To analyze the disease burden of acute lymphoid leukemia(ALL) and its changing trends in China and globally from 1990 to 2021, aiming to provide a theoretical basis for disease prevention, treatment, and policy formulation.

To analyze the disease burden and trends of motor neuron disease(MND) in China and globally from 1990 to 2021, providing evidence for the formulation of relevant health strategies inChina.

Aim To explore the relationship between serum levels of proprotein convertase subtilisin/kexin type 9(PCSK9),macrophage migration inhibitory factor(MIF)and the severity of coronary artery lesions in patients with coro-nary heart disease(CHD).Methods A cross-sectional study was conducted involving 139 patients with CHD and 69 control subjects who underwent coronary angiography during the same period,all of whom were admitted to the People's Hospital of Xinjiang Uygur Autonomous Region from November 2023 to May 2024.Clinical data and coronary angiography results were collected,and the severity of coronary artery stenosis was quantitatively assessed using the Gensini score.Pa-tients with the Gensini scores＞0 were classified into three groups based on tertiles:the mild stenosis group(1～18 points,54 cases),the moderate stenosis group(19～36 points,54 cases),and the severe stenosis group(＞36 points,54 ca-ses).Serum levels of PCSK9 and MIF were measured by ELISA kit.Results Serum levels of PCSK9 and MIF were significantly higher in the CHD group than those in the control group(P＜0.05).Multivariable Logistic regression analy-sis revealed that high levels of serum PCSK9 and MIF were independent risk factors for CHD.Spearman correlation analy-sis showed that serum PCSK9 and MIF levels were positively correlated with Gensini score(rs=0.619 6 and r,=0.411 4,both P＜0.001).Further subgroup analysis showed that serum total cholesterol and low density lipoprotein cholesterol lev-els were significantly increased in patients with high-level PCSK9,while patients with high-level MIF had higher inflamma-tory coefficients such as systemic inflammatory response index(SIRI)and systemic immune-inflammation index(SII)(all P＜0.05).Conclusion Serum levels of PCSK9 and MIF are positively correlated with the severity of coronary artery stenosis.High levels of serum PCSK9 and MIF are independent risk factors for CHD.

Objective Jiangtang Tiaozhi Formula(JTTZF)is highly effective in improving glycolipid metabolism disorder.However,its exact mechanism of action has not been fully elucidated.This study aims to explore the potential targets and mechanisms of JTTZF in improving glycolipid metabolism disorder through network pharmacology,molecular docking,molecular dynamics simulations,and experimental validation.Methods Glycolipid metabolism disorder-related targets were obtained from the GeneCards database,while the relevant action targets of the main active ingredients of JTTZF were obtained from the CTD and SwissTargetPrediction databases.Protein-protein interaction(PPI)networks were constructed using STRING and Cytoscape.After selecting the potential key targets,Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were conducted through the Metascape database,and a network map of"herb-active ingredient-target-pathway"was constructed.Molecular docking was carried out using AutoDock vina and PyMOL software to verify the correlation between the main components of JTTZF and the core targets.Molecular dynamics simulation was conducted for optimal core protein-compound complexes obtained by molecular docking.A mouse glycolipid metabolism disorder model was established,and the results of network pharmacology were verified by in vivo experiments.Results Topological analysis of the PPI network revealed ten core targets,including TNF,CTNNB1,AKT1,NF-κB1,ESR1,FN1,TP53,IL-1β,IL-6,and EGFR.GO functional enrichment analysis showed that these targets were mainly related to signal transduction and transcriptional regulation.KEGG pathway analysis showed that these targets were related to lipid and atherosclerosis pathway.Molecular docking results reported that the core active ingredient of JTTZF has a certain binding affinity with AKT1,FN1,and IL-6.Molecular dynamics simulations revealed good binding ability between lovastatin,coptisine,salvianolic acid B,and AKT1.Animal experiments showed that JTTZF may reduce blood glucose and blood lipid levels and improve glycolipid metabolism disorder by down-regulating the expression of AKT1,TP53,and inflammatory regulators in lipid and atherosclerotic pathway,inhibiting the expression of FN1 and EGFR,and increasing the expression of CTNNB1 and ESR1.Conclusion JTTZF participates in the regulation of lipid and atherosclerotic pathway,and comprehensively regulates glucose and lipid metabolism and improves atherosclerotic lesions,thereby preventing and treating the occurrence and development of glycolipid metabolism disorder and its complications.

