1.Research on The Role of Dopamine in Regulating Sleep and Wakefulness Through Exercise
Li-Juan HOU ; Ya-Xuan GENG ; Ke LI ; Zhao-Yang HUANG ; Lan-Qun MAO
Progress in Biochemistry and Biophysics 2025;52(1):88-98
		                        		
		                        			
		                        			Sleep is an instinctive behavior alternating awakening state, sleep entails many active processes occurring at the cellular, circuit and organismal levels. The function of sleep is to restore cellular energy, enhance immunity, promote growth and development, consolidate learning and memory to ensure normal life activities. However, with the increasing of social pressure involved in work and life, the incidence of sleep disorders (SD) is increasing year by year. In the short term, sleep disorders lead to impaired memory and attention; in the longer term, it produces neurological dysfunction or even death. There are many ways to directly or indirectly contribute to sleep disorder and keep the hormones, including pharmacological alternative treatments, light therapy and stimulus control therapy. Exercise is also an effective and healthy therapeutic strategy for improving sleep. The intensities, time periods, and different types of exercise have different health benefits for sleep, which can be found through indicators such as sleep quality, sleep efficiency and total sleep time. So it is more and more important to analyze the mechanism and find effective regulation targets during sleep disorder through exercise. Dopamine (DA) is an important neurotransmitter in the nervous system, which not only participates in action initiation, movement regulation and emotion regulation, but also plays a key role in the steady-state remodeling of sleep-awakening state transition. Appreciable evidence shows that sleep disorder on humans and rodents evokes anomalies in the dopaminergic signaling, which are also implicated in the development of psychiatric illnesses such as schizophrenia or substance abuse. Experiments have shown that DA in different neural pathways plays different regulatory roles in sleep behavior, we found that increasing evidence from rodent studies revealed a role for ventral tegmental area DA neurons in regulating sleep-wake patterns. DA signal transduction and neurotransmitter release patterns have complex interactions with behavioral regulation. In addition, experiments have shown that exercise causes changes in DA homeostasis in the brain, which may regulate sleep through different mechanisms, including cAMP response element binding protein signal transduction, changes in the circadian rhythm of biological clock genes, and interactions with endogenous substances such as adenosine, which affect neuronal structure and play a neuroprotective role. This review aims to introduce the regulatory effects of exercise on sleep disorder, especially the regulatory mechanism of DA in this process. The analysis of intracerebral DA signals also requires support from neurophysiological and chemical techniques. Our laboratory has established and developed an in vivo brain neurochemical analysis platform, which provides support for future research on the regulation of sleep-wake cycles by movement. We hope it can provide theoretical reference for the formulation of exercise prescription for clinical sleep disorder and give some advice to the combined intervention of drugs and exercise. 
		                        		
		                        		
		                        		
		                        	
2.Value of third lumbar skeletal muscle mass index in predicting the prognosis of patients with acute-on-chronic liver failure
Yewen HAN ; Jing LI ; Ninghui ZHAO ; Jia YAO ; Juan WANG
Journal of Clinical Hepatology 2025;41(4):698-702
		                        		
		                        			
		                        			ObjectiveTo investigate the value of third lumbar skeletal muscle mass index (L3-SMI) in predicting the long-term prognosis of patients with acute-on-chronic liver failure (ACLF), and to provide a useful tool for prognostic scoring of ACLF patients. MethodsA retrospective analysis was performed for the data of 126 patients who underwent abdominal computed tomography (CT) scanning and were diagnosed with ACLF in Shanxi Bethune Hospital from December 2017 to December 2021, including clinical indicators, biochemical parameters, and model for end-stage liver disease (MELD) score, and L3-SMI was calculated. The independent-samples t test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. The receiver operating characteristic (ROC) curve was used to assess the diagnostic value of L3-SMI and other variables (MELD score and Child-Pugh score), and the DeLong test was used for comparison of the area under the ROC curve (AUC). ResultsAmong the 126 patients enrolled, 44 (35%) died within 2 years and 82 (65%) survived. Compared with the survival group, the death group had significantly higher age, incidence rate of ascites, international normalized ratio, MELD score, and Child-Pugh score (all P<0.05) and a significantly lower value of L3-SMI [38.40 (35.95 — 46.29) cm²/m² vs 44.19 (40.20 — 48.58) cm²/m², Z=-2.855, P=0.004]. L3-SMI had an AUC of 0.720 in predicting 2-year mortality in ACLF patients, with a sensitivity of 63.6% and a specificity of 80.5%, and a combination of L3-SMI, MELD score, and Child-Pugh score had a significantly better AUC than a combination of MELD score and Child-Pugh score in predicting 2-year mortality (0.809 vs 0.757, Z=2.015, P<0.05). ConclusionL3-SMI has a high predictive value for the prognosis of ACLF patients, and the combination of L3-SMI、MELD score and Child-Pugh score has a higher predictive value for ACLF patients, and the inclusion of L3-SMI or sarcopenia in the conventional prognostic scores of ACLF patients may increase the ability to predict disease progression. 
		                        		
