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.

Ferroptosis, a programmed cell death modality discovered and defined in the last decade, is primarily induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System X_c^--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.

[摘 要] 目的：探讨基于新型单载体SynNotch系统构建的局部分泌IL-2的CAR-T细胞（Syn.CD19.IL-2 CAR-T细胞）对传统CD19 CAR-T细胞功能的影响。方法：基于本课题组前期构建的单载体SynNotch系统，将CD19特异性FMC63抗体与IL-2表达模块整合，通过自失活逆转录病毒载体转导T细胞制备Syn.CD19.IL-2 CAR-T细胞。诱导验证实验分为Syn.CD19.IL-2 CAR-T细胞组和未转导T细胞组，通过ELISA检测抗原刺激后IL-2分泌水平。采用CFSE染色法检测在Syn.CD19.IL-2 CAR-T细胞存在时，CD19 CAR-T细胞与肿瘤Raji-Luc或SW620-CD19-Luc细胞共培养时，IL-2的分泌对CD19 CAR-T细胞增殖的影响。流式细胞术检测CD69表达，观察在Syn.CD19.IL-2 CAR-T细胞分泌IL-2的情况下，CD19 CAR-T细胞与Raji-Luc细胞共培养时的激活情况。结果：成功构建自失活逆转录病毒载体Syn.CD19.IL-2 CAR，制备出Syn.CD19.IL-2 CAR-T细胞，病毒滴度 > 1×107拷贝/mL，转导效率达37.1%。抗原刺激后，SynNotch CAR-T细胞IL-2分泌量显著高于未转导T细胞（P < 0.001）。在Syn.CD19.IL-2 CAR-T细胞分泌IL-2时，CD19 CAR-T细胞具有更强的增殖能力和更高的活化水平（均P < 0.001）。结论：成功构建的Syn.CD19.IL-2 CAR-T细胞能显著增强CD19 CAR-T细胞的增殖和活化能力。

Objective To investigate the prevalence of common diseases among primary and secondary school students in Yichang City from 2019 to 2022, and to provide a scientific basis for formulating effective intervention measures in the future. Methods By random cluster sampling , 7 schools in urban areas and 5 schools in suburban counties were selected to screen common diseases such as myopia, dental caries, obesity and abnormal spinal curvature. Descriptive epidemiological methods were employed for statistical analysis. Results A total of 17 023 primary and secondary school students were screened from 2019 to 2022. The overall detection rate of common diseases from high to low was myopia (54.12%), caries (36.75%), overweight (15.17%), obesity (11.88%), malnutrition (5.80%), and abnormal spinal curvature (3.49%). The detection rates of myopia and abnormal curvature of the spine showed an increasing trend with years and school stages, while the detection rates of malnutrition and dental caries showed a decreasing trend with years and school stages. The detection rates of overweight and obesity showed no trend difference with years, and the detection rates of obesity showed a decreasing trend with school stages. The rates of myopia, overweight and obesity were higher in urban areas than those in suburban counties, and the rate of dental caries was higher in suburban counties than that in urban areas. The prevalence of overweight, obesity, and malnutrition in boys was higher than that in girls. The prevalence of myopia and dental caries in girls was higher than that in boys. The above differences were statistically significant (all P<0.05). Conclusion Myopia, dental caries, obesity, and abnormal curvature of the spine are the current focus of the prevention and treatment of common diseases in students. There are great differences between different regions, school stages, and genders. The ^“tripartite linkage^” of schools, families, and communities should be achieved with the joint efforts of the education and health departments to actively take targeted intervention measures to reduce the prevalence.

Primary open angle glaucoma(POAG)is the most common type of glaucoma, with common causes including variations in trabecular tissue and increased venous pressure. POAG has a certain genetic tendency, and POAG with an autosomal dominant inheritance pattern is mainly caused by single gene mutations. Studies have found that the pathogenesis of POAG may be related to key pathogenic genes(MYOC, OPTN, WDR 36), as well as mitochondrial dysfunction, oxidative stress, and epigenetic regulation. At present, the clinical treatment options for POAG mainly include enhancing trabecular meshwork function, inhibiting aqueous humor production, neuroprotection and regeneration of retinal ganglion cells, and applying gene editing technology, all of which have achieved certain results. However, there is no unified research on the relationship between the occurrence of POAG and genes, as well as treatment plans. The article explores new targets and treatment strategies for POAG gene therapy by analyzing the role of genes in the pathogenesis of POAG, aiming to provide reference for clinical treatment of this disease.

