“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.

Background: The development of frailty at hospital discharge affects the clinical outcomes in severe coronavirus disease 2019 (COVID-19) survivors who had no frailty before hospitalization. We aimed to describe the prevalence of new frailty using the clinical frailty scale (CFS) and evaluate its associated factors in patients with severe COVID-19 without pre-existing frailty before hospitalization. Methods: We performed a secondary analysis of clinical data from a nationwide retrospective cohort collected from 22 hospitals between January 1, 2020 and August 31, 2021. The patients were at least 19 years old and survived until discharge after admission to the intensive care unit (ICU) because of severe COVID-19. Development of new frailty was defined as a CFS score ≥5 at hospital discharge. Results: Among 669 severe COVID-19 survivors without pre-existing frailty admitted to the ICU, the mean age was 65.2±12.8 years, 62.5% were male, and 50.2% received mechanical ventilation (MV). The mean CFS score at admission was 2.4±0.9, and new frailty developed in 27.8% (186/483). In multivariate analysis, older age, cardiovascular disease, CFS score of 3–4 before hospitalization, increased C-reactive protein level, longer duration of corticosteroid treatment, and use of MV and extracorporeal membrane oxygenation were identified as factors associated with new-onset frailty. Conclusion Our study suggests that new frailty is not uncommon and is associated with diverse factors in survivors of severe COVID-19 without pre-existing frailty.

Background: The development of frailty at hospital discharge affects the clinical outcomes in severe coronavirus disease 2019 (COVID-19) survivors who had no frailty before hospitalization. We aimed to describe the prevalence of new frailty using the clinical frailty scale (CFS) and evaluate its associated factors in patients with severe COVID-19 without pre-existing frailty before hospitalization. Methods: We performed a secondary analysis of clinical data from a nationwide retrospective cohort collected from 22 hospitals between January 1, 2020 and August 31, 2021. The patients were at least 19 years old and survived until discharge after admission to the intensive care unit (ICU) because of severe COVID-19. Development of new frailty was defined as a CFS score ≥5 at hospital discharge. Results: Among 669 severe COVID-19 survivors without pre-existing frailty admitted to the ICU, the mean age was 65.2±12.8 years, 62.5% were male, and 50.2% received mechanical ventilation (MV). The mean CFS score at admission was 2.4±0.9, and new frailty developed in 27.8% (186/483). In multivariate analysis, older age, cardiovascular disease, CFS score of 3–4 before hospitalization, increased C-reactive protein level, longer duration of corticosteroid treatment, and use of MV and extracorporeal membrane oxygenation were identified as factors associated with new-onset frailty. Conclusion Our study suggests that new frailty is not uncommon and is associated with diverse factors in survivors of severe COVID-19 without pre-existing frailty.

OBJECTIVE: To explore the efficacy and apoptosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute myeloid leukemia (AML) with ASXL1 mutation. METHODS: The clinical data of 80 AML patients with ASXL1 mutation treated in our hospital from January 2019 to December 2021 were retrospectively analyzed. The clinical characteristics of the patients were summarized, and the therapeutic effect and prognostic factors of allo-HSCT for the patients were analyzed. RESULTS: Among the 80 patients, 38 were males and 42 were females, and the median age was 39(14-65) years. There were 17 patients in low-risk group, 25 patients in medium-risk group and 38 patients in high-risk group. ASXL1 mutation co-occurred with many other gene mutations, and the frequent mutated genes were TET2 (71.25%), NRAS (18.75%), DNMT3A (16.25%), NPM1 (15.00%), CEBPA (13.75%). Among medium and high-risk patients, 29 underwent allo-HSCT, while 34 received chemotherapy. The 2-year overall survival (OS) rate and disease-free survival (DFS) rate of the allo-HSCT group were 72.4% and 70.2%, while those of the chemotherapy group were 44.1% and 34.0%, respectively. The statistical analysis showed significant differences between the two groups (both P < 0.01). Multivariate analysis showed that age at transplantation >50- years and occurrence of acute graft-versus-host disease after transplantation were poor prognostic factors for OS and DFS in transplantation patients. CONCLUSION Allo-HSCT can improve the prognosis of AML patients with ASXL1 mutation.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Mutation ; Adult ; Repressor Proteins/genetics* ; Adolescent ; Retrospective Studies ; Aged ; Nucleophosmin ; Young Adult ; Transplantation, Homologous ; Prognosis ; Survival Rate