		                        		
		                        		
		                        	
3.Key Points for Quality Management in Phase Ⅰ Clinical Trials of Anti-Tumor Drugs
Li GONG ; Bin LIAO ; Jie SHEN ; Juan ZHAO ; Yi GONG ; Xiaoxiao LU ; Huiyao YANG ; Sha LI ; Yongsheng LI
Cancer Research on Prevention and Treatment 2025;52(5):347-354
		                        		
		                        			
		                        			Phase Ⅰ clinical trials play a crucial role in the research and development of new drugs, serving as the initial studies to assess their safety, tolerability, effectiveness, and pharmacokinetic properties in humans. These trials involve uncertainties regarding safety and efficacy. Comprehensive management of all aspects of phase Ⅰ clinical trials for anti-tumor drugs is crucial to protect the rights and safety of participants. This article provides an in-depth analysis of the key points and precautions necessary for effective quality control throughout the process. The analysis is informed by guidelines such as the “Good Clinical Practice for Drugs” “Key Points and Judgment Principles for Drug Registration Verification” “Key Points and Judgment Principles for Supervision and Inspection of Drug Clinical Trial Institutions” and the standard operating procedures for quality control of the center. Topics discussed include informed consent, inclusion criteria, experimental drugs, biological samples, adverse events, and serious adverse events. The goal is to standardize quality control in phase Ⅰ clinical trials of anti-tumor drugs, ensure the authenticity and reliability of clinical trial data, and protect the rights and safety of participants.
		                        		
		                        		
		                        		
		                        	
4.Neuroplasticity Mechanisms of Exercise-induced Brain Protection
Li-Juan HOU ; Lan-Qun MAO ; Wei CHEN ; Ke LI ; Xu-Dong ZHAO ; Yin-Hao WANG ; Zi-Zheng YANG ; Tian-He WEI
Progress in Biochemistry and Biophysics 2025;52(6):1435-1452
		                        		
