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 trends in disease burden due to childhood asthma in China from 1990 to 2021 and to project the disease burden from 2022 to 2035, so as to provide insights into formulation of the control interventions for childhood asthma in China. Methods: The prevalent case, agestandard prevalence, disability-adjusted life years (DALYs) and agestandard DALYs rate of children with asthma at ages of 0 to 14 years and their 95% uncertainty interval (UI) in China from 1990 to 2021 were extracted from the Global Burden of Disease (GBD) database. The temporal trends in the disease burden of childhood asthma were evaluated with estimated annual percentage change (EAPC) and its 95% confidence interval (CI), and the disease burden due to asthma was projected among children at ages of 0 to 14 years in China using a Bayesian age-period-cohort (BAPC) model from 2022 to 2035. Results: There were 9.368 3 million (95%UI=6.410 7 million to 14.026 1 million) prevalent cases of asthma among children at ages of 0 to 14 years in China in 2021, contributing to 0.387 9 million (95%UI=0.216 1 million to 0.668 8 million) DALYs loss. The prevalent cases and DALYs of asthma decreased by 37.28% and 52.55% among children at ages of 0 to 14 years in China in 2021 compared with 1990, and the agestandardized prevalence [EAPC=-0.70%, 95%CI=-1.26% to -0.13%)] and DALY rates [EAPC=-1.71%, 95%CI=-2.32% to -1.10%)] also appeared a tendency towards a decline. From 1990 to 2021, the prevalent cases, prevalence, DALYs and DALYs rate of asthma were all higher among male children than among female children, and the disease burden of asthma was higher among children at ages of 5 to 9 years than at other age groups. BAPC model predicted a decline in both prevalent cases and DALYs of asthma among children at ages of 0 to 14 years in China from 2022 to 2035, with 6.759 6 million prevalent cases and DALYs of 0.228 4 million personyears in 2035, while the prevalence and DALYs rates were projected to rise to 5 143.35/105 and 173.75/105 in 2035. Conclusions Despite a reduction in the disease burden of asthma among children at ages of 0 to 14 years in China from 1990 to 2021, the prevalence remained high. The disease burden due to asthma is projected to appear a decline among children at ages of 0 to 14 years in China from 2022 to 2035; however, the prevalence and DALYs rates still rise. Intensified control measures and targeted interventions are required to reduce the disease burden of childhood asthma.

ObjectiveTo investigate the effect of Shaoyaotang on T helper cell 17/regulatory T lymphocyte（Th17/Treg） cell balance in ulcerative colitis and decipher the intervention mechanism based on glucose metabolism reprogramming. MethodsThe mouse model of ulcerative colitis was established by the dextran sulfate sodium （DSS） method. Forty-eight C57BL/6 mice were randomly allocated into normal， model， Western drug control （mesalazine， 0.39 g·kg^-1·d^-1）， Shaoyaotang （15.54 g·kg^-1·d^-1）， inhibitor （2-deoxy-D-glucose， 2-DG， 100 mg·kg^-1·d^-1）， and inhibitor （2-DG， 100 mg·kg^-1·d^-1） + Shaoyaotang （15.54 g·kg^-1·d^-1） groups. Mice were administrated with the corresponding drugs by gavage for 7 days. The general conditions and the colon injury degree were observed 24 h after the last administration. The expression of interleukin （IL）-10 and IL-17 in the colon tissue was detected by immunohistochemical staining. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were performed to determine the protein and mRNA levels， respectively， of hypoxia-inducing factor-1α （HIF-1α）， lactate dehydrogenase （LDHA）， and hexokinase 2 （HK2） in the colon tissue. Th17/Treg cell differentiation was detected by flow cytometry. Enzyme-linked immunosorbent assay was employed to measure the levels of lactic acid and glucose in the colon tissue and IL-10， IL-17， and IL-6 in the serum. ResultsCompared with the normal group， the model group showed decreases in body weight and disease activity index （DAI） （P<0.05）， elevations in levels of HIF-1α， LDHA， HK2， IL-17， IL-6， Th17 cells， lactic acid， and glucose in the colon tissue （P<0.05）， and declines in the levels of of IL-10 and Treg cells （P<0.05）. Compared with the model group， the drug administration groups showed increases in body weight and DAI （P<0.05）， declines in levels of HIF-1α， LDHA， HK2， IL-17， IL-6， Th17 cells， lactic acid， and glucose in the colon tissue （P<0.05）， and rises in levels of IL-10 and Treg cells （P<0.05）. Shaoyaotang+2-DG group had the most obvious effect. ConclusionShaoyaotang can relieve diarrhea and bloody stool in mice with ulcerative colitis by restoring the Th17/Treg cell balance via regulation of glucose metabolism reprogramming， thus playing a role in the treatment of ulcerative colitis.

