“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 Arsenic is an environmentally harmful substance that causes hepatic insulin resistance and liver damage, increasing the risk of type 2 diabetes mellitus. Objective To explore whether the insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) is involved in insulin resistance in HepG2 cells after arsenic exposure through the peroxisome-proliferator-activated receptor γ (PPAR-γ) / glucose transporter 4 (GLUT4) pathway. Methods Cell viability was determined using cell counting kit 8 (CCK8) and an appropriate NaAsO₂ infection dose was determined. A cellular arsenic exposure model of HepG2 cells was established by four concentrations of NaAsO₂ solution for 24 h (the experiment was divided into four groups: 0, 2, 4, and 8 μmol·L⁻¹); HepG2 cells were firstly treated with pcDNA3.1-IGF2BP2 and pcDNA3.1-NC respectively for 6 h, then with 8 μmol·L⁻¹ NaAsO₂ for 24 h to establish a IGF2BP2 overexpression cell model (the experiment was divided into 4 groups: control, NaAsO₂, NaAsO₂+pcDNA3.1-IGF2BP2, and NaAsO₂+pcDNA3.1-NC); finally the cells were subject to 100 nmol·L⁻¹ insulin stimulation for 30 min. Glycogen and glucose in HepG2 cells were determined by glycogen and glucose assay kits; mRNA expression levels of IGF2BP2 were measured by quantitative real-time PCR; protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in HepG2 were detected by Western blot (WB); and the binding of IGF2BP2 to PPAR-γ and PPAR-γ to GLUT4 was verified by co-immunoprecipitation (CO-IP) experiment. Results The results of CCK8 experiment showed a dose-effect relationship between NaAsO₂ concentration and cell viability. When the concentration of NaAsO₂ was ≥4 μmol·L⁻¹ , the cell viabilities were lower than that of the control group (P <0.05). With the increasing dose of NaAsO₂ infection, reduced glucose consumption and glycogen levels in HepG2 cells were found in the 2, 4, and 8 μmol·L⁻¹ NaAsO₂ treatment groups compared to the control group (P <0.05). The difference between the mRNA expression level of IGF2BP2 in the HepG2 cells treated with 4 or 8 μmol L⁻¹ NaAsO₂ and the control group was significant (P <0.05). In the IGF2BP2 overexpression cell model, compared with the control group, glucose consumption and glycogen levels were lowered in the NaAsO₂ group (P <0.05), the mRNA expression level of IGF2BP2 and the protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in the cell membrane were all decreased (P <0.05). Compared with the NaAsO₂ group, the glucose consumption and glycogen levels were increased in the NaAsO₂+pcDNA3.1-IGF2BP2 group (P <0.05), and the mRNA expression level of IGF2BP2 and the protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in the cell membrane were all increased (P <0.05). The results of CO-IP experiments showed that IGF2BP2 interacted with PPAR-γ as well as PPAR-γ with GLUT4 protein. Conclusion IGF2BP2 is involved in arsenic exposure-induced insulin resistance in HepG2 cells by acting on the PPAR-γ/GLUT4 pathway.

BACKGROUND:Individuals with chronic ankle instability are prone to inversion ankle sprains during landing.Moderately increasing the foot toe-out angle during landing may reduce the occurrence of inversion ankle sprains,but no studies have directly demonstrated this effect. OBJECTIVE:To explore the effect of increased toe-out angle during landing on the peak inversion angle,peak angular velocity,and the time to peak inversion among individuals with and without chronic ankle instability. METHODS:A total of 60 participants were recruited for this study,including 30 individuals with chronic ankle instability and 30 without chronic ankle instability.The study utilized a simulated sprain apparatus for drop-landing tests,featuring a platform that could tilt forward by 24° and inward by 15°,thus simulating the foot position during an ankle inversion sprain.Participants were required to perform drop-landing tests under two landing conditions:natural landing and toe-out landing,with the latter involving a greater foot toe-out angle,over 150%more than the former.Kinematic data of participants were recorded using a 12-camera three-dimensional motion capture system.Data analysis was conducted using two-way repeated measures analysis of variance and Spearman correlation analysis. RESULTS AND CONCLUSION:(1)Significant main effects of condition were found for peak inversion angle during drop-landing(P<0.001,η2 p=0.270),peak inversion velocity(P=0.015,η2 p=0.098),and peak inversion time(P<0.001,η2 p=0.260);a significant main effect of group was found for peak inversion velocity(P=0.029,η2 p=0.080).(2)There were significant negative correlations between the foot toe-out angle at landing and the peak ankle inversion angle(P=0.021,r=-0.310;P=0.042,r=-0.278)as well as the peak inversion time(P=0.018,r=-0.312;P=0.021,r=-0.309)in both chronic ankle instability and non-chronic ankle instability groups.Moreover,a significant negative correlation was also found between the foot toe-out angle and peak inversion velocity in the chronic ankle instability group(P=0.021,r=-0.312).(3)It is indicated that increasing the foot toe-out angle at landing can reduce the peak inversion angle,peak inversion velocity,and the peak inversion time during landing in patients with chronic ankle instability and non-chronic ankle instability,thereby decreasing the risk of ankle inversion sprains.

