ObjectiveTo explore the target of Erzhiwan in reducing myocardial injury in ovariectomized mice through non-targeted myocardial metabolomics combined with experimental verification. MethodsOvariectomized mouse model was selected， 40 female C57BL/6 mice were randomly divided into sham operation group， model group， estrogen group（estradiol valerate， 1.3×10^-4 g·kg^-1）， Erzhiwan low and high dose groups（3.12， 9.36 g·kg^-1）， with 8 mice in each group. Each administration group was given the corresponding dose of Erzhiwan by gavage， and the sham operation group and model group were given equal volume of distilled water by gavage for 12 weeks. Echocardiography was used to detect cardiac function， hematoxylin-eosin（HE） staining was used to observe myocardial morphological changes， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of estrogen， N-terminal pro-brain natriuretic peptide（NT-proBNP）， hypersensitive troponin T（hs-TnT）， total cholesterol（TC）， triglyceride（TG）， low density lipoprotein cholesterol（LDL-C）， high density lipoprotein cholesterol（HDL-C）， interleukin（IL）-1β， IL-18 and tumor necrosis factor-α（TNF-α）. The non-targeted metabolomics of mouse myocardium were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， and the differential metabolites and corresponding metabolic pathways were obtained. The mRNA expression levels of phosphatidylinositol 3-kinase（PI3K） and protein kinase B（Akt） in mouse myocardial tissues were detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the protein expression levels of PI3K， Akt， phosphorylated（p）-Akt were detected by Western blot. ResultsCompared with the sham operation group， the model group showed abnormal cardiac function， increased myocardial fiber space， cardiomyocyte atrophy， sarcoplasmic aggregation， and occasional dissolution or rupture of muscle fiber， the level of estrogen in the serum was decreased， the levels of NT-proBNP， hs-TnT， IL-1β， IL-18， TNF-α， TG， TC and LDL-C were increased， and the level of HDL-C was decreased（P<0.01）. Compared with the model group， Erzhiwan could increase the level of estrogen， improve the abnormal cardiac function， reduce the pathological injury of myocardial tissue， decrease the levels of myocardial injury markers（NT-proBNP， hs-TnT） and inflammatory factors（IL-1β， IL-18， TNF-α）， decrease the levels of TG， TC， LDL-C， and increased the level of HDL-C（P<0.01）. The results of non-targeted myocardial metabolomics showed that 31 of the 162 differential metabolites between the model group and sham operation group were significantly adjusted after administration of Erzhiwan， which were mainly glycerol phospholipid metabolites. Pathway enrichment results showed that Erzhiwan mainly affected glycerophospholipid metabolic pathway， PI3K-Akt pathway， cyclic guanosine monophosphate（cGMP）-protein kinase G（PKG） pathway and other metabolic pathways. Compared with the sham operation group， the levels of phosphatidylcholine（PC， 11 types） and phosphatidylethanolamine（PE， 5 types） in mouse myocardial tissue of the model group were increased（P<0.05， P<0.01）， and the mRNA and protein expressions of PI3K and p-Akt were decreased（P<0.05， P<0.01）. Compared with the model group， the levels of PC（11 types） and PE（5 types） were decreased（P<0.05， P<0.01） in myocardial tissue of Erzhiwan group， the mRNA and protein expressions of PI3K and p-Akt were elevated（P<0.01）. ConclusionErzhiwan can alleviate the pathological injury of myocardium in ovariectomized mice， improve the abnormal cardiac function， improve lipid metabolism disorder， and reduce the levels of myocardial injury markers and inflammatory factors， which involves a number of signaling and metabolic pathways in the heart， among which glycerophospholipid metabolism pathway and PI3K/Akt pathway may have key roles.

