Objective:To analyze the correlation between peripheral blood lymphocyte subsets, especially B cells, and the relapse of autoimmune encephalitis (AE).Methods:A retrospective analysis was conducted on patients with AE who were diagnosed and treated in Peking Union Medical College Hospital from January 2012 to January 2023. The clinical data including gender, age and changes in related indicators of CD19 +B cells, CD16/56 +NK cells, CD3 +T cells, CD4 +T cells, CD8 +T cells, IgG, IgA, and IgM before and after recurrence were analyzed.Binary Logistic regression analysis was applied to the study of correlation between AE recurrence and gender, age, CD19 +B cells, CD16/56 +NK cells, CD3 +T cells, CD4 +T cells, CD8 +T cells, IgG, IgA and IgM. The receiver operating characteristic (ROC) curves of the cells that affect AE recurrence (CD19 +B cells, CD16/56 +NK cells, CD3 +T cells, CD4 +T cells and CD8 +T cells) were plotted separately. Results:A total of 198 eligible AE patients were included, including 98 males and 100 females, aged (39.52±17.91) years. Among these patients, 78 cases had relapses, with a recurrence rate of 39.4%. The results of Logistic regression analysis showed that CD19 +B cells ( B=0.006, P<0.001), CD16/56 +NK cells ( B=0.004, P<0.05), CD3 +T cells ( B=-0.011, P<0.05), CD4 +T cells ( B=0.014, P<0.05) and CD8 +T cells ( B=0.010, P<0.05) were highly correlated with the relapse of AE. ROC curve analysis showed that CD19 +B cells (area under the curve: 0.833, P<0.001, critical value: 73.5/μl; sensitivity: 69.2%, specificity: 86.7%), CD3 +T cells (area under the curve: 0.784, P<0.001), CD4 +T cells (area under the curve: 0.808, P<0.001), and CD8 +T cells (area under the curve: 0.742, P<0.001) all had a certain predictive value for AE relapse. Among all the indicators, the area under the curve of CD19 +B cells was the largest, which had a higher value in predicting AE recurrence. Conclusion:The increase in peripheral blood CD19 +B cells has high predictive value for the relapse of AE.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective:To develop the Nutrition Impact Symptom Scale for Colorectal Cancer Patients.Methods:Guided by the theory of unpleasant symptoms, the initial draft of the scale was formed through literature research, expert consultation, and small sample pre-survey. From March to May 2023, convenience sampling was used to select 127 colorectal cancer patients who visited Jiangsu Cancer Hospital as the research subject for item analysis and reliability and validity testing of the scale.Results:The final scale consisted of five dimensions and a total of 17 items. The content validity index of the scale was from 0.83 to 1.00, with an average content validity index of 0.97. Exploratory factor analysis extracted five common factors, and the cumulative variance contribution rate was 61.622%. The total Cronbach's α coefficient of the scale was 0.708, and the coefficients for each dimension were 0.762, 0.642, 0.625, 0.510, and 0.644, respectively. The half reliability coefficient of the scale was 0.824.Conclusions:The development process of the Nutrition Impact Symptom Scale for Colorectal Cancer Patients is scientific, with good reliability and validity, and can be used to evaluate the nutrition impact symptom of colorectal cancer patients.

