Objective To understand the respiratory pathogen infection of acute fever and respiratory symptoms in a hospital in Jinan City,explore its epidemiological characteristics,and provide reference for the scientific diagnosis and treatment of acute respiratory infection in this region.Methods Patients who underwent respiratory pathogen IgM antibody detection at Shandong Provincial Hospital Affiliated to Shandong First Medical University from Janu-ary 2018 to June 2024 were selected as the research subjects.IgM antibody detection was performed on 9 common respiratory pathogens by magnetic particle chemiluminescence method.Pathogen detection of patients stratified by genders,age,season,and years was analyzed.Results A total of 19 463 patients were included in the analysis,out of which 6 933 patients were detected with at least one kind of pathogen,accounting for 35.62％.The top three pathogens with high detection rates were Mycoplasma pneumoniae(MP),influenza B virus(FluB),and influenza A virus(FluA),with detection rates of 17.14％,13.62％,and 4.58％,respectively.The detection rates of single and multiple pathogens were 28.57％and 7.05％,respectively.The detection rate of females was higher than that of males(38.02％ vs 33.78％),with statistically significant difference(P＜0.001).With the increase of age,the total detection of respiratory pathogens first decreased,then increased.Detection rate of respiratory pathogens was highest in winter(41.59％)and lowest in autumn(31.23％).The total detection rate decreased year by year.Conclusion Respiratory pathogen infection in this region is mainly caused by MP and FluB,with minors being the high-risk population and winter being the peak season.In recent years,the detection rate has been decreasing year by year.Effort should be made to strengthen the prevention and treatment of high-risk populations during the peak season,so as to avoid large-scale regional epidemics.

Objective To investigate the relationship between serum microRNA-30a-5p(miR-30a-5p),Runt-associated transcription factor 2(RUNX2)and the severity and prognosis of patients with sepsis-induced acute lung injury(ALI).Methods A total of 193 patients with sepsis-induced ALI(ALI group)and 54 pa-tients with simple sepsis(non-ALI group)admitted to the Fifth Affiliated Hospital of Xinjiang Medical Uni-versity from January 2021 to February 2024 were selected,and the patients with sepsis-induced ALI were di-vided into a mild ALI group(57 cases),a moderate ALI group(64 cases),and a severe ALI group(72 cases)according to the oxygenation index,and were divided into a death group(71 cases)and a survival group(122 cases)according to the 28 day prognosis situation.Serum miR-30a-5p level was detected by real time fluores-cent quantitative PCR,serum RUNX2 level was detected by enzyme-linked immunosorbent assay,and the binding sites of miR-30a-5p and RUNX2 were predicted by online database.Pearson's correlation coefficient was used to analyze the correlation between miR-30a-5p and RUNX2 in patients with sepsis-induced ALI,and Spearman's correlation coefficient was used to analyze the correlation between serum miR-30a-5p,RUNX2 levels and oxygenation index in patients with sepsis-induced ALI.With the prognosis of patients with sepsis-induced ALI as the dependent variable,multivariate unconditional Logistic regression was used to determine their influencing factors,and receiver operating characteristic curve was plotted to evaluate the prognostic val-ue of serum miR-30a-5p and RUNX2 levels in patients with sepsis-induced ALI.Results Compared with the non-ALI group,serum miR-30a-5p level was lower and RUNX2 level was higher in the ALI group(t=-11.749,11.691,P＜0.001).There was a binding site between miR-30a-5p and RUNX2 at the 3'-untranslat-ed region 3 348-3 354.miR-30a-5p was negatively correlated with RUNX2 in patients with sepsis-induced ALI(r=-0.759,P＜0.001).The level of serum miR-30a-5p increased in the severe ALI group,the moderate ALI group and the mild ALI group in turn(P＜0.001),and the level of RUNX2 decreased in the severe ALI group,the moderate ALI group and the mild ALI group in turn(P＜0.001).Oxygenation index was negative-ly correlated with serum miR-30a-5p level(r=-0.749,P＜0.001),and positively correlated with RUNX2 level in patients with sepsis-induced ALI(r=0.723,P＜0.001).Independent protective factors for death in patients with sepsis-induced ALI were increased oxygenation index(OR=0.988,95％CI:0.981-0.996,P＜0.05),elevated miR-30a-5p(OR=0.814,95％CI:0.744-0.892,P＜0.05),and independent risk factors were increased Sequential Organ Failure Assessment(SOFA)score(OR=1.391,95％CI:1.116-1.734,P＜0.05),elevated blood lactate(OR=1.824,95％CI:1.211-2.748,P＜0.05),and elevated RUNX2(OR=1.366,95％CI:1.170-1.595,P＜0.05).The area under the curve of serum miR-30a-5p and RUNX2 levels combined to predict the death in patients with sepsis-induced ALI was 0.895(95％CI:0.842-0.934),which was greater than 0.788(95％CI:0.724-0.844)of serum miR-30a-5p and 0.786(95％CI:0.721-0.842)of RUNX2 levels alone(Z=4.015,3.746,P＜0.001).Conclusion Increased miR-30a-5p level and decreased RUNX2 level are associated with the aggravation of the disease and the increased risk of death in patients with sepsis-induced ALI.The combination of serum miR-30a-5p and RUNX2 levels has relatively high value in pre-dicting the prognosis of patients with sepsis-induced ALI.