Objective: To establish a prediction model for high-risk cardiovascular disease (CVD) among residents aged 35 to 75 years, so as to provide the basis for improving CVD prevention and control measures. Methods: Permanent residents aged 35 to 75 years were selected from Dongcheng District, Beijing Municipality using the stratified random sampling method from 2018 to 2023. Demographic information, lifestyle, waist circumference and blood biochemical indicators were collected through questionnaire surveys, physical examinations and laboratory tests. Influencing factors for high-risk CVD among residents aged 35 to 75 years were identified using a multivariable logistic regression model, and a prediction model for high-risk CVD was established. The predictive effect was evaluated using the receiver operating characteristic (ROC) curve. Results: A total of 6 968 individuals were surveyed, including 2 821 males (40.49%) and 4 147 females (59.51%), and had a mean age of (59.92±9.33) years. There were 1 155 high-risk CVD population, with a detection rate of 16.58%. Multivariable logistic regression analysis showed that gender, age, smoking, central obesity, systolic blood pressure, fasting blood glucose, triglyceride and low-density lipoprotein cholesterol were influencing factors for high-risk CVD among residents aged 35 to 75 years (all P<0.05). The area under the ROC curve of the established prediction model was 0.849 (95%CI: 0.834-0.863), with a sensitivity of 0.693 and a specificity of 0.863, indicating good discrimination. Conclusion The model constructed by eight factors including demographic characteristics, lifestyle and blood biochemical indicators has good predictive value for high-risk CVD among residents aged 35 to 75 years.

Objective To construct programmed cell death protein-ligand 1(PD-LI)^hi tolerogenic dendritic cell (tol-DC) derived from bone marrow of DA rats and identify its immunological function. Methods DA rat bone marrow cells were extracted, combined with recombinant mouse granulocyte macrophage colony-stimulating factor and recombinant mouse interleukin (IL)-4, and cultured for 6 days in vitro to induce the differentiation of bone marrow cells into immature dendritic cells (imDC). Lipopolysaccharide was used to stimulate cell maturation and cultured for 2 days to collect mature dendritic cells (mDC). PD-L1 lentiviral vector virus stock solution or equivalent dose lentiviral stock solution was added, and PD-L1^hitol-DC and Lv-imDC were collected after culture for 2 days. The morphology of PD-L1^hitol-DC was observed by inverted phase contrast microscope and transmission electron microscope. Real-time fluorescence quantitative reverse transcription polymerase chain reaction, Western blotting and flow cytometry were used to detect the expression level of specific markers on cell surface. CD8⁺T cells derived from Lewis rat spleen were co-cultured with imDC, mDC, Lv-imDC and PD-L1^hitol-DC, respectively. The levels of inflammatory factors in the supernatant of each group were detected by enzyme-linked immunosorbent assay. The apoptosis of T cells and the differentiation of regulatory T cells (Treg) in each group were analyzed by flow cytometry. Results The morphology of PD-L1^hitol-DC modified by PD-L1 gene was consistent with tol-DC characteristics, and the expression levels of CD80, CD86 and major histocompatibility complex (MHC) on the surface were low. After mixed culture with CD8⁺ T cells, the levels of IL-10 and transforming growth factor (TGF) -β1 in the supernatant of PD-L1^hitol-DC group were higher, the levels of tumor necrosis factor (TNF) -α and IL-17A were lower, and the apoptosis of T cells and Treg differentiation were increased. Conclusions Overexpression of PD-L1 through lentiviral vectors may successfully induce the construction of bone-marrow derived PD-L1^hitol-DC in DA rats, promote the secretion of anti-inflammatory factors and T cell apoptosis, induce the differentiation of Treg, and inhibit the immune response of allogeneic CD8⁺T cells, which provides experimental basis for the next organ transplantation immune tolerance study.

