The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

Purpose: This study assessed the performance of the ultrasound-guided attenuation parameter (UGAP) in diagnosing and grading hepatic steatosis in patients with metabolic dysfunctionassociated steatotic liver disease (MASLD). Magnetic resonance imaging proton density fat fraction (MRI-PDFF) served as the reference standard. Methods: Patients with hepatic steatosis were enrolled in this prospective study and underwent UGAP measurements. MRI-PDFF values of ≥5%, ≥15%, and ≥25% were used as references for the diagnosis of steatosis grades ≥S1, ≥S2, and S3, respectively. Spearman correlation coefficients and area under the receiver operating characteristic curves (AUCs) were calculated. Results: Between July 2023 and June 2024, the study included 88 patients (median age, 40 years; interquartile range [IQR], 36 to 46 years), of whom 54.5% (48/88) were men and 45.5% (40/88) were women. Steatosis grades exhibited the following distribution: 22.7% (20/88) had S0, 50.0% (44/88) had S1, 21.6% (19/88) had S2, and 5.7% (5/88) had S3. The success rate for UGAP measurements was 100%. The median UGAP value was 0.74 dB/cm/MHz (IQR, 0.65 to 0.82 dB/ cm/MHz), and UGAP values were positively correlated with MRI-PDFF (r=0.77, P<0.001). The AUCs of UGAP for the diagnoses of ≥S1, ≥S2, and S3 steatosis were 0.91, 0.90, and 0.88, respectively. In the subgroup analysis, 98.4% (60/61) of patients had valid controlled attenuation parameter (CAP) values. UGAP measurements were positively correlated with CAP values (r=0.65, P<0.001). Conclusion Using MRI-PDFF as the reference standard, UGAP demonstrates good diagnostic performance in the detection and grading of hepatic steatosis in patients with MASLD.

Objective To explore the influencing factors of acute kidney injury in severe burn patients,and to construct a visual risk nomogram model.Methods A total of 390 patients with severe burn admitted to the Institute of Burn Frostbite and Tissue Function Reconstruction of Chinese People's Armed Police Force Specialty Medical Center from January 2018 to January 2022 were collected as an internal training data set,and 50 patients with severe burn admitted from February to December 2022 were collected as an external validation data set.The 390 patients of the internal training data set were divided into the acute kidney injury group and the non-acute kidney injury group according to the occurrence of acute kidney injury,and the baseline data of patients in the two groups were compared.Univariate and multivariate Logistic regression were used to analyze the risk factors of acute kidney injury in severe burn patients of the internal training data set,and a nomogram model was drawn.Subsequently,the model was verified both internally and externally.Kaplan-Meier analysis and Log-rank test were used to compare the 90-day survival rate of patients between the acute kidney injury group and the non-acute kidney injury group.Results The burn area(OR=1.18,95%CI:1.06 to 2.36,P=0.004),sequential organ failure assessment(SOFA)score(OR=1.81,95%CI:1.21 to 5.92,P<0.001),inhalation injury(OR=3.21,95%CI:1.23 to 6.35,P<0.001),neutrophil to lymphocyte ratio(NLR)(OR=1.22,95%CI:1.05 to 3.65,P<0.001)and albumin(ALB)(OR=0.78,95%CI:0.57 to 0.92,P=0.011)were the independent risk factors for the development of acute kidney injury in severe burn patients.The nomogram model was established by the above factors.The area under the receiver operating characteristic curve(AUC)of the internal training data set was 0.833(95%CI:0.752 to 0.935),the sensitivity was 81.2%,and the specificity was 83.2%.The AUC of the external validation data set was 0.842(95%CI:0.762 to 0.912),the sensitivity 87.2%,and the specificity was 78.7%.The 90-day survival rate of patients in the acute kidney injury group after burns was significantly lower than that in the non-acute kidney injury group(P<0.001).Conclusion Larger burn area,higher SOFA score,combined inhalation injury,increased NLR,and decreased ALB level are the risk factors for the occurrence of acute kidney injury in severe burn patients,which are related to the 90-day survival rate of patients after burns.The nomogram model based on the risk factors can provide certain reference for clinical individualized prevention and treatment of acute kidney injury in severe burn patients.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Aim To explore the therapeutic effect and mechanism of Qingjie Huagong decoction in modulating PI3K/AKT/NF-κB signaling pathway in inflammatory response of acute pancreatitis(AP)mice.Methods Twenty-four mice were randomly divided into Blank group,Model group,Ustekin group,and Qingjie Hua-gong decoction group,with six mice in each group.The AP model was prepared by using rain frogin.Serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α lev-els were detected by ELISA;the pancreatic pathology was detected by HE staining;the expressions of PI3K,AKT,and NF-κB-related proteins and mRNAs were de-tected by immunohistochemistry,Western blot,and RT-qPCR.Results Compared with the blank group,the model group showed obvious pathological damage to the pancreas,with significantly higher serum α-AMS,PN-LP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels(P＜0.01),and significantly higher levels of PI3K,AKT,and NF-κB-related proteins and mRNA expression(P＜0.01).Compared with the model group,both the Qingjie Huagong decoction group and the ustekin group improved the histopathological changes in the pancreas of AP mice,decreased the serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels,and down-reg-ulated the expression levels of pancreatic PI3K,AKT,NF-κB-related proteins and mRNA(P＜0.05 or P＜0.01).Conclusion Qingjie Huagong decoction may inhibit the inflammatory response and protect pancreat-ic tissues by regulating the expression of PI3K/AKT/NF-κB signaling pathway.

