BACKGROUND:Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis.Previous studies have shown that baicalein has protective effects against cerebral ischemia-reperfusion injury,and can also reduce blood sugar and complications in diabetic mice,but its role and mechanism in diabetic cerebral infarction remain unclear. OBJECTIVE:To explore the effect of wogonin on nerve injury in rats with diabetic cerebral infarction and its mechanism. METHODS:Sprague-Dawley rats were randomly divided into six groups:control group,model group,low-dose wogonin group,medium-dose wogonin group,high-dose wogonin group,and high-dose wogonin+Ras homolog gene family member A(RhoA)activator group.Except for the control group,the other rats were established with diabetes and cerebral ischemia models using intraperitoneal injection of streptozotocin and middle cerebral artery occlusion.Low,medium-and high-dose wogonin groups were intragastrically given 10,20,40 mg/kg wogonin,respectively;high-dose wogonin+RhoA activator group was intragastrically given 40 mg/kg wogonin and intraperitoneally injected 10 mg/kg lysophosphatidic acid;control group and model group were given the same amount of normal saline once a day for 7 consecutive days.Rats in each group were evaluated for neurological deficits and their blood glucose levels were measured after the last dose.TTC staining was applied to detect the volume of cerebral infarction.Hematoxylin-eosin staining was applied to observe pathological changes in brain tissue.ELISA kit was applied to detect tumor necrosis factor-α,interleukin-6,malondialdehyde,and superoxide dismutase levels in brain tissue.Western blot was applied to detect the protein expression of RhoA and Rho-associated protein kinase(ROCK)2 in brain tissue. RESULTS AND CONCLUSION:Compared with the control group,the neuronal structure of rats in the model group was severely damaged,with cell necrosis and degeneration,the neurological deficit score,blood glucose level,and infarct volume were significantly elevated(P<0.05),the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue were significantly increased(P<0.05),and the superoxide dismutase level was decreased(P<0.05).Compared with the model group,the low-,medium-,and high-dose wogonin groups showed improved neuronal damage,reduced cell degeneration and necrosis,a significant reduction in neurological deficit score,blood glucose level,infarct volume,and the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue,and an increase in the superoxide dismutase level(P<0.05).Compared with the high-dose wogonin group,the high-dose wogonin+RhoA activator group significantly weakened the improvement in the above indexes of rats with diabetic cerebral infarction(P<0.05).To conclude,wogonin can improve the blood glucose level in rats with diabetic cerebral infarction,reduce cerebral infarction and nerve injury,and its mechanism may be related to the inhibition of RhoA/ROCK signaling pathway.

“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.

Traditional Chinese medicine (TCM) has historically played a pivotal role in the prevention and treatment of warm diseases, establishing a comprehensive theoretical framework that underpins its practices. The distinctive and indispensable contributions of aromatic Chinese herbs in dispelling harmful influences and mitigating the spread of these diseases are well recognized; however, further investigation is warranted to elucidate their systematic properties and regularities, and the theory of aromatic Chinese herbs in preventing and treating warm diseases still needs to be comprehensively summarized. This study employs the principles rooted in TCM, with particular emphasis on the framework for warm diseases. An analysis of the disease mechanisms, transmission dynamics, and preventive strategies is conducted during the early stage of infection, throughout the course of the disease, and in the post-illness phase. Furthermore, the characteristics and applications of aromatic Chinese herbs are integrated with insights drawn from modern pharmacological research to explore their specific roles in the prevention and management of warm diseases. The utilization of aromatic Chinese herbs manifests in a variety of therapeutic effects: aromatic medicinals purging filth and dispelling pathogens for preventing epidemic disease, aromatic medicinals regulation for relieving superficies syndrome and dispersing evils, aromatic medicinals ventilation the lung to relieve cough and asthma, aromatic medicinals resolving the dampness to awaken the spleen and stomach, aromatic medicinals opening the orifices to restore consciousness, aromatic and pungent medicinals to regulate qi, aromatic medicinals dredging the vessels to activate blood circulation and dissipate blood stasis, and aromatic medicinals clearing latent heat from the yin level. These properties facilitate tailored approaches to address the diverse manifestations of warm diseases and their associated symptoms, providing clear guidance for clinical application to achieve pre-disease prevention, active disease treatment, complication prevention, and post-recovery relapse avoidance. The use of aromatic Chinese herbs in preventing and treating warm diseases demonstrates theoretical, practical, systematic, and regular characteristics. The theory of the properties of aromatic Chinese herbs has been expanded and sublimated in clinical practice, and its scientific connotation has been expounded in modern research. Under the guidance of the theory of treatment based on syndrome differentiation, and by taking into account the distinct stages and pathologies of warm diseases, the rational selection of aromatic Chinese herbs can improve the clinical efficacy.

The pathogenesis of Alzheimer's disease(AD)is complex and unclear.Existing drugs can only alleviate its symp-toms,and there is an urgent need to develop effective therapeutic drugs.As the representative drugs of tonic and enlightening medicine,ginseng and acorus calamus have pharmacological effects to improve memory,improve learning ability and reduce cognitive impairment,which are commonly used in Chinese med-icine for the treatment of dementia.The combination of ginseng and acorus calamus can further promote the active ingredients in-to brain to exert their medicinal effects,and delay the process of AD through anti-inflammatory,anti-oxidative stress,modulation of neuronal-synaptic plasticity and other multiple pathways,with multi-level,multi-system and multi-target action characteristics.This paper attempts to summarize the existing research results and lay the foundation for further exploring the synergistic mech-anism of action of ginseng-acorus calamus combination and the dose-effect relationship of the combination,so as to provide a sci-entific basis for the development of innovative Chinese medicines for the prevention and treatment of AD.