AIM: To investigate the effects of insulin-like growth factor 1(IGF-1)on the secretion of transforming growth factor β2(TGF-β2), matrix metalloproteinase 2(MMP-2)and hypoxia-inducible factor 1α(HIF-1α)in human scleral fibroblasts(HSF)and their mechanism.METHODS: The cells were cultured with IGF-1 and PI3K/AKT pathway inhibitor LY294002, respectively. CCK-8 method was used to detect cell viability and determine the optimal concentration and time of drug action. Cell migration activity was observed by cell scratch method. To determine the effects of IGF-1 on HSF cells and the regulatory role of PI3K/AKT pathway, HSF cells were divided into control group(without drugs), IGF-1(80 μg/L)group, IGF-1+LY294002(80 μg/L+5 mmol/L)group, and LY294002(5 mmol/L)group, and were cultured for 24 h; the protein expression levels of TGF-β2, MMP-2, HIF-1α, PI3K and AKT were detected by Western blot; the fluorescence expression of TGF-β2, MMP-2 and HIF-1α was detected by cellular immunofluorescence.RESULTS: The results of CCK-8 showed that the cell viability of the 80 μg/L IGF-1 group cultured with different concentrations of IGF-1 was the highest(all P<0.05), and the cell viability of the 80 μg/L IGF-1 group at 24 h was the highest under different culture times. Therefore, the concentration of IGF-1 was selected as 80 μg/L for 24 h. The viability of cells cultured with different concentrations of LY294002 gradually decreased from 6 h(all P<0.05). According to the IC50 value, therefore, the concentration of LY294002 was selected as 5 mmol/L for 24 h. The cell scratch results showed that compared with the control group, the cell mobility of 40 μg/L and 80 μg/L IGF-1 groups was increased(all P<0.05). Compared with the control group, cell mobility in the 2.5 and 5 mmol/L LY294002 groups was decreased(all P<0.05). Western blot results showed that compared with the control group, the protein expressions of TGF-β2, MMP-2, HIF-1α, PI3K and AKT in the IGF-1 group were increased, while those in the LY294002 group were decreased(all P<0.05). Compared with the IGF-1 group, the expression levels of TGF-β2, MMP-2, HIF-1α, PI3K and AKT in the IGF-1+LY294002 group were decreased(all P<0.05). The results of cell immunofluorescence showed that compared with the control group, the fluorescence expressions of TGF-β2, MMP-2 and HIF-1α in the IGF-1 group were increased, while those in the LY294002 group were decreased(all P<0.05). Compared with the IGF-1 group, the fluorescence expressions of TGF-β2, MMP-2 and HIF-1α in the IGF-1+LY294002 group were significantly decreased(all P<0.05).CONCLUSION: IGF-1 promoted the proliferation and migration of human HSF. IGF-1 may up-regulate the expression of TGF-β2, MMP-2 and HIF-1α in HSF through the PI3K/AKT signaling pathway, and participate in the occurrence and development of myopia.

Parkinson’s disease (PD) is a common neurodegenerative disorder with profound impact on patients’ quality of life and long-term health, and early detection and intervention are particularly critical. In recent years, the search for precise and reliable biomarkers has become one of the key strategies to effectively address the clinical challenges of PD. In this paper, we systematically evaluated potential biomarkers, including proteins, metabolites, epigenetic markers, and exosomes, in the peripheral blood of PD patients. Protein markers are one of the main directions of biomarker research in PD. In particular, α‑synuclein and its phosphorylated form play a key role in the pathological process of PD. It has been shown that aggregation of α-synuclein may be associated with pathologic protein deposition in PD and may be a potential marker for early diagnosis of PD. In terms of metabolites, uric acid, as a metabolite, plays an important role in oxidative stress and neuroprotection in PD. It has been found that changes in uric acid levels may be associated with the onset and progression of PD, showing its potential as an early diagnostic marker. Epigenetic markers, such as DNA methylation modifications and miRNAs, have also attracted much attention in Parkinson’s disease research. Changes in these markers may affect the expression of PD-related genes and have an important impact on the onset and progression of the disease, providing new research perspectives for the early diagnosis of PD. In addition, exosomes, as a potential biomarker carrier for PD, are able to carry a variety of biomolecules involved in intercellular communication and pathological regulation. Studies have shown that exosomes may play an important role in the pathogenesis of PD, and their detection in blood may provide a new breakthrough for early diagnosis. It has been shown that exosomes may play an important role in the pathogenesis of PD, and their detection in blood may provide new breakthroughs in early diagnosis. In summary, through in-depth evaluation of biomarkers in the peripheral blood of PD patients, this paper demonstrates the important potential of these markers in the early diagnosis of PD and in the study of pathological mechanisms. Future studies will continue to explore the clinical application value of these biomarkers to promote the early detection of PD and individualized treatment strategies.

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.

