OBJECTIVE: To construct machine learning prediction model for sepsis-associated encephalopathy (SAE), and analyze the application value of the model on early identification of SAE risk in elderly septic patients. METHODS: Patients aged over 60 years with a primary diagnosis of sepsis admitted to intensive care unit (ICU) from 2008 to 2023 were selected from Medical Information Mart for Intensive Care-IV 2.2 (MIMIC-IV 2.2). Demographic variables, disease severity scores, comorbidities, interventions, laboratory indicators, and hospitalization details were collected. Key factors associated with SAE were identified using univariate Logistic regression analysis. The data were randomly divided into training and validation sets in a 7 : 3 ratio. Multivariable Logistic regression analysis was conducted in the training set and visualized using a nomogram model for prediction of SAE. The discrimination of the model was evaluated in the validation set using the receiver operator characteristic curve (ROC curve), and its calibration was assessed using calibration curve. Furthermore, multiple machine learning algorithms, including multi-layer perceptron (MLP), support vector machine (SVM), naive bayes (NB), gradient boosting machine (GBM), random forest (RF), and extreme gradient boosting (XGB), were constructed in the training set. Their predictive performance was subsequently evaluated on the validation set. Taking the XGB model as an example, the interpretability of the model through the SHapley Additive exPlanations (SHAP) algorithm was enhanced to identify the key predictive factors and their contributions. RESULTS: A total of 2 204 septic patients were finally enrolled, of whom 840 developed SAE (38.1%). A total of 21 variables associated with SAE were screened through univariate Logistic regression analysis. Multivariable Logistic regression analysis showed that endotracheal intubation [odds ratio (OR) = 0.40, 95% confidence interval (95%CI) was 0.19-0.88, P < 0.001], oxygen therapy (OR = 0.76, 95%CI was 0.53-0.95, P = 0.023), tracheotomy (OR = 0.20, 95%CI was 0.07-0.53, P < 0.001), continuous renal replacement therapy (CRRT; OR = 0.32, 95%CI was 0.15-0.70, P < 0.001), cerebrovascular disease (OR = 0.31, 95%CI was 0.16-0.60, P < 0.001), rheumatic disease (OR = 0.44, 95%CI was 0.19-0.99, P < 0.001), male (OR = 0.68, 95%CI was 0.54-0.86, P = 0.001), and maximum anion gap (AG; OR = 0.95, 95%CI was 0.93-0.97, P < 0.001) were associated with an decreased probability of SAE, and age (OR = 1.05, 95%CI was 1.03-1.06, P < 0.001), acute physiology score III (APSIII; OR = 1.02, 95%CI was 1.01-1.02, P < 0.001), Oxford acute severity of illness score (OASIS; OR = 1.04, 95%CI was 1.03-1.06, P < 0.001), and length of hospital stay (OR = 1.01, 95%CI was 1.01-1.02, P < 0.001) were associated with an increased probability of SAE. A nomogram model was constructed based on these variables. In the validation set, ROC curve analysis showed that the model achieved an area under the ROC curve (AUC) of 0.723, and the calibration curve showed good consistency between the predicted probability of the model and the observed probability. Among the machine learning algorithms, including MLP, SVM, NB, GBM, RF, and XGB, the SVM model and RF model demonstrated relatively good predictive performance, with AUC of 0.748 and 0.739, respectively, and the sensitivity was both exceeding 85%. The predictive performance of the XGB model was explained through SHAP analysis, and the results indicated that APSIII score (SHAP value was 0.871), age (SHAP value was 0.521), and OASIS score (SHAP value was 0.443) were important factors affecting the predictive performance of the model. CONCLUSIONS The machine learning-based SAE prediction model exhibits good predictive capability and holds significant application value for the early identification of SAE risk in elderly septic patients.
Humans ; Machine Learning ; Aged ; Sepsis-Associated Encephalopathy ; Sepsis/complications* ; Intensive Care Units ; Logistic Models ; Middle Aged ; Male ; ROC Curve ; Female ; Bayes Theorem ; Nomograms ; Support Vector Machine ; Algorithms

