eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

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Objective: To characterize the incidence density of systematic lupus erythematosus (SLE) in Yinzhou District of Ningbo from 2016 to 2021, and compare the age and gender specific differences. Methods: A retrospective cohort study was conducted based on the related data from 2015 to 2021 collected from the Health Information Platform of Yinzhou. Suspected SLE cases in local residents were identified by fuzzy matching of International Classification of Diseases 10^th edition code "M32" or Chinese text "lupus". The classification criteria from Systemic Lupus International Collaboration Clinics-2012 and The European League Against Rheumatism/American College of Rheumatology-2019 were used for case verification. SLE cases were identified with specific algorithm based on verification results, and new cases were identified with 1 year as the washout period. The incidence density and 95%CI were estimated by Poisson distribution. Results: From 2016 to 2021, a total of 1 551 921 permanent residents were registered in Yinzhou, in whom 51.52% were women. The M(Q₁,Q₃) age at enrollment was 40.38 (27.54, 53.54) years. The M(Q₁,Q₃) of follow-up person-years was 3.83 (0.41, 5.83) years. There were 451 new SLE cases, in which 352 were women (78.05%). The 6-year incidence density was 8.14/100 000 person-years (95%CI: 7.41/100 000 person-years-8.93/100 000 person-years) for the total population, 3.68/100 000 person-years (95%CI: 2.99/100 000 person-years-4.48/100 000 person-years) for men and 12.37/100 000 person-years (95%CI: 11.11/100 000 person-years- 13.73/100 000 person-years) for women. The incidence density in men appeared a small peak at 20-29 years old, and began to increase with age from 40 years old. The incidence density in women was highest in age group 20-29 years (16.57/100 000 person-years) and remained to be high until 30-79 years old. The incidence density of SLE in Yinzhou show no significant temporal trend from 2016 to 2021 (men: P=0.848; women: P=1.000). Conclusions: The incidence density of SLE in Yinzhou from 2016 to 2021 was similar to those of other areas in China. SLE has a high incidence in women, especially in the young and elderly, suggesting that more attention should be paid to the diagnosis and treatment of SLE in women.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Asian People ; Incidence ; Lupus Erythematosus, Systemic/diagnosis* ; Retrospective Studies ; China/epidemiology*

Objective: To construct a cervical cancer risk prediction model based on nested case-control study design and Yinzhou Health Information Platform in Ningbo, and provide reliable reference for self-risk assessment of cervical cancer in local women. Methods: In local women aged 25-75 years old who had no history of cervical cancer registered in Yinzhou before October 31, 2018, a follow up was conducted for at least three years, the patients who developed cervical cancer during the follow up period were selected as the case group and matched with a control group at a ratio of 1∶10. The prediction indicators before the onset was used in model construction. Variables were selected by Lasso-logistic regression, the variables with non-zero β were selected to fit the logistic regression model and Bootstrap was used for internal validation. The discrimination of the model was evaluated by area under the receiver operating characteristic curve(AUROC), and the calibration was evaluated by calibration curve and Hosmer-Lemeshow test. Results: The prediction indicators included in the final model were age, smoking status, history of cervicitis, history of adenomyosis, HPV testing, and thinprep cytologic test. The AUROC calculated in the internal validation was 0.740 (95%CI:0.739-0.740), and the calibration curve was almost identical with the ideal curve, P=0.991 in Hosmer-Lemeshow test, indicating that the model discrimination and calibration were good. Conclusions: In this study, a simple and practical cervical cancer risk prediction model was developed. The model can be used in general population with strong interpretability, good discrimination and calibration in internal validation, which can provide a reference for women to assess their risk of cervical cancer.

OBJECTIVE: To explore the effects of Ena/VASP gene family on the expression of glycoprotein (GP) Ib-IX complex in human megakaryoblastic leukemia Dami cells. METHODS: SiRNAs targeting Ena/VASP gene family were designed and synthesized to interfere Enah, EVL and VASP gene expression. When the siRNAs were transfected into Dami cells by using Lipofectamine^TM 2000 for 48 h, the expression of GPIb-IX complex was detected by quantitative real-time PCR, Western blot and flow cytometry. RESULTS: We successfully established siVASP , siEVL and si Enah Dami cell lines. And it was found that the expression of GPIb-IX complex had no evident reduction in siEVL or siVASP Dami cells at both mRNA and protein level, while the total protein and membrane protein of GPIb-IX complex were obviously reduced when Enah was knocked down. CONCLUSION Enah could affect the expression of GPIb-IX complex in human megakaryoblastic leukemia Dami cells, but the underlying mechanism still needs to be further explored.
Humans ; Cell Line ; Platelet Glycoprotein GPIb-IX Complex/metabolism* ; Leukemia/metabolism* ; Blood Platelets/metabolism*