Solid organ transplantation has significantly prolonged the survival of patients with end-stage diseases. However, long-term use of immunosuppressants will increase the risk of post-transplantation diabetes mellitus (PTDM) in the recipients, thereby elevating the risk of infection, cardiovascular disease and death. In recent years, with persistent improvement of diagnostic criteria of PTDM, clinicians have deepened the understanding of this disease. Compared with type 2 diabetes mellitus, PTDM significantly differs in pathophysiological characteristics and clinical progression. Hence, different treatment strategies should be adopted. Early identification of risk factors of organ transplant recipients, early diagnosis and intervention are of significance for improving the quality of life of recipients, prolonging the survival of grafts and reducing the fatality of recipients. Therefore, the diagnosis, incidence and risk factors of PTDM were reviewed in this article, aiming to provide reference for clinicians to deliver prompt diagnosis and intervention for PTDM.

With persistent breakthrough and maturity of surgical procedures and postoperative immunosuppressive therapy, the survival rate of liver transplant recipients and grafts has been significantly increased. The shortage of donor liver has become the main obstacle for clinical development of liver transplantation. How to expand the source of donor liver has become an urgent issue. Groundbreaking progresses have been made in the use of common marginal donor livers in clinical liver transplantation, such as elderly donor liver, steatosis donor liver, viral hepatitis donor liver and liver from donation after cardiac death. Nevertheless, multiple restrictions still exist regarding the use of marginal donor liver. Consequently, the definition of marginal donor liver and research progress in the application of common marginal donor livers were reviewed, and the opportunities and challenges of mariginal donoor liver were illustrated, aiming to provide reference for expanding the donor pool for clinical liver transplantation and bringing benefits to more patients with end-stage liver disease.

Objective To explore the effect of scutellarin on lipopolysaccharide(LPS)induced neuroinflammation in BV-2 microglia cells.Methods BV-2 microglia were cultured and randomly divided into 6 groups:control group(Ctrl),cyclic GMP-AMP synthetase(cGAS)inhibitor RU320521 group(RU.521 group),LPS group,LPS+RU.521 group,LPS+scutellarin pretreatment group(LPS+S)and LPS+S+RU.521 group.The expressions of cGAS,stimulator of interferon gene(STING),nuclear factor kappa B(NF-κB),phosphorylated NF-κB(p-NF-κB),neuroinflammatory factors PYD domains-containing protein 3(NLRP3)and tumor necrosis factor α(TNF-α)in BV-2 microglia were detected by Western blotting and immunofluorescent double staining(n= 3).Results Western blotting and immunofluorescent double staining showed that compared with the control group,the expression of cGAS,STING,p-NF-κB,NLRP3 and TNF-α in BV-2 microglia increased significantly after LPS induction(P<0.05),while the expression of cGAS,STING,p-NF-κB,NLRP3 and TNF-α in LPS+S group were significantly lower than those in LPS group(P<0.05).Treatment with cGAS pathway inhibitor RU.521 showed similar effects as the pre-treatment group with scutellarin.In addition,the change of NF-κB in each group was not statistically significant(P>0.05).Conclusion Scutellarin inhibits the neuroinflammation mediated by BV-2 microglia cells,which may be related to cGAS-STING signaling pathway.

