“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.

Objective To observe the effectiveness of fluorescence labeling-based assay bundle intervention in the prevention and control of multidrug-resistant organism(MDRO)infection.Methods Patients who were detected MDRO in a hospital from January to December 2022 were selected as the research subjects.MDRO monitoring data and implementation status of prevention and control measures were collected.Fluorescence labeling assay was adopted to monitor the cleaning and disinfection effectiveness of the surrounding object surface of the bed units.Based on the bundled prevention and control measures as well as management mode of the pre-intervention group,the post-intervention group implemented enhanced rectification measures for the problems found by the pre-interven-tion group.Changes in relevant indicators between January-June 2022(before intervention)and July-December 2022(after intervention)were compared.Results There were 136 MDRO-infected patients in the pre-intervention group,208 MDRO strains were detected and 10 healthcare-associated infection(HAI)occurred.There were 128 MDRO-infected patients in the post-intervention group,198 MDRO strains were detected and 9 HAI occurred.Af-ter intervention,the total detection rates of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-re-sistant Acinetobacter baumannii(CRAB),and total MDRO from patients decreased significantly compared to before intervention(all P＜0.05).After intervention,the detection rates of MRSA,carbapenem-resistant Pseudomonas aeruginosa(CRPA),CRAB,and total MDRO from the surrounding object surface were all lower than those before intervention(all P＜0.05).The detection rate of MDRO from surrounding object surface before intervention was 34.52％,which showed a decreased trend after intervention(P＜0.05).The clearance rate of fluorescent labeled markers before intervention was 41.84％,which showed an upward trend after implementing intervention measures(from July to December),and increased to 85.00％at the end of intervention(November-December).The comp-liance rates of issuing isolation medical orders,placing isolation labels,using medical supplies exclusively,and cor-rectly handling medical waste after intervention have all increased compared to before intervention(all P＜0.05).Conclusion Adopting fluorescence labeling-based assay bundle intervention can effectively improve the effectiveness of MDRO infection prevention and control.

To further enhance the immune effect of the foot-and-mouth disease (FMD) virus-like particles (VLPs) vaccine, this study prepared FMDV VLPs-zeolitic imidazolate (framework-8, ZIF-8) complexes with different particle sizes. We used a biomimetic mineralization method with Zn²⁺ and 2-methylimidazole in different concentration ratios to investigate the effect of size on the immunization effect. The results showed that FMDV VLPs-ZIF-8 with three different sizes were successfully prepared, with an approximate size of 70 nm, 100 nm, and 1 000 nm, respectively. Cytotoxicity and animal toxicity tests showed that all three complexes exhibited excellent biological safety. Immunization tests in mice showed that all three complexes enhanced the titers of neutralizing and specific antibodies, and their immune effects improved as the size of the complexes decreased. This study showed that ZIF-8 encapsulation of FMDV VLPs significantly enhanced their immunogenic effect in a size-dependent manner.
Animals ; Mice ; Foot-and-Mouth Disease/prevention & control* ; Foot-and-Mouth Disease Virus ; Antibodies, Neutralizing ; Immunity, Humoral ; Immunization ; Vaccines, Virus-Like Particle ; Antibodies, Viral ; Viral Vaccines

AIM: To report 5 cases with drug-induced bilateral acute ciliochoroidal effusion(DBACE)and myopic shift, with or without ocular hypertension(OHT), summarize patients' clinical characteristics and recovery process of DBACE, and investigate the possible pathophysiological mechanism.METHODS:A retrospective observational case study conducted from June 2017 to February 2021. The included patients were subjected to a series of ocular examinations listed as follows: 1)best corrected visual acuity; 2)intraocular pressure(IOP); 3)slit-lamp microscopy; 4)fundus photography; 5)ultrasound biomicroscopy(UBM); 6)subjective optometry; 7)axial length and anterior chamber depth. All patients were followed up every 2d until the diopters were completely restored to the state before the disease onset.RESULTS:In total, 5 patients aged 10-45 years old, including 3 female and 2 male patients, were enrolled in this study. All patients were bilaterally involved(5/5), and had myopic shift(5/5), of whom 3 patients had OHT(3/5). With the increase of age, myopic shift decreased, while OHT increased. Based on OHT, the dynamic aggravation process of DBACE was subdivided into 2 stages, stage 1(myopic shift without OHT)and stage 2(myopic shift with OHT). With the deterioration of DBACE, when myopic shift approached or exceeded the minimum amplitude of accommodation(MAA), IOP gradually rose, and DBACE progressed from stage 1 to stage 2. With the recovery of DBACE after discontinuing the suspicious drugs, DBACE in stage 2 first returned to stage 1, and then returned to normal.CONCLUSION:Pathophysiological mechanism of DBACE was subdivided into 2 stages, including stage 1(myopic shift without OHT)and stage 2(myopic shift with OHT). The transition between the two stages depends on the imbalance between myopic shift and MAA.