Objective:To analyze the clinical characteristics and prognosis of patients with stiff-person syndrome (SPS) associated with glutamic acid decarboxylase (GAD) antibodies.Methods:A retrospective analysis was conducted on demographic characteristics, clinical manifestations, auxiliary examination results, treatment, and prognosis of patients with GAD antibody-related SPS treated at Peking Union Medical College Hospital from January 2015 to July 2023.Results:A total of 33 patients were included, comprising 26 females (78.8%) and 7 males (21.2%), with an onset age of (42±12) years and a disease duration of 24.0 (10.5, 37.5) months. Two cases (6.1%) were diagnosed with tumors, including 1 case with invasive thymoma and 1 case with small cell lung cancer. The majority of patients (87.9%, 29/33) presented with stiffness of trunk and proximal limb muscles, 42.4% (14/33) of patients exhibited episodic spasm, and 54.5% (18/33) of patients were triggered by stimuli such as sound and light. Babinski or Chaddock reflexes were elicited in 33.3% (11/33) of patients. Some patients (36.4%, 16/33) had concurrent limbic encephalitis/epilepsy or cerebellar ataxia (referred to as complex SPS). The median cerebrospinal fluid (CSF) white blood cell count was 2×10 6/L [quartile: 1×10 6/L, 6×10 6/L; range: (0-30)×10 6/L], with mild elevation in 28.0% (7/25) of patients. Multi-channel surface electromyography in 14 out of 21 cases (66.7%) suggested synchronous contraction of agonist and antagonist muscles in a relaxed state. The modified Rankin Scale (mRS) score during the acute phase was 4 (3, 4). All patients received treatment with benzodiazepines or baclofen. Thirty patients (90.9%, 30/33) received first-line immunotherapy, 3 patients (9.1%, 3/33) received second-line immunotherapy with rituximab, and 14 (42.4%, 14/33) received mycophenolate mofetil as long-term immunotherapy. The follow-up period was 16 (10, 42) months, with a median best mRS score of 2; 66.7% (22/33) of patients had a favorable functional prognosis (mRS score≤2), and the recurrence rate was 30.0% (9/30). At the last follow-up, the median mRS score was 2, and 53.3% (16/30) of patients had a favorable functional prognosis. Prognosis was not significantly correlated with gender, age, clinical type, or CSF white blood cell level (all P>0.05). Conclusions:SPS is one of the main clinical phenotypes of GAD antibody-related neuroimmune diseases, commonly observed in middle-aged women, and exhibits a chronic progressive course. Only a minority of patients have concomitant tumors. The diagnosis relies on typical symptoms, GAD antibody testing, and electromyography examination. The initial immune therapy yields good results, but the prognosis for recurrent patients is poor.

Objective:To evaluate the significance of copy number variation (CNV) and metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) in the diagnosis of meningeal carcinomatosis (MC).Methods:Ten patients with MC diagnosed in the Department of Neurology of Peking Union Medical College Hospital from March 2022 to June 2022 were consecutively enrolled in this study. The patients were diagnosed according to the criteria of the Chinese expert consensus on the diagnosis of MC by the Chinese Society of Infectious Diseases and Cerebrospinal Fluid Cytology, and the diagnosis of MC was confirmed by CSF cytology. The control group included 10 patients who were diagnosed as autoimmune encephalitis or viral encephalitis. CSF mNGS and CNV analysis were performed simultaneously in all the patients.Results:Of the 10 patients with MC, 6 had lung adenocarcinoma, 4 had breast cancer. CSF mNGS and CNV analysis detected large CNV in 8 of 10 patients with MC, including 4 patients with breast cancer and 4 patients with lung cancer. The results of pathogenic microorganism analysis of CSF mNGS in all the patients were negative. Meanwhile, large CNV was not detected in the control group.Conclusions:CSF CNV can serve as a diagnostic marker for MC. The combination of mNGS and CNV analysis has demonstrated a high positive rate in the diagnosis of MC. The dual-omics analysis of pathogenic microorganisms and CNV has been proposed as a potential strategy to further expand the clinical utility of CSF mNGS in the realm of auxiliary diagnosis.

The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, IrtAB, plays a vital role in the replication and viability of Mycobacterium tuberculosis (Mtb), where its function is to import iron-loaded siderophores. Unusually, it adopts the canonical type IV exporter fold. Herein, we report the structure of unliganded Mtb IrtAB and its structure in complex with ATP, ADP, or ATP analogue (AMP-PNP) at resolutions ranging from 2.8 to 3.5 Å. The structure of IrtAB bound ATP-Mg2+ shows a "head-to-tail" dimer of nucleotide-binding domains (NBDs), a closed amphipathic cavity within the transmembrane domains (TMDs), and a metal ion liganded to three histidine residues of IrtA in the cavity. Cryo-electron microscopy (Cryo-EM) structures and ATP hydrolysis assays show that the NBD of IrtA has a higher affinity for nucleotides and increased ATPase activity compared with IrtB. Moreover, the metal ion located in the TM region of IrtA is critical for the stabilization of the conformation of IrtAB during the transport cycle. This study provides a structural basis to explain the ATP-driven conformational changes that occur in IrtAB.
Siderophores/metabolism* ; Iron/metabolism* ; Mycobacterium tuberculosis/metabolism* ; Cryoelectron Microscopy ; Adenosine Triphosphate/metabolism* ; ATP-Binding Cassette Transporters

