“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.

ObjectiveTo evaluate the clinical efficacy of Huayu Tongluo Formula （化瘀通络方， HTF） in patients with mid-stage diabetic kidney disease of blood stasis syndrome and explore its potential mechanisms. MethodsA multi-center， randomized， double-blind， placebo-controlled clinical trial was conducted. Ninety patients of mid-stage diabetic kidney disease of blood stasis syndrome were divided into a control group of 46 cases and a treatment group of 44 cases. Both groups received conventional western medicine treatment， the treatment group additionally taking HTF， while the control group taking a placebo of the formula. The treatment was administered once daily for 24 weeks. The primary outcomes included 24-hour urine total protein （24 h-UTP）， serum albumin （Alb）， glycated hemoglobin （HbA1c）， and serum creatinine （Scr）.The secondary outcomes included changes in levels of endothelin-1 （ET-1）， nitric oxide （NO）， vascular endothelial growth factor （VEGF）， and traditional Chinese medicine （TCM） syndrome scores before and after treatment. Clinical efficacy was evaluated based on TCM syndrome scores and overall disease outcomes. Adverse reactions and endpoint events were recorded. ResultsIn the treatment group after treatment， 24 h-UTP， ET-1， and VEGF levels significantly decreased （P＜0.05）， Alb and NO levels significantly increased （P＜0.05）； while the TCM syndrome scores for edema， lumbar pain， numbness of limbs， dark purple lips， dark purple tongue or purpura， and thin， rough pulse all significantly decreased （P＜0.05）. In the control group， no significant changes were observed in any of the indicators after treatment （P＞0.05）.Compared with the control group， the treatment group showed significant reductions in 24 h-UTP， ET-1， and VEGF levels， and increases in Alb and NO levels （P＜0.05）. The TCM syndrome scores for edema， lumbar pain， dark purple tongue or purpura， and thin， rough pulse were all lower in the treatment group than in the control group （P＜0.05）. The total effective rate of TCM syndrome in the treatment group was 59.09% （26/44）， and the overall clinical effective rate was 45.45% （20/44）. In the control group， these rates were 15.22% （7/46） and 8.7% （4/46）， respectively， with the treatment group showing significantly better outcomes （P＜0.05）. A total of 7 adverse events occurred across both groups， with no significant difference （P＞0.05）. No endpoint events occurred during the study. ConclusionOn the basis of conventional treatment of Western medicine， HTF can further reduce urinary protein levels and improve clinical symptoms in patients with mid-stage diabetic kidney disease of blood stasis syndrome. The mechanism may be related to its effects on endothelial function.

Objective To understand the current situation of nutrition literacy of primary and secondary school students in Shijingshan District of Beijing, and analyze its influencing factors, and to put forward targeted suggestions for improving the students’ nutrition literacy and promoting their healthy growth. Methods A multi-stage stratified cluster sampling method was used to select 2480 primary and secondary school students and their parents from 5 primary schools, 3 middle schools and 1 high school in Shijingshan District. The multivariate logistic regression model was used to analyze the factors influencing the attainment rate of nutrition literacy. Results The median score of nutrition literacy of 2480 primary and secondary school students from grades 1 to 12 was 77.86 (in hundred-mark system), the quartile range (IQR) was 16.96, and the attainment rate of nutrition literacy was 42.46%. The cognitive level (45.12%) was higher than the skill level (41.20%) among students from grades 3 to 12. In terms of skills, the attainment rate of food preparation was the lowest, at 30.38%. The scores of nutrition literacy of girls were higher than those of boys, and the scores of primary school students were higher than those of secondary school students. Students with different levels of caregiver’s education, family income, and family food environment had different scores of nutrition literacy, and the differences were statistically significant (P<0.05). Multivariate logistic regression analysis showed that the attainment rate of nutrition literacy was closely related to student’s gender and study stage, caregiver’s education level, and family food environment. Conclusion The nutrition literacy of primary and secondary school students in Shijingshan District still needs to be improved, especially in the aspect of skills. Targeted nutrition education should be carried out.