Bungarus Parvus, a precious animal Chinese medicinal material used in clinical practice, is believed to be first recorded in Ying Pian Xin Can published in 1936. This study was carried out to analyze the names, geographical distribution, morphological characteristics, ecological habits, poisonousness, and medicinal parts by consulting ancient Chinese medical books and local chronicles, Chinese Pharmacopeia, different processing standards of trditional Chinese medicine(TCM) decoction pieces, and modern literatures. The results showed that the earliest medicinal record of Bungarus Parvus was traced to 1894. In 1930, this medicinal material was used in the formulation of Annao Pills. The original animal, Bungarus multicinctus, was recorded by the name of "Bojijia" in 1521. The morphological characteristics, ecological habits, and poisonousness of the original animal are the same in ancient and modern records. The geographical distribution is similar between the ancient records and modern documents such as China Medicinal Animal Fauna. The dried body of young B. multicinctus is used as Bungarus Parvus, which lack detailed references. As a matter of fact, it is still inconclusive whether there are differences between young snakes and adult snakes in terms of active ingredients, pharmacological effects, and clinical applications. This study clarified the medicinal history and present situation of Bungarus Parvus. On the basis of the results, it is suggested that systematic comparison on young and adult B. multicinctus should be carried out to provide references for revising the medicinal parts of B. multicinctus.
Animals ; Bungarus ; Snakes ; China ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal

Humans ; Child ; Primary Myelofibrosis/genetics* ; Prognosis ; Mutation

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Objective:To establish a risk prediction model for neonatal asphyxia in cesarean section and test its application effect.Methods:This was a retrospective study. We retrospectively analyzed the clinical data of 2 244 infants (modeling group) who were delivered by cesarean section in Affiliated Hospital of Weifang Medical University from April 2021 to December 2021. Newborns were divided into asphyxia group ( n=176) and non-asphyxia group ( n=2 068) according to the occurrence of neonatal asphyxia. Logistic regression was used to screen the risk factors of neonatal asphyxia in cesarean section and a line chart model was established to predict the risk. Another 683 neonates were selected as validation group for external validation of the model from January to March in 2022. Results:Five factors including preterm birth, fetal distress, fetal growth restriction, abnormal S/D value of umbilical artery and umbilical cord around the neck were included in the prediction model. The area under ROC curve of the modeling group was 0.902, the Youden index was 0.687, the sensitivity was 0.837, and the specificity was 0.850. Hosmer-lemeshow test showed that χ2=1.79, and P=0.877. In the validation group, the area under ROC curve was 0.823, the Youden index was 0.555, the sensitivity was 0.835, and the specificity was 0.720. It showed that the model had a good fitting effect and identification validity. Conclusions:The risk prediction model has a good clinical application value in the prediction of neonatal asphyxia in cesarean section, and provides reference for obstetricians to take preventive management measures of neonatal asphyxia in time.

Inflammation, abnormal cholesterol metabolism, and macrophage infiltration are involved in the destruction of the extracellular matrix of the nucleus pulposus (NP), culminating in intervertebral disc degeneration (IDD). Whether nimbolide (Nim), a natural extract, can alleviate IDD is unclear. In this study, we demonstrated that Nim promotes cholesterol efflux and inhibits the activation of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by activating sirtuin 1 (SIRT1) in nucleus pulposus cells (NPCs) during inflammation. Thus, Nim balanced matrix anabolism and catabolism of NPCs. However, the inhibition of SIRT1 significantly attenuated the effects of Nim. We also found that Nim promoted the expression of SIRT1 in RAW 264.7, which enhanced the proportion of M2 macrophages by facilitating cholesterol homeostasis reprogramming and impeded M1-like macrophages polarization by blocking the activation of inflammatory signaling. Based on these results, Nim can improve the microenvironment and facilitate matrix metabolism equilibrium in NPCs. Furthermore, in vivo treatment with Nim delayed IDD progression by boosting SIRT1 expression, modulating macrophage polarization and preserving the extracellular matrix. In conclusion, Nim may represent a novel therapeutic strategy for treating IDD.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens