1.Exploring Chemical Constituent Distribution in Blood/Brain(Hippocampus) and Emotional Regulatory Effect of Raw and Vinegar-processed Products of Citri Reticulatae Pericarpium Viride
Yi BAO ; Yonggui SONG ; Qianmin LI ; Zhifu AI ; Genhua ZHU ; Ming YANG ; Huanhua XU ; Qin ZHENG ; Yiting HUANG ; Zihan GAO ; Dan SU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):189-197
ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride(CRPV), and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts, as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards, databases, and relevant literature were utilized for compound annotation, with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups, including the blank group, model group, diazepam group(2.5 mg·kg-1), raw CRPV low/high dose groups(0.6, 1.2 g·kg-1), and vinegar-processed CRPV low/high dose groups(0.6, 1.2 g·kg-1), with 10 mice per group. Except for the blank group, all other groups underwent chronic restraint stress(2 h·d-1) for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling, with a total treatment duration of 10 d. Following model-based drug administration, mice underwent open-field, forced swimming, and elevated plus maze tests. After anesthesia with isoflurane, whole brains were collected from each group of mice, and hippocampi were dissected. Reactive oxygen species(ROS) level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei(NeuN) and peroxisome proliferator-activated receptor alpha(PPARα) expressions in hippocampal tissue. Then, pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders, exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV, with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds, including 20 flavonoids, 20 flavonoid glycosides, 3 triterpenes, 3 phenolic acids, 1 alkaloid, and 6 other compounds. Twenty-one components were detected in blood(15 methoxyflavones, 4 flavonoid glycosides, and 2 phenolic acids), with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues(all common to both forms). In regulating emotional disorders, Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology, particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS(P<0.05). ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing, but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway, thereby negatively regulating ROS generation in the hippocampus, reducing oxidative stress, and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards, pharmacodynamic material research, and active drug development of raw and vinegar-processed CRPV.
2.Targeted Regulation of Inflammation-related Signaling Pathways by Traditional Chinese Medicine for Prevention and Treatment of Atherosclerosis: A Review
Shuang ZHAO ; Mingxue ZHANG ; Ning LIU ; Jianan SU ; Yuhan AO ; Jing LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):273-283
Atherosclerosis (AS) is the main pathological basis of cardiovascular diseases and seriously threatens human quality of life. Its prevention and treatment urgently need breakthroughs. The inflammatory response, which runs through the physiological and pathological evolution process of AS, is one of the important mechanisms for AS occurrence. Currently, the treatment methods for AS in Western medicine are relatively mature. However, they have adverse reactions such as abnormal liver and kidney function, drug tolerance, target vessel restenosis, and stent thrombosis, which remain the key bottleneck restricting clinical efficacy. Traditional Chinese medicine (TCM), characterized by multiple components, multiple targets, and multi-pathway synergy, shows unique clinical application potential and efficacy advantages in the intervention of AS. This article reviewed the research progress of TCM in intervening in AS by regulating inflammatory-related signaling pathways, such as nuclear factor-κB (NF-κB), Toll-like receptors (TLRs), mitogen-activated protein kinase (MAPK), and Janus kinase/signal transducer and activator of transcription (JAK/STAT), in the past five years. It summarized the combined mechanism of action of TCM monomers, TCM pairs, and compound preparations in inhibiting the inflammatory cascade reaction through multiple targets, regulating lipid metabolism disorders, and improving vascular endothelial dysfunction and the imbalance of the microenvironment. It deepened the research on the molecular mechanism of TCM in anti-AS, so as to provide a scientific basis for the clinical transformation application and related theoretical research of TCM in anti-AS.