DPP4 is a serine exopeptidase that is immobilized on the cell membrane and plays a crucial regulatory role in various physiological and pathological activities within the human body.In addition to acting as a transcription factor to regulate the tran-scription and expression of downstream target genes,DPP4 also functions as a transcription-independent regulator through pro-tein-protein interactions.In recent studies,DPP4 has been strongly linked to various diseases,and several substances with the potential to target DPP4 have been identified.This paper mainly reviews the multifunctionality of DPP4 in regulating vari-ous aspects of energy metabolism,inflammation,tissue repair and carcinogenesis in the body.It also reviews the screening of in vitro inhibitors of DPP4 and its research progress in regulating chronic liver disease,based on the pathological development process of chronic liver disease.

Objective To explore the clinical efficacies of different surgical methods for elderly patients with lumbar tuberculosis.Methods The clinical data of 289 elderly patients with lumbar tuberculosis admitted to Hebei Chest Hospital from August 2018 to August 2021 were retrospectively analyzed.According to surgical methods,the patients were divided into the posterior group(109 cases),the anterior and posterior combination group(81 cases),and the anterior group(99 cases).The time of bone graft and fusion,operation time,hospital stay,intraoperative blood loss,and complications of the three groups were collected and compared among the three groups.The spine Cobb angle was regularly determined,the correction degree was calculated;the levels of erythrocyte sedimentation rate(ESR),white blood cell count(WBC),and C-reactive protein(CRP)were collected and compared among the three groups;and the Frankel grading and visual analogue scale(VAS)scores of the three groups were compared.Results After a 2-year follow-up,there was no significant difference in the time of bone graft and fusion among the three groups(P>0.05),the anterior group had the shortest operation time,the posterior group had the shortest hospital stay,and the lowest intraoperative blood loss and incidence of complications,with statistically significant differences(P<0.05).The correction degree of the anterior and posterior combination group was better than that of the posterior group and the anterior group(P<0.05),and the Cobb angles after operation and at the last follow-up in the posterior group was better(P<0.05).The anterior and posterior combination group had better improvement effect on CRP and ESR at the last follow-up(P<0.05),the WBC level of the posterior group was lower(P<0.05).The proportions of patients in grade E of Frankel grading at the last follow-up in the three groups were higher than those after surgery(P<0.05);compared with the preoperative period,the VAS scores at the last follow-up of the three groups decreased(P<0.05),and the VAS score of the posterior group was lower(P<0.05).Conclusion The effects of anterior surgery,posterior surgery and anterior and posterior combined surgery in the treatment of elderly lumbar tuberculosis are good,and the approach method can be scientifically and reasonably formulated according to patients' physical condition to improve the clinical treatment effect.

The leukocyte immunoglobulin-like receptor LILRB4(ILT3 or CD85k),a member of the immunosuppressive re-ceptor family,is expressed predominantly on the cell membranes of immune cells of myeloid origin,and exerts an immunosuppressive effect in immune regulation by activating either the autoinhibitory motif(ITIM)or by inhibiting Fc receptor activation motif(ITAM).In tumors,activation of LILRB4 receptor generates an immunosuppressive tumor microenvironment that assists in tumor invasion and metastasis,and in inflammatory diseases,LILRB4 is expressed on a variety of cells,such as monocytes,macrophages,mast cells,etc.,and attenuates inflammatory responses.Currently,LILRB4 has become a therapeutic target for tumors and various inflammatory diseases,and anti-LILRB4 monoclonal antibodies against acute myeloid leukemia(AML)have entered clinical trials.This review dis-cusses LILRB4 in terms of its structural distribution,signaling,therapeutic targets,and new drug development.

Objective To explore the changes in macrophage infiltration behavior during the dynamic evolution of thrombi following the formation of acute carotid artery thrombosis occlusion(ACTO).Methods 15 healthy male New Zealand rabbits were selected to establish an ACTO model by causing injury to the rabbit carotid artery using surgical sutures treated with ferric chloride.All rabbits were randomly divided into 5 groups according to the end-point time using the random number table method,namely 24-hour group,1 week group,4week group,8 week group,and 12week group postoperatively,with 3 rabbits in each group.At 24 hours post-operation,the ACTO model was examined by DS A.At 24 hours,1 week,4 weeks,8 weeks,and 12 weeks post-operation,samples were taken from the thrombotic arterial segment of the 3 rabbits in each group and embedded in paraffin.The thrombus samples were stained with hematoxylin-eosin(HE)and Martius scarlet blue(MSB)to analyze changes in thrombus morphology and composition(including red blood cells,fibrin and collagen fibers).Orbit Imaging Analysis software was used for semi-quantitative analysis of the thrombus composition components.Using immunohistochemistry to detect the distribution of MO and M2 macrophages in thrombi,aimed to summarize the dynamic evolution of thrombus morphology,composition,and macrophage infiltration behavior at different stages following ACTO occurrence.Results The 24-hour DSA results indicated that all experimental rabbits successfully established the ACTO model.(1)HE staining showed a continuous increase in thrombus size from 24 hours to 1 week.By 4 weeks,signs of thrombus dissolution appeared,and at 8 weeks,neovascularization was observed within the thrombus.By 12 weeks,signs of fibrosis were evident in the thrombus.(2)MSB