Objective:To investigate effects of mesalazine(MS)on proliferation,apoptosis and inflammatory injury of cell model of ulcerative colitis(UC)induced by lipopolysaccharide(LPS),as well as transforming growth factor-β1(TGF-β1)/Smad signaling pathway effect in this study.Methods:Human colonic epithelial cells NCM-460 cultured in vitro were induced UC model by LPS,and divided into Con group(no treatment),LPS group(1 mg/L LPS),MS group(0.1,0.2,0.4 mg/L MS+1 mg/L LPS)and inhibitor group(10 μmol/L TGF-β1/Smad signaling pathway inhibitor LY2109761+0.2 mg/L MS+1 mg/L LPS).Cell morphology,proliferation,apoptosis and levels of inflammatory factors and TGF-β1/Smad pathway-related markers were examined by inverted microscope,EdU assay,Hoechst 33258 staining,ELISA and Western blot.Results:LPS treatment highly induced cell proliferation rate and Smad7 pro-tein level compared with Con group,while apoptotic cells,inflammatory factors TNF-α and IL-6,soluble interleukin-2 receptor(sIL-2R)release,as well as TGF-β1,p-Smad2,p-Smad3 protein expressions were increased;the above effects induced by LPS was reversed by MS in a dose-dependent manner(P<0.05).Compared with 0.2 mg/L MS group,NCM-460 cells proliferation rate and Smad7 expression were increased,while apoptotic cells,TNF-α and IL-6,sIL-2R releases,and TGF-β1,p-Smad2,p-Smad3 protein expressions were decreased(P<0.05).Conclusion:MS can attenuate LPS-induced apoptosis and inflammatory injury in NCM-460 cells,and this protection was possibly through suppressing TGF-β1/Smad signaling pathway.

BACKGROUND:Intramedullary nails and locking plates are widely used in the treatment of proximal humeral fractures,but there is no consensus on the choice of internal fixation. OBJECTIVE:To compare the biomechanical stability of intramedullary nails and locking plates in the treatment of two-part and three-part proximal humeral fractures by finite element analysis. METHODS:CT data of the humerus of a volunteer were collected and imported into Minics 21.0,Geomagic Wrap,Soildwork 2017,and Abaqus 2021 to establish finite element models of two-part and three-part fractures treated with two internal fixation methods,respectively.Group A:two-part fracture fixed with intramedullary nail model;group B:two-part fracture fixed with locking plate model;group C:three-part fracture fixed with intramedullary nail model;group D:three-part fracture fixed with locking plate model.The stress distribution,displacement degree,and maximum value of the humerus and internal fixation were compared and analyzed. RESULTS AND CONCLUSION:(1)The maximum stress and maximum displacement of the humerus were the smallest in the model of group A,and the maximum stress and maximum displacement of the humerus were the largest in the model of group D.The stress of the locking plate group was mainly concentrated in the medial inferior part of the humeral head and the screw hole area,while the stress of the intramedullary nail group was mainly concentrated around the fracture line and the lateral inferior part of the surgical neck of the humerus.There is no significant difference in displacement distribution between the two.It is mainly concentrated in the distal humerus.(2)The maximum stress value of the intramedullary nail was the lowest in the model of group A,and the maximum stress value of the locking plate was the highest in the model of group D.The maximum stress of the two internal fixations was mainly concentrated in the talar screw and the connection with the internal fixation.The stress cloud distribution of the locking steel plate was concentrated,while the stress cloud distribution of the intramedullary nail was more uniform.(3)The results showed that compared with the locking plate,the intramedullary nail had more biomechanical advantages,and this advantage was more obvious in three-part fractures.

Objective To observe the effects of Levo-tetrahydropalmatine(l-THP)on the expression,regression and relapse of conditioned place preference(CPP)in ketamine induced rats,and to detect the content of dopamine(DA)in the striatum(caudate putamen,CPu)of the rat brain at different time points.Methods Ketamine addiction rat model was established by CPP.The effects of l-THP on the expression,regression and relapse of ketamine induced rat CPP were investigated using CPP score as the index.The content of DA in CPu of rats was determined by ultra-performance liquid chromatography coupled to tandem mass spectrometry(UPLC-MS/MS)after ketamine administration and l-THP intervention at 30 min,60 min,90 min,120 min and 150 min.Results It indicated that 1-THP could decrease the expression of CPP in ketamine induced rats,promote the process of CPP resolution and inhibit the process of relapse.In addition,l-THP combined with ketamine administration significantly inhibited the ketamine-induced increase in DA content in the CPu of the rats.Conclusion The mechanism of l-THP inhibiting the reward effect of ketamine may be related to blocking DA receptors and reducing the release of DA neurotransmitters.l-THP has potential implications for the treatment of ketamine addiction.

