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.

Objective: To investigate the impact of extracurricular physical activity on heart rate variability (HRV) among primary and secondary school students in Chengdu City, so ao to provide references for scientific exercise prescription. Methods: Using a convenient sampling method, 1 323 primary and secondary students were enrolled from central Chengdu who underwent physical fitness assessments at Sichuan Provincial Institute of Sports Science from September 2020 to January 2022. According to the standards of the National Physical Fitness Monitoring Center, boys and girls were divided into groups with and without extracurricular physical exercise habits. HRV was monitored using the SA-3000P device. Key HRV parameters were evaluated separately by gender, including standard deviation of normal to normal intervals (SDNN), root mean square of successive differences (rMSSD), total power (TP), low frequency power (LF) and high frequency power (HF). Statistical analyses were employed by t-test, Mann-Whitney U-test and Chi square test. Results: lgSDNN, lgrMSSD, TP, LF and HF in the group without extracurricular physical exercise habit [boys:(1.67±0.13)ms, (1.59±0.20)ms, (7.34±0.73)ms 2, (6.11±0.74)ms 2, (6.05±0.87)ms 2; girls:(1.67± 0.13)ms , (1.59±0.19)ms, (7.35±0.60)ms 2, (6.06±0.69)ms 2, (6.12±0.87)ms 2] were lower than those in the group with extracurricular physical exercise habit [boys:(1.75±0.13)ms, (1.72±0.18)ms, (7.69±0.62)ms 2, (6.41±0.76)ms 2, (6.44±0.79)ms 2；girls:(1.73±0.13)ms, (1.68±0.20)ms, (7.60±0.65)ms 2, (6.26±0.86)ms 2, (6.36±0.90)ms 2] ( t =-8.24, -8.75, -6.54, -5.35 , -6.33；-5.10，-4.90，-4.47，-2.71，-2.93, all P ＜0.01). Only the group of boys without extracurricular physical exercise habits showed a decrease in lgLF/HF [0.04(-0.19,0.27)] compared to the group with extracurricular physical exercise habits [ -0.03 (-0.25,0.20)] ( Z=-2.01, P <0.05). When the score classes of autonomic nerve activity, stress index and fatigue index were compared between boys and girls groups without and with extracurricular physical exercise habits, the proportion of boys normal and above scores increased from 79.3%, 84.1%, 71.8% to 91.4%, 95.7%, 87.3%, respectively, and the differences were statistically significant ( χ 2=47.42, 63.66, 38.28); the proportion of girls normal score and above increased from 79.8%, 85.7%, 75.0% to 85.4%, 92.1%, 79.4%, and the differences were statistically significant ( χ 2=48.31, 22.18, 22.22) (all P <0.01). Conclusion The primary and secondary school students who have the habit of extracurricular physical exercise have enhanced compliance in indicators related to HRV, showing more complex heart rate variability.

Background::Clinical opportunistic screening is a cost-effective cancer screening modality. This study aimed to establish an easy-to-use diagnostic model serving as a risk stratification tool for identification of individuals with malignant gastric lesions for opportunistic screening.Methods::We developed a questionnaire-based diagnostic model using a joint dataset including two clinical cohorts from northern and southern China. The cohorts consisted of 17,360 outpatients who had undergone upper gastrointestinal endoscopic examination in endoscopic clinics. The final model was derived based on unconditional logistic regression, and predictors were selected according to the Akaike information criterion. External validation was carried out with 32,614 participants from a community-based randomized controlled trial.Results::This questionnaire-based diagnostic model for malignant gastric lesions had eight predictors, including advanced age, male gender, family history of gastric cancer, low body mass index, unexplained weight loss, consumption of leftover food, consumption of preserved food, and epigastric pain. This model showed high discriminative power in the development set with an area under the receiver operating characteristic curve (AUC) of 0.791 (95% confidence interval [CI]: 0.750–0.831). External validation of the model in the general population generated an AUC of 0.696 (95% CI: 0.570–0.822). This model showed an ideal ability for enriching prevalent malignant gastric lesions when applied to various scenarios.Conclusion::This easy-to-use questionnaire-based model for diagnosis of prevalent malignant gastric lesions may serve as an effective prescreening tool in clinical opportunistic screening for gastric cancer.