Objective:To explore the epidemiology, clinical features and prognosis of pseudorabies virus (PRV) infection in human.Methods:A case of human PRV encephalitis combined with acute retinal necrosis (ARN) in the First Affiliated Hospital of Zhengzhou University in May 2020 was reported. The epidemiology, clinical features, neuroimaging, cerebrospinal fluid (CSF), next-generation sequencing (NGS), treatment and prognosis of human PRV infection were summarized and analyzed with the previous published data.Results:The present case was a 38-year-old man who developed high fever, headache, cognitive decline, recurrent epileptic seizures after butchering a pig. Brain magnetic resonance imaging showed lesions in the insular lobes, temporal lobes, cingulate gyrus, frontal lobes, basal ganglia and hippocampus, with more significant signals on the left side. Afterwards, bilateral ARN occurred and resulted in his blindness. PRV DNA was detected from the aqueous humor. By literature review, a total of 20 cases (including this case) were analyzed. Most patients (95%, 19/20) had the history of direct contact with swine. The median incubation period was 7 days. The infection normally caused encephalitis (95%, 19/20), some cases with endophthalmitis (60%, 12/20). Based on the neuroimaging of the 19 patients, the lesions in neuroimaging were mainly in limbic system, especially in insular (17/19) and temporal lobes (17/19). The basal ganglia was often involved (9/19).The PRV-DNA was detected by NGS in CSF or intraocular fluid. Antiviral drugs and adjuvant treatment, including immunoglobulin and/or corticoid therapy, were effective to only few cases. Most patients (90%, 18/20) had the sequelae of severe impairment of daily living (modified Rankin Scale scores≥3).Conclusions:The cardinal clinical characteristics of human PRV infection are progressive panencephalitis and endophthalmitis, with an unfavorable outcome. The history of exposure to sick swine and typical neuroimaging suggest PRV infection. NGS of CSF and/or intraocular fluid is the dependable diagnostic method.

Antibodies to glutamic acid decarboxylase (GAD) have been associated with several neurological syndromes, including stiff-person syndrome, cerebellar ataxia and epilepsy. This article critically reviews the main clinical characteristics and the evidence on the pathogenicity of GAD antibodies.

Clinical data of a child with acquired immunodeficiency syndrome characterized by ischemic stroke who was admitted to the Pediatric Intensive Care Unit of Children′s Hospital Affiliated to Soochow University in January 2019 were retrospectively analyzed.The child is a 6 years and 4 months old boy with a history of thrombocytopenic purpura and recurrent respiratory infections.The main complaint was " the right limb weakness for more than 10 days" . The head magnetic resonance imaging (MRI) revealed extensive abnormal signals in the bilateral frontal and parietal lobes and the formation of softening foci in the left thalamus and outer capsule.Blood routine showed white blood cell 4.88×10 9/L, lymphocyte ratio 0.291, lymphocyte count 1.42×10 9/L, hemoglobin 99 g/L, and platelet 23×10 9/L.Lymphocyte subsets included CD3 + 84.1%, CD3 + CD4 + 0.2%, CD3 + CD8 + 61.4%, CD4 + /CD8 + 0, CD3 -CD 19+ 9.2%, CD3 -CD 16+ 56+ 6.1%, and CD 19+ CD 23+ 5.8%.Pretransfusion tests suggested human immunodeficiency virus (HIV) (+ ), and that other results were negative.Both parents of the child were infected with HIV.This paper demonstrates that neurological involvement is not rare in HIV infection, and stroke is the most common cause of clinical focal neurological deficits in HIV-infected children.Screening with MRI is recommended for high-risk children with neurologic symptoms or neurocognitive dysfunction.

Objective:To analyze the social family factors influencing language delay in children with the age ranging from 18 to 42 months in Xiamen.Methods:A prospective cohort study was conducted to evaluate children with language delay (case group) and normal controls (control group) in Child Health Clinic and Developmental Behavior Clinic of the First Affiliated Hospital of Xiamen University between July 2017 and July 2019 via a self-made questionnaire and a language development scale, and the case-control ratio was 1∶4.The chi- square test, Logistic regression and generalized multifactor dimensionality reduction (GMDR) were adopted for statistical analysis, and the correction analysis was performed with Bonferroni correction. Results:A total of 126 children with language delay were collected in the case group, with the ratio of male to female being 2.05∶1.00. The control group was included 504 cases.There was no significant difference in gender and age between both groups.The chi- square test showed that there were statistical differences in maternal culture and screen time distribution between both groups ( P<0.05/13). Besides, the multivariate Logistic regression analysis suggested that significant risk factors for language delay in children included maternal culture, maternal-child interaction, and screen time.The GMDR analysis showed that screen time was the optimal single-mode for children at risk of language delay, while maternal culture and screen time constituted a statistically different two-factor model.Moreover, the marital-child interaction was included into the three-factor model. Conclusions:Screen time and maternal culture were the most important risk factors for language delay in children of Xiamen, and both factors would interact with maternal-child interaction, which could exert impacts on language delay in children.