Objective To investigate the characteristics and influencing factors of mental health status of permanent residents in Yichang, Hubei Province. Methods A total of 9 576 permanent residents aged 18 years and older from Yichang City were selected by a multistage random sampling method between June and October 2022. The PHQ-9 was used to assess the residents’ depressive symptoms, the GAD-7 was used to assess their anxiety symptoms, the ISI was used to assess their insomnia status, and the PCL-5 was used to assess their stress status. The influence factors of depression and anxiety were analyzed using χ2 test and logistic regression. Results A total of 9 122 valid questionnaires were completed. The detection rate of depression, anxiety, insomnia, and stress symptoms were 29.98%, 19.03%, 11.97% and 1.58%, respectively. Gender, education level, monthly family income, self-rated health status, mental health literacy level, total GAD-7 score, total ISI score, and total PCL-5 score were the main factors that caused residents' anxiety symptoms, while gender, education level, self-rated health status, total PHQ-9 score, total ISI score, and total PCL-5 score were the main factors that caused residents' anxiety symptoms. Conclusion The prevalence of depression and anxiety is high among the permanent residents in Yichang, while the situation of insomnia and stress is relatively good. Measures such as improving the level of mental health literacy can be taken to improve mental health level of residents in Yichang.

ObjectiveTo investigate the effect and mechanism of total saponins from Panax japonicus （TSPJ） on white adipose tissue （WAT） browning/brown adipose tissue （BAT） activation in C57BL6/J male mice fed on a high-fat diet （HFD）. MethodThirty-two C57BL6/J male mice （8-week-old） were randomly divided into a normal group， a model group， a low-dose TSPJ group， and a high-dose TSPJ group. The mice in the low-dose and high-dose TSPJ groups were given TSPJ for four months by gavage at 25， 75 mg·kg^-1·d^-1， respectively， and those in the other groups were given 0.5% sodium carboxymethyl cellulose （CMC-Na） accordingly. After four months of feeding， all mice were placed at 4 ℃ for acute cold exposure， and the core body temperature was monitored. Subsequently， all mice were sacrificed， and BAT and inguinal WAT （iWAT） were separated rapidly to detect the corresponding indexes. Hematoxylin-eosin （HE） staining was used to observe the morphological changes in each group. The effect of TSPJ on the mRNA expression of uncoupling protein 1 （UCP1）， fatty acid-binding protein 4 （FABP4）， cytochrome C （CytC）， PR domain-containing protein 16 （PRDM16）， elongation of very long chain fatty acids protein 3 （ELOVL3）， peroxisome proliferator-activated receptor γ （PPARγ）， and peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α） in iWAT and BAT was detected by Real-time polymerase chain reaction （Real-time PCR）. Western blot was also used to detect the protein expression of UCP1， PRDM16， PPARγ， and PGC-1α in BAT and iWAT of each group. The effect of TSPJ on UCP1 expression in BAT and iWAT was detected by immunohistochemistry. Result① Compared with the model group， TSPJ could decrease the body weight and proportions of iWAT and BAT in the HFD-induced mice （P<0.05， P<0.01）. ② The body temperature of mice in the model group decreased compared with that in the normal group in the acute cold exposure tolerance test （P<0.05）. The body temperature in the high-dose TSPJ group increased compared with that in the model group （P<0.01）. ③ Compared with the normal group， the model group showed increased adipocyte diameter in iWAT and BAT and decreased number of adipocytes per unit area. Compared with the model group， the TSPJ groups showed significantly reduced cell diameter and increased number of cells per unit area， especially in the high-dose TSPJ group. ④ Compared with the normal group， the model group showed decreased mRNA expression of FABP4， UCP1， CytC， PRDM16， ELOVL3， PGC-1α， and PPARγ in adipose tissues of mice （P<0.05， P<0.01）. Compared with the model group， after intervention with TSPJ， the mRNA expression was significantly up-regulated （P<0.05， P<0.01）. ⑤ Compared with the normal group， the model group showed decreased protein expression of UCP1， PRDM16， PPARγ， and PGC-1α in adipose tissues of mice （P<0.05， P<0.01）. Compared with the model group， after intervention with TSPJ， the protein expression increased significantly （P<0.05， P<0.01）. ConclusionTSPJ could induce the browning of iWAT/BAT activation and enhance adaptive thermogenesis in obese mice induced by HFD. The underlying mechanism may be attributed to the activation of the PPARγ/PGC-1α signaling pathway.