		                        			
		                        			Neuroscience is a significant frontier discipline within the natural sciences and has become an important interdisciplinary frontier scientific field. Brain is one of the most complex organs in the human body, and its structural and functional analysis is considered the “ultimate frontier” of human self-awareness and exploration of nature. Driven by the strategic layout of “China Brain Project”, Chinese scientists have conducted systematic research focusing on “understanding the brain, simulating the brain, and protecting the brain”. They have made breakthrough progress in areas such as the principles of brain cognition, mechanisms and interventions for brain diseases, brain-like computation, and applications of brain-machine intelligence technology, aiming to enhance brain health through biomedical technology and improve the quality of human life. Due to limited understanding and comprehension of neuroscience, there are still many important unresolved issues in the field of neuroscience, resulting in a lack of effective measures to prevent and protect brain health. Therefore, in addition to actively developing new generation drugs, exploring non pharmacological treatment strategies with better health benefits and higher safety is particularly important. Epidemiological data shows that, exercise is not only an indispensable part of daily life but also an important non-pharmacological approach for protecting brain health and preventing neurodegenerative diseases, forming an emerging research field known as motor neuroscience. Basic research in motor neuroscience primarily focuses on analyzing the dynamic coding mechanisms of neural circuits involved in motor control, breakthroughs in motor neuroscience research depend on the construction of dynamic monitoring systems across temporal and spatial scales. Therefore, high spatiotemporal resolution detection of movement processes and movement-induced changes in brain structure and neural activity signals is an important technical foundation for conducting motor neuroscience research and has developed a set of tools based on traditional neuroscience methods combined with novel motor behavior decoding technologies, providing an innovative technical platform for motor neuroscience research. The protective effect of exercise in neurodegenerative diseases provides broad application prospects for its clinical translation. Applied research in motor neuroscience centers on deciphering the regulatory networks of neuroprotective molecules mediated by exercise. From the perspectives of exercise promoting neurogenesis and regeneration, enhancing synaptic plasticity, modulating neuronal functional activity, and remodeling the molecular homeostasis of the neuronal microenvironment, it aims to improve cognitive function and reduce the incidence of Parkinson’s disease and Alzheimer’s disease. This has also advanced research into the molecular regulatory networks mediating exercise-induced neuroprotection and facilitated the clinical application and promotion of exercise rehabilitation strategies. Multidimensional analysis of exercise-regulated neural plasticity is the theoretical basis for elucidating the brain-protective mechanisms mediated by exercise and developing intervention strategies for neurological diseases. Thus,real-time analysis of different neural signals during active exercise is needed to study the health effects of exercise throughout the entire life cycle and enhance lifelong sports awareness. Therefore, this article will systematically summarize the innovative technological developments in motor neuroscience research, review the mechanisms of neural plasticity that exercise utilizes to protect the brain, and explore the role of exercise in the prevention and treatment of major neurodegenerative diseases. This aims to provide new ideas for future theoretical innovations and clinical applications in the field of exercise-induced brain protection. 
		                        		
		                        		
		                        		
		                        	
5.The Regulatory Mechanisms of Dopamine Homeostasis in Behavioral Functions Under Microgravity
Xin YANG ; Ke LI ; Ran LIU ; Xu-Dong ZHAO ; Hua-Lin WANG ; Lan-Qun MAO ; Li-Juan HOU
Progress in Biochemistry and Biophysics 2025;52(8):2087-2102
		                        		
		                        			
		                        			As China accelerates its efforts in deep space exploration and long-duration space missions, including the operationalization of the Tiangong Space Station and the development of manned lunar missions, safeguarding astronauts’ physiological and cognitive functions under extreme space conditions becomes a pressing scientific imperative. Among the multifactorial stressors of spaceflight, microgravity emerges as a particularly potent disruptor of neurobehavioral homeostasis. Dopamine (DA) plays a central role in regulating behavior under space microgravity by influencing reward processing, motivation, executive function and sensorimotor integration. Changes in gravity disrupt dopaminergic signaling at multiple levels, leading to impairments in motor coordination, cognitive flexibility, and emotional stability. Microgravity exposure induces a cascade of neurobiological changes that challenge dopaminergic stability at multiple levels: from the transcriptional regulation of DA synthesis enzymes and the excitability of DA neurons, to receptor distribution dynamics and the efficiency of downstream signaling pathways. These changes involve downregulation of tyrosine hydroxylase in the substantia nigra, reduced phosphorylation of DA receptors, and alterations in vesicular monoamine transporter expression, all of which compromise synaptic DA availability. Experimental findings from space analog studies and simulated microgravity models suggest that gravitational unloading alters striatal and mesocorticolimbic DA circuitry, resulting in diminished motor coordination, impaired vestibular compensation, and decreased cognitive flexibility. These alterations not only compromise astronauts’ operational performance but also elevate the risk of mood disturbances and motivational deficits during prolonged missions. The review systematically synthesizes current findings across multiple domains: molecular neurobiology, behavioral neuroscience, and gravitational physiology. It highlights that maintaining DA homeostasis is pivotal in preserving neuroplasticity, particularly within brain regions critical to adaptation, such as the basal ganglia, prefrontal cortex, and cerebellum. The paper also discusses the dual-edged nature of DA plasticity: while adaptive remodeling of synapses and receptor sensitivity can serve as compensatory mechanisms under stress, chronic dopaminergic imbalance may lead to maladaptive outcomes, such as cognitive rigidity and motor dysregulation. Furthermore, we propose a conceptual framework that integrates homeostatic neuroregulation with the demands of space environmental adaptation. By drawing from interdisciplinary research, the review underscores the potential of multiple intervention strategies including pharmacological treatment, nutritional support, neural stimulation techniques, and most importantly, structured physical exercise. Recent rodent studies demonstrate that treadmill exercise upregulates DA transporter expression in the dorsal striatum, enhances tyrosine hydroxylase activity, and increases DA release during cognitive tasks, indicating both protective and restorative effects on dopaminergic networks. Thus, exercise is highlighted as a key approach because of its sustained effects on DA production, receptor function, and brain plasticity, making it a strong candidate for developing effective measures to support astronauts in maintaining cognitive and emotional stability during space missions. In conclusion, the paper not only underscores the centrality of DA homeostasis in space neuroscience but also reflects the authors’ broader academic viewpoint: understanding the neurochemical substrates of behavior under microgravity is fundamental to both space health and terrestrial neuroscience. By bridging basic neurobiology with applied space medicine, this work contributes to the emerging field of gravitational neurobiology and provides a foundation for future research into individualized performance optimization in extreme environments. 
		                        		