BACKGROUND:The pathogenesis of autoimmune hepatitis has not been clearly elucidated.Circular RNA(CircRNA)is a research hotspot in the field of RNA and is involved in the pathogenesis of many autoimmune diseases.However,the role of CircRNA in autoimmune hepatitis remains unclear. OBJECTIVE:To investigate the relationship between CircRNA(CircRNA)and concanavalin A induced liver injury in mice with autoimmune hepatitis. METHODS:Bioinformatics analysis was performed on CircRNA profiles selected by previous microarray technology,including gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,so as to explore the potential biological functions of these differentially expressed genes.Twelve C57BL/6 mice were randomized into normal group and model group(n=6 per group).Autoimmune hepatitis model was established by tail vein injection of concanavalin A in the model group.Mice were killed at 12 hours after modeling to extract mouse liver and peripheral blood.The expression levels of CircRNAs were verified by qRT-PCR.Serum alanine aminotransferase and aspartate aminotransferase levels were detected by colorimetric method.The levels of oxidative stress indexes malondialdehyde and nitric oxide in mouse liver were detected by microplate method.The correlation between oxidative stress level and liver injury index was analyzed. RESULTS AND CONCLUSION:The results of GO analysis showed that the target genes with up-regulated CircRNAs expression were mainly involved in the biological processes of SNARE complex assembly regulation(P=0.004),their molecular functions were mainly metal ion binding(P=0.000 29),and the cell components were mainly enriched in CORVET complex(P=0.075).The biological processes involved in the down-regulated circRNAs target genes were mainly"negative regulation of pancreatic secretion"(P=0.000 42),the molecular functions were mainly"transcriptional activator activity"(P=0.025),and the cell components were mainly enriched in"extracellular components"(P=0.006).KEGG results showed that the target genes with up-regulated CircRNAs expression were mainly enriched in the"base excision-repair"signaling pathways(P=0.026).Compared with the normal group,serum alanine aminotransferase and aspartate aminotransferase levels and the levels of malondialdehyde and nitric oxide in mouse liver in the model group were significantly increased(P＜0.01).Compared with the normal group,the expression of two selected CircRNAs(mmu-circ-0001520 and mmu-circ-0001577)was increased in the model group(P＜0.05).Spearman correlation analysis showed that the expression of mmu-circ-0001520 and mmu-circ-0001577 was positively correlated with alanine aminotransferase,aspartate aminotransferase,malondialdehyde and nitric oxide.To conclude,the differential expression of CircRNAs is correlated with liver injury in autoimmune hepatitis mice.mmu-circ-0001520 and mmu-circ-0001577 are expected to be diagnostic biomarkers and therapeutic targets for autoimmune hepatitis.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

To revise GBZ 188 Technical Specification for Occupational Health Surveillance based on national laws, regulations, standards, specifications and legal documents of occupational disease, and combination with the actual situation in China. The main modifications are as follows: the occupational health surveillance for workers exposed to toluene (xylene may implement by reference), bromopropane, methyl iodide, ethylene oxide, chloroacetic acid, indium and its compounds, coal tar, coal tarasphalt, asphalt, β-naphthylamine, dust of metal and its compounds(tin, iron, antimony, barium and its compounds), hard metal dust, erionite dust, low temperature, laser, tick-borne encephalitis virus, Borrelia burgdorferi, and human immunodeficiency virus, for scraper or grind operators, and underground workers using squatting or kneeling position, crawling position, side-lying position, or shoulder position for a long period of time are included. The emergency health screening for workers exposed to arsenic, fluorine and its inorganic compounds, and acrylamide are included. The occupational medical examination (OME) for workers exposed to amino and nitro compounds of benzene, phosgene, monomethylamine, organic fluorine and dimethyl sulfate has been adjusted and made mandatory, with corresponding assessments required upon leaving the job. The special occupational health surveillance for workers exposed to mycobacterium tuberculosis and hepatitis virus is removed. The OME conclusion of reexamination is removed, and standardize recheck/additional inspection requirements. The optional items in OME performed before, during and after leaving post are removed, but the optional items in emergency medical examination are retained. Additional OME items are added. The Guideline for OME Summary Reports is added as informative appendix, and so on. The revised GBZ 188 Technical Specification for Occupational Health Surveillance is more scientific and practical.