3.Targeted Regulation of Inflammation-related Signaling Pathways by Traditional Chinese Medicine for Prevention and Treatment of Atherosclerosis: A Review
Shuang ZHAO ; Mingxue ZHANG ; Ning LIU ; Jianan SU ; Yuhan AO ; Jing LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):273-283
Atherosclerosis (AS) is the main pathological basis of cardiovascular diseases and seriously threatens human quality of life. Its prevention and treatment urgently need breakthroughs. The inflammatory response, which runs through the physiological and pathological evolution process of AS, is one of the important mechanisms for AS occurrence. Currently, the treatment methods for AS in Western medicine are relatively mature. However, they have adverse reactions such as abnormal liver and kidney function, drug tolerance, target vessel restenosis, and stent thrombosis, which remain the key bottleneck restricting clinical efficacy. Traditional Chinese medicine (TCM), characterized by multiple components, multiple targets, and multi-pathway synergy, shows unique clinical application potential and efficacy advantages in the intervention of AS. This article reviewed the research progress of TCM in intervening in AS by regulating inflammatory-related signaling pathways, such as nuclear factor-κB (NF-κB), Toll-like receptors (TLRs), mitogen-activated protein kinase (MAPK), and Janus kinase/signal transducer and activator of transcription (JAK/STAT), in the past five years. It summarized the combined mechanism of action of TCM monomers, TCM pairs, and compound preparations in inhibiting the inflammatory cascade reaction through multiple targets, regulating lipid metabolism disorders, and improving vascular endothelial dysfunction and the imbalance of the microenvironment. It deepened the research on the molecular mechanism of TCM in anti-AS, so as to provide a scientific basis for the clinical transformation application and related theoretical research of TCM in anti-AS.
4.Meta-analysis of the efficacy and safety of rituximab in the treatment of primary Sjögren syndrome
Jigao LI ; Ruilin LIU ; Zihua WANG ; Hejun WANG ; Peipei SU ; Quan ZHOU
China Pharmacy 2025;36(5):619-623
OBJECTIVE To evaluate the efficacy and safety of rituximab (RTX) in the treatment of primary Sjögren syndrome (pSS). METHODS Randomized controlled trials (RCTs) on the effects of RTX (trial group) versus placebo (control group) in the treatment of pSS were searched from the Cochran Library, PubMed, Embase, Medline, Web of Science, VIP, CNKI, Wanfang, and other databases during the inception to February 2024. After literature screening and quality evaluation, meta-analysis was performed by using RevMan 5.3 software. RESULTS Seven RCTs were finally included, involving a total of 518 patients. Results of meta-analysis showed that European League Against Rheumatism Sjögren syndrome disease activity index (ESSDAI) score [MD=-1.17, 95%CI(-1.52, -0.82), P<0.000 01] and oral dryness visual analogue scale (VAS) score [MD=-3.97, 95%CI (-5.08, -2.86), P<0.000 01] in the trial group were significantly lower than the control group; unstimulated salivary flow rate [SMD=0.64, 95%CI(0.41, 0.87), P<0.000 01] and Schirmer score [MD=0.19, 95%CI(0.18, 0.20), P<0.000 01] were significantly higher than the control group. There was no statistical significance in response rate [RD=0.10, 95%CI(-0.04, 0.23), P=0.16], fatigue VAS score [MD=-12.50, 95%CI(-35.14, 10.15), P=0.28], European League Against Rheumatism Sjögren syndrome patient reported index (ESSPRI) score [MD=0.33, 95%CI(-0.53, 1.18), P=0.46], Short-form 36 health survey physical component summary (SF36-PCS) score [MD=0.90, 95%CI(-2.97, 4.78), P=0.65], SF-36 mental component summary (SF36-MCS) score [MD=0.11, 95%CI(-0.41, 0.63), P=0.68], total salivary gland ultrasound score [SMD=-1.91, 95%CI(-4.01, 0.19), P=0.07] or the incidence of adverse drug reactions [OR=1.15,95%CI(0.62,2.13),P=0.66] between 2 groups. CONCLUSIONS RTX has advantages in the improvement of ESSDAI score, unstimulated salivary flow rate, Schirmer score and oral dryness VAS score in pSS patients, and has a good safety profile. However, it did not exhibit significant improvement in fatigue VAS score, ESSPRI score, SF36-PCS score, SF36-MCS score or response rates.