Objective To investigate the changing distribution and antibiotic resistance profiles of clinical isolates of Staphylococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Staphylococcus according to the unified protocol of CHINET(China Antimicrobial Surveillance Network)using disk diffusion method and commercial automated systems.The CHINET antimicrobial resistance surveillance data from 2015 to 2021 were interpreted according to the 2021 CLSI breakpoints and analyzed using WHONET 5.6.Results During the period from 2015 to 2021,a total of 204,771 nonduplicate strains of Staphylococcus were isolated,including 136,731(66.8％)strains of Staphylococcus aureus and 68,040(33.2％)strains of coagulase-negative Staphylococcus(CNS).The proportions of S.aureus isolates and CNS isolates did not show significant change.S.aureus strains were mainly isolated from respiratory specimens(38.9±5.1)％,wound,pus and secretions(33.6±4.2)％,and blood(11.9±1.5)％.The CNS strains were predominantly isolated from blood(73.6±4.2)％,cerebrospinal fluid(12.1±2.5)％,and pleural effusion and ascites(8.4±2.1)％.S.aureus strains were mainly isolated from the patients in ICU(17.0±7.3)％,outpatient and emergency(11.6±1.7)％,and department of surgery(11.2±0.9)％,whereas CNS strains were primarily isolated from the patients in ICU(32.2±9.7)％,outpatient and emergency(12.8±4.7)％,and department of internal medicine(11.2±1.9)％.The prevalence of methicillin-resistant strains was 32.9％in S.aureus(MRSA)and 74.1％in CNS(MRCNS).Over the 7-year period,the prevalence of MRSA decreased from 42.1％to 29.2％,and the prevalence of MRCNS decreased from 82.1％to 68.2％.MRSA showed higher resistance rates to all the antimicrobial agents tested except trimethoprim-sulfamethoxazole than methicillin-susceptible S.aureus(MSSA).Over the 7-year period,MRSA strains showed decreasing resistance rates to gentamicin,rifampicin,and levofloxacin,MRCNS showed decreasing resistance rates to gentamicin,erythromycin,rifampicin,and trimethoprim-sulfamethoxazole,but increasing resistance rate to levofloxacin.No vancomycin-resistant strains were detected.The prevalence of linezolid-resistant MRCNS increased from 0.2％to 2.3％over the 7-year period.Conclusions Staphylococcus remains the major pathogen among gram-positive bacteria.MRSA and MRCNS were still the principal antibiotic-resistant gram-positive bacteria.No S.aureus isolates were found resistant to vancomycin or linezolid,but linezolid-resistant strains have been detected in MRCNS isolates,which is an issue of concern.

AIM To study the chemical constituents from flower buds of Magnolia biondii Pamp.and their in vitro acetylcholinesterase inhibitory activities.METHODS The 50% acetone extract from the flower buds of M.biondii was isolated and purified by Diaion HP-20,Toyopearl HW-40C,ODS and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The in vitro acetylcholinesterase inhibitory activities of these compounds were determined according to previous method established by research group.RESULTS Seventeen compounds were isolated and identified as crassifolioside(1),magnoloside B(2),rutin(3),isoquercitrin(4),quercetin(5),northalifoline(6),cordysinin B(7),thymidine(8),indazole(9),dihydrodehydrodiconiferyl alcohol(10),aesculetin(11),C-veratroylglycol(12),3,4-dihydroxyphenylethanol(13),3-methoxy-4-hydroxyphenylethanol(14),3,4-dihydroxybenzoic acid(15),2,4,6-trimethoxyphenol(16),syringic acid(17).CONCLUSION Compounds 1-17 are isolated from this plant for the first time,none of which show acetylcholinesterase inhibitory activities at the concentration of 20 μmol/L.

Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.

