“Runner’s high” refers to a momentary sense of pleasure that suddenly appears during running or other exercise activities, characterized by anti-anxiety, pain relief, and other symptoms. The neurobiological mechanism of “runner’s high” is unclear. This review summarizes human and animal models for studying “runner’s high”, analyzes the neurotransmitters and neural circuits involved in runner’s high, and elucidates the evidence and shortcomings of researches related to “runner’s high”. This review also provides prospects for future research. Research has found that exercise lasting more than 30 min and with an intensity exceeding 70% of the maximum heart rate can reach a “runner’s high”. Human experiments on “runner’s high” mostly use treadmill exercise intervention, and evaluate it through questionnaire surveys, measurement of plasma AEA, miRNA and other indicators. Animal experiments often use voluntary wheel running intervention, and evaluate it through behavioral experiments such as conditional place preference, light dark box experiments (anxiety), hot plate experiments (pain sensitivity), and measurement of plasma AEA and other indicators. Dopamine, endogenous opioid peptides, endogenous cannabinoids, brain-derived neurotrophic factor, and other substances increase after exercise, which may be related to the “runner’s high”. However, attention should be paid to the functional differences of these substances in the central and peripheral regions, as well as in different brain regions. Moreover, current studies have not identified the targets of the neurotransmitters or neural factors mentioned above, and further in-depth researches are needed. The mesolimbic dopamine system, prefrontal cortex-nucleus accumbens projection, ventral hippocampus-nucleus accumbens projection, red nucleus-ventral tegmental area projection, cerebellar-ventral tegmental area projection, and brain-gut axis may be involved in the regulation of runner’s high, but there is a lack of direct evidence to prove their involvement. There are still many issues that need to be addressed in the research on the neurobiological mechanisms of “runner’s high”. (1) Most studies on “runner’s high” involve one-time exercise, and the characteristics of changes in “runner’s high” during long-term exercise still need to be explored. (2) The using of scales to evaluate subjects lead to the lacking of objective indicators. However, some potential biomarkers (such as endocannabinoids) have inconsistent characteristics of changes after one-time and long-term exercise. (3) The neurotransmitters involved in the formation of the “runner’s high” all increase in the peripheral and/or central nervous system after exercise. Attention should be paid to whether peripheral substances can enter the blood-brain barrier and the binding effects of neurotransmitters to different receptors are completely different in different brain regions. (4) Most of the current evidence show that some brain regions are activated after exercise. Is there a functional circuit mediating “runner’s high” between these brain regions? (5) Although training at a specific exercise intensity can lead to “runner’s high”, most runners have not experienced “runner’s high”. Can more scientific training methods or technological means be used to make it easier for people to experience the “runner’s high” and thus be more willing to engage in exercise? (6) The “runner’s high” and “addiction” behaviors are extremely similar, and there are evidences that exercise can reverse addictive behaviors. However, why is there still a considerable number of people in the sports population and even athletes who smoke or use addictive drugs instead of pursuing the “pleasure” brought by exercise? Solving the problems above is of great significance for enhancing the desire of exercise, improving the clinical application of neurological and psychiatric diseases through exercise, and enhancing the overall physical fitness of the population.

This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*

This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Glucose/metabolism* ; Cell Line ; Inflammation/genetics* ; Oxygen/metabolism* ; Pyrazines/pharmacology* ; Microglia/metabolism* ; NF-E2-Related Factor 2/immunology* ; NF-kappa B/immunology* ; Toll-Like Receptor 4/immunology* ; Anti-Inflammatory Agents/pharmacology* ; Humans

Ferroptosis has received great attention as an iron-dependent programmed cell death for efficient cancer therapy. However, with the accumulation of iron in tumor cells, the antioxidant system is activated by reducing glutathione (GSH) with glutathione peroxidase 4 (GPX4), which critically limits the ferroptosis therapeutic effect. Herein, an iron and GPX4 silencing siRNA (siGPX4) co-encapsulated ferritin nanocage (HFn@Fe/siGPX4) was developed to enhance ferroptosis by disruption of redox homeostasis and inhibition of antioxidant enzyme synergistically. The siGPX4 were loaded into the nanocages by pre-incubated with iron, which could significantly improve the loading efficiency of the gene drugs when compared with the reported gene drug loading strategy by ferritin nanocages. And more iron was overloaded into the ferritin through the diffusion method. When HFn@Fe/siGPX4 was taken up by human breast cancer cell MCF-7 in a TfR1-mediated pathway, the excess iron ions in the drug delivery system could for one thing induce ferroptosis by the production of reactive oxygen species (ROS), for another promote siGPX4 escaping from the lysosome to exert gene silencing effect more effectively. Both the in vitro and in vivo results demonstrated that HFn@Fe/siGPX4 could significantly inhibit tumor growth by synergistical ferroptosis. Thus, the developed HFn@Fe/siGPX4 afforded a combined ferroptosis strategy for ferroptosis-based antitumor as well as a novel and efficient gene drug delivery system.