5.Mechanism of agomelatine alleviating anxiety-and depression-like behaviors in APP/PS1 transgenic mice
Tian LI ; Yuhua REN ; Yanping GAO ; Qiang SU
Chinese Journal of Tissue Engineering Research 2025;29(6):1176-1182
BACKGROUND:Agomelatine is a clinically proven treatment for neuropsychiatric symptoms,such as anxiety and depression.Furthermore,our previous study has demonstrated that agomelatine ameliorates cognitive behaviors,hippocampal synaptic plasticity,and brain pathology in a mouse model of Alzheimer's disease.However,it remains unclear whether agomelatine can improve anxiety and depression-like behaviors in Alzheimer's disease model mice. OBJECTIVE:To investigate the improving effects of agomelatine on anxiety-and depression-like behaviors in APP/PS1 transgenic mice and its underlying molecular mechanisms. METHODS:(1)Eighteen APP/PS1 transgenic mice were randomly divided into model control group(n=9)and model intervention group(n=9).Another wild-type mice were randomized into control group(n=9)and intervention group(n=9).Model intervention group and intervention group were intraperitoneally injected with 10 mg/kg agomelatine per day for 31 continuous days.Behavioral experiments,including the elevated cross maze and forced swimming tests,and mRNA sequencing of the hippocampus were then performed.(2)Mouse hippocampal neuronal cell lines(HT22)and brain microvascular endothelial cell lines(bEnd.3)were cultured and divided into four groups:blank group without any drug,drug group with 20 μmol/L agomelatine,model group with 10 μmol/L β-amyloid 1-42,and experimental group with 10 μmol/L β-amyloid 1-42+20 μmol/L agomelatine.After 24 hours of incubation,protein expression of S416p-tau and S9p-GSK3β in HT22 cells was detected by immunoblotting,and protein expression of low-density lipoprotein receptor-related protein 1 and glycosylation end-product receptor in bEnd.3 cells was detected by immunoblotting. RESULTS AND CONCLUSION:In the elevated plus maze test,the time spent in the open arms(P<0.01)and the entries into open arms(P<0.05)in the mice of model control group were evidently lower than those in the control group,whereas those were obviously increased in the model intervention group compared with the model control group(P<0.05).Forced swimming test results showed that the immobile time exhibited a marked increase in the model control group compared with the control group(P<0.05),but it was significantly decreased in the model intervention group compared with the model control group(P<0.05).Hippocampal tissue mRNA sequencing showed that agomelatine enhanced the expression of low-density lipoprotein receptor-related protein 1 in the hippocampus of APP/PS1 mice.Western blot analysis revealed that the level of S416p-tau in HT22 cells was higher in the model group than the blank group(P<0.05),while it was markedly decreased in the experimental group compared with the model group(P<0.05);the level of S9p-GSK3β in HT22 cells was higher in the drug group than the blank group(P<0.05)as well as higher in the experimental group than the model group(P<0.05).Moreover,the expression of low-density lipoprotein receptor-related protein 1 in bEnd.3 cells was higher in the experimental group than the model group(P<0.05).To conclude,agomelatine can alleviate anxiety-and depression-like behaviors in Alzheimer's disease mice by promoting the clearance of β-amyloid and phosphorylated tau.
6.Decompression mechanism of symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous
Chunlin ZHANG ; Zhaohua HOU ; Xu YAN ; Yan JIANG ; Su FU ; Yongming NING ; Dongzhe LI ; Chao DONG ; Xiaokang LIU ; Yongkui WANG ; Zhengming CAO ; Tengyue YANG
Chinese Journal of Tissue Engineering Research 2025;29(9):1810-1819
BACKGROUND:Traditional surgery for lumbar disc herniation involves extensive excision of tissue surrounding the nerve for decompression and removal of protruding lumbar intervertebral discs,which poses various risks and complications such as nerve damage causing paralysis,lumbar instability,herniation recurrence,intervertebral space infection,and adjacent vertebral diseases. OBJECTIVE:To propose the symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous technique for lumbar spine symmetrically decompression,showing the induced resorption of herniated nucleus pulpous phenomenon and early clinical efficacy,and then analyze its decompression mechanism. METHODS:214 patients with lumbar disc herniation at Department of Orthopedics,First Affiliated