It has been demonstrated that long-term space flights have a significantly greater impact on the cardiovascular, skeletal, and nervous systems of astronauts. The structural and functional alterations in the skeletal and muscular systems resulting from exposure to weightlessness can lead to the development of low back pain, significantly impairing the ability of astronauts to perform tasks and respond to emergencies. Both space flight and simulated microgravity have been shown to result in low back pain among astronauts, with the following factors identified as primary contributors to this phenomenon. The occurrence of intervertebral disc (IVD) edema results in the stimulation of type IV mechanoreceptors, which subsequently activate nociceptive afferents. The protrusion of an IVD causes compression of the spinal nerve roots. Furthermore, the elongation of the vertebral column and/or the diminished lumbar curvature of the spine exert traction on the dorsal root nerves. Paravertebral muscle degeneration leads to the inhibition of decreased nociceptive activity of the wide-dynamic range neurons of the spinal dorsal horn. Moreover, endogenous pain descending facilitation triggered by conditioning stimulation can be enhanced via the thalamic mediodorsal nuclei, while endogenous pain descending inhibition triggered by conditioning stimulation can be weakened via the thalamic ventromedial nuclei. Psychological factors may contribute to the development of low back pain. The mechanisms governing the generation, maintenance, and alleviation of low back pain in weightlessness differ from those observed in normal gravitational environments. This presents a significant challenge for space medicine research. Therefore, the elucidation of the occurrence and development mechanism of low back pain in weightlessness is important for the prevention and treatment during space flight. To reduce the incidence of low back pain during long-term missions on the space station, astronauts may choose to wear specialized space clothing that can provide axial physiological loads, designed to stimulate both musculature and skeletal structures, mitigating potential increases in vertebral column length, diminished lumbar curvature, and intervertebral disc edema and/or muscular atrophy. Additionally, assuming a “fetal tuck position” described as the knees to chest position may increase lumbar IVD hydrostatic pressure, subsequently reducing disc volume, rectifying diminished lumbar curvature, and alleviating dorsal root nerve tensions. Moreover, this position may reduce type IV mechanoreceptor facilitation and nerve impulse propagation from the sinuvertebral nerves of the annulus fibrosus. Elongated posterior soft tissues (apophyseal joint capsules and ligaments) with spinal flexion may potentially stimulate type I and II mechanoreceptors. It is also recommended to exercise the paraspinal muscles to prevent and alleviate the decrease in their cross-sectional area and maintain their structure and function. Photobiomodulation has been proved to be an effective means of activating the pain descending inhibition pathway of the central nervous system. In addition, astronauts should be encouraged to participate in mission-related activities and strive to avoid psychological problems caused by the long-term confinement in a small space station. The article presents a concise review of potential causes and targeted treatment strategies for low back pain induced by space flight or simulated microgravity in recent years. Its objective is to further elucidate the mechanisms underlying the occurrence and development of low back pain in weightless environments while providing scientific evidence to inform the development of guidelines for preventing, treating, and rehabilitating low back pain during long-term space flights.

Objective To assess the risk of hearing loss caused by occupational noise exposure in workers in an automobile manufacturing plant in Tianjin, China, and to perform risk management. Methods Occupational health field investigation and noise exposure measurements were conducted from July to December 2023, and physical examination data were collected. ISO 1999:2013(E) Acoustics-Estimation of Noise-Induced Hearing Loss and WS/T 754-2016 ^“Guidelines for Risk Management of Occupational Disease Hazards Caused by Noise^” were used to predict the risk of high-frequency hearing loss and occupational noise induced deafness for operational workers and make a risk classification. Results The noise intensity of each workshop was 79.4 to 95.5 dB(A), and the maximum noise intensity of welding and stamping exceeded the standard. The results of the assessment showed that the noise level remained unchanged, and the risk of HFHL and ONID in workers increased as the predicted age and length of service increased. It was predicted that after the age of 40, the maximum risk of hearing loss in welding workers would be high risk, and the risk of stamping workers would be at higher risk, suggesting that welding and stamping were the key control posts of noise hazards in the enterprise. The N50 prediction values of permanent hearing threshold displacement caused by potential noise at all frequencies for final assembly and painting workers were lower than the measured values. Conclusion The consequences of hearing loss for workers in the welding and stamping shop noise operations at this automobile manufacturing plant are relatively serious and require risk management.