Objective To analyze the nonlinear relationship between hypothermic machine perfusion (HMP) parameters and delayed graft function (DGF) and optimize the construction of a predictive model for DGF. Methods The data of 923 recipients who underwent kidney transplantation from deceased donors were retrospectively analyzed. According to the occurrence of DGF, the recipients were divided into DGF group (n=823) and non-DGF group (n=100). Donor data, HMP parameters and recipient data were analyzed for both groups. The nonlinear relationship between HMP parameters and the occurrence of DGF was explored based on restricted cubic splines (RCS). Over-sampling, under-sampling and balanced sampling were used to address the imbalance in the proportion of DGF to construct logistic regression predictive models. The area under the curve (AUC) of each model was compared in the validation set, and a nomogram model was constructed. Results Donor BMI, cold ischemia time of the donor kidney, and HMP parameters (initial and final pressures, resistance, and perfusion time) were significantly different between the DGF and non-DGF groups (all P<0.05). The RCS analysis revealed a threshold-like nonlinear relationship between HMP parameters and the risk of DGF. Among the models constructed using different sampling methods, the balanced sampling model had the highest AUC. Using this model, a nomogram was constructed to stratify recipients based on risk scores. Recipients in the high-risk group had higher serum creatinine levels at 1, 6, and 12 months after kidney transplantation compared to those in the low-risk group (all P<0.05). Conclusions There is a nonlinear relationship between HMP parameters and the risk of DGF, and the threshold is helpful for organ quality assessment and monitoring of graft function after transplantation. The predictive model for DGF constructed on the base of balanced sampling algorithms helps perioperative decision-making and postoperative graft function monitoring of kidney transplantation.

Objective To investigate whether evodiamine(EVO)can alleviate liver injury in septic rats by influencing the nucleo-tide-binding and oligomerization domain(NOD)-like receptor protein 3(NLRP3)/interleukin-1 β(IL-1β)/caspase-1 signaling pathway.Methods A rat model of sepsis-induced liver damage was constructed,and the successfully modeled rats were assigned to the model,L-EVO,M-EVO,H-EVO(administered orally at 4,8,and 16 mg/kg of EVO),and H-EVO+NLRP3(administered orally at 16 mg/kg of EVO+intraperitoneal injection of 1 mg/kg of NLRP3 signaling pathway activator sodium salt)groups,each with ten rats.In addition,ten normal rats were selected as the control group(that is,the sham surgery group,without ligation or puncture,using the same steps as for the model group).The control and model groups were administered with equal amounts of physiological saline once daily for 28 d,consecutively.A reagent kit was used to assess rat liver function.Hematoxylin and eosin(HE)staining was used to analyze pathological changes in the liver tissue.Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)staining was used to assess apoptosis in liver tissue cells.ELISA was used to analyze IL-6,tumor necrosis factor α(TNF-α),and IL-1β levels in serum.Western blotting was used to detect changes in protein expression of the NLRP3/IL-1β/caspase-1 signaling pathway components in liver tissues.Results For the control group,the liver tissues of rats in the model group lost their normal structure,with an uneven distribution of liver cells accompanied by edema and vacuoles.For the model group,the L-EVO,M-EVO,and H-EVO groups exhibited a relatively neat arrangement of liver tissue cells,reduced edema,and vacuoles.As the dose increased,the morphology of liver tissue cells recovered significantly.For the H-EVO group,the H-EVO+NLRP3 group exhibited a disordered arrangement of liver tissue cells with edema and vacuoles.For the control group,the model group showed increased alanine aminotransferase(ALT),aspartate aminotransferase(AST),liver tissue cell apoptosis rate,serum IL-6,TNF-α,and IL-1β levels,and expression of NLRP,IL-1β,and caspase-1 protein in the liver tissue(P＜0.05).For the model group,the L-EVO,M-EVO,and H-EVO groups showed lower ALT,AST,liver tissue cell apoptosis rate,serum IL-6,TNF-α,and IL-1β levels,and expression of NLRP,IL-1β,and caspase-1 protein in the liver tissue(P＜0.05).For the H-EVO group,the H-EVO+NLRP3 group had higher ALT,AST,liver tissue cell apoptosis rate,serum IL-6,TNF-α,and IL-1β levels,and expression of NLRP,IL-1β,and caspase-1 pro-tein in the liver tissue(P＜0.05).Conclusion EVO can alleviate liver injury in septic rats by influencing the NLRP3/IL-1β/caspase-1 signaling pathway.