ObjectiveTo investigate the effect of Shaoyaotang on T helper cell 17/regulatory T lymphocyte（Th17/Treg） cell balance in ulcerative colitis and decipher the intervention mechanism based on glucose metabolism reprogramming. MethodsThe mouse model of ulcerative colitis was established by the dextran sulfate sodium （DSS） method. Forty-eight C57BL/6 mice were randomly allocated into normal， model， Western drug control （mesalazine， 0.39 g·kg^-1·d^-1）， Shaoyaotang （15.54 g·kg^-1·d^-1）， inhibitor （2-deoxy-D-glucose， 2-DG， 100 mg·kg^-1·d^-1）， and inhibitor （2-DG， 100 mg·kg^-1·d^-1） + Shaoyaotang （15.54 g·kg^-1·d^-1） groups. Mice were administrated with the corresponding drugs by gavage for 7 days. The general conditions and the colon injury degree were observed 24 h after the last administration. The expression of interleukin （IL）-10 and IL-17 in the colon tissue was detected by immunohistochemical staining. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were performed to determine the protein and mRNA levels， respectively， of hypoxia-inducing factor-1α （HIF-1α）， lactate dehydrogenase （LDHA）， and hexokinase 2 （HK2） in the colon tissue. Th17/Treg cell differentiation was detected by flow cytometry. Enzyme-linked immunosorbent assay was employed to measure the levels of lactic acid and glucose in the colon tissue and IL-10， IL-17， and IL-6 in the serum. ResultsCompared with the normal group， the model group showed decreases in body weight and disease activity index （DAI） （P<0.05）， elevations in levels of HIF-1α， LDHA， HK2， IL-17， IL-6， Th17 cells， lactic acid， and glucose in the colon tissue （P<0.05）， and declines in the levels of of IL-10 and Treg cells （P<0.05）. Compared with the model group， the drug administration groups showed increases in body weight and DAI （P<0.05）， declines in levels of HIF-1α， LDHA， HK2， IL-17， IL-6， Th17 cells， lactic acid， and glucose in the colon tissue （P<0.05）， and rises in levels of IL-10 and Treg cells （P<0.05）. Shaoyaotang+2-DG group had the most obvious effect. ConclusionShaoyaotang can relieve diarrhea and bloody stool in mice with ulcerative colitis by restoring the Th17/Treg cell balance via regulation of glucose metabolism reprogramming， thus playing a role in the treatment of ulcerative colitis.

