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Diabetes mellitus (DM) is a disease caused by dysfunction or disruption of pancreatic islets. The advent and development of microfluidic organoids-on-a-chip platforms have facilitated reproduce of complex and dynamic environment for tissue or organ development and complex disease processes. For the research and treatment of DM, the platforms have been widely used to investigate the physiology and pathophysiology of islets. In this review, we first highlight how pancreatic islet organoids-on-a-chip have improved the reproducibility of stem cell differentiation and organoid culture. We further discuss the efficiency of microfluidics in the functional evaluation of pancreatic islet organoids, such as single-islet-sensitivity detection, long-term real-time monitoring, and automatic glucose adjustment to provide relevant stimulation. Then, we present the applications of islet-on-a-chip technology in disease modeling, drug screening and cell replacement therapy. Finally, we summarize the development and challenges of islet-on-a-chip and discuss the prospects of future research. Graphical Abstract

This study was undertaken to update and evaluate long-term seizure outcomes in patients with autoimmune encephalitis (AE) based on a large cohort study with long follow-up.In this prospective observational registry study, we analyzed data from patients with AE mediated by common types of neuronal surface antibodies (anti-N-methyl-d-aspartate receptor [NMDAR], anti-leucine-rich glioma-inactivated 1 [LGI1]/contactin-associated protein-like 2 [Caspr2], anti-γ-aminobutyric acid type B receptor [GABAOf 320 AE patients, 75.9% had acute seizures, among whom90% of patients had their last seizure within 12 months of disease onset. During our follow-up, 21 (9.3%) patients experienced seizure recurrence. Patients with anti-GABASeizure recurrence occurred in a small number of patients and chronic epilepsy occurred in 3.1% of patients during prolonged follow-up. Across all types of AE, risk factors for seizure recurrence were IEDs or seizures captured on EEG in the acute phase; for anti-NMDAR encephalitis, female sex was also a risk factor.

This study was undertaken to investigate the association between human leukocyte antigen (HLA) genotype and clinical characteristics of anti-LGI1 encephalitis.HLA genotyping was performed in 34 patients with anti-LGI1 encephalitis admitted to West China Hospital between April 2014 and May 2021, as well as in 305 healthy controls. The online tool NetMHCIIpan 4.0 and AutoDock Vina software were used to predict binding between LGI1 peptide and HLA class II molecules.Risk of anti-LGI1 encephalitis was strongly associated with the DRB1*03:01 allele (odds ratio [OR] = 4.31, 95% confidence interval [CI] = 1.96-9.25, corrected p = 2.75 × 10The strong association between anti-LGI1 encephalitis and certain HLA class II alleles supports a primary autoimmune origin for the disease. Carriers of the DRB1*03:01 allele in Chinese patients with anti-LGI1 encephalitis are more likely to be female, to suffer earlier disease onset, and to respond better to immunotherapy.

ObjectiveTo address the effects of high dose steroids on in-hospital infection and neurologic outcome in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis patients.MethodsWe retrospectively reviewed the clinical data of anti-NMDAR encephalitis patients in West China Hospital, the Third Hospital of Mianyang and Mianyang Central Hospital between October 2011 and August 2020. The development of infections, inflammatory factors, neurologic outcome at discharge and risk factors for in-hospital infection were assessed in patients with and without high dose steroid therapy before and after immunotherapy. Least absolute shrinkage and selection operator (LASSO) regression and logistic regression models were established to assess risk factors for in-hospital infection.ResultsA total of 278 patients with anti-NMDAR encephalitis were included in the study. Thirty-four patients received high dose methylprednisolone (IVMP) therapy only, 84 patients received intravenous immunoglobulin (IVIG) therapy, and 160 patients received IVIG and IVMP therapy. Compared with the IVIG group, IVIG + IVMP group had a higher infection rate (64.38% vs 39.29%,P< 0.001), a higher incidence of noninfectious complications (76.25% vs 61.90%,P= 0.018) and a higher modified Rankin Scale (mRS) score at discharge from the hospital (3 vs 2,P< 0.001). Inflammatory indicators, including white blood cell (WBC) count, neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII), were higher (9.93 vs 5.65, 6.94 vs 3.47 and 1.47 vs 0.70, respectively,P< 0.001) in the IVIG + IVMP group than in the IVIG group. Moreover, lymphocyte-to-monocyte ratio (LMR) was lower (2.20 vs 2.54,P= 0.047) in the IVIG + IVMP group. The LASSO model showed that mRS score on admission, seizure, body temperature, uric acid (URIC), cerebrospinal fluid immunoglobulin G (CSF IgG), NLR and LMR were risk factors for in-hospital infection. The prediction model exhibited an area under the curve (AUC) of 0.885.ConclusionsHigh dose steroids therapy was significantly associated with higher in-hospital infectious complication rates and a poor short-term prognosis in relatively severe anti-NMDAR encephalitis patients. The established prediction model might be helpful to reduce the risk of in-hospital infection.