Cysteine dioxygenase 1 (CDO1) gene is a non-heme structured, iron-containing metalloenzyme involved in the conversion of cysteine to cysteine sulfinic acid to regulate cysteine accumulation in vivo. Elevated levels of cysteine have been shown to be cytotoxic and neurotoxic, and this is the first important step in the breakdown of cysteine metabolism in mammalian tissues. The human CDO1 gene is located on chromosome 5q23.2. Studies have shown that deletion or epigenetic silencing of this chromosomal region contributes to tumorigenesis. It is highly expressed in the liver and placenta, and weakly in the heart, brain and pancreas. CDO1 is a tumor suppressor gene (TSG) with a wide range of functions, which can be involved in various biological processes such as tumor cell proliferation, differentiation, apoptosis and iron death, thus affecting the tumor development. CDO1 is epigenetically regulated in human cancers, compared to normal tissues. The CDO1’s mRNA or protein expression levels were significantly down-regulated in tumor tissues, whereas promoter DNA methylation of the CDO1 gene usually accumulates with the progression of human cancers. Aberrant hypermethylation on the CDO1 promoter is a common event in tumor cells, which leads to transcriptional inactivation and silencing of the CDO1 gene. High frequency of methylation of CDO1 gene promoter methylation region in a variety of tumors including breast, oesophageal, lung, bladder, gastric and colorectal cancers. CDO1 gene promoter methylation levels reflect cancer progression and malignant tumorigenesis, which is a common molecular indicator explaining poor prognosis in human cancers. Treatment with 5-aza-2′-deoxycytidine (a drug that promotes demethylation) reactivated the CDO1 expression in most cancer cell lines, indicating that the transcriptional expression of CDO1 is closely correlated with its promoter methylation level, CDO1 gene promoter methylation and tumor progression have also received increasing attention from researchers. It was found that CDO1 gene promoter hypermethylation can be used as an early tumor marker for clinical aid diagnosis and helps to differentiate cancerous from benign diseases. It was also found that CDO1 promoter DNA methylation showed reliable tumor monitoring potential in human body fluids, and furthermore, the degree of CDO1 promoter methylation was strongly correlated with resistance to chemotherapy with tumor drugs, which would be helpful in evaluating the efficacy of chemotherapeutic drugs. Thus, CDO1, a common promoter methylation gene in human cancers, is closely associated with the development of a wide range of tumors and is one of the most promising candidate genes for assessing tumor-specific epigenetic changes. This article reviews the biological functions of CDO1 and its promoter DNA methylation in tumors, focusing on the mechanism of CDO1 DNA promoter methylation in tumors, with a view to providing theoretical guidance for the clinical diagnosis and treatment of tumors with CDO1 as a potential therapeutic target.

There are huge differences between tumor cells and normal cells in material metabolism, and tumor cells mainly show increased anabolism, decreased catabolism, and imbalance in substance metabolism. These differences provide the necessary material basis for the growth and reproduction of tumor cells, and also provide important targets for the treatment of tumors. Ferroptosis is an iron-dependent form of cell death characterized by an imbalance of iron-dependent lipid peroxidation and lipid membrane antioxidant systems in cells, resulting in excessive accumulation of lipid peroxide, causing damage to lipid membrane structure and loss of function, and ultimately cell death. The regulation of ferroptosis involves a variety of metabolic pathways, including glucose metabolism, lipid metabolism, amino acid metabolism, nucleotide metabolism and iron metabolism. In order for tumor cells to grow rapidly, their metabolic needs are more vigorous than those of normal cells. Tumor cells are metabolically reprogrammed to meet their rapidly proliferating material and energy needs. Metabolic reprogramming is mainly manifested in glycolysis and enhancement of pentose phosphate pathway, enhanced glutamine metabolism, increased nucleic acid synthesis, and iron metabolism tends to retain more intracellular iron. Metabolic reprogramming is accompanied by the production of reactive oxygen species and the activation of the antioxidant system. The state of high oxidative stress makes tumor cells more susceptible to redox imbalances, causing intracellular lipid peroxidation, which ultimately leads to ferroptosis. Therefore, in-depth study of the molecular mechanism and metabolic basis of ferroptosis is conducive to the development of new therapies to induce ferroptosis in cancer treatment. Ferroptosis, as a regulated form of cell death, can induce ferroptosis in tumor cells by pharmacologically or genetically targeting the metabolism of substances in tumor cells, which has great potential value in tumor treatment. This article summarizes the effects of cellular metabolism on ferroptosis in order to find new targets for tumor treatment and provide new ideas for clinical treatment.

Objective To investigate the relationship of replication factor C subunit 2(RFC2)with the prognosis of glioblastoma(GBM)and cell proliferation,as well as its underlying molecular pathway in GBM development.Methods Using bioinformatics methods,cell cycle genes were screened as independent prognostic factors for GBM.Combined with clinical indicators,a risk scoring model for GBM patients was established and validated.The target gene RFC2 was analyzed with GO,KEGG,and GSEA.U87 GBM cells at logarithmic growth stage were transfected with lentivirus and divided into different groups(control,ShRFC2 # 1,and shRFC2 # 2 groups).qRT-PCR,Western blotting,Edu staining,and cloning assay were used to detect mRNA expression,protein expression,and cell proliferation.Results The expression of RFC2 was upregulated in GBM and showed an obvious upregulation trend with the increase of pathological grade of glioma.The analyses of gene function and pathway indicated that RFC2 was involved in the processes of sister chromosome segregation,chromosome segregation,organelle fission,and mitosis by promoting the transition of G1 to S phase during cell cycle.qRT-PCR and Western blotting showed that compared with the control group,the amount of mRNA and translated protein in the knockdowned groups decreased(P＜0.000 1).The positive rate of Edu staining and the colony forming ability decreased(P＜0.000 1,P＜0.001).Conclusion RFC2 is highly expressed in glioblastoma and associated with pathological grade of glioma and poor prognosis of patients.It also promotes the cell proliferation function of glioblastoma.RFC2 may be a potential biomarker and therapeutic target for glioblastoma.