Research on IgG4-related disease (IgG4-RD), an autoimmune condition recognized to be a unique disease entity only two decades ago, has processed from describing patients' symptoms and signs to summarizing its critical pathological features, and further to investigating key pathogenic mechanisms. Challenges in gaining a better understanding of the disease, however, stem from its relative rarity-potentially attributed to underrecognition-and the absence of ideal experimental animal models. Recently, with the development of various high-throughput techniques, "omics" studies at different levels (particularly the single-cell omics) have shown promise in providing detailed molecular features of IgG4-RD. While, the application of omics approaches in IgG4-RD is still at an early stage. In this paper, we review the current progress of omics research in IgG4-RD and discuss the value of machine learning methods in analyzing the data with high dimensionality.
Humans ; Immunoglobulin G4-Related Disease/metabolism* ; Immunoglobulin G/metabolism* ; Machine Learning ; Animals ; Proteomics/methods*

To investigate the promoting effect of insulin-like growth factor 2(IGF-2)on cancer by mediating Treg immune activity in rats with gastric cancer,total of 40 healthy male SD rats were selected and subcutaneously inoculated with gastric cancer SGC-7901 cell line in the right axilla to establish a gastric cancer model.The model rats were randomly divided into a model group,a low-dose group(25 μg/kg IGF-2),a medium dose group(50 μg/kg IGF-2)and a high-dose group(100 μg/kg IGF-2),with 10 rats in each group.After continuous 14 days of administration,the tumor volume,tumor mass,thymus and spleen weight of rats in the 4 groups were observed and recorded for calculate tumor inhibition rate,thymus index and spleen index.Furthermore,Treg and Th17 levels in blood were detected by flow cytometry,tumor histopathological morphology was observed by hematoxylin-eosin staining,the apoptosis of gastric cancer cells was detected by TUNEL,and the expression of PI3K/Akt signaling pathway in tumor tissues of rats in 4 groups were detected by Western blotting.Data showed that the spleen index and thymus index of each dose group were lower than those of the model group,and showed a significant decreasing trend with the increase of the dosage,while the tumor promotion rate showed an increasing trend(P<0.05).Compared with the model group,IGF inhibited the apoptosis rate of cancer cells in each dose group in a dose-dependent manner(P<0.05).With the increase of IGF-2 dose,Treg,Th17 and Treg/Th17 all increased significantly(P<0.05)in IGF groups.The expression levels of p-Akt and CYP19A1 proteins in different dose groups were higher than those in the model group.As the dosage increased,the expression levels of p-Akt and CYP19A1 proteins showed a significant increase trend(P<0.05).Taken together,IGF-2 can promote tumor growth in gastric cancer rats,and its mechanism may relate to disrupting the immune function balance of Treg/Th17 cells through up-regulation of PI3K/Akt signaling pathway,thus inhibiting tumor cell apoptosis.

Humans ; Lupus Vasculitis, Central Nervous System/pathology* ; Magnetic Resonance Imaging/methods* ; Diffusion Tensor Imaging/methods* ; Patients ; Lupus Erythematosus, Systemic/pathology* ; Brain/pathology*

OBJECTIVE To provide standardized guidance for the clinical application and management of biosimilars， and promote their widespread and rational use in clinical treatment. METHODS The design， planning， and drafting process as well as the full report of Evidence-based Guideline for the Management of Clinical Application of Biosimilars in China （2024 Edition） followed the WHO Handbook for Guideline Development （2nd edition）， which fully considered the best current evidence from evidence-based medicine， multidisciplinary expert experience， and patient preferences and values. Grading of Recommendations Assessment， Development， and Evaluation （GRADE） approach was adopted to evaluate the quality of evidence and determine the strength of recommendations. RESULTS & CONCLUSIONS Evidence-based Guideline for the Management of Clinical Application of Biosimilars in China （2024 Edition） presented 10 recommendations including 7 strong recommendations and 3 weak recommendations. The recommendations covered the entire process of clinical application and management of biosimilars. Medical institutions and relevant health regulatory departments can refer to this guideline for the scientific management of the extrapolation of unapproved indications of biosimilars. Healthcare providers can refer to this guideline for pre-treatment assessments， patient education， pre-treatment regimen before administration， and dosage regimen adjustments. Multidisciplinary medical teams can refer to this guideline to provide pharmacovigilance and patient management throughout the treatment process.