OBJECTIVE: To explore the role of semaphorin 4D (Sema4D) in immunoglobulin A (IgA) -mediated immune abnormalities in B lymphocytes of pediatric Henoch-Schonlein purpura (HSP). METHODS: One hundred HSP children admitted to Hengshui People's Hospital from January 2022 to January 2023 were selected as HSP group, and one hundred healthy children as control group. Sema4D expression was detected, and the relationship between Sema4D expression in children's serum and skin lesions and clinical characteristics of children was analyzed. Sema4D expression on the surface of lymphocytes of HSP children was detected. Different concentrations of human recombinant Sema4D protein was used to stimulate peripheral blood mononuclear cells in HSP children in vitro. The expression level of IgA in the supernatant was detected to verify whether Sema4D mediates immune abnormalities through IgA secreted by B lymphocytes. RESULTS: The Sema4D level in the HSP group was significantly higher than that in the control group (P <0.001). Sema4D level in HSP children with severe, renal involvement, and joint involvement was higher than those with mild to moderate disease, and no renal or joint involvement (all P <0.001). Compared with control group, IgA level, CD8 ⁺ T lymphocyte proportion, and CD19 ⁺ B lymphocyte proportion in the HSP group were significantly higher but CD4 ⁺ T lymphocyte proportion was lower (all P <0.001). The expression levels of Sema4D on the surface of CD4 ⁺ T lymphocytes, CD8 ⁺ T lymphocytes, and CD19 ⁺ B lymphocytes in the HSP group were significantly higher than those in the control group (all P <0.001). With the increase of human recombinant Sema4D protein concentration, the level of IgA expression in HSP children gradually increased (P <0.05). Correlation analysis showed that Sema4D was significantly positively correlated with IgA (r =0.667). CONCLUSION HSP children show high expression of Sema4D, especially on the surface of T and B lymphocytes. The shedding of Sema4D from membrane surface may stimulate B lymphocytes to secrete IgA by binding to CD72, leading to immune abnormalities.
Humans ; IgA Vasculitis/immunology* ; Semaphorins/metabolism* ; B-Lymphocytes/metabolism* ; Immunoglobulin A/immunology* ; Child ; Antigens, CD/metabolism* ; Male ; Female ; Child, Preschool

BACKGROUND: The atherogenic index of plasma (AIP) has been shown to be positively correlated with cardiovascular disease in previous studies. However, it is unclear whether elderly people with long-term high AIP levels are more likely to develop coronary heart disease (CHD). Therefore, the aim of this study was to investigate the relationship between AIP trajectory and CHD incidence in elderly people. METHODS: 19,194 participants aged ≥ 60 years who had three AIP measurements between 2018 and 2020 were included in this study. AIP was defined as log₁₀ (triglyceride/high-density lipoprotein cholesterol). The group-based trajectory model was used to identify different trajectory patterns of AIP from 2018 to 2020. Cox proportional hazards models were used to estimate the hazard ratio (HR) with 95% CI of CHD events between different trajectory groups from 2020 to 2023. RESULTS: Three different trajectory patterns were identified through group-based trajectory model: the low-level group (n = 7410, mean AIP: -0.25 to -0.17), the medium-level group (n = 9981, mean AIP: 0.02-0.08), and the high-level group (n = 1803, mean AIP: 0.38-0.42). During a mean follow-up of 2.65 years, a total of 1391 participants developed CHD. After adjusting for potential confounders, compared with the participants in the low-level group, the HR with 95% CI of the medium-level group and the high-level group were estimated to be 1.24 (1.10-1.40) and 1.43 (1.19-1.73), respectively. These findings remained consistent in subgroup analyses and sensitivity analyses. CONCLUSIONS There was a significant correlation between persistent high AIP level and increased CHD risk in the elderly. This suggests that monitoring the long-term changes in AIP is helpful to identify individuals at high CHD risk in elderly people.

Background: The development of frailty at hospital discharge affects the clinical outcomes in severe coronavirus disease 2019 (COVID-19) survivors who had no frailty before hospitalization. We aimed to describe the prevalence of new frailty using the clinical frailty scale (CFS) and evaluate its associated factors in patients with severe COVID-19 without pre-existing frailty before hospitalization. Methods: We performed a secondary analysis of clinical data from a nationwide retrospective cohort collected from 22 hospitals between January 1, 2020 and August 31, 2021. The patients were at least 19 years old and survived until discharge after admission to the intensive care unit (ICU) because of severe COVID-19. Development of new frailty was defined as a CFS score ≥5 at hospital discharge. Results: Among 669 severe COVID-19 survivors without pre-existing frailty admitted to the ICU, the mean age was 65.2±12.8 years, 62.5% were male, and 50.2% received mechanical ventilation (MV). The mean CFS score at admission was 2.4±0.9, and new frailty developed in 27.8% (186/483). In multivariate analysis, older age, cardiovascular disease, CFS score of 3–4 before hospitalization, increased C-reactive protein level, longer duration of corticosteroid treatment, and use of MV and extracorporeal membrane oxygenation were identified as factors associated with new-onset frailty. Conclusion Our study suggests that new frailty is not uncommon and is associated with diverse factors in survivors of severe COVID-19 without pre-existing frailty.