Hospital of Zhengzhou University from March 2021 to May 2023 were enrolled in this study.Among them,81 patients received conservative treatment as the control group,and 133 patients received symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous treatment as the trial group.Before surgery,immediately after surgery(7-14 days),and early after surgery(over 1 year),MRI images were used to measure the volume changes of lumbar disc herniation.CT images were used to measure the posterior displacement distance of the lumbar spinous process ligament complex,as well as the width and height of the lateral recess.Japanese Orthopaedic Association scores were used to evaluate the patient's neurological function recovery. RESULTS AND CONCLUSION:(1)Control group:81 patients with lumbar disc herniation were treated conservatively,with a total of 171 herniated lumbar discs.The average follow-up time was(22.7±23.1)months.The first and second MRI measurements of 171 herniated lumbar discs showed herniated lumbar disc volumes of(551.6±257.9)mm3 and(792.2±330.4)mm3,respectively,with an average volume increase rate of(53.2±44.4)%,showing statistically significant differences(P<0.001).Out of 171 herniated lumbar discs,4 experienced natural shrinkage,with an absorption ratio of 2.3%(4/171)and an absorption rate of(24.5±9.9)%.(2)Trial group:133 patients with lumbar disc herniation had a total of 285 herniated lumbar discs.(1)Immediately after surgery:All patients were followed up immediately after surgery.229 out of 285 herniated lumbar discs experienced retraction,with an absorption ratio of 80.3%(229/285)and an average absorption rate of(21.5±20.9)%,with significant and complete absorption accounting for 6.5%.There were a total of 70 herniated lumbar discs in the upper lumbar spine,with an absorption ratio of 85.7%(60/70),an average absorption rate of(23.1±19.5)%,and a maximum absorption rate of 86.6%.There were 215 herniated lumbar discs in the lower lumbar spine,with an absorption ratio of 78.6%(169/215),an average absorption rate of(21.0±21.3)%,and a maximum absorption rate of 83.2%.Significant and complete absorption of the upper and lower lumbar vertebrae accounted for 5.7%and 6.5%,respectively,with no statistically significant difference(P>0.05).The average distance of posterior displacement of the spinous process ligament complex immediately after surgery was(5.2±2.8)mm.There were no significant differences in the width and height of the left and right lateral recess before and immediately after surgery(P>0.05).The Japanese Orthopaedic Association score immediately after surgery increased from(10.1±3.4)before surgery to(17.0±4.8),and the immediate effective rate after surgery reached 95.6%.(2)Early postoperative period:Among them,46 patients completed the early postoperative follow-up.There were 101 herniated lumbar discs,with an absorption ratio of 94%(95/101)and an average absorption rate of(36.9±23.7)%.Significant and complete absorption accounted for 30.6%,with a maximum absorption rate of 100%.Out of 101 herniated lumbar discs,3 remained unchanged in volume,with a volume invariance rate of 2.97%(3/101).Out of 101 herniated lumbar discs,3 had an increased volume of herniated lumbar discs,with an increase ratio of 2.97%(3/101)and an increase rate of(18.5±18.4)%.The Japanese Orthopaedic Association score increased from preoperative(9.3±5.1)to(23.5±4.0),with an excellent and good rate of 93.4%.(3)The early postoperative lumbar disc herniation absorption ratios of the control group and trial group were 2.3%and 85.9%,respectively,with statistically significant differences(P<0.001).(4)Complications:There were two cases of incision exudation and delayed healing in the trial group.After conservative treatment such as dressing change,no nerve injury or death occurred in the incision healing,and no cases underwent a second surgery.(5)It is concluded that symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous is a new method for treating lumbar disc herniation that can avoid extensive excision of the"ring"nerve and achieve satisfactory early clinical efficacy.It does not damage the lumbar facet joints or alter the basic anatomical structure of the lateral recess,fully preserves the herniated lumbar discs,and can induce significant or even complete induced resorption of herniated nucleus pulpous.Symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous provides a new basis and method for the clinical treatment of lumbar disc herniation.