BACKGROUND:In recent years,there have been many studies on the mechanism of exosomal non-coding RNA in gestational diabetes mellitus,but there is a lack of the latest systematic review of exosomes from different sources,especially placental sources. OBJECTIVE:To summarize the changes and potential roles of microRNA(miRNA),long non-coding RNA(lncRNA),circular RNA(circRNA),and exosomes in gestational diabetes mellitus to provide potential targets for early screening and treatment of clinical gestational diabetes mellitus. METHODS:A literature search was conducted on PubMed,Web of Science,China National Knowledge Infrastructure,WanFang Data,and VIP databases to retrieve relevant articles on non-coding RNA or exosomal non-coding RNA in relation to gestational diabetes mellitus.A total of 74 articles were included for review. RESULTS AND CONCLUSION:(1)Non-coding RNAs play important pathological and physiological roles in the lifecycle activities,and increasing evidences suggest that non-coding RNAs are involved in the occurrence and development of gestational diabetes mellitus by regulating various physiological functions.This provides a new direction for the research of gestational diabetes mellitus.(2)Exosomes are widely present in the human body.Various cells can secrete exosomes,such as red blood cells,epithelial cells,and placental cells.Non-coding RNAs found in exosomes from different sources have been demonstrated to play a role in the pathogenesis,diagnosis,and treatment of gestational diabetes mellitus.(3)MiRNA and gestational diabetes mellitus:The role of peripheral blood miRNA in gestational diabetes mellitus is mainly to affect the functions of trophoblast cells,pancreatic beta cells and blood glucose levels in gestational diabetes mellitus;placental miRNA can reflect the severity of gestational diabetes and impair the function of trophoblast cells.(4)LncRNA and gestational diabetes mellitus:Peripheral blood lncRNA can induce insulin resistance through the phosphatidylinositol 3-kinase/protein kinase B pathway and may provide new insights for the diagnosis and treatment of gestational diabetes mellitus;placental lncRNA can regulate proliferation and migration of placental trophoblast cells,promoting the occurrence and development of gestational diabetes mellitus.(5)CircRNA and gestational diabetes mellitus:Peripheral blood and placental circRNA can induce the occurrence and development of gestational diabetes mellitus by impairing the proliferation,migration and metabolism of placental trophoblast cells.(6)Non-coding RNA in exosomes and gestational diabetes mellitus:Peripheral blood non-coding RNA in exosomes can affect gestational diabetes mellitus blood glucose levels and glucose homeostasis,and participate in the occurrence and development of gestational diabetes mellitus by influencing placental function.(7)Non-coding RNA has the potential to serve as biomarkers for early diagnosis of gestational diabetes mellitus.Additionally,engineered exosomes can better achieve targeted therapy for gestational diabetes mellitus.These latest findings provide a reference for both basic research and clinical translation of gestational diabetes mellitus.(8)In the future,improvements in the extraction and purification methods of peripheral blood exosomes should be improved,and factors such as race,diet and physical activity should be excluded to improve the reproducibility of results.Further prospective clinical studies are required to explore the clinical application of circulating non-coding RNA and exosomes in the prediction and diagnosis of gestational diabetes mellitus.

Background::Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.Methods::In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort.Results::In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone.Conclusion::ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.Trial Registration::Chictr.org.cn: ChiCTR2200059599.

Subclinical seizures (SCS) are paroxysmal electroencephalogram (EEG) events that do not accompany obvious subjective or objective behavioral changes. They are not uncommon in EEG monitoring, with an intracranial EEG detection rate of about 50%-60%, significantly higher than the scalp EEG detection rate of about 10%. SCS most frequently occur in patients with temporal lobe epilepsy. In terms of EEG characteristics, SCS often remain confined to the epileptogenic zone but can also spread outside of it. Their value in localizing the epileptogenic zone is comparable to that of clinical seizures (CS). Additionally, the concordance between SCS and CS localization is associated with favorable surgical outcomes, indicating the significant value of SCS in focal epilepsy. A systematic review of domestic and international research on SCS is provided in this paper, aiming to enhance understanding in this area.