Objective:To understand the incidence trend of brucellosis over time in Shandong Province from 2004 to 2023, and provide evidence for the prevention and control of brucellosis.Methods:The incidence data of brucellosis in Shandong from 2004 to 2023 were collected from China Disease Prevention and Control Information System. The annual change percentage (APC) and annual average change percentage (AAPC) of the incidence rate were calculated by using Joinpoint regression model. A age-period-cohort model was used to analyze changes in brucellosis incidence with age, period, and birth cohort.Results:The average annual incidence of brucellosis was 1.76/100 000 in Shandong from 2004 to 2023. The Joinpoint regression analysis results showed that the reported incidence of brucellosis increased by an average of 92.0% and 18.9% each year from 2004 to 2010 and from 2010 to 2014, respectively, and decreased by an average of 0.2% each year from 2014 to 2023. The results of APC model showed that the incidence of brucellosis increased first and then decreased with age ( χ2=176.92, P<0.001), and incidence of brucellosis showed slow increase and rapid increase first, then decrease ( χ2=2 921.03, P<0.001) over time. The risk for brucellosis reached peak in 2016 ( RR=5.29, 95% CI: 4.96-5.65) and became the lowest in 2006 ( RR=0.24, 95% CI: 0.21-0.28). The incidence increased in later birth cohort ( χ2=348.88, P<0.001), the AAPCs of all the age groups were between 15.0% and 40.0%, and the older the age, the greater the risk ( χ2=348.77, P<0.001). Conclusions:From 2004 to 2023, the reported incidence of brucellosis in Shandong showed a significant age-period-cohort effect, which increased first and then decreased, first increased and then decreased with age, increased slowly and rapidly first, then decreased over time, and increased in later birth cohort. It is necessary to conduct targeted prevention and control, health education to reduce the risk for brucellosis.

Objective:To investigate the drug resistance gene characteristics, plasmid characteristics and genome tracing of Shigella sonnei causing a bacillary dysentery outbreak in Shandong Province. Methods:Sixty-five Shigella sonnei strains isolated from a 2021 outbreak in a county of Shandong Province were analyzed using antimicrobial susceptibility testing, whole genome sequencing (WGS), characterization of resistance and virulence genes, plasmid profiling, core genome multilocus sequence typing (cgMLST), and single nucleotide polymorphism (SNP) analysis. Results:All isolates had the same resistance phenotype and genotypes and were multidrug-resistant ESBL-producing Shigella sonnei, carrying important virulence genes. Plasmid analysis revealed a conserved genetic arrangement, pil( M/ N/ O2/ P)-tra( F/ H/ J/ K/ N/ O/ P/ Q)-IS Ecp1- blaCTX-M-14-Tn 903- yub( J/ I/ F/ G/ E/ D), and shared across strains from diverse regions and bacterial species. The cgMLST and SNP analyses demonstrated concordant clustering, with all 65 outbreak-related strains forming a single cluster alongside human-derived strains from Guangxi. Conclusion:The ESBL-producing Shigella sonnei responsible for the outbreak shares a homologous relationship with Guangxi human-derived strains, and the detected resistance plasmids and virulence genes underscore the need to strengthen drug resistance surveillance and genome tracing.

Objective:To understand the incidence trend of brucellosis over time in Shandong Province from 2004 to 2023, and provide evidence for the prevention and control of brucellosis.Methods:The incidence data of brucellosis in Shandong from 2004 to 2023 were collected from China Disease Prevention and Control Information System. The annual change percentage (APC) and annual average change percentage (AAPC) of the incidence rate were calculated by using Joinpoint regression model. A age-period-cohort model was used to analyze changes in brucellosis incidence with age, period, and birth cohort.Results:The average annual incidence of brucellosis was 1.76/100 000 in Shandong from 2004 to 2023. The Joinpoint regression analysis results showed that the reported incidence of brucellosis increased by an average of 92.0% and 18.9% each year from 2004 to 2010 and from 2010 to 2014, respectively, and decreased by an average of 0.2% each year from 2014 to 2023. The results of APC model showed that the incidence of brucellosis increased first and then decreased with age ( χ2=176.92, P<0.001), and incidence of brucellosis showed slow increase and rapid increase first, then decrease ( χ2=2 921.03, P<0.001) over time. The risk for brucellosis reached peak in 2016 ( RR=5.29, 95% CI: 4.96-5.65) and became the lowest in 2006 ( RR=0.24, 95% CI: 0.21-0.28). The incidence increased in later birth cohort ( χ2=348.88, P<0.001), the AAPCs of all the age groups were between 15.0% and 40.0%, and the older the age, the greater the risk ( χ2=348.77, P<0.001). Conclusions:From 2004 to 2023, the reported incidence of brucellosis in Shandong showed a significant age-period-cohort effect, which increased first and then decreased, first increased and then decreased with age, increased slowly and rapidly first, then decreased over time, and increased in later birth cohort. It is necessary to conduct targeted prevention and control, health education to reduce the risk for brucellosis.