7.The risk prediction models for anastomotic leakage after esophagectomy: A systematic review and meta-analysis
Yushuang SU ; Yan LI ; Hong GAO ; Zaichun PU ; Juan CHEN ; Mengting LIU ; Yaxie HE ; Bin HE ; Qin YANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(02):230-236
Objective To systematically evaluate the risk prediction models for anastomotic leakage (AL) in patients with esophageal cancer after surgery. Methods A computer-based search of PubMed, EMbase, Web of Science, Cochrane Library, Chinese Medical Journal Full-text Database, VIP, Wanfang, SinoMed and CNKI was conducted to collect studies on postoperative AL risk prediction model for esophageal cancer from their inception to October 1st, 2023. PROBAST tool was employed to evaluate the bias risk and applicability of the model, and Stata 15 software was utilized for meta-analysis. Results A total of 19 literatures were included covering 25 AL risk prediction models and 7373 patients. The area under the receiver operating characteristic curve (AUC) was 0.670-0.960. Among them, 23 prediction models had a good prediction performance (AUC>0.7); 13 models were tested for calibration of the model; 1 model was externally validated, and 10 models were internally validated. Meta-analysis showed that hypoproteinemia (OR=9.362), postoperative pulmonary complications (OR=7.427), poor incision healing (OR=5.330), anastomosis type (OR=2.965), preoperative history of thoracoabdominal surgery (OR=3.181), preoperative diabetes mellitus (OR=2.445), preoperative cardiovascular disease (OR=3.260), preoperative neoadjuvant therapy (OR=2.977), preoperative respiratory disease (OR=4.744), surgery method (OR=4.312), American Society of Anesthesiologists score (OR=2.424) were predictors for AL after esophageal cancer surgery. Conclusion At present, the prediction model of AL risk in patients with esophageal cancer after surgery is in the development stage, and the overall research quality needs to be improved.
8.Dihuang Yinzi Improves Cognitive Function of Mouse Model of Learning and Memory Impairments by Regulating Synaptic Plasticity via SIRT2
Wenting WANG ; Yangjing HAO ; Wenna SU ; Qinqing LI ; Shifeng CHU ; Junlong ZHANG ; Wenbin HE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):9-17
ObjectiveTo investigate the effects of Dihuang Yinzi on the cognitive function in the mouse model of learning and memory impairments induced by scopolamine (SCOP) and explore the treatment mechanism. MethodsA mouse model of learning and memory impairment was induced by intraperitoneal injection of SCOP. Sixty male C57BL/6J mice were randomized into six groups: control (0.9% NaCl, n=10), model (SCOP 1 mg·kg-1·d-1, n=10), low-, medium-, and high-dose Dihuang Yinzi (SCOP 1 mg·kg-1·d-1 + Dihuang Yinzi 5.5, 11.0, and 22.0 g·kg-1·d-1, n=10), and donepezil (SCOP 1 mg·kg-1·d-1 + donepezil 0.84 mg·kg-1·d-1, n=10). Mice were administrated with corresponding drugs for 6 weeks. Modeling started in the 4th week, and mice in other groups except the control group were injected with SCOP intraperitoneally 40 min after daily gavage. Behavioral testing began in the 5th week, 30 min after modeling each day. The Morris water maze and novel object recognition tests were carried out to evaluate the spatial learning and memory function of mice. Nissl staining was employed to observe the survival of neurons and Nissl bodies in the hippocampal CA1 region. Western blot was employed to determine the protein levels of silent information regulator 2 (SIRT2), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor 1 (GluA1), protein kinase A (PKA), cAMP response element-binding protein (CREB), phosphorylated-CREB (p-CREB), postsynaptic density protein 95 (PSD95), growth-associated protein-43 (GAP-43), and synaptophysin (SYN) in the hippocampus. Immunofluorescence was used to detect the expression of doublecortin (DCX) in the hippocampal dentate gyrus (DG) region. ResultsCompared with the control group, the model group showed impaired learning and memory (P<0.01), obvious neuronal damage in the hippocampal CA1 region, a reduction in neuron survival (P<0.01), a decrease in DCX expression in the hippocampal DG region (P<0.01), down-regulated proteins levels of GluA1, PKA, p-CREB/CREB, PSD95, SYN, and GAP-43 in the hippocampal tissue (P<0.05, P<0.01), and an up-regulated protein level of SIRT2 (P<0.01). Compared with the model group, the medium- and high-dose Dihuang Yinzi groups and the donepezil group showed improvements in learning and memory (P<0.05, P<0.01), while the low-, medium-, and high-dose Dihuang Yinzi groups and the donepezil group had increased neuron survival (P<0.05, P<0.01). The medium-dose Dihuang Yinzi group and the donepezil group showed increased DCX expression (P<0.05, P<0.01). The medium- and high-dose Dihuang Yinzi groups and the donepezil group showed up-regulation in the protein levels of GluA1, PKA, p-CREB/CREB, PSD95, SYN, and GAP-43 (P<0.05, P<0.01) and down-regulation in the protein level of SIRT2 (P<0.01). ConclusionDihuang Yinzi can improve the cognitive function in the mouse model of learning and memory impairments induced by SCOP by inhibiting the upregulation of SIRT2, activating the PKA/CREB signaling pathway, improving synaptic plasticity, and reducing hippocampal neuronal damage.