Objective To understand the respiratory pathogen infection of acute fever and respiratory symptoms in a hospital in Jinan City,explore its epidemiological characteristics,and provide reference for the scientific diagnosis and treatment of acute respiratory infection in this region.Methods Patients who underwent respiratory pathogen IgM antibody detection at Shandong Provincial Hospital Affiliated to Shandong First Medical University from Janu-ary 2018 to June 2024 were selected as the research subjects.IgM antibody detection was performed on 9 common respiratory pathogens by magnetic particle chemiluminescence method.Pathogen detection of patients stratified by genders,age,season,and years was analyzed.Results A total of 19 463 patients were included in the analysis,out of which 6 933 patients were detected with at least one kind of pathogen,accounting for 35.62％.The top three pathogens with high detection rates were Mycoplasma pneumoniae(MP),influenza B virus(FluB),and influenza A virus(FluA),with detection rates of 17.14％,13.62％,and 4.58％,respectively.The detection rates of single and multiple pathogens were 28.57％and 7.05％,respectively.The detection rate of females was higher than that of males(38.02％ vs 33.78％),with statistically significant difference(P＜0.001).With the increase of age,the total detection of respiratory pathogens first decreased,then increased.Detection rate of respiratory pathogens was highest in winter(41.59％)and lowest in autumn(31.23％).The total detection rate decreased year by year.Conclusion Respiratory pathogen infection in this region is mainly caused by MP and FluB,with minors being the high-risk population and winter being the peak season.In recent years,the detection rate has been decreasing year by year.Effort should be made to strengthen the prevention and treatment of high-risk populations during the peak season,so as to avoid large-scale regional epidemics.

Objective To investigate whether evodiamine(EVO)can alleviate liver injury in septic rats by influencing the nucleo-tide-binding and oligomerization domain(NOD)-like receptor protein 3(NLRP3)/interleukin-1 β(IL-1β)/caspase-1 signaling pathway.Methods A rat model of sepsis-induced liver damage was constructed,and the successfully modeled rats were assigned to the model,L-EVO,M-EVO,H-EVO(administered orally at 4,8,and 16 mg/kg of EVO),and H-EVO+NLRP3(administered orally at 16 mg/kg of EVO+intraperitoneal injection of 1 mg/kg of NLRP3 signaling pathway activator sodium salt)groups,each with ten rats.In addition,ten normal rats were selected as the control group(that is,the sham surgery group,without ligation or puncture,using the same steps as for the model group).The control and model groups were administered with equal amounts of physiological saline once daily for 28 d,consecutively.A reagent kit was used to assess rat liver function.Hematoxylin and eosin(HE)staining was used to analyze pathological changes in the liver tissue.Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)staining was used to assess apoptosis in liver tissue cells.ELISA was used to analyze IL-6,tumor necrosis factor α(TNF-α),and IL-1β levels in serum.Western blotting was used to detect changes in protein expression of the NLRP3/IL-1β/caspase-1 signaling pathway components in liver tissues.Results For the control group,the liver tissues of rats in the model group lost their normal structure,with an uneven distribution of liver cells accompanied by edema and vacuoles.For the model group,the L-EVO,M-EVO,and H-EVO groups exhibited a relatively neat arrangement of liver tissue cells,reduced edema,and vacuoles.As the dose increased,the morphology of liver tissue cells recovered significantly.For the H-EVO group,the H-EVO+NLRP3 group exhibited a disordered arrangement of liver tissue cells with edema and vacuoles.For the control group,the model group showed increased alanine aminotransferase(ALT),aspartate aminotransferase(AST),liver tissue cell apoptosis rate,serum IL-6,TNF-α,and IL-1β levels,and expression of NLRP,IL-1β,and caspase-1 protein in the liver tissue(P＜0.05).For the model group,the L-EVO,M-EVO,and H-EVO groups showed lower ALT,AST,liver tissue cell apoptosis rate,serum IL-6,TNF-α,and IL-1β levels,and expression of NLRP,IL-1β,and caspase-1 protein in the liver tissue(P＜0.05).For the H-EVO group,the H-EVO+NLRP3 group had higher ALT,AST,liver tissue cell apoptosis rate,serum IL-6,TNF-α,and IL-1β levels,and expression of NLRP,IL-1β,and caspase-1 pro-tein in the liver tissue(P＜0.05).Conclusion EVO can alleviate liver injury in septic rats by influencing the NLRP3/IL-1β/caspase-1 signaling pathway.