Objective:To analyze the clinical outcomes of initial radioactive iodine 131I therapy (RIT) for patients with familial differentiated thyroid cancer (FDTC) and sporadic differentiated thyroid cancer (SDTC), along with their influencing factors. Methods:The clinical data of 120 FDTC and 480 SDTC patients who received RIT at the Department of Nuclear Medicine, Tianjin Medical University General Hospital from January 2016 to January 2022 were retrospectively analyzed. These patients, categorized into the FDTC and SDTC groups, were further divided into three subgroups based on their response to initial RIT: no evidence of disease (NED), biochemical persistence of disease (BPD), or structural/functional persistence of disease (S/FPD). For the NED subgroup, the disease-free survival (DFS) was analyzed. For the BPD and S/FPD subgroups, the progression-free survival (PFS) was investigated. Furthermore, risk factors for failure to reach the NED status were identified.Results:After initial RIT, 56 (46.7%), 50 (41.7%), 14 (11.6%) patients in the FDTC group reached the NED, BPD, and S/FPD statuses, respectively, while 284 (59.1%), 160 (33.3%), 36 (7.5%) and SDTC patients in the SDTC group were in the NED, BPD, and S/FPD statuses, respectively ( χ2 = 10.10, P = 0.013). The last follow-up revealed that 71 (59.1%), 36 (30.1%), 13 (10.8%) patients in the FDTC group were in the NED, BPD and S/FPD statuses, respectively, while 337 (70.2%), 114 (23.7%), 29 (6.1%) patients in the SDTC group reached the NED, BPD and S/FPD statuses, respectively ( χ2 = 8.99, P = 0.026). The F-NED and S-NED subgroups exhibited 5-year DFS rates of 92.4% and 97.4%, respectively, the F-BPD and S-BPD subgroups displayed 5-year PFS rates of 88.3% and 90.8%, respectively, while the F-S/FPD and S-S/FPD subgroups yielded in 5-year PFS rates of 78.2% and 79.6%, respectively. Univariate binary logistic regression analysis indicated that the maximum diameter of tumors, T stage, M stage, recurrence risk stratification, and postoperative stimulated thyroglobulin (p-sTg) were correlated with the achievement of the NED status ( χ2=6.37-13.10, P < 0.05). Multivariable binary logistic regression analysis showed that T stage and p-sTg were independent risk factors in the achievement of the NED status ( χ2=0.11-11.33, P < 0.05). Conclusions:The response to initial RIT assists in guiding the development of subsequent treatment and follow-up strategies for DTC patients. Given that the SDTC patients exhibited better outcomes than the FDTC patients, more alertness should be paid to the RIT for FDTC patients. For patients with higher p-sTg and T stage, the initial RIT dose and follow-up interval should be increased and reduced respectively as appropriate.

OBJECTIVE To create a highly effective algorithm for automatically generating easily confused drug catalogs （ECDC）， as well as to develop a management system for ECDC based on this algorithm， in order to improve the management efficiency of ECDC. METHODS This study， based on Levenshtein distance algorithm， delved deeply into the automatic identification mechanism of easily confused drugs and the screening method for determining similarity thresholds， ultimately leading to the development of an algorithm for automatically generating ECDC. Besides a management system was designed and developed， using SQL Server 2008 R2 Express as the data storage platform and Visual Basic.NET as the programming language. RESULTS The similarity threshold δ played a crucial role in the algorithm for automatically generating ECDC. As the value of δ gradually increased， the total count of easily confused drugs decreased gradually， while the count of drug groups exhibited a pattern of initially increasing and then decreasing. Practically， ECDC could be created using either the generic or varietal names of drugs， with corresponding similarity thresholds of 0.75 and 0.83. Furthermore， ECDC management system had significantly reduced the time required to establish a catalog from about one week to less than one hour， resulting in a substantial enhancement in work efficiency. CONCLUSIONS The algorithm used to automatically generate ECDC is highly efficient and rapid， offering robust technical assistance for the management of easily confused drugs. Implementing the ECDC system can greatly reduce the time cost related to building and maintaining the catalogs， thus significantly improving the efficiency of managing ECDC.

Platycodonis Radix is the dry root of Platycodon grandiflorum of Campanulaceae, which has a variety of pharmacological effects and is a commonly used bulk Chinese medicine. In this study, the chloroplast genome sequences of six P. grandiflorum from different producing areas has been sequenced with Illumina HiSeq X Ten platform. The specific DNA barcodes were screened, and the germplasm resources and genetic diversity were analyzed according to the specific barcodes. The total length of the chloroplast genome of 6 P. grandiflorum samples was 172 260-172 275 bp, and all chloroplast genomes showed a typical circular tetrad structure and encoded 141 genes. The comparative genomics analysis and results of amplification efficiency demonstrated that trnG-UCC and ndhG_ndhF were the potential specific DNA barcodes for identification the germplasm resources of P. grandiflorum. A total of 305 P. grandiflorum samples were collected from 15 production areas in 9 provinces, for which the fragments of trnG-UCC and ndhG_ndhF were amplificated and the sequences were analyzed. The results showed that trnG-UCC and ndhG_ndhF have 5 and 11 mutation sites, respectively, and 5 and 7 haplotypes were identified, respectively. The combined analysis of the two sequences formed 13 haplotypes (named Hap1-Hap13), and Hap4 is the main genotype, followed by Hap1. The unique haplotypes possessed by the three producing areas can be used as DNA molecular tags in this area to distinguish from the germplasm resources of P. grandiflorum from other areas. The haplotype diversity, nucleotide diversity and genetic distance were 0.94, 4.79×10^-3 and 0.000 0-0.020 3, respectively, suggesting that the genetic diversity was abundant and intraspecific kinship was relatively close. This study laid a foundation for the identification of P. grandiflorum, the protection and utilization of germplasm resources, and molecular breeding.

Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.