ObjectiveTo investigate the effect of Zhizi Dahuang decoction （ZZDHT） in the treatment of alcoholic liver disease （ALD） by improving oxidative stress in hepatic neutrophils. MethodsNetwork pharmacology was used to obtain the chemical components of ZZDHT and their corresponding action targets and analyze the potential targets and functional pathways of ZZDHT in the treatment of ALD. The non-target metabolomics technology was used to observe the changes in the metabolites of ZZDHT in mouse serum and liver. The mice were given ZZDHT at a dose twice as much as the middle dose concentration by gavage， and serum and liver samples were collected at six time points after gavage （10 minutes， 30 minutes， 1 hour， 2 hours， 4 hours， and 6 hours） and were then mixed for mass spectrometry （administration group with 18 mice）， while the 18 mice in the control group were given an equal volume of normal saline by gavage. Ultra-performance liquid chromatography was used for rapid isolation and identification of the metabolites of ZZDHT in serum and liver tissue， and the effective constituents of ZZDHT were validated. Male C57BL/6J mice， aged 8 weeks， were randomly and equally divided into control group， model group， and low-， middle-， and high-dose ZZDHT groups， with 10 mice in each group. All mice except those in the control group were used to establish a mouse model of ALD （NIAAA model mice）， and at the same time， the mice in the administration groups were given low-， middle-， and high-dose ZZDHT by gavage， while those in the control group and the model group were given an equal volume of normal saline by gavage. The serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and triglyceride （TG） were measured； PCR was used to measure the gene expression levels of related inflammation， oxidative stress， and neutrophil indicators in the liver； ELISA was used to measure the levels of related inflammation and oxidative stress indicators in serum； superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， and malondialdehyde （MDA） were measured to observe the level of oxidative stress in the liver； HE staining， myeloperoxidase staining， and oil red staining were used to observe liver injury， neutrophil infiltration， and lipid deposition. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsA total of 53 active components and 227 target genes were obtained for ZZDHT， and there were 8685 target genes of ALD， resulting in 222 common target genes between these two groups of genes. Core pathways included the interleukin-6 signaling pathway and the TNF signaling pathway. The non-targeted metabolic analysis of ZZDHT obtained 225 metabolites in mouse liver and 227 metabolites in serum， among which there were 126 common metabolites. The core pathways of liver metabolites included glycerolipid metabolism and inflammatory mediator regulation of TRP channels， and the core pathways of serum metabolites included the AMPK signaling pathway and oxidative phosphorylation， all of which were associated with oxidative stress- and inflammation-related pathways. Compared with the model group， the low-， middle-， and high-dose ZZDHT groups had significant reductions in the serum levels of ALT， AST， and TG （all P<0.05）， and the middle-dose ZZDHT group had significant reductions in the levels of Ly6g， Ncf1， Ncf2， IL-6， TNF-α， IL-1β， MDA， 4-HNE， Gp91， and P22 in the liver （all P<0.05）， a significant increase in the level of SOD （P<0.05）， a significant reduction in the serum level of 4-HNE （P<0.05）， and a significant increase in the level of GSH-Px （P<0.05）. There were significant improvements in fat deposition and neutrophil infiltration in the liver of mice in the middle-dose ZZDHT group （both P<0.05）. ConclusionZZDHT significantly reduces oxidative stress and inflammatory response in NIAAA model mice.

