh-like cells contribute to the pathogenesis of EAE.

Background The stroke induced by ischemia of brain remains high incidence and death rate. The study wanted to confirm the effects of Quaking 6 (QKI 6) on the protection role in neurons of rat model of cerebral ischemia/reperfusion injury (CIRI). Material and methods The rat model with CIRI induced by middle cerebral artery occlusion was well established and rat neurons were isolated to characterize the effects of QKI 6 mediated by sirtuin 1 (SIRT1) on synthesis of triglyceride in neuron and neuronal apoptosis via activation of SIRT1‐peroxisome proliferater‐activated receptor (PPAR)γ‐ peroxisome proliferator‐activated receptor coactivator (PGC)‐1α signaling pathway. Results The expression levels of SIRT1 or QKI 6, and acetylation level of QKI 6 were decreased in neurons of rat model with CIRI. QKI 6 deacetylated and mediated by SIRT1 that contributed to suppressing the progression of neuronal apoptosis in rat through promoting synthesis of triglyceride in vivo and in vitro via SIRT1‐PPARγ‐PGC‐1α signaling pathway, then inhibiting CIRI. Conclusions Our results demonstrated SIRT1 deacetylates QKI 6, the RNA‐binding protein, that affects significantly the synthesis of triglyceride in neurons of CIRI rat model. Moreover, it activated transcription factor peroxisome proliferator‐activated receptorγ coactivator‐1α (PGC‐1α) through post‐transcriptional regulation of the expression of PPARγ, and further enhanced synthesis of triglyceride, thereby restrained the progression of neural apoptosis and CIRI. Our results demonstrated SIRT1 deacetylates QKI 6, the RNA‐binding protein, that affects significantly the synthesis of triglyceride in neurons of CIRI rat model. Moreover, it activated transcription factor PGC‐1α through post‐transcriptional regulation of the expression of PPARγ, and further enhanced synthesis of triglyceride, thereby restrained the progression of neural apoptosis and CIRI.

Anti-contactin-associated protein-like 2 (CASPR2) antibody-associated autoimmune encephalitis is commonly characterized by limbic encephalitis with clinical symptoms of mental and behavior disorders, cognitive impairment, deterioration of memory, and epilepsy. The classical lesions reported are located at the medial temporal lobe or hippocampus, whereas prominent brainstem lesions have not been addressed to date. Herein, we reported two patients mimicking progressive brainstem infarction with severe neurological manifestations. On brain magnetic resonance imaging (MRI), prominent brainstem lesions were noted, although multifocal lesions were also shown in the juxtacortical and subcortical white matters, basal ganglia, hippocampus, and cerebellar hemisphere. Unexpectedly and interestingly, both cases had detectable CASPR2 antibodies in sera, and an exclusive IgG1 subclass was documented in the further analysis. They were treated effectively with aggressive immunosuppressive therapies including corticosteroids, intravenous immunoglobulin G, and rituximab, with the first case achieving a rapid remission and the other undergoing a slow but gradual improvement. To the best of our knowledge, this is the first report on prominent brainstem involvement with definite MRI lesions in anti-CASPR2 antibody-associated autoimmune encephalitis, which helps to expand the clinical spectrum of this rare autoimmune disease and update the lesion patterns in the CNS.

In this paper, adaptive fuzzy fault-tolerant control (AFFTC) for the attitude control system of a hypersonic gliding vehicle (HGV) experiencing an actuator fault is proposed. Actuator faults of the HGV are considered with respect to its actual structure and actuator characteristics. The HGV’s attitude system is firstly represented by a T–S fuzzy model, and then a normal T–S fuzzy controller is designed. A reinforcement learning (RL)-based policy iterative solution algorithm is proposed for the solving of the T-S fuzzy controller. Then, based on the normal T–S controller, a fuzzy FTC controller is proposed in which the control matrices can improve themselves according to the special fault. An integral reinforcement learning (IRL)-based solving algorithm is proposed to reduce the dependence of the design methods on the HGV model. Simulations on three different kinds of actuator faults show that the designed IRL-based FTC can ensure a reliable flight by the HGV.