Background: The development of frailty at hospital discharge affects the clinical outcomes in severe coronavirus disease 2019 (COVID-19) survivors who had no frailty before hospitalization. We aimed to describe the prevalence of new frailty using the clinical frailty scale (CFS) and evaluate its associated factors in patients with severe COVID-19 without pre-existing frailty before hospitalization. Methods: We performed a secondary analysis of clinical data from a nationwide retrospective cohort collected from 22 hospitals between January 1, 2020 and August 31, 2021. The patients were at least 19 years old and survived until discharge after admission to the intensive care unit (ICU) because of severe COVID-19. Development of new frailty was defined as a CFS score ≥5 at hospital discharge. Results: Among 669 severe COVID-19 survivors without pre-existing frailty admitted to the ICU, the mean age was 65.2±12.8 years, 62.5% were male, and 50.2% received mechanical ventilation (MV). The mean CFS score at admission was 2.4±0.9, and new frailty developed in 27.8% (186/483). In multivariate analysis, older age, cardiovascular disease, CFS score of 3–4 before hospitalization, increased C-reactive protein level, longer duration of corticosteroid treatment, and use of MV and extracorporeal membrane oxygenation were identified as factors associated with new-onset frailty. Conclusion Our study suggests that new frailty is not uncommon and is associated with diverse factors in survivors of severe COVID-19 without pre-existing frailty.

Background: The development of frailty at hospital discharge affects the clinical outcomes in severe coronavirus disease 2019 (COVID-19) survivors who had no frailty before hospitalization. We aimed to describe the prevalence of new frailty using the clinical frailty scale (CFS) and evaluate its associated factors in patients with severe COVID-19 without pre-existing frailty before hospitalization. Methods: We performed a secondary analysis of clinical data from a nationwide retrospective cohort collected from 22 hospitals between January 1, 2020 and August 31, 2021. The patients were at least 19 years old and survived until discharge after admission to the intensive care unit (ICU) because of severe COVID-19. Development of new frailty was defined as a CFS score ≥5 at hospital discharge. Results: Among 669 severe COVID-19 survivors without pre-existing frailty admitted to the ICU, the mean age was 65.2±12.8 years, 62.5% were male, and 50.2% received mechanical ventilation (MV). The mean CFS score at admission was 2.4±0.9, and new frailty developed in 27.8% (186/483). In multivariate analysis, older age, cardiovascular disease, CFS score of 3–4 before hospitalization, increased C-reactive protein level, longer duration of corticosteroid treatment, and use of MV and extracorporeal membrane oxygenation were identified as factors associated with new-onset frailty. Conclusion Our study suggests that new frailty is not uncommon and is associated with diverse factors in survivors of severe COVID-19 without pre-existing frailty.

Sinisan is a classical prescription developed and applied by ancient medical experts and it is first recorded in the Treatise on Cold Damage written by ZHANG Zhongjing in the Eastern Han Dynasty. Later physicians have modified this prescription based on this original one. The bibliometrics methods were used to analyze the key information and research trend of Sinisan. According to the inclusion and exclusion criteria， 69 pieces of effective data were extracted， involving 67 ancient traditional Chinese medicine （TCM） books. The results showed that the name， composition， and decocting methods of Sinisan in later generations were inherited from the original record in the Treatise on Cold Damage. The original plants of medicinal materials used in Sinisan are basically clear. We recommend Bupleuri Radix as the dried root of Bupleurem scorzonerifolium， Paeoniae Radix Alba as the dried root of Paeonia lactiflora， Aurantii Fructus as the dried fruit of Citrus aurantium， Glycyrrhizae Radix et Rhizoma as the dry root and rhizome of Glycyrrhiza uralensis. Raw materials of Bupleuri Radix and Paeoniae Radix Alba， Aurantii Fructus stir-fried with bran， and stir-fried Glycyrrhizae Radix et Rhizoma should be used for preparation of Sinisan. According to measurement system in the Han Dynasty， a bag of Sinisan is composed of 1.25 g Bupleuri Radix， 1.25 g Paeoniae Radix Alba， 1.25 g Aurantii Fructus， and 1.25 g Glycyrrhizae Radix et Rhizoma. The materials should be grounded into coarse powder and taken with a proper amount of rice soup， 3 times a day. Sinisan has the effects of regulating qi movement and harmonizing the liver and spleen. It can be used for treating reversal cold in limbs and cold damage. In modern clinical practice， Sinisan can be used to treat chronic gastritis， irritable bowel syndrome， and dyspepsia. The above research results provide scientific reference for the future research and development of Sinisan.