ObjectiveTo investigate the potential mechanism of Renshen Yangrongtang in alleviating myelosuppression by regulating the expression of reactive oxygen species （ROS）， myeloperoxidase （MPO）， and neutrophil extracellular traps （NETs）. MethodsK562 cells were divided into blank group， etoposide group （40 μmol·L^-1）， and etoposide+Renshen Yangrongtang freeze-dried powder groups with low-， medium-， and high-dose （2， 4， 8 g·L^-1）. Liquid chromatography-mass spectrometry （LC-MS） was used to determine the freeze-dried powder of Renshen Yangrongtang. Enzyme-Linked Immunosorbent Assay （ELISA） was used to detect ROS， MPO， and NETs expression in each group. Western blot analysis was performed to assess intracellular MPO and NE expressions. Twenty 8-week-old male mice were randomly divided into blank group， etoposide group （100 mg·kg^-1）， and etoposide + Renshen Yangrongtang groups with low-， medium-， and high-dose （0.1， 0.5， 2.0 g·kg^-1）. Except for the blank group that received PBS via gavage at room temperature， and the etoposide group that received an intraperitoneal injection for 3 days， the remaining groups received gavage of Renshen Yangrongtang for 14 consecutive days after 3 days of etoposide administration. The peripheral blood related indicators were detected through an automated hematology analyzer； Western blot analysis was performed to assess MPO and neutrophil elastase （NE） expression changes in the marrow cells of mice. Enzyme-linked immunosorbent assay （ELISA） was used to detect ROS， MPO， and NETs changes in the marrow cells of mice. MPO and NE on femur bones were stained through immunohistochemistry. Scanning electron microscopy was used to analyze the structural changes of NETs in the marrow cells of mice after drug administration. ResultsLC-MS results showed that the freeze-dried powder of Renshen Yangrongtang contained complete technical materials such as Chinese angelica， Astragalus mongholicus， and ginseng. In K562 cells， compared with the etoposide group， ELISA results indicated that the concentrations of MPO， ROS， and NETs in the etoposide + Renshen Yangrongtang medium and high-dose groups were decreased （P<0.05， P<0.01）， and Western blot data showed that the etoposide high-dose group significantly reduced the expression of MPO and NE protein in K562 cells （P<0.05， P<0.01）. In vivo， compared with the etoposide group， the number of RBC， WBC， and PLT in the etoposide+Renshen Yangrongtang high-dose group increased significantly （P<0.05）. ELISA results suggested that in the etoposide+Renshen Yangrongtang low-， medium-， and high-dose groups， the concentration of mice ROS， MPO， and NETs significantly decreased （P<0.05， P<0.01）. Western blot results revealed that compared with the etoposide group， the expressions of MPO and NE in the marrow cells of mice in the etoposide + Renshen Yangrongtang low-， medium- and high-dose groups were significantly decreased （P<0.05， P<0.01）. Scanning electron microscopy observations revealed that Renshen Yangrongtang reduced the NETs structure generation in the marrow cells of mice after the influence of etoposide. ConclusionRenshen Yangrongtang can alleviate etoposide-induced myelosuppression by inhibiting ROS/MPO and reducing the formation of intracellular NETs.

Recurrent spontaneous abortion （RSA） is a common gynecological disease during pregnancy， clinically characterized by repeated spontaneous abortions， yet its pathological mechanism remains incompletely understood. Traditional Chinese medicine attributes the pathogenesis of RSA to the deficiency of Chong Ren and the lack of fetal solidity. It has amassed experience in treating RSA， with Shoutaiwan being widely utilized for addressing miscarriage symptoms such as habitual abortion due to kidney deficiency， bleeding during pregnancy， and fetal movement. In recent years， there has been a gradual increase in experimental studies on the application of Shoutaiwan in treating RSA and on related experiments. These studies have demonstrated that Shoutaiwan preserves the fetus mainly by modulating hormone balance， alleviating immune inflammation， and enhancing blood coagulation equilibrium during pregnancy. Besides， through the modulation of key signaling pathways such as nuclear factor， erythroid 2 like 2 （Nrf2）/heme oxygenase-1 （HO-1） and Janus kinase 1 （JAK1）/signal transducer and activator of transcription （STAT）， as well as mitogen-activated protein kinase （MAPK）， Shoutaiwan has improved cellular antioxidant capacity， adjusted the phenotype of trophoblast and metaphase cells， and inhibited immune rejection， thus improving the pregnancy success rate. These findings not only elucidate the diverse biological foundations underlying Shoutaiwan's efficacy in treating RSA but also offer a scientific rationale for its clinical application and further mechanism research. Nonetheless， there remains a dearth of systematic reviews on RSA treatment with Shoutaiwan. Therefore， this review summarizes and synthesizes existing research findings to systematically analyze existing literature and studies， delving deeply into the principal pharmacological effects and associated signaling pathways of Shoutaiwan in regulating RSA. It aims to establish crucial reference points for its clinical application in RSA treatment and future experiments and research.