Objective To investigate the characteristics of adverse drug event(ADE)related to tacrolimus(Tac)in pediatric solid organ transplant recipients.Methods The data were retrieved from the US Food and Drug Administration Adverse Event Reporting System database from the first quarter of 2004 to the second quarter of 2023.The ADE data of pediatric organ transplant recipients with Tac as the primary suspected drug were extracted.The relationship between Tac and ADE was quantitatively analyzed by proportional imbalance method.Basic characteristics and signal strength of ADE related to Tac were analyzed.ADE related to Tac in children of different ages and different types of organ transplantation were analyzed.Results A total of 1 443 children's ADE reports involving Tac were screened,including 188 cases(13.0％)of heart transplantation,668 cases(46.3％)of liver transplantation,531 cases(36.8％)of kidney transplantation and 56 cases(3.9％)of lung transplantation.The median age of children was 10 years old.The top three countries with ADE reporting were the United States,France and the United Kingdom.China reported 26 cases,accounting for 1.8％.Infection and infectious diseases accounted for the highest proportion(20.96％)in ADE related to Tac,including EB virus and cytomegalovirus infection,etc.Infection and infectious diseases occupied the largest proportion of ADE related to Tac in children of different ages,whereas the pathogen types were different.Rejection,unstable immunosuppression level and renal function damage were also common ADE related to Tac in children of all ages.Nervous system disease was the main ADE in heart transplant recipients,while infection and infectious diseases were more common in liver and kidney transplant recipients.Rejection was the most common ADE in lung transplant recipients.Conclusions ADE related to Tac possess different distribution characteristics in different types of organ transplantation.Extensive attention should be paid to individualized drug monitoring and risk assessment in pediatric organ transplant recipients,thereby optimizing Tac treatment and reducing the risk of ADE.

Objective To explore the molecular mechanisms and cell-cell interactions in the injury process of pancreatic islet transplantation.Methods Single-cell transcriptome data from mouse islets treated with inflammatory factors were used,and data processing was performed using the Seurat package,with integrated data to remove batch effects.Cell subpopulations were annotated based on known markers.Cell-cell interactions in the inflammatory factor-treated group were analyzed using the CellChat package,and inferred based on the expression of cell surface receptors and ligands.Gene set enrichment analysis was used to clarify the biological processes enriched in β-cells after treatment with inflammatory factors.Finally,differentially expressed transcription factors were identified and verified using microarray datasets of donor islet ischemic injury and Western blotting.Results A total of 7 different cell subpopulations were found in mouse islets,with β-cells being the most abundant.Cell-cell interaction network analysis showed that the number and strength of interactions between ductal cells and other cells were the highest.Gene set enrichment analysis showed that after treatment with inflammatory factors,the immune response was positively enriched in β-cells,while peptide hormone metabolism,bile acid metabolism,and ion homeostasis were downregulated.The common differential transcription factors identified in the mouse single-cell transcriptome and the microarray dataset of donor islet ischemic injury were early growth response 1(EGR1),nuclear factor-κB inhibitor α(NFKBIA),and activating transcription factor 3(ATF3).Among them,NFKBIA and ATF3 were upregulated,while EGR1 was downregulated.The expression of EGR1 protein was downregulated after 24 h,48 h,and 72 h of cold ischemia.Conclusions EGR1 is a transcription factor closely related to islet cold ischemia,and future research should focus on the specific mechanisms of EGR1 and its downstream target genes,in order to provide more effective strategies for clinical treatment of islet transplantation.