AIM To observe the effects of Yiqi Jiedu Tongluo Formula(YQJDTL)on renal microvascular endothelial function and prevention of renal injury in a rat model of type 2 diabetes mellitus(T2DM).METHODS The SD rats were randomly divided into a normal group and a model group.The model group was administered with high-fat diet combined with a single intraperitoneal injection of STZ to establish the T2DM model.The successfully modeled rats were randomly divided into the model group,the canagliflozin group(9 mg/kg),and the low-dose and high-dose YQJDTL groups(4.77,9.45 g/kg).The corresponding doses of the drug were administered by gavage for a total of 12 weeks,during which the rats underwent observation of their general condition and blood glucose changes.After the end of administration,the rats had their levels of renal index,24-hour UP,serum SCr,BUN,TC,TG,HDL-C,LDL-C,ET-1 and NOS measured;their changes in renal microvasculature and the degree of renal fibrosis observed using HE staining,Masson staining,PAS staining,and PASM staining;their ultrastructure of the glomeruli observed using transmission electron microscopy;their renal protein expressions of TGF-β,SMAD2,SMAD3,Col-1,VEGFA and PKC detected by immunohistochemical staining and Western blot;and their renal mRNA expressions of VEGFA,TGF-β,SMAD2 determined by RT-qPCR.RESULTS Compared with the model group,the high-dose YQJDTL group showed decreased levels of renal index,blood glucose,TG,TC,HDL,24 h UP,BUN,SCr and ET-1(P＜0.05,P＜0.01);increased LDL and NOS levels(P＜0.05,P＜0.01);reduced renal inflammatory infiltration and fibrosis degree,inhibited fusion of foot processes and thickening of basement membrane;decreased renal protein expressions of TGF-β,SMAD2,SMAD3,VEGFA,PKC and Col-1(P＜0.05,P＜0.01);and decreased mRNA expressions of VEGFA,TGF-β and SMAD2(P＜0.01).CONCLUSION In the rat models of T2DM,YQJDTL can reduce their levels of blood glucose and lipids by improving the renal indices levels and the renal microvascular endothelial functions to alleviate renal fibrosis and microangiopathy as well,and the mechanism may be associated with the down-regulated expressions of TGF-β/SMAD and VEGF pathway-related proteins.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