We describe an unusual case of corticosteroid-responsive autoimmune meningoencephalomyelitis with linear perivascular gadolinium enhancement but in the absence of anti- glial fibrillary acidic protein (GFAP) antibodies (ABs) in the cerebral spinal fluid (CSF).The patient's clinical symptoms, brain magnetic resonance imaging (MRI) features, serum and CSF analysis and treatment were reviewed.A 47-year-old female experienced a subacute course with bilateral lower limbs weakness, unsteady walking, and dysuria. Brain MRI revealed typical radial perivascular gadolinium enhancement extending from the lateral ventricles to the white matter; MRI spine revealed lesions distributed in the entire spinal cord. Immunohistochemical staining of a brain biopsy revealed CD3+ T cells and CD20+ B cells cuffing around brain vessels, accompanied by CD68+ macrophages. CSF was negative for anti-GFAP ABs while serum was positive for anti-GFAP ABs (1:100). The patient responded well to corticosteroid.There are no uniform diagnostic criteria for autoimmune GFAP astrocytopathy. Our case suggested the importance of typical MRI findings in the diagnosis of this rare disease. Early treatments are very important to alleviate symptoms.

Objectives To evaluate the long-term cognitive or neuropsychiatric outcomes and potential risk factors associated with prolonged cognitive deficits or neuropsychiatric symptoms in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Methods In this cohort follow-up study, patients with a definitive diagnosis of anti-NMDAR encephalitis from the inpatient of West China Hospital between June 2012 and December 2017 were included and underwent a prospective cognitive and neuropsychiatric assessment every 3 months by cognitive impairment rating scale, Neuropsychiatric Inventory (NPI) and/or Montreal Cognitive Assessment. Results Up to 97.5% patients had severe cognitive deficits and neuropsychiatric symptoms in acute phase. Decreasing proportion of patients with prolonged cognitive deficits was observed and time dependent. At 2 years' follow-up, 7.8% of patients with cognitive deficits were unable to complete some previous activities or return to work. The risk factors associated with persistent cognitive deficits included age of disease onset over 40 years old (HR, 1.77; 95% CI, 1.11-2.82; P = .01) and with clinical relapses (HR, 2.22; 95% CI, 1.21-4.09; P = .02). The predictors of prolonged neuropsychiatric symptoms included clinical relapses (HR, 2.79; 95% CI, 1.21-6.43; P = .02). Among the 12 neuropsychiatric symptoms of NPI, irritability was shown as the most prevalent and persistent. Conclusions Combined cognitive and neuropsychiatric assessment and intervention are essential elements of comprehensive care of anti-NMDAR encephalitis.

Long-term cognitive and neuropsychiatric outcomes of anti-gamma-aminobutyric-acid B receptor (anti-GABA

IgG4-related disease (IgG4-RD) is an immune-mediated condition that affects multiple organ systems with tumorlike swelling. Here, for the first time, we report a rare case of IgG4-RD that involves the cerebral parenchyma, intramedullary spinal cord and lymph nodes. The diagnosis of IgG4-RD was made based on histological features, multi organ involvement and high serum IgG4 levels. The patient responded well to glucocorticoid treatment. Our case broadens the phenotypic presentation for the neurological sequelae of IgG4-RD.

Primary sclerosing cholangitis is a chronic cholestatic liver disease, whose pathogenesis remains poorly understood. Several studies have shown that PSC patients harbor an impaired gut microbiota. A recent study confirmed that PSC patients displayed a bacterial dysbiosis, characterized by an increased abundance of three different bacteria: Klebsiella pneumoniae, Proteus mirabilis and Enterococcus gallinarum. This study also provides evidence for a possible mechanism of action of these bacteria: notably the formation of pores in gut epithelium leading to an increased gut permeability and the induction of liver inflammation characterized by an increased proportion of T helper 17 (TH17) cells. For the first time, strong data demonstrate not only an association between gut microbiota and primary sclerosing cholangitis but also a possible causal link.

ObjectiveTo analyze the cost of autoimmune encephalitis (AE) in China for the first time.MethodsPatients who were newly diagnosed with antibody-positive AE (anti-NMDA receptor [NMDAR], anti-γ aminobutyric acid type B receptor [GABABR], antileucine-rich glioma-inactivated 1 [LGI1], and anticontactin-associated protein-2 [CASPR2]) at West China Medical Center between June 2012 and December 2018 were enrolled, and a cost-of-illness study was performed retrospectively. Data on clinical characteristics, costs, and utilization of sources were collected from questionnaires and the hospital information system.ResultsOf the 208 patients reviewed, the mean direct cost per patient was renminbi (RMB) 94,129 (United States dollars [USD] 14,219), with an average direct medical cost of RMB 88,373 (USD 13,349). The average inpatient cost per patients with AE was RMB 86,810 (USD 13,113). The direct nonmedical cost was much lower than the direct medical cost, averaging RMB 5,756 (USD 869). The direct cost of anti-LGI1/CASPR2 encephalitis was significantly lower than that of anti-NMDAR encephalitis and anti-GABABR encephalitis. The length of stay in the hospital was significantly associated with the direct cost.ConclusionsThe financial burden of AE is heavy for Chinese patients, and there are significant differences between different types of AE.