OBJECTIVE: To assess health equity in the Yangtze River region to improve understanding of the correlation between hand, foot, and mouth disease (HFMD) and socioeconomic factors. METHODS: From 2014-2016, data on HFMD incidence, population statistics, economic indicators, and meteorology from 26 cities along the Yangtze River were analyzed. A multi-city random-effects meta-analysis was performed to study the relationship between temperature and HFMD transmission, and health equity was assessed with respect to socio-economic impact. RESULTS: Over the study period, 919,458 HFMD cases were reported, with Shanghai (162,303) having the highest incidence and Tongling (5,513) having the lowest. Males were more commonly affected (male-to-female ratio, 1.49:1). The exposure-response relationship had an M-shaped curve, with two HFMD peaks occurring at 4 °C and 26 °C. The relative risk had two peaks at 1.30 °C (1.834, 95% CI: 1.204-2.794) and 31.4 °C (1.143, 95% CI: 0.901-1.451), forming an M shape, with the first peak higher than the second. The most significant impact of temperature on HFMD was observed between -2 °C and 18.1 °C. The concentration index (0.2463) indicated moderate concentration differences, whereas the Theil index (0.0418) showed low inequality in distribution. CONCLUSION The incidence of HFMD varied across cities, particularly with changes in temperature. Economically prosperous areas showed higher risks, indicating disparities. Targeted interventions in these areas are crucial for mitigating the risk of HFMD.
Female ; Humans ; Male ; China/epidemiology* ; Cities/epidemiology* ; Hand, Foot and Mouth Disease/transmission* ; Incidence ; Risk Factors ; Temperature

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

Objective　To explore the mediating role of cognitive function in the association between literacy level and depressive symptoms in middle-aged and elderly people in China. Methods　 Using the fourth national follow-up data of the China Health and Elderly Care Tracking Survey 2018, 8 124 middle-aged and elderly people aged 45 years and above were included as the study subjects. The PROCESS 4.0 program was used to test the mediating effect of cognitive function between literacy level and depressive symptoms, and the Bootstrap method was used for the mediator variable validation. Results The detection rate of depressive symptoms among middle-aged and elderly people in China was 38.10%. After controlling for gender, place of residence, marital status, smoking, alcohol consumption, and exercise, literacy level was a negative predictor of depressive symptoms in middle-aged and elderly people (β =－0.480, t =－11.248, P<0.001). Cognitive function accounted for 58.75% of the amount of mediating effect between literacy level and depressive symptoms. Conclusion 　Literacy level and cognitive function are associated with depressive symptoms in middle-aged and elderly people. Literacy level can influence depressive symptoms directly or indirectly through the mediation of cognitive dysfunction.