Objective To construct a rational and efficient bed resource allocation management model to reduce pre-hos-pital waiting times,ensure patient safety,and improve satisfaction.Methods Based on lean management principles,a bed re-source allocation management model was developed and continuously optimized.The study compared bed turnover rates and effi-ciency indices,as well as preoperative waiting times for surgical patients,average length of stay,patient satisfaction,and anxiety incidence before and after the implementation of the lean model to evaluate its effectiveness.Results After implementing the lean bed resource allocation model,the bed efficiency index increased by 14.29％,and bed turnover rates improved by 3.34％.The average preoperative waiting time for surgical patients decreased by 100％,and the average length of stay reduced by 87.71％.Patient satisfaction increased by 2.4％,while anxiety incidence dropped by 28.1％.Conclusion The implementa-tion of a lean bed resource allocation model can enhance hospital bed efficiency,shorten preoperative waiting times for surgical patients,reduce average length of stay,and improve patient satisfaction.

Objective To investigate the curative effect of cocktail combined with tranexamic acid(TXA)on total knee arthroplasty(TKA)under the concept of enhanced recovery after surgery(ERAS).Methods Seventy patients with knee osteoarthritis who received unilateral TKA treatment admitted to the Second Affiliated Hospital of Bengbu Medical College from September 2020 to July 2022 were ret-rospectively analyzed.According to different treatment methods,they were divided into experimental group and control group,with 35 ca-ses in each group.Under the guidance of ERAS concept,the experimental group received injected intraarticular mixture of cocktail and TXA during the operation,while the control group received injected intraarticular mixture of cocktail and normal saline.Postoperative drainage volume,hemoglobin(Hb)decline and total blood loss at 3 days after operation,blood transfusion rate,first ambulation time,length of hospital stay,postoperative pain visual analogue scale(VAS)、knee range of motion(ROM)and HSS score at different time points after operation,delayed wound healing,wound infection and incidence of deep vein thrombosis were compared between the two groups.Results The postoperative drainage volume,decline of Hb and total blood loss at 3 days after operation,blood transfusion rate in the experimental group were less than those of the control group,the differences were statistically significant(P＜0.05).The first ambu-lation time and length of hospital stay in the experimental group were significantly lower than those of the control group,the difference were statistically significant(P＜0.05).There were no significant differences in pain VAS score at 1 day,2 days,3 days,7 days,14 days af-ter operation between two groups(P＞0.05).There were no significant differences in ROM at 7 days,14 days after operation and HSS score at 4 weeks,12 weeks after operation between two groups(P＞0.05).Conclusion Under the concept of ERAS,intraarticular in-jection of cocktail combined with TXA in TKA can effectively reduce postoperative blood loss,improve postoperative pain,reduce periop-erative risks,and promote better early postoperative rehabilitation,the clinical effect is significant.

Objective:Childhood traumatic experiences greatly influenced the brain network activities of patients with depression,and there is an urgent need to explore the temporal dynamics for these changes.This study aims to investigate the abnormalities of resting-state electroencephalogram(EEG)microstates in eye-open state of depressed adolescents and to explore the correlations between their EEG microstates and the childhood traumatic experience. Methods:Using resting-state EEG microstate analysis,we explored the temporal dynamics of brain activity in patients with adolescent depression.This study selected 66 adolescents with depression as a patient group,and 27 healthy adolescents as a healthy control group.A modified k-means clustering algorithm was used to classify the 64-channel resting-state EEG data into different microstates.Independent sample t-tests were used to compare the microstate parameters between the 2 groups and further assciations between these parameters and childhood traumatic experience in patients were explored via using Spearman correlation. Results:In this study,significant differences were observed in the occurrence and transition probabilities of EEG microstates between the healthy control and the patient group.Notably,there was a statistically significant difference(P＜0.05)in the occurrence of microstate A across 2 groups,exhibiting a negative correlation with the emotional abuse component within the childhood trauma scores(Spearman's rho=-0.31,P=0.013).Furthermore,patient-specific,non-random transitions from microstate B to A(Spearman's rho=-0.30,P=0.015)and C to A(Spearman's rho=-0.31,P=0.013)were inversely associated with the scores of emotional abuse factors from childhood trauma in the patient group,showing statistically significant differences when comparing to the healthy controls(P＜0.05).Upon stratification into quartiles based on the emotional abuse factor scores,the occurrence of microstate A,as well as the transition rates from microstates B to A and C to A,retained statistical significance following adjustment for multiple comparisons(all P＜0.05). Conclusion:The abnormal temporal dynamics in brain networks of adolescents with depression are linked to childhood emotional abuse.Those who have suffered severe emotional abuse may show greater impairments in the brain's visual and central executive networks.EEG microstate analysis could be a potential tool for detecting adolescent depression with severe childhood trauma.