		                        		
		                        		
		                        	
6.Mechanism of β-sitosterol regulating the PON1/Caspase-3 pathway to alleviate sodium iodate-induced retinal injury
Xiaoli LI ; Wei WANG ; Juan LI ; Zhaoxia ZHAO
International Eye Science 2025;25(11):1728-1734
		                        		
		                        			
		                        			 AIM: To investigate the protective effect of β-sitosterol on retinal structure and function and its underlying molecular mechanism in a sodium iodate(NaIO3)-induced mouse model of dry age-related macular degeneration(ARMD).METHODS: A dry ARMD mouse model was established by NaIO3 injection. The therapeutic effect of β-sitosterol intervention was evaluated using fundus photography, histopathology(HE staining), and electroretinography(ERG). Network pharmacology was employed to screen potential targets of β-sitosterol in ARMD, and molecular docking was used to validate the binding ability between β-sitosterol and these targets. The impact of β-sitosterol on ARPE-19 cell viability and apoptosis pathways was analyzed using CCK-8 assay, Hoechst staining, and Western blotting.RESULTS: The β-sitosterol significantly alleviated structural damage in the retinas of model mice(increased retinal and outer nuclear layer thickness, reduced yellowish-white drusen-like deposits)and functional impairment(partial restoration of a-wave and b-wave amplitudes). Network pharmacology identified PON1 as a key target of β-sitosterol; molecular docking demonstrated that β-sitosterol binds to PON1 via hydrophobic interactions and hydrogen bonds. In vitro experiments showed that β-sitosterol(10 μmol/L)significantly increased ARPE-19 cell viability(P<0.01), reduced apoptosis(P<0.01), upregulated PON1 expression(P<0.01), and concurrently suppressed cleaved-Caspase3 expression(P<0.01).CONCLUSION: The β-sitosterol likely protects against oxidative stress-induced retinal damage by modulating PON1 to suppress the Caspase3-dependent apoptotic pathway. These findings provide experimental evidence supporting the development of β-sitosterol as a novel therapeutic agent for dry ARMD. 
		                        		
		                        		
		                        		
		                        	
7.Relationship between short-chain fatty acids in the gingival crevicular fluid and peri-odontitis of stage Ⅲ or Ⅳ
Yuru HU ; Juan LIU ; Wenjing LI ; Yibing ZHAO ; Qiqiang LI ; Ruifang LU ; Huanxin MENG
Journal of Peking University(Health Sciences) 2024;56(2):332-337
		                        		