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype

OBJECTIVE: To investigate the significance of anti-histidyl tRNA synthetase (Jo-1) antibody in idiopathic inflammatory myopathies (IIM) and its diseases spectrum. METHODS: We enrolled all the patients who were tested positive for anti-Jo-1 antibody by immunoblotting in Peking University People's Hospital between 2016 and 2022. And the patients diagnosed with anti-synthetase antibody syndrome (ASS) with negative serum anti-Jo-1 antibody were enrolled as controls. We analyzed the basic information, clinical characteristics, and various inflammatory and immunological indicators of the patients at the onset of illness. RESULTS: A total of 165 patients with positive anti-Jo-1 antibody were enrolled in this study. Among them, 80.5% were diagnosed with connective tissue disease. And 57.6% (95/165) were diagnosed with IIM, including ASS (84/165, 50.9%), immune-mediated necrotizing myopathy (7/165, 4.2%) and dermatomyositis (4/165, 2.4%). There were 23.0% (38/165) diagnosed with other connective tissue disease, mainly including rheumatoid arthritis (11/165, 6.7%), undifferentiated connective tissue disease (5/165, 3.0%), interstitial pneumonia with autoimmune features (5/165, 3.0%), undifferentiated arthritis (4/165, 2.4%), Sjögren's syndrome (3/165, 1.8%), systemic lupus erythematosus (3/165, 1.8%), systemic vasculitis (3/165, 1.8%), and so on. Other cases included 3 (1.8%) malignant tumor patients, 4 (2.4%) infectious cases and so on. The diagnoses were not clear in 9.1% (15 /165) of the cohort. In the analysis of ASS subgroups, the group with positive serum anti-Jo-1 antibody had a younger age of onset than those with negative serum anti-Jo-1 antibody (49.9 years vs. 55.0 years, P=0.026). Clinical manifestations of arthritis (60.7% vs. 33.3%, P=0.002) and myalgia (47.1% vs. 22.2%, P=0.004) were more common in the ASS patients with positive anti-Jo-1 antibody. With the increase of anti-Jo-1 antibody titer, the incidence of the manifestations of arthritis, mechanic hands, Gottron sign and Raynaud phenomenon increased, and the proportion of abnormal creatine kinase and α-hydroxybutyric dehydrogenase index increased in the ASS patients. The incidence of myalgia and myasthenia were significantly more common in this cohort when anti-Jo-1 antibody-positive ASS patients were positive for one and more myositis specific antibodies/myositis associated autoantibodies (P < 0.05). CONCLUSION The disease spectrum in patients with positive serum anti-Jo-1 antibody includes a variety of diseases, mainly ASS. And anti-Jo-1 antibody can also be found in many connective tissue diseases, malignant tumor, infection and so on.
Humans ; Middle Aged ; Myalgia ; Myositis/epidemiology* ; Autoantibodies ; Connective Tissue Diseases ; Arthritis, Rheumatoid ; Neoplasms

Some kinds of chronic sialadenitis were recognized during the recent years. They have specific pathogenesis, clinical and histopathologic appearances, and require specific treatment. IgG4-related sialadenitis (IgG4-RS) is one of the immune-mediated diseases, characterized by tumefactive lesions. The incidence of IgG4-RS obviously increased during the past 30 years. The study on the potential relationship between occupational exposure to chemical substances and the incidence of IgG4-RS showed that subjects with occupational exposure to agents known to cause IgG4-RD had an increased risk for IgG4-RS. Surgical excision of involved SMG could not control the disease progression, which is not recommended for treatment of IgG4-RS. The combination of glucocorticoid and steroid-sparing agents is effective for treating IgG4-RS, and restores salivary gland function. Radioiodine induced sialadenitis (RAIS) is one of the common complications of postoperative adjuvant treatment of differentiated thyroid cancer by ¹³¹I. The incidence of the disease is related to radiation dosage. Clinically, the patients suffered from swelling and tenderness in the buccal or submandibular regions, especially during the mealtime. Imaging appearances are similar to those of chronic obstructive sialadenitis. Conservative managements, such as gland massage, sialagogues, are the mainstream methods in the treatment of RAIS. Sialendoscopy is feasible for RAIS, but not as effective as conventional obstructive sialadenitis (COS). Therefore the prevention of RAIS is crucial. Eosinophilic sialodochitis (ES) is a new type of chronic inflammatory disease of the salivary gland related to allergy. It has characteristics of swelling of multiple major salivary glands, strip-like gelatinous plugs discharged from the duct orifice of the gland, elevated level of serum IgE and eosinophils in peripheral blood, infiltration of eosinophils and IgE positive plasma cells in the tissues, allergic history, increased expression of allergy-related cytokines, such as IL-4, IL-5, IL-13, and eotaxin, which suggest allergic reactions as a potential pathogenesis of the disease. The clinical, laboratory, histological, and immunohistochemical characteristics of ES are significantly different from conventional obstructive sialadenitis (COS). Therefore, it is suitable to separate ES from COS. Conservative managements, such as self-maintenance therapy and anti- allergic modality are the choices of treatment for ES. Based on the results of our comprehensive studies a new classification of chronic sialadenitis is suggested.
Humans ; Immunoglobulin G ; Iodine Radioisotopes ; Salivary Glands ; Sialadenitis/etiology* ; Submandibular Gland