ObjectiveTo investigate the role and possible mechanism of action of rhubarb decoction （RD） retention enema in improving inflammatory damage of brain tissue in a rat model of mild hepatic encephalopathy （MHE）. MethodsA total of 60 male Sprague-Dawley rats were divided into blank group （CON group with 6 rats） and chronic liver cirrhosis modeling group with 54 rats using the complete randomization method. After 12 weeks， 40 rats with successful modeling which were confirmed to meet the requirements for MHE model by the Morris water maze test were randomly divided into model group （MOD group）， lactulose group （LT group）， low-dose RD group （RD1 group）， middle-dose RD group （RD2 group）， and high-dose RD group （RD3 group）， with 8 rats in each group. The rats in the CON group and the MOD group were given retention enema with 2 mL of normal saline once a day； the rats in the LT group were given retention enema with 2 mL of lactulose at a dose of 22.5% once a day； the rats in the RD1， RD2， and RD3 groups were given retention enema with 2 mL RD at a dose of 2.5， 5.0， and 7.5 g/kg， respectively， once a day. After 10 days of treatment， the Morris water maze test was performed to analyze the spatial learning and memory abilities of rats. The rats were analyzed from the following aspects： behavioral status； the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） and the level of blood ammonia； pathological changes of liver tissue and brain tissue； the mRNA and protein expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （AKT）， and mammalian target of rapamycin （mTOR） in brain tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the MOD group， the RD1， RD2， and RD3 groups had a significantly shorter escape latency （all P<0.01）， significant reductions in the levels of ALT， AST， IL-1β， IL-6， TNF-α， and blood ammonia （all P<0.05）， significant alleviation of the degeneration， necrosis， and inflammation of hepatocytes and brain cells， and significant reductions in the mRNA and protein expression levels of PI3K， AKT， and mTOR in brain tissue （all P<0.05）， and the RD3 group had a better treatment outcome than the RD1 and RD2 groups. ConclusionRetention enema with RD can improve cognitive function and inflammatory damage of brain tissue in MHE rats， possibly by regulating the PI3K/AKT/mTOR signaling pathway.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of Guangdong Province,China. Methods This study included individuals aged 28 days-85 years.A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens,including RVA,using a Gastrointestinal Pathogen Panel,followed by genotyping,virus isolation,and complete sequencing to assess the genetic diversity of RVA. Results The overall RVA infection rate was 14.59%(103/706),with an irregular epidemiological pattern.The proportion of co-infection with RVA and other pathogens was 39.81%(41/103).Acute gastroenteritis is highly prevalent in young children aged 0-1 year,and RVA is the key pathogen circulating in patients 6-10 months of age with diarrhea.G9P[8](58.25%,60/103)was found to be the predominant genotype in the RVA strains,and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis.Recombination analysis showed that gene reassortment events,selection pressure,codon usage bias,gene polymorphism,and post-translational modifications(PTMs)occurred in the G9P[8]and G3P[8]strains. Conclusion This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China,further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity.Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

Objective To explore the clinical value of vaginoscopy in the diagnosis and treatment of uterine cavity diseases in virgins.Methods We retrospectively reviewed the data of 450 patients who underwent vaginoscopy and traditional hysteroscopy in Obstetrics and Gynecology Hospital,Fudan University from Jan 2020 to Dec 2023,including vaginoscopy group(n=232)and traditional hysteroscopy group(n=218).The average ages of the two groups were 24.9±4.7 years and 25.5±5.4 years,and there was no significant difference between the two groups(P>0.05).The operation time,estimated blood loss,fluid deficit,false passage,surgical failure,incidence of complications and postoperative pain score were compared between vaginoscopy group and traditional hysteroscopy group.Results Compared with the traditional hysteroscopy group,the average operation time in the vaginoscopy group was shorter,the fluid deficit was less,and the VAS pain score was lower,but the rate of surgical failure was higher(7.8%vs.0),all the differences were statistically significant(P<0.05).In terms of complications,the incidence of false passage in the vaginoscopy group was less(0 vs.3.2%)and the rate of hymen injury was lower(0 vs.85.3%),the differences were statistically significant(P<0.05).There was no significant difference in the estimated blood loss between the two groups,and the incidence of postoperative infection was similar in both groups.There were no complications such as uterine perforation and air embolism in both groups.Conclusion Vaginoscopy is safe and effective,more minimally invasive than traditional hysteroscopy,does not damage the hymen,and is suitable for virgins.This technology is worthy of clinical application.