The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized three-dimensional (3D) chromatin architecture and dynamics remains poorly understood. Here by combining imaging and sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to detachment of lamina-associated domains (LADs) from the nuclear periphery accompanied with global chromatin redistribution and decompaction. Consequently, the inter-chromosomal as well as inter-compartment interactions are increased, but the structure of topologically associating domains (TADs) is not affected. Using live-cell genomic loci tracking, we further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nucleoplasm. Taken together, our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance, chromatin compaction, genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics, supporting their crucial roles in chromatin higher-order structure and chromatin dynamics.
Chromatin ; Chromosomes ; Genome ; Humans ; Lamin Type B/genetics*

Adaptation, Psychological ; Adolescent ; COVID-19 ; Child ; China ; Cross-Sectional Studies ; Female ; Humans ; Male ; SARS-CoV-2

ObjectiveTo investigate the changes and potential effects of differentially expressed microRNAs (miRNAs) in the development and progression of liver injury in a mouse model of autoimmune hepatitis (AIH) induced by concanavalin A (ConA). MethodsEight healthy male specific pathogen-free C57BL/6 mice were randomly divided into model group and control group, with four mice in each group. The mice in the model group were given tail vein injection of ConA 15 mg/kg, and those in the control group were given an equal volume of normal saline. All mice were sacrificed after 8 hours of modeling, Total RNA in liver tissue was extracted, gene microarray was used to screen out differentially expressed miRNAs, and target prediction and function analysis were performed for upregulated and downregulated miRNAs. The independent samples t-test was used for comparison of differentially expressed miRNAs between two groups. ResultsThe principal component analysis showed that the inter-group difference of the data extracted by gene microarray met the conditions for further analysis. Compared with the control group, the model group had 31 upregulated miRNAs and 18 downregulated miRNAs in mouse liver, which had a regulatory relationship with 959 target genes (601 upregulated genes and 358 downregulated genes). GO analysis showed that in the model group, the target genes of the upregulated miRNAs mainly had the molecular functions such as “DNA binding” (P=1.47×10-6), participated in the biological processes such as “transcription, DNA-templated” (P=2.36×10-7), and were mainly enriched in the cellular components such as “neuronal cell body” (P=5.99×10-6), while the target genes of the downregulated miRNAs had the molecular functions such as “RNA polymerase II proximal promoter sequence-specific DNA binding” (P=2.49×10-6), participated in the biological processes such as “regulation of transcription, DNA-templated” (P=1.64×10-11), and were mainly enriched in the cellular components such as “nucleoplasm” (P=4.30×10-10). KEGG pathway enrichment analysis showed that the target genes of the upregulated miRNAs were mainly enriched in “Endocytosis” (P=0.000 4), while the target genes of the downregulated miRNAs were mainly enriched in the “Hippo signaling pathway” (P=0.004), and the above functional analysis results were statistically significant (P＜0.05). ConclusionThere are differentially expressed miRNAs in the pathogenesis of AIH, and these differentially expressed miRNAs can provide new targets for the clinical treatment of AIH.

Waldenström macroglobulinemia (WM) is a rare lymphoma without a curable treatment method, which is characterized by MYD88 and CXCR4 gene mutations. The study on clinical manifestations, the pathological and genomic features has led to a series of promising clinical protocols. This article reviews the safety and efficacy of drugs including alkylating agents, proteasome inhibitors, monoclonal antibodies, and Bruton tyrosine kinase (BTK) inhibitors in WM patients combined with the latest research of the individualized treatment for WM at the 59th American Society of Hematology (ASH) Annual Meeting, so as to analyze the feasibility of basic genomic treatment and current integrated regimens for WM.

Splenic marginal zone lymphoma (SMZL) and nodal marginal zone lymphoma (NMZL) are rare indolent chronic B-cell lymphomas. Clinical research has made a great progress thanks to the developments of genomic studies and a large number of overlapping mutational profiles involving NOTCH, BCR and nuclear factor κB (NF-κB) signaling, chromatin remodeling, and the cytoskeleton. This paper reviews the recent progress of biological characteristics and treatment progress of SMZL and NMZL in indolent lymphoma combined with the 59th American Society of Hematology (ASH) Annual Meeting.