Objective To analyze the morphological alterations of corpus callosum in children with spastic cerebral palsy(SCP)using three-dimensional magnetization prepared rapid acquisition gradient echo(3D-MPRAGE)technology and to investigate the correlation between morphological indexes and gross motor function.Methods Sagittal T1WI 3D-MPRAGE data was collected from 136 children with SCP(SCP group)and 132 age-and gender-matched healthy controls(HC)(HC group),and the gross motor function measure-88(GMFM-88)was applied to assess the gross motor function.Independent sample t-test was used to compare the corpus callosum surface area,volume,maximum anterior-posterior diameter,median sagittal area(total area and area of Ⅰ-Ⅴ zone)between the two groups.Partial correlation analysis was performed to calculate the correlation between morphological indexes of the corpus callosum and GMFM-88 with age as a covariate.Results Children under 3 years old,the corpus callosum surface area of the SCP group(3 914.51 mm2±1 207.97 mm2)was lower than that of the HC group(5 725.51 mm2±1 412.66 mm2).The volume of the corpus callosum(6 108.46 mm3±2 803.97 mm3)in the SCP group was lower than that of the HC group(11 297.96 mm3±4 109.02 mm3).Also,the maximum anterior-posterior diameter of the corpus callosum in the SCP group(53.40 mm±6.31 mm)was lower than that of the HC group(57.74 mm±6.04 mm)(all P<0.05).Children over 3 years old,the corpus callosum surface area of the SCP group(4 970.06 mm2±1 191.31 mm2)was lower than that of the HC group(6 372.55 mm2±1 445.59 mm2).The volume of the corpus callosum(8 330.20 mm3±2 888.20 mm3)in the SCP group was lower than that of the HC group(13 599.82 mm3±3 429.81 mm3)(all P<0.05).Partial correlation analysis showed significant correlation between corpus callosum volume,median sagittal area and gross motor score(P<0.01)with age as a covari-ate.Conclusion The 3D-MPRAGE technology can be useful for the comprehensive assessment of morphological alterations of the corpus callosum in SCP.The corpus callosum volume,and median sagittal area may become neuroimaging references for the assess-ment of motor development in cerebral palsy(CP).

BACKGROUND:The threaded conical implant has a good ability to control micro movements and is conducive to immediate loading.However,the effects of double-threaded conical cylindrical implants and conical cylindrical implants on stress distribution and initial stability of implant-bone interface after immediate loading have not been reported. OBJECTIVE:To investigate the impact of double-threaded conical cylindrical implants and conical cylindrical implants on the biological distribution of the implant and the surrounding bone interface during immediate loading in the mandibular molar region. METHODS:(1)Three-dimensional finite element analysis:Conical beam CT scans of the mandible and first molar of a volunteer were used to develop a basal model of the mandible.The double-threaded conical cylindrical implants and conical cylindrical implants were assembled with the mandibular models,and an immediate-load(or delayed implantation)implant model(a total of four models)for the first mandibular molar was established.Loads in four directions(100 N):axial,lingual and buccal 45°,mesial and distal,and buccal and lingual,were applied to the central fossa of each model's crown.Three-dimensional finite element method was used to analyze the implant displacement and the stress distribution at the implant-bone interface.(2)In vitro experiment:With the assistance of the oral implant robot,the double-threaded conical cylindrical implants and conical cylindrical implants were implanted on the same artificial bone pieces,separately,and the immediate load model of immediate implant implantation(or delayed implantation)was established in vitro(a total of four groups of models).Osstell resonance frequency analyzer and SmartPeg sensor were used to measure the implant stability coefficient in four vertical directions:front,rear,left,and right measurements,evaluate the initial stability,and verify the finite element analysis results. RESULTS AND CONCLUSION:(1)The displacement difference between double-threaded conical cylindrical implants and conical cylindrical implants was small when the immediate loading of delayed implantation was applied,but the maximum stress value of conical cylindrical implant-bone interface was greater than that of double-threaded conical cylindrical implant-bone interface.When the immediate loading of immediate implantation was applied,the maximum stress value and the maximum displacement of bone around the implant appeared when the load was applied in mesiodistal direction.The stress value of the conical cylindrical implant reached 298.84 MPa and the maximum displacement was 0.31 mm,both of which were larger than that of the double-threaded conical cylindrical implant.(2)The results of in vitro experiments showed that the stability coefficient of the double-threaded conical cylindrical implant was greater than that of the conical cylindrical implant.(3)Compared with the conical cylindrical implant,the double-threaded conical cylindrical implant has higher initial stability under immediate loading,suggesting that the use of double-threaded conical cylindrical implant should be given priority in clinical immediate loading.