ObjectiveGQDs has become a superstar among zero-dimensional carbon-based materials. As one of the most abundant and important biological elements, its unique optical properties, high dispersion and biocompatibility have attracted extensive attention from scientists. This paper aims to investigate the effect of GQDs on cell viability, apoptosis and inflammatory factor expression in RAW264.7 macrophages and evaluate cell imaging capability of GQDs in vitro, which could provide theoretical basis for the safe application of GQDs in biomedical field. MethodsGraphene oxide was prepared by modified Hummer’s method. H₂O₂ and W₁₈O₄₉ interacted with each other under hydrothermal conditions to produce hydroxyl radicals, which can cut graphene oxide into GQDs using a top-down approach. The microstructure of GQDs was analyzed in detail by X-ray powder diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy, atomic force microscopy, scanning electron microscopy and Fourier infrared transform. The biocompatibility of GQDs on macrophage was evaluated by CCK-8 and dead/alive staining. Flow cytometry results showed the apoptosis of RAW264.7 macrophages induced by GQDs. mRNA expression of inflammatory factors was evaluated byRT-qPCR. Cell imaging was exhibited by laser scanning confocal. ResultsHydroxyl radicals are produced by H₂O₂ and W₁₈O₄₉ under hydrothermal conditions, which contribute to cut graphene oxide into 3-5 nm GQDs in one step. The quantum yield of this method is 43%. Fluorescence lifetime of these blue GQDs is 1.67 ns. The Zigzag-type site and defect state of the triplet carbene radical lead to the excitation wavelength dependence of GQDs, and the optimal excitation and emission wavelengths are 330 nm and 400 nm, respectively. The boundary effect and amphiphilicity of quantum dots make GQDs possess abundant functional groups, vacancy defects and high dispersion, which results in GQDs exhibits good water solubility. RAW264.7 macrophages are incubated with different concentration in DEME medium for 24 h, 48 h and 72 h to evaluate cell. The survival rate of RAW264.7 cells is significantly dependent on the concentration and time of GQDs. CCK-8 and dead/alive staining show that GQDs have high biocompatibility. The effect of 200 mg/L GQDs on apoptosis of RAW264.7 cells is revealed by the scatter plot of bivariate flow cytometry. Under the stimulation of LPS+INF‑γ, the expression of TNF-α was increased in RAW264.7 cells, which co-acted with other cytokines to participate in the immune response of RAW264.7 cells in vitro, and mediated the production of IL-1β inflammatory factor in RAW264.7 cells, thereby inducing apoptosis of RAW264.7 cells. The results of RT-qPCR showed that GQDs can inhibit the growth of RAW264.7 cells in vitro, and stimulate them to increase TNF-α expression in RAW264.7 cells, which make cell membrane rupture and produce IL-1β inflammatory factors to induce cell apoptosis. The high biocompatibility of GQDs is attributed to the rich oxygen-containing functional groups (―COOH, ―OH, and CO) on the surface of GQDs, which makes its surface negatively charged and easy to be swallowed into the cell interior when interacting with the cell membrane with low affinity. Transmission electron microscopy (TEM) observed that the GQDs were swallowed into the cells. Furthermore, laser confocal results displayed that blue GQDs has certain ability of cell imaging in vitro. ConclusionThe water solubility, low toxicity, fluorescence properties and the induction effect of inflammatory factors of GQDs provide broad prospects for their application in the field of immunotherapy and cell imaging in the future.

Purpose To analyze the relationship between different molecular types and imaging manifestations of simultaneous bilateral breast cancer.Materials and Methods Eighty-one patients with simultaneous bilateral breast cancer confirmed by surgery and pathology in the Affiliated Hospital of Qingdao University from January 2016 to May 2022 were retrospectively analyzed,80 patients received mammography and 38 patients received MRI.Imaging features referred to the 5th edition of the breast imaging reporting and data system standards.Molecular typing was evaluated and classified according to the 2013 revised St.Gallen international expert consensus recommended the determination.The clinicopathological and imaging features of the index and contralateral breast cancer were compared,and the imaging features of different molecular types of the index and contralateral breast cancer were also compared.Results There were statistically significant differences in histological types and molecular typing between the index and contralateral cancers(x2=39.72,12.23,P＜0.05).Mammograph showed that the index cancer was mostly a mass(51.9％,40/77),while the contralateral cancer was mostly calcification(38.4％,28/73);the index cancer was mostly polymorphic calcification(68.8％,22/32),while the contralateral cancer was mostly amorphous calcification(45.2％,19/42)(x2=33.15,10.47,P＜0.05).There was a statistically significant difference in the MRI enhancement between the index cancer and the contralateral cancer(x2=6.79,P＜0.05).For contralateral cancer,mammograms showed statistically significant differences in the four molecular subtypes on tumor density,as well as MRI enhancement patterns,early enhancement degree,and time-signal intensity curve(x2=26.72,7.49,8.95,13.44,12.85,P＜0.05).There was a significant difference in the distribution of calcification among the four molecular subtypes on the X-ray of the first cancer(x2=20.15,P＜0.05).Conclusion The molecular typing and some imaging characteristics of simultaneous bilateral breast cancer are different,and some imaging characteristics can provide reference for predicting the molecular typing of simultaneous bilateral breast cancer.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.