Objective To identify M1 macrophage-related genes in rejection after kidney transplantation and construct a risk prediction model for renal allograft survival. Methods GSE36059 and GSE21374 datasets after kidney transplantation were downloaded from Gene Expression Omnibus (GEO) database. GSE36059 dataset included the samples from the recipients with rejection and stable allografts. Using this dataset, weighted gene co-expression network analysis (WGCNA) and differential analysis were conducted to screen the M1 macrophage-related differentially expressed gene (M1-DEG). Then, GSE21374 dataset (including the follow-up data of graft loss) was divided into the training set and validation set according to a ratio of 7∶3. In the training set, a multivariate Cox's model was constructed using the variables screened by least absolute shrinkage and selection operator (LASSO), and the ability of this model to predict allograft survival was evaluated. CIBERSORT was employed to analyze the differences of infiltrated immune cells between the high-risk group and low-risk group, and the distribution of human leukocyte antigen (HLA)-related genes was analyzed between two groups. Gene set enrichment analysis (GSEA) was used to further clarify the biological process and pathway enrichment in the high-risk group. Finally, the database was employed to predict the microRNA (miRNA) interacting with the prognostic genes. Results In the GSE36059 dataset, 14 M1-DEG were screened. In the GSE21374 dataset, Toll-like receptor 8 (TLR8), Fc gamma receptor 1B (FCGR1B), BCL2 related protein A1 (BCL2A1), cathepsin S (CTSS), guanylate binding protein 2(GBP2) and caspase recruitment domain family member 16 (CARD16) were screened by LASSO-Cox regression analysis, and a multivariate Cox's model was constructed based on these 6 M1-DEG. The area under curve (AUC) of receiver operating characteristic of this model for predicting the 1- and 3-year graft survival was 0.918 and 0.877 in the training set, and 0.765 and 0.736 in the validation set, respectively. Immune cell infiltration analysis showed that the infiltration of rest and activated CD4⁺ memory T cells, γδT cells and M1 macrophages were increased in the high-risk group (all P < 0.05). The expression level of HLA I gene was up-regulated in the high-risk group. GSEA analysis suggested that immune response and graft rejection were enriched in the high-risk group. CTSS interacted with 8 miRNA, BCL2A1 and GBP2 interacted with 3 miRNA, and FCGR1B interacted with 1 miRNA. Conclusions The prognostic risk model based on 6 M1-DEG has high performance in predicting graft survival, which may provide evidence for early interventions for high-risk recipients.

Objective:To explore the temporal distribution of high level of BK virus(BKV) viruria after kidney transplantation(KT)and the association of high level of viruria with clinical factors and specific human leukocyte antigen(HLA)sites in donors and recipients.Methods:From January 1, 2017 to December 31, 2019, clinical data were retrospectively reviewed for 212 recipients of cadaveric KT.A high level of urinary BKV viruria was defined as urinary BKV-DNA quantification>10 7(copies/ml)after KT while 212 recipients with the same gender composition below the threshold during the same period were selected as low-level controls.Clinical data and HLA sites of two groups were statistically analyzed and risk factors for high level of viruria screened by univariate and multifactorial Logistic regressions. Results:The median time to initial high-level BKV infection in urine after RT was 125.5 days.Based upon univariate Logistic analysis, delayed graft function(DGF)and HLA-A24 of recipient were risk factors for high-level BKV infection in urine while HLA-DQ9 of donor acted as a protective factor.Through multivariate Logistic analysis, DGF( OR=2.18, 95% CI 1.18~4.01, P=0.012)and HLA-A24( OR=1.63, 95% CI 1.06~2.53, P=0.027)of recipient were independent risk factors for high-level BKV infection in urine.And HLA-DQ9 of donors( OR=0.58, 95% CI 0.36~0.91, P=0.019)was an independent protective factor. Conclusions:High level of BKV viruria after RT is associated with donor/recipient-specific HLA sites.Early risk factor stratification and protective factors of recipients can aid in tailoring postoperative immunosuppression and screening program and developing T cell-associated vaccines.