OBJECTIVE: To describe the distribution characteristics of inflammatory bowel disease among permanent residents in Yinzhou District, Ningbo City, and to understand the disease burden and development trend of inflammatory bowel disease in this area. METHODS: Using the retrospective cohort design, we collected the registration information of all permanent residents in the residents' health files of the Yinzhou Regional Health Information Platform from 2010 to 2020, and used electronic medical records to follow up their inflammatory bowel disease visits. A one-year wash-out period was set, and the patients who were diagnosed with the primary diagnosis for the first time after one year of registration were re-garded as new cases. The incidence density and 95% confidence interval (CI) of inflammatory bowel disease were estimated by Poisson distribution. RESULTS: From 2011 to 2020, a total of 1 496 427 permanent residents in Yinzhou District were included, of which 729 996 were male (48.78%). The total follow-up person-years were 8 081 030.82, and the median follow-up person-years were 5.41 [interquartile range (IQR): 5.29]. During the study period, there were 1 217 new cases of inflammatory bowel disease, of which males (624 cases, 51.27%) were more than females (593 cases, 48.73%). The total incidence density was 15.06/100 000 person-years (95%CI: 14.23, 15.93). Among all new cases, there were 1 106 cases (90.88%) of ulcerative colitis, with an incidence density of 13.69 per 100 000 person-years (95%CI: 12.89, 14.52); 70 cases (5.75%) of Crohn's disease, with an incidence density of 0.87 per 100 000 person-years (95%CI: 0.68, 1.09); and 41 cases (3.37%) of indeterminate colitis, with an incidence density of 0.51 per 100 000 person-years (95%CI: 0.36, 0.69). The median age of onset of ulcerative colitis was 50.82 years old (IQR: 18.77), with the highest proportion (15.01%) in the 45-49 years group. The incidence density of ulcerative colitis gradually increased with age, reaching a relatively high level in the 45-49 years group (20.53/100 000 person-years; 95%CI: 17.63, 23.78), followed by a slight increase. And the incidence density in the 65-69 years group was the highest (25.44/100 000 person-years; 95%CI: 20.85, 30.75), with a rapid decrease in the 75-79 years group. The median age of onset of Crohn's disease was 44.34 years (IQR: 33.41), with the highest proportion (12.86%) in the 25-29 years group. Due to the small number of new cases of Crohn's disease, the age distribution fluctuated greatly, with peaks both in young and old people. From 2011 to 2020, the incidence density of inflammatory bowel disease in Yinzhou District was at a low level from 2011 to 2013, and showed a rapid upward trend from 2014 to 2016, reaching a peak of 24.62 per 100 000 person-years in 2016 (95%CI: 21.31, 28.30), and slightly decreased in 2017-2020. CONCLUSION The incidence density of inflammatory bowel disease in Yinzhou District from 2011 to 2020 was at a relatively high level, and medical institutions and health departments need to pay attention to the burden of disease caused by it.
Adolescent ; Adult ; Chronic Disease ; Colitis, Ulcerative/epidemiology* ; Crohn Disease/epidemiology* ; Female ; Humans ; Incidence ; Inflammatory Bowel Diseases/epidemiology* ; Male ; Middle Aged ; Retrospective Studies

Objective: To establish a sustainable updated literature data warehouse for global vaccine safety assessment, and provide data support for evidence-based vaccine safety assessment. Methods: Semi-automated construction and updating of a literature data warehouse were achieved through the continuous integration of standard operating steps of evidence-based reviews with artificial intelligence technologies. Following the standard procedure of a systematic literature review, the literatures about vaccine safety assessment published before November 29, 2020 were retrieved from 9 databases including OVID, Scopus, Web of Science, Cochrane Library, and ClinicalTrails.org in English and Wanfang, CNKI, VIP, and SinoMed in Chinese. Literatures were screened for two rounds in a semi-automatic manner (by artificial intelligence literature processing system and manual work) according to the inclusion/exclusion criteria. Furthermore, the literatures were classified according to the types of vaccines and adverse events. The updating strategy was established, and the literature data warehouse was updated regularly. Experts were organized to select specific vaccine safety topics and carry out special demonstration studies. Results: More than 0.41 million articles were retrieved. According to the inclusion/exclusion criteria, 23 304 articles were included after two rounds of screening. At present, we have selected and completed three prior topics as demonstration studies, including the systematic review of "DPT (diphtheria, pertussis and tetanus) vaccine and encephalopathy/encephalitis", and the classified management of literatures about allergic purpura and brachial plexus neuritis. Conclusions: The sustainable updated literature data warehouse of vaccine safety can provide high-quality research data for vaccine safety research, including evidence support for immunization related policy-making and adjustment and vaccine safety-related methodological research or clinical tool development; and further demonstration studies can provide references for building a new methodological framework system for timely and efficient completion of the evidence-based assessment of vaccine safety.
Artificial Intelligence ; Data Warehousing ; Humans ; Tetanus ; Tetanus Toxoid ; Whooping Cough/prevention & control*