9.The Neurobiological Mechanisms of Runner’s High
Yun-Teng WANG ; Jia-Qi LIANG ; Wan-Tang SU ; Li ZHAO ; Yan LI
Progress in Biochemistry and Biophysics 2025;52(2):358-373
“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.
10.Textual Research on Historical Evolution and Key Information of Classical Famous Formula of Da Qinjiaotang
Na LI ; Jianying BAI ; Fuping LI ; Xiufen ZHANG ; Di LU ; Yishuo BAI ; Cuixiang WANG ; Kun SU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):201-211
Da Qinjiaotang is the 54th formula of the 100 formulas in the Catalogue of Ancient Classical Formulas (the first batch) ,and it originated from the Collection of Writings on the Mechanism of Disease, Suitability of Qi, and Safeguarding of Life Discussed in Plain Questions. Da Qinjiaotang is composed of Gentiana macrophylla, Glycyrrhizae Radix et Rhizoma, Ligusticum chuanxiong, Angelica sinensis, Paeonia lactiflora, Asari Radix et Rhizoma, Notopterygium incisum, Saposhnikoviae Radix, Scutellariae Radix, Gypsum, Angelica dahurica, Atractylodis Macrocephalae Rhizoma, Rehmanniae Radix, Rehmanniae Radix Praeparata, Poria, and Angelicae Pubescentis Radix. It is a classical formula for treating strokes. Da Qinjiaotang is widely used in modern clinical practices for treating ischemic stroke, peripheral facial paralysis, cervical spondylosis, rheumatic arthritis, neurodermatitis, and other multisystem diseases. Therefore, following the Principles of Textual Research on the Key Information of Ancient Classical Famous Formulas, the authors collected the ancient Chinese medical literature of Da Qinjiaotang by the method of bibliometrics and screened out 177 valid data, involving 100 ancient books of traditional Chinese medicine. Based on the historical evolution, composition, dosage, method of preparation, and preparation of the original medicinal materials of Da Qinjiaotang, a systematic study was carried out. It was found that among the 175 records of the main diseases and syndromes, stroke (144) was the most, accounting for 82.29% of the total diseases and syndromes. Later generations mostly followed the practice of LIU Wansu in using Da Qinjiaotang to treat stroke caused by "weak blood and inability to nourish tendon", featuring "hands and feet cannot move, stiff tongue hinders speaking", as well as other symptoms, such as slant of the mouth, hemiplegia, numbness of the limbs, paroxysmal pain, and acerbic syncope. The treatment scope was expanded, covering tendon dryness, clonic convulsion, spasm syndrome, and arthralgia syndrome. At the same time, it was found that there was a controversy between "internal wind" and "external wind" in the treatment of stroke by Da Qinjiaotang. LIU Wansu thought that stroke was caused by internal factors, created the theory of "hot stroke", and used Da Qinjiaotang to treat "internal wind". Many doctors in later generations focused on treating the "external wind" of "internal deficiency and evil". There were 76 valid data on the composition of drugs, 59 of which had doses for each drug. It was suggested to use the modern conversion dosage of the original formula, with 41.30 g per dose. The drug should be boiled in 600 mL water until 300 mL, decocted once, and taken in a warm state after removing the dregs anytime. Through the analysis and study of the ancient books about Da Qinjiaotang, the paper clarified its historical evolution and confirmed its key information, so as to provide the ancient literature evidence for the research and development of the classical famous formula Daqinjiaotan and its better clinical application.

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