This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

Objective: This study explored whether anxiety and core self-evaluation mediate the relationship between negative life events and depressive symptoms in adolescents of the Yi ethnic minority in China. Methods: In this cross-sectional study, a convenience sample of 627 Yi adolescents 10–19 years old (252 males, 40.2%) from primary, middle and high schools in Liangshan Prefecture in China completed the Adolescent Self-Rating Life Events Checklist (ASLEC) to report on negative life events, the Second Edition of the Beck Depression Inventory (BDI-II) to report on depressive symptoms, the Core Self-Evaluations Scale (CSES) to describe core self-evaluation, and the Screen for Child Anxiety-Related Emotional Disorders (SCARED) to report anxiety symptoms. Results: In Pearson correlation analysis, total score and dimension subscores on the ASLEC correlated positively with total score and dimension subscores on the SCARED survey as well as with total score on the BDI. Total ASLEC score and dimension subscores correlated negatively with total CSES score. Mediation analysis indicated that negative life events affected depressive symptoms directly, as well as indirectly via core self-evaluation (mediating effect was 0.087; 95% confidence interval [CI], 0.063–0.113; p<0.001). The chain-mediated pathway effect was significant (mediating effect was 0.017; 95% CI, 0.011–0.026; p<0.001). Conclusion Yi adolescents in Liangshan Prefecture show certain prevalence of anxiety and depression, and they score relatively low on core self-evaluation. In this ethnic group, negative life events can affect depressive symptoms directly as well as indirectly through chain-mediated effects of anxiety and core self-evaluation.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.

Objective: This study explored whether anxiety and core self-evaluation mediate the relationship between negative life events and depressive symptoms in adolescents of the Yi ethnic minority in China. Methods: In this cross-sectional study, a convenience sample of 627 Yi adolescents 10–19 years old (252 males, 40.2%) from primary, middle and high schools in Liangshan Prefecture in China completed the Adolescent Self-Rating Life Events Checklist (ASLEC) to report on negative life events, the Second Edition of the Beck Depression Inventory (BDI-II) to report on depressive symptoms, the Core Self-Evaluations Scale (CSES) to describe core self-evaluation, and the Screen for Child Anxiety-Related Emotional Disorders (SCARED) to report anxiety symptoms. Results: In Pearson correlation analysis, total score and dimension subscores on the ASLEC correlated positively with total score and dimension subscores on the SCARED survey as well as with total score on the BDI. Total ASLEC score and dimension subscores correlated negatively with total CSES score. Mediation analysis indicated that negative life events affected depressive symptoms directly, as well as indirectly via core self-evaluation (mediating effect was 0.087; 95% confidence interval [CI], 0.063–0.113; p<0.001). The chain-mediated pathway effect was significant (mediating effect was 0.017; 95% CI, 0.011–0.026; p<0.001). Conclusion Yi adolescents in Liangshan Prefecture show certain prevalence of anxiety and depression, and they score relatively low on core self-evaluation. In this ethnic group, negative life events can affect depressive symptoms directly as well as indirectly through chain-mediated effects of anxiety and core self-evaluation.

Objective: This study explored whether anxiety and core self-evaluation mediate the relationship between negative life events and depressive symptoms in adolescents of the Yi ethnic minority in China. Methods: In this cross-sectional study, a convenience sample of 627 Yi adolescents 10–19 years old (252 males, 40.2%) from primary, middle and high schools in Liangshan Prefecture in China completed the Adolescent Self-Rating Life Events Checklist (ASLEC) to report on negative life events, the Second Edition of the Beck Depression Inventory (BDI-II) to report on depressive symptoms, the Core Self-Evaluations Scale (CSES) to describe core self-evaluation, and the Screen for Child Anxiety-Related Emotional Disorders (SCARED) to report anxiety symptoms. Results: In Pearson correlation analysis, total score and dimension subscores on the ASLEC correlated positively with total score and dimension subscores on the SCARED survey as well as with total score on the BDI. Total ASLEC score and dimension subscores correlated negatively with total CSES score. Mediation analysis indicated that negative life events affected depressive symptoms directly, as well as indirectly via core self-evaluation (mediating effect was 0.087; 95% confidence interval [CI], 0.063–0.113; p<0.001). The chain-mediated pathway effect was significant (mediating effect was 0.017; 95% CI, 0.011–0.026; p<0.001). Conclusion Yi adolescents in Liangshan Prefecture show certain prevalence of anxiety and depression, and they score relatively low on core self-evaluation. In this ethnic group, negative life events can affect depressive symptoms directly as well as indirectly through chain-mediated effects of anxiety and core self-evaluation.