Objective:To investigate the drug resistance gene characteristics, plasmid characteristics and genome tracing of Shigella sonnei causing a bacillary dysentery outbreak in Shandong Province. Methods:Sixty-five Shigella sonnei strains isolated from a 2021 outbreak in a county of Shandong Province were analyzed using antimicrobial susceptibility testing, whole genome sequencing (WGS), characterization of resistance and virulence genes, plasmid profiling, core genome multilocus sequence typing (cgMLST), and single nucleotide polymorphism (SNP) analysis. Results:All isolates had the same resistance phenotype and genotypes and were multidrug-resistant ESBL-producing Shigella sonnei, carrying important virulence genes. Plasmid analysis revealed a conserved genetic arrangement, pil( M/ N/ O2/ P)-tra( F/ H/ J/ K/ N/ O/ P/ Q)-IS Ecp1- blaCTX-M-14-Tn 903- yub( J/ I/ F/ G/ E/ D), and shared across strains from diverse regions and bacterial species. The cgMLST and SNP analyses demonstrated concordant clustering, with all 65 outbreak-related strains forming a single cluster alongside human-derived strains from Guangxi. Conclusion:The ESBL-producing Shigella sonnei responsible for the outbreak shares a homologous relationship with Guangxi human-derived strains, and the detected resistance plasmids and virulence genes underscore the need to strengthen drug resistance surveillance and genome tracing.

Aim To explore the relationship between serum levels of proprotein convertase subtilisin/kexin type 9(PCSK9),macrophage migration inhibitory factor(MIF)and the severity of coronary artery lesions in patients with coro-nary heart disease(CHD).Methods A cross-sectional study was conducted involving 139 patients with CHD and 69 control subjects who underwent coronary angiography during the same period,all of whom were admitted to the People's Hospital of Xinjiang Uygur Autonomous Region from November 2023 to May 2024.Clinical data and coronary angiography results were collected,and the severity of coronary artery stenosis was quantitatively assessed using the Gensini score.Pa-tients with the Gensini scores＞0 were classified into three groups based on tertiles:the mild stenosis group(1～18 points,54 cases),the moderate stenosis group(19～36 points,54 cases),and the severe stenosis group(＞36 points,54 ca-ses).Serum levels of PCSK9 and MIF were measured by ELISA kit.Results Serum levels of PCSK9 and MIF were significantly higher in the CHD group than those in the control group(P＜0.05).Multivariable Logistic regression analy-sis revealed that high levels of serum PCSK9 and MIF were independent risk factors for CHD.Spearman correlation analy-sis showed that serum PCSK9 and MIF levels were positively correlated with Gensini score(rs=0.619 6 and r,=0.411 4,both P＜0.001).Further subgroup analysis showed that serum total cholesterol and low density lipoprotein cholesterol lev-els were significantly increased in patients with high-level PCSK9,while patients with high-level MIF had higher inflamma-tory coefficients such as systemic inflammatory response index(SIRI)and systemic immune-inflammation index(SII)(all P＜0.05).Conclusion Serum levels of PCSK9 and MIF are positively correlated with the severity of coronary artery stenosis.High levels of serum PCSK9 and MIF are independent risk factors for CHD.

Objective Jiangtang Tiaozhi Formula(JTTZF)is highly effective in improving glycolipid metabolism disorder.However,its exact mechanism of action has not been fully elucidated.This study aims to explore the potential targets and mechanisms of JTTZF in improving glycolipid metabolism disorder through network pharmacology,molecular docking,molecular dynamics simulations,and experimental validation.Methods Glycolipid metabolism disorder-related targets were obtained from the GeneCards database,while the relevant action targets of the main active ingredients of JTTZF were obtained from the CTD and SwissTargetPrediction databases.Protein-protein interaction(PPI)networks were constructed using STRING and Cytoscape.After selecting the potential key targets,Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were conducted through the Metascape database,and a network map of"herb-active ingredient-target-pathway"was constructed.Molecular docking was carried out using AutoDock vina and PyMOL software to verify the correlation between the main components of JTTZF and the core targets.Molecular dynamics simulation was conducted for optimal core protein-compound complexes obtained by molecular docking.A mouse glycolipid metabolism disorder model was established,and the results of network pharmacology were verified by in vivo experiments.Results Topological analysis of the PPI network revealed ten core targets,including TNF,CTNNB1,AKT1,NF-κB1,ESR1,FN1,TP53,IL-1β,IL-6,and EGFR.GO functional enrichment analysis showed that these targets were mainly related to signal transduction and transcriptional regulation.KEGG pathway analysis showed that these targets were related to lipid and atherosclerosis pathway.Molecular docking results reported that the core active ingredient of JTTZF has a certain binding affinity with AKT1,FN1,and IL-6.Molecular dynamics simulations revealed good binding ability between lovastatin,coptisine,salvianolic acid B,and AKT1.Animal experiments showed that JTTZF may reduce blood glucose and blood lipid levels and improve glycolipid metabolism disorder by down-regulating the expression of AKT1,TP53,and inflammatory regulators in lipid and atherosclerotic pathway,inhibiting the expression of FN1 and EGFR,and increasing the expression of CTNNB1 and ESR1.Conclusion JTTZF participates in the regulation of lipid and atherosclerotic pathway,and comprehensively regulates glucose and lipid metabolism and improves atherosclerotic lesions,thereby preventing and treating the occurrence and development of glycolipid metabolism disorder and its complications.