		                        			
		                        			Objective:To analyze the concentration of formic acid,propionic acid and butyric acid in gingival crevicular fluid(GCF)of patients with stages Ⅲ and Ⅳ periodontitis,and their relationship with periodontitis.Methods:The study enrolled 37 systemically healthy patients with periodontitis and 19 healthy controls who visited Department of Periodontology,Peking University School and Hospital of Sto-matology from February 2008 to May 2011.Their GCFs were collected from the mesial-buccal site of one molar or incisor in each quadrant.Periodontal clinical parameters,including plaque index(PLI),probing depth(PD),bleeding index(BI),and attachment loss(AL).Concentrations of formic acid,propionic acid and butyric acid in the supernatant of the GCFs were analyzed by high-performance capil-lary electrophoresis(HPCE).The prediction ability of formic acid,propionic acid and butyric acid with the risk of periodontitis and the differences between grade B and grade C periodontitis were analyzed.Results:In this study,32 patients with stage Ⅲ and 5 patients with stage Ⅳ were enrolled,including 9 patients with grade B and 28 patients with grade C.Clinical periodontal variables in the patients with pe-riodontitis were significantly higher than those in the control group(P<0.001).Formic acid was signifi-cantly lower in periodontitis than that in the control group[5.37(3.39,8.49)mmol/L vs.12.29(8.35,16.57)mmol/L,P<0.001].Propionic acid and butyric acid in periodontitis were significantly higher than those in the control group:Propionic acid,10.23(4.28,14.90)mmol/L vs.2.71(0.00,4.25)mmol/L,P<0.001;butyric acid,2.63(0.47,3.81)mmol/L vs.0.00(0.00,0.24)mmol/L,P<0.001.There was no significant difference in formic acid,propionic acid and butyric acid concentrations between grade B and grade C periodontitis(P>0.05).Propionic acid and butyric acid in the deep pocket were significantly higher than in the shallow pocket,while the concentration of formic acid decreased with the increase of PD.Propionic acid(OR=1.51,95%CI:1.29-1.75)and butyric acid(OR=3.72,95%CI:1.93-7.17)were risk factors for periodontitis,while formic acid(OR=0.87,95%CI:0.81-0.93)might be a protective factor for periodontitis.Propionic acid(AUC=0.852,95%CI:0.805-0.900),butyric acid(AUC=0.889,95%CI:0.841-0.937),f(formic acid,AUC=0.844,95%CI:0.793-0.895)demonstrated a good predictive capacity for the risk of periodontitis.Conclusion:The concentration of formic acid decrease in the GCF of periodontitis patients,which is a protective factor for periodontitis,its reciprocal have good predictive capacity.However,propionic acid and butyric acid increase,which are risk factors for periodontitis and have good predictive capacity.The concentration of formic acid,propionic acid,and butyric acid vary with probing depth,but there is no significant difference between grade B and grade C periodontitis.
		                        		
		                        		
		                        		
		                        	
8.Effects and mechanism of Setaria italica extract on improving sleep in insomnia mice
Juan WANG ; Chenzi LYU ; Cairong ZHAO ; Hongyu ZHAO ; Zi’ang LI ; Xiang HAN ; Xianglong MENG ; Shuosheng ZHANG
China Pharmacy 2024;35(3):322-326
		                        		
		                        			
		                        			OBJECTIVE To investigate the effects of Setaria italica extract on improving insomnia model mice and to explore its potential mechanisms. METHODS The mice were randomly assigned into blank group, model group, positive control group (diazepam, 2.6 mg/kg), and S. italica extract low-dose, medium-dose and high-dose groups (1.2, 2.4, 4.8 g/kg), with 10 mice in each group. Except for the blank group, all other groups received intraperitoneal injection of para-chlorophenylalanine (PCPA) to establish the insomnia model. After modeling, the blank group and model group were given a constant volume of normal saline intragastrically, and administration groups were given relevant medicine intragastrically, with a volume of 0.01 mL/g, once a day, for 7 consecutive days. After the administration, the open-field test was conducted to observe the praxiological changes of mice, and to determine the levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HTAA) in the hippocampal tissue, as well as the contents of 5-HT, brain-derived neurotrophic factor (BDNF), interleukin-2 (IL-2), IL-6, B-cell lymphoma-2 (Bcl- 2), and Bcl-2-associated X protein (Bax) in the serum. The expression of phosphoinositide 3-kinase/protein kinase B/nuclear factor- κB (PI3K/Akt/NF-κB) signaling pathway related protein was determined in the hippocampus of mice. RESULTS Compared with the model group, the total exercise time of mice in S. italica extract high-dose group was significantly prolonged, but the total rest time was significantly shortened (P<0.01); the number of standing times and modification times were significantly reduced (P< 0.01). The contents of 5-HT, BDNF, and Bcl-2 in serum, and Bcl-2/Bax were significantly increased, while the contents of IL-2, IL-6, and Bax were significantly reduced (P<0.05 or P< 0.01). The content of 5-HTAA in the hippocampal tissue and 202104010910029);the phosphorylation levels of PI3K and Akt proteins were increased significantly, while the phosphorylation level of NF-κB p65 protein was decreased significantly (P<0.05).CONCLUSIONS High-dose of S. italica extract demonstrates significant therapeutic effects on insomnia in mice, and the mechanism of which may be associated with the regulation of PI3K/Akt/NF-κB signaling pathway.
		                        		
