Multiple sclerosis is thought to involve aberrant immune responses to myelin autoantigens. Haematopoietic stem-cell transplantation (HSCT) is in clinical trials for progressive multiple sclerosis based on the rationale that it destroys aberrant immune system, while recapitulation of lymphocyte ontogeny might alter the immune system and slow down disease progression. This study was undertaken to analyse characteristics of the T-cell receptor (TCR) repertoire, serum cytokine profile and the T-cell responses to myelin basic protein (MBP) in the reconstituted immune system in progressive multiple sclerosis. The study revealed that, following autologous HSCT, the T-cell immunity recovered in two distinctive phases. The first phase was characterized by limited T-cell immunity as a result of selective expansion of pre-existing T cells commonly expressing the TCR beta chain variable region (TCR BV) 20 and increased serum cytokine production during the first several months. The second phase of T-cell reconstitution coincided with increased thymic T-cell output 9-12 months after HSCT. T cells reconstituted from stem-cell grafts had the distinctive properties of comprehensive T-cell immunity and a broad TCR repertoire. T cells recognizing MBP were initially depleted by immunoablation and rapidly expanded from the reconstituted T-cell repertoire in 12 months. The reconstituted MBP-reactive T cells exhibited a broader epitope recognition repertoire while maintaining the same skewed reactivity pattern compared with that seen at baseline. The findings have important implications in the understanding of the role of HSCT as a potential treatment for multiple sclerosis.

Introduction The ongoing coronavirus disease 2019 (COVID-19) outbreak impacts the mental health of patients, health workers, and the public. The level of impact on the mental health of orthodontic patients in treatment is unknown. The objective of the study was to evaluate the mental health of orthodontic patients in China during the early stage of the pandemic. Methods An online survey was conducted on a convenience sample of anonymous participants. The questionnaire, in Chinese (Mandarin), comprised 5 sections. Sections 1-3 included demographic, epidemical, and orthodontic status of the patients. Section 4 assessed mental health-related to orthodontics. Section 5 was the Kessler-10 Mental Distress Scale. A total of 48 orthodontists were invited to distribute the questionnaires to their patients. Descriptive statistics, principal component analysis, K-means cluster analysis, and bivariate logistics regression analysis were performed with significance set at P <0.05. Results Questionnaires were collected from 558 patients (104 males, 354 females; mean age 24.78 ± 6.33 years). The prevalence of mental distress was 38% (174/458). Higher odds ratios were associated with female participants, missed appointments, and Hubei residence. The type of orthodontic appliance was associated with the anxiety of prolonged treatment duration. The manner of communication with patients regarding the postponement of appointments was associated with patients' concerns of prolonged treatment duration. The frequency of contact from dentists was associated with patients' independence. Conclusions Over one-third of orthodontic patients experienced mental distress during the pandemic. Multiple factors affected the level of anxiety of orthodontic patients, such as the type of orthodontic appliance, time since last dental visit, manner of communication with the orthodontist, and the localities of the pandemic progression.

The dynamics, duration, and nature of immunity produced during SARS-CoV-2 infection are still unclear. Here, we longitudinally measured virus-neutralising antibody, specific antibodies against the spike (S) protein, receptor-binding domain (RBD), and the nucleoprotein (N) of SARS-CoV-2, as well as T cell responses, in 25 SARS-CoV-2-infected patients up to 121 days post-symptom onset (PSO). All patients seroconvert for IgG against N, S, or RBD, as well as IgM against RBD, and produce neutralising antibodies (NAb) by 14 days PSO, with the peak levels attained by 15–30 days PSO. Anti-SARS-CoV-2 IgG and NAb remain detectable and relatively stable 3–4 months PSO, whereas IgM antibody rapidly decay. Approximately 65% of patients have detectable SARS-CoV-2-specific CD4+ or CD8+ T cell responses 3–4 months PSO. Our results thus provide critical evidence that IgG, NAb, and T cell responses persist in the majority of patients for at least 3–4 months after infection.

Vasoactive intestinal peptide (VIP) has a unique property of regulating T(h)1 and T(h)2 immunity of CD4+ T cells. In this study, we demonstrated, for the first time, that differential expression of VIP receptors and a compensatory mechanism directly affect the responsiveness of CD4+ T cells and their T(h)1 and T(h)2 properties to VIP. The expression of VIP receptor-1 (VPAC1) and VPAC2 in CD4+ T cells changed reciprocally in the context of the activation state. In activated CD4+ T cells of healthy individuals, markedly decreased VPAC1 expression was compensated for by increased expression of VPAC2 induced by T cell activation. In contrast, there was altered expression of VPAC2 in activated CD4+ T cells derived from multiple sclerosis (MS) patients, which rendered CD4+ T cells less responsive to VIP and skewed the system to a predominantly in a T(h)1 direction. Detailed characterization with agonist peptides of VIP showed that residues Met and Ser at positions 17 and 25 of VIP were critical to its regulatory properties through interaction with VAPC2. Furthermore, altered levels of VPAC2 expression in T cells of MS patients were not associated with single-nucleotide polymorphism in the encoding region of the VPAC2 gene but with gene regulation as characterized by a distinct DNA footprinting pattern in the promoter region of the VPAC2 gene in MS as compared with controls. This study has provided new evidence for an intrinsic mechanism associated with an aberrant, pro-inflammatory state of CD4+ T cells in MS.

Objective To retrospectively review the impact of the outbreak of coronavirus disease 2019 (COVID‐19) on services in the oral emergency room. Materials and methods A statistical analysis of epidemiological characteristics and the patients’ diagnoses and treatments in the Emergency Department of Peking University Hospital of Stomatology during the outbreak of COVID‐19 in 2020 compared with those in 2019 in Beijing, China. Results There were fewer total visits in 2020 than in 2019 ( P = 0.001), and the proportions of patients who were children, adolescents and elderly people were lower in 2020 than in 2019 ( P < 0.001). The proportions of patients with acute toothache and infections were higher in 2020 than in 2019, and the proportions of patients with maxillofacial trauma and non‐emergencies were lower in 2020 than in 2019 ( P < 0.001). Drug treatment for acute pulpitis was used more often in 2020 than in 2019, and endodontic treatment and examination consultations were less common in 2020 than in 2019 ( P = 0.022). Conclusions The outbreak of COVID‐19 affected the patient population and structure of disease types and oral services in the emergency room. The number of visits to the oral emergency room and the proportions of the patients who were children, adolescents and elderly people were reduced, meanwhile the percentage of emergency cases, except trauma, and conservative treatments increased during the outbreak of COVID‐19.