Context Up to 40% polycystic ovary syndrome (PCOS) patients have prediabetes, an optimal pharmacotherapy regimen for diabetes prevention in PCOS is yet to be established. Objective To evaluate clinical efficacy of exenatide (EX), metformin (MET) or combination (COM) for prediabetes in PCOS. Design Randomized, open-label, parallel-group controlled trial. Setting Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine. Patients PCOS with prediabetes (fasting plasma glucose 5.6-6.9 mmol/L and/or 2-h post glucose 7.8-11.0 mmol/L on OGTT). 150 out of 183 eligible enrollees completed the study. Intervention EX (10-20 μg daily), MET (1500-2000 mg daily), or COM (EX plus MET) for 12 weeks. Main Outcome Measures Sustained remission rate of prediabetes (primary endpoint, a normal OGTT after 12 weeks of treatment followed by 12 weeks of washout on no drug treatment) along with anthropometric, hormonal, metabolic, and pancreatic β-cell function parameters (secondary endpoints) and potential mechanisms were assessed. Results IGT was found the dominant prediabetes phenotype. Overall sustained prediabetes remission rate was 50.7%. Remission rate of COM group (64%, 32/50) or EX group (56%, 28/50) was significantly higher than that of MET group (32%, 16/50) (p = 0.003 and 0.027, respectively). EX was associated with superior suppression of 2-hour glucose increment in OGTT. A two-step hyperglycemic clamp study further revealed that EX had led to higher postprandial insulin secretion as compared to MET, potentially explaining the higher remission rate. Conclusions As compared to MET monotherapy, EX or COM achieved higher rate of remission of prediabetes among PCOS patients by improving postprandial insulin secretion.

Background We conducted this study to describe detailed the clinical characteristics, ancillary test results and treatment response of a group of Chinese patients with anti‐IgLON5 disease. Methods We recruited 13 patients with positive IgLON5 antibodies in serum and/or cerebrospinal fluid from nine tertiary referral centers. Patients were enrolled from February 2017 to July 2021. We retrospectively collected information on the presenting and main symptoms, treatment response and follow‐up outcomes. Results The median age of onset for symptoms was 60 (range: 33–73) years and six of the 13 patients were females. The predominant clinical presentations included sleep disturbance (eight patients) and cognitive impairment (seven patients), followed by movement disorders (six patients). Parainfectious cause seemed plausible. Notably, we identified the first case of possible Epstein‐Barr virus (EBV)‐related anti‐IgLON5 disease. Coexisting neural autoantibodies were identified in two patients. Furthermore, two patients had other autoimmune diseases. The IgG subclass was determined in four patients, including two with dominant IgG4 subtype and two with dominant IgG1 subtype. Additionally, 10 patients were treated with immunotherapy and four patients exhibited improvement. Overall, six of 10 patients for whom follow‐up results were assessable had favorable clinical outcomes (modified Rankin Scale score ≤2). Conclusions The clinical spectrum of anti‐IgLON5 disease is variable. Our results highlight a boarder spectrum of anti‐IgLON5 disease.

BackgroundThe novel coronavirus disease 2019 (COVID-19) pandemic has given rise to fear and panic in the public. Although hospitals in China reduced outpatient visits and restricted inpatient admission to lower the risk of transmission of COVID-19, this has significantly affected patients in need of medical attention, for example, patients with emotional disorders.AimsThis study aimed to compare the beliefs towards COVID-19 among outpatients with emotional disorders (ie, anxiety or depression) with those of family caregivers and the general public and examine factors that shape the beliefs towards COVID-19 among outpatients with emotional disorders.MethodsSurvey data from 570 outpatients with anxiety or depression disorders, 449 family caregivers and 470 general public subjects were collected. Multiple stepwise regression analyses were used to describe participants’ level of concern, prevention attitude and positive expectations towards the COVID-19 outbreak.ResultsAbout 70.9% of outpatients had to postpone their mental health treatment; 43.2% of patients admitted that their mental health was adversely affected by the COVID-19 outbreak—these patients tended to be older, male and less educated. After controlling for age and education level, outpatients with emotional disorders had significantly lower levels of concerns but more negative expectations towards COVID-19, compared with family caregivers and the public. Multivariate linear stepwise regression analysis showed that age, education and the perception of the impact of COVID-19 on one’s existing mental illness were significantly associated with outpatients’ beliefs about the epidemic.ConclusionOutpatients with anxiety or depression disorders were relatively less focused on the COVID-19 outbreak, but the impact of the infection was found to be independently associated with their beliefs towards COVID-19. In addition, outpatients who were older and of low educational levels particularly held more negative beliefs about the epidemic, which may place them at a higher risk for poor mental health.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower motor neurons, leading to paralysis and eventually death. Symptomatic treatments such as inhibition of salivation, alleviation of muscle cramps, and relief of spasticity and pain still play an important role in enhancing the quality of life. To date, riluzole and edaravone are the only two drugs approved by the Food and Drug Administration for the treatment of ALS in a few countries. While there is adequate consensus on the modest efficacy of riluzole, there are still open questions concerning the efficacy of edaravone in slowing the disease progression. Therefore, identification of novel therapeutic strategies is urgently needed. Impaired autophagic process plays a critical role in ALS pathogenesis. In this review, we focus on therapies modulating autophagy in the context of ALS. Furthermore, stem cell therapies, gene therapies, and newly-developed biomaterials have great potentials in alleviating neurodegeneration, which might halt the disease progression. In this review, we will summarize the current and prospective therapies for ALS.