BACKGROUND:In the past,it was necessary to cut off the pronator quadratus muscle in the treatment of distal radius fractures.Failure to repair the pronator quadratus muscle can lead to a series of complications. OBJECTIVE:To explore the clinical efficacy of different methods of preserving the pronator quadratus muscle combined with a palmar steel plate in the treatment of distal radius fractures. METHODS:Clinical data of 66 patients with distal radius fractures were retrospectively included,divided into the traditional Henry approach group(group A),the split brachioradialis tendon approach group(group B),and the posterior pronator quadratus muscle approach group(group C),with 22 patients in each group.Postoperative internal fixation,fracture healing,and postoperative complications were observed in the three groups.The visual analog scale score of postoperative wrist pain and forearm rotation angle were compared among the three groups.The Dienst Joint Scale was used to evaluate the wrist function of patients. RESULTS AND CONCLUSION:(1)The surgical time,intraoperative blood loss,and fracture healing time of groups B and C were significantly lower than those of group A(P<0.01).There was no significant difference in intraoperative blood loss and fracture healing time between groups B and C,but the surgical time was shorter in group B.(2)The anteroposterior and lateral wrist X-ray examination 3 days and 1 and 3 months after surgery exhibited that there were no significant differences in radial height,palm angle,and ulnar deviation angle among the three groups(P>0.05).No significant difference was detected in various indicators during the same phase among the three groups(P>0.05).(3)At a follow-up of 12 months after surgery,there were no significant differences in visual analog scale scores and forearm rotation angle among the three groups.However,the evaluation results at 1 and 3 months after surgery demonstrated significant differences in visual analog scale scores and forearm rotation angle among the three groups(P<0.05).Among them,group C had a lower visual analog scale score and a larger forearm rotation angle.(4)According to the Dienst joint scoring standard,the excellent and good rate of wrist joint function evaluation was 86%(19/22),91%(20/22),and 95%(21/22)in groups A,B,and C,respectively 12 months after surgery.(5)All patients did not experience any postoperative vascular or neurological damage or surgical site infection.Group A had three cases of tendon irritation,two cases of traumatic arthritis,and two cases of carpal tunnel syndrome.In group B,tendon irritation occurred in 1 case and joint stiffness in 1 case.There was 1 case of traumatic arthritis and 1 case of carpal tunnel syndrome in group C.(6)It is suggested that different surgical methods for treating distal radius fractures have achieved good clinical results.Placing a steel plate under the pronator muscle can alleviate early postoperative pain,promote early activity,and restore normal life.The brachioradialis tendon approach has more advantages in exposing intraoperative fractures and can shorten the surgical time.

Objective:To study the feasibility of magnetic resonance imaging(MRI)technique with amide proton transfer(APT)in predicting the prognosis of cerebral stroke.Methods:A total of 71 patients with acute cerebral stroke who admitted to the Nanjing First Hospital,Nanjing Medical University from September 2022 to May 2023 were selected.All of them underwent the test of National Institute of Health Stroke Scale(NIHSS),and received the MRI examination with chemical exchange saturation transfer(CEST).According to the modified Rankin scale(mRS)values of 1-month follow-up,they were divided into favorable recovery group(mRS<2,44 cases)and poor group(mRS≥2,27 cases).The asymmetric magnetization transfer ratio(MTRasym)image(APT)was obtained by analyzing data with special software.And then,the difference(△APTw)of APT values between ischemic zone and contralateral normal tissue was further calculated.The △APTw values of two groups were compared and analyzed,and the Pearson correlation analysis was adopted to analyze the correlation among △APTw,NIHSS and mRS.The receiver operating characteristics(ROC)curve was drawn,and the area under curve(AUC)of ROC curve was calculated.Results:There were significant positive correlations among △APTw,NIHSS and mRS scores(R2=0.659,0.522,P<0.001),and the differences of △APTW,NIHSS and mRS scores between the favorable recovery group and poor group were significant(t=5.73,6.36,13.92,P<0.05),respectively.The AUC value was 0.886,and the sensitivity and specificity of prediction were respectively 77.8%and 95.5%.The positive and negative predictive values were respectively 91.3%and 87.5%.Conclusion:APT imaging technique has feasibility in predicting the prognosis of acute cerebral ischemic stroke.