BACKGROUND:Spine osteoarthritis is a chronic inflammatory disease of the spine,articular ligaments,and tendons,and is the main cause of chronic low back pain.Artificial tiger bone powder has anti-inflammatory and pain-relieving biological effects,so it is expected to provide a new strategy for targeted therapy of spinal osteoarthritis.OBJECTIVE:To investigate the mechanism of artificial tiger bone meal in regulating the expression level of interleukin-23/interleukin-17 immune axis in improving spine osteoarthritis in rats.METHODS:Sixty SD rats were randomly divided into blank control group,model group,artificial tiger bone meal low-,medium-and high-dose groups,with 12 rats in each group.Except for the blank control group,osteoarthritis models were established in the other groups by injecting 0.1 mL of iodoacetic acid into the joint cavity of the lumbar vertebral joint capsule of the rats.15 days after modeling,the artificial tiger bone meal low,medium and high dose groups were treated by intragastric administration of 120,240 and 480 mg/kg per day respectively.The blank control group and model group were given the same volume of normal saline by gavage.After 21 days of treatment,the expression levels of interleukin-17,interleukin-23,matrix metalloproteinase-3,and chemokine receptor-6 in rat spinal articular cartilage were measured by western blot assay.The expression levels of related inflammatory factors in rat serum were detected by ELISA.The degree of joint injury and degeneration in rats was observed by hematoxylin-eosin staining and safranin O-fast green staining.RESULTS AND CONCLUSION:(1)The results of western blot assay showed that the expression levels of interleukin 17,interleukin 23,matrix metalloproteinase 3,and chemokine receptor 6 in the articular cartilage of rats in the artificial tiger bone meal high-dose group were significantly lower than those in the model group(P＜0.05).(2)ELISA results showed that compared with the model group,the artificial tiger bone meal medium-and high-dose groups had a significant down-regulating effect on the levels of serum interleukin 17,tumor necrosis factor α,interleukin 1β,and matrix metalloproteinase 3(P＜0.05).(3)Hematoxylin-eosin staining and saffron O-solid green staining showed that the infiltration and proliferation of synovial inflammatory cells in each treatment group of artificial tiger bone meal were significantly improved compared with the model group,and the pathological inflammation Osteoarthritis Research Society International score and Mankin's score in the medium-and high-dose groups of artificial tiger bone meal were significantly reduced(P＜0.05).(4)It is suggested that artificial tiger bone meal could significantly improve the inflammation and degeneration of spinal facet joints caused by iodoacetic acid chemical stimulation.Among them,the effect of the high-dose group was more significant.The mechanism may be to inhibit the expression of interleukin-23/interleukin-17 immune axis-related inflammatory factors and improve the immune microenvironment of articular cartilage.

Objective To explore the influencing factors of acute kidney injury in severe burn patients,and to construct a visual risk nomogram model.Methods A total of 390 patients with severe burn admitted to the Institute of Burn Frostbite and Tissue Function Reconstruction of Chinese People's Armed Police Force Specialty Medical Center from January 2018 to January 2022 were collected as an internal training data set,and 50 patients with severe burn admitted from February to December 2022 were collected as an external validation data set.The 390 patients of the internal training data set were divided into the acute kidney injury group and the non-acute kidney injury group according to the occurrence of acute kidney injury,and the baseline data of patients in the two groups were compared.Univariate and multivariate Logistic regression were used to analyze the risk factors of acute kidney injury in severe burn patients of the internal training data set,and a nomogram model was drawn.Subsequently,the model was verified both internally and externally.Kaplan-Meier analysis and Log-rank test were used to compare the 90-day survival rate of patients between the acute kidney injury group and the non-acute kidney injury group.Results The burn area(OR=1.18,95%CI:1.06 to 2.36,P=0.004),sequential organ failure assessment(SOFA)score(OR=1.81,95%CI:1.21 to 5.92,P<0.001),inhalation injury(OR=3.21,95%CI:1.23 to 6.35,P<0.001),neutrophil to lymphocyte ratio(NLR)(OR=1.22,95%CI:1.05 to 3.65,P<0.001)and albumin(ALB)(OR=0.78,95%CI:0.57 to 0.92,P=0.011)were the independent risk factors for the development of acute kidney injury in severe burn patients.The nomogram model was established by the above factors.The area under the receiver operating characteristic curve(AUC)of the internal training data set was 0.833(95%CI:0.752 to 0.935),the sensitivity was 81.2%,and the specificity was 83.2%.The AUC of the external validation data set was 0.842(95%CI:0.762 to 0.912),the sensitivity 87.2%,and the specificity was 78.7%.The 90-day survival rate of patients in the acute kidney injury group after burns was significantly lower than that in the non-acute kidney injury group(P<0.001).Conclusion Larger burn area,higher SOFA score,combined inhalation injury,increased NLR,and decreased ALB level are the risk factors for the occurrence of acute kidney injury in severe burn patients,which are related to the 90-day survival rate of patients after burns.The nomogram model based on the risk factors can provide certain reference for clinical individualized prevention and treatment of acute kidney injury in severe burn patients.