Background Anti-IgLON5 disease is a rare neurological disorder associated with autoantibodies against the neuronal cell adhesion protein, IgLON5. Cellular investigations with human IgLON5 antibodies have suggested an antibody-mediated pathogenesis, but whether human IgLON5 autoantibodies can induce disease symptoms in mice is yet to be shown. Moreover, the effects of anti-IgLON5 autoantibodies on neurons and the precise molecular mechanisms in vivo remain controversial. Methods We investigated the effects of anti-IgLON5 antibodies in vivo and evaluated their long-term effects. We used two independent passive-transfer animal models and evaluated the effects of the antibodies on mouse behaviors at different time points from day 1 until day 30 after IgG infusion. A wide range of behaviors, including tests of locomotion, coordination, memory, anxiety, depression and social interactions were established. At termination, brain tissue was analyzed for human IgG, neuronal markers, glial markers, synaptic markers and RNA sequencing. Results These experiments showed that patient’s anti-IgLON5 antibodies induced progressive and irreversible behavioral deficits in vivo. Notably, cognitive abnormality was supported by impaired average gamma power in the CA1 during novel object recognition testing. Accompanying brain tissue studies showed progressive increase of brain-bound human antibodies in the hippocampus of anti-IgLON5 IgG-injected mice, which persisted 30 days after the injection of patient’s antibodies was stopped. Microglial and astrocyte density was increased in the hippocampus of anti-IgLON5 IgG-injected mice at Day 30. Whole-cell voltage clamp recordings proved that anti-IgLON5 antibodies affected synaptic homeostasis. Further western blot investigation of synaptic proteins revealed a reduction of presynaptic (synaptophysin) and post-synaptic (PSD95 and NMDAR1) expression in anti-IgLON5 IgG-injected mice. Conclusions Overall, our findings indicated an irreversible effect of anti-IgLON5 antibodies and supported the pathogenicity of these antibodies in vivo.

Evidence has shown that aberrant angiogenesis is an integral part of Alzheimer's disease (AD). Angiogenesis is a complex process requiring successive activation of a rather large series of factors. The aim of this study was to determine which angiogenesis molecule(s) abnormalities were changed in plasma of AD subjects and whether plasma levels of angiogenesis factors were associated with cognitive function and risk of AD. Discovery-phase antibody arrays were used to detect plasma concentrations of 55 angiogenesis-related factors. Enzyme-linked immunosorbent assays (ELISAs) in a large cohort were further performed to identify the association of plasma angiogenesis factors with AD. We found that plasma angiogenin (ANG) and tissue inhibitor of matrix metalloproteinase-4 (TIMP-4) levels were higher in patients with AD than those in normal subjects. Significantly higher ANG and TIMP-4 were observed in the severe AD group relative to the mild AD. There were different levels of plasma ANG and TIMP-4 compared with vascular dementia and other dementias. Age or gender had no major effects on levels of these proteins. Plasma ANG and TIMP-4 levels tended to be higher in ApoE ε4 carriers compared with non-carriers, but not significantly. A multiple regression analysis after adjusting for covariates revealed correlations between plasma ANG and TIMP-4 and the MMSE and CDR. Higher plasma ANG and TIMP-4 levels were associated with significant AD risk. These results demonstrate that plasma ANG and TIMP-4 may reflect the severity of cognitive function impairment, and higher levels were associated with risk of AD.

Immune checkpoint inhibitors (ICIs) are being used in patients with various advanced malignancies, and patient outcomes have improved considerably. Although ICIs can effectively treat tumors, 30–60% of patients experience immune-related adverse events (irAEs). Autoimmune encephalitis (AE) is a rare irAE that has become a novel topic in neuroimmunology and has received increasing attention in recent years. Herein, we report a rare case of GAD65-antibody–associated AE after metastatic small cell lung cancer treatment with pembrolizumab. The patient received IVIg therapy for AE and continuous pembrolizumab therapy without suspension of tumor treatment. At 1 year follow-up, both the patient’s AE symptoms and tumors were stable. We consider that the treatment of ICI-associated AE should be more individualized with prudent decision-making and should balance the tumor progression and AE treatment. In addition, we have also comprehensively reviewed the literature of ICI-associated AE, and summarized the clinical features, treatment, and prognosis of AE caused by ICI, thus broadening our understanding of the neurological complications caused by ICI.

Objectives: Since the novel coronavirus disease (COVID-19) outbreak started in late 2019, the older population has accounted for a large proportion of severe and fatal cases. This study investigated the mental state and attitudes of older Chinese adults during this epidemic. Design: Cross-sectional online surveys on a convenience sample of China's general population at two different time points. Online surveys were disseminated through popular Chinese social media applications. Adults 18 or older living in China during the initial (N ¼ 1148) and second stages (N ¼ 470) were included in the survey. The Worries, Strategies, and Confidence Questionnaire was created to assess worries and awareness of the disease. Results: Combined responses (N ¼ 1618), 76.1% were female and about 7.0% were 60 years or above. In the first wave, older adults were found less likely to worry about being infected by COVID-19 (p < 0.05) and reported less attention paid to protective measures (p ¼ 0.004) than young adults. However, as the disease evolved, older participants in the second wave were more worried than young adults (p ¼ 0.027) and older adults in the first wave (p ¼ 0.001). Conclusions: During the epidemic of COVID-19, watchfulness of the epidemic among older Chinese adults fluctuated over time. Initially, they were slow to respond proactively, but their worries gradually increased. Health care and social service professionals need to address the vulnerabilities of older adults to this public health crisis.