		                        		
		                        		
		                        	
9.The evaluation of maturity of heterotopic ossification by SPECT/CT fusion bone imaging
Peiling LI ; Zhenjiang ZHAO ; Yuke LIU ; Juan WEI ; Zhiping GUO
Journal of Practical Radiology 2024;40(2):270-274
		                        		
		                        			
		                        			Objective To evaluate the maturity and metabolic status of heterotopic ossification(HO)by single-photon emission computed tomography(SPECT)/CT fusion bone imaging.Methods The clinical and SPECT/CT fusion bone imaging data of 57 patients with HO confirmed by pathology or follow-up were analyzed retrospectively.HO was graded by CT,and the characteristics of radioactive concentration of HO were analyzed.Results Of 57 cases,single lesion in 52 cases,and multiple lesions in 5 cases,with a total of 63 lesions,mostly located in the hip joint(55.6%,35/63)and thigh(19.0%,12/63).There were 41 lesions in the middle stage and 22 lesions in the late stage.In the visual evaluation of SPECT/CT fusion bone imaging,the middle stage lesions were mostly clumps or flakes,with moderate or high radioactive concentration(75.6%,31/41),furthermore,the concentration range was larger than or equal to the total or limited range of CT ossification(21/41,50.1%),with high concentration mainly located in the mixed areas of ossification density.The concentration of the late stage lesions was mostly non-radioactive(72.7%,16/22).Conclusion SPECT/CT fusion bone imaging can show the range,degree and maturity of HO radioactive concentration,and can accurately locate the area with osteoblastic activity,which provides scientific basis for the selection of surgical timing.
		                        		
		                        		
		                        		
		                        	
10.Construction of nursing quality evaluation index system for pediatric orthopedics
Nan WANG ; Wei JIN ; Yanzhen HU ; Jie HUANG ; Dan ZHAO ; Juan XING ; Changhong LI ; Yanan HU ; Yi LIU ; Xuemei LU ; Zheng YANG
Chinese Journal of Practical Nursing 2024;40(9):655-664
		                        		
		                        			
		                        			Objective:To construct a representative index system for evaluating pediatric orthopedic nursing quality, providing a basis for hospital pediatric orthopedic nursing quality assessment and monitoring.Methods:From April to July 2023, using the "structure-process-outcome" three-dimensional quality structure model as the theoretical framework, a literature review was conducted, and an item pool was formulated. Through two rounds of Delphi method expert consultations, the hierarchical analysis method was finally employed to determine the indicators and their weights at each level.Results:The effective recovery rates of the questionnaire of the two rounds of expert consultations were 100% (20/20), the authority coefficients of experts were 0.87 and 0.88, the coefficients of variation were 0.00 to 0.27 and 0.00 to 0.24. The Kendell harmony coefficients of the second and third indicators in the two rounds of inquiry were 0.140, 0.166 and 0.192, 0.161(all P<0.05). The final pediatric orthopedic nursing quality evaluation index system included 3 primary indicators, 21 secondary indicators and 83 tertiary indicators. Among the primary indicators, the weight of process quality was the highest at 0.493 4, followed by outcome quality at 0.310 8, and the lowest was structural quality at 0.195 8. In the secondary indicators, "assessment criteria of limb blood circulation" had the highest weight at 0.099 8. Conclusions:The constructed pediatric orthopedic nursing quality evaluation index system covers key aspects and is more operationally feasible. It provides better guidance for nursing interventions and quality control.
		                        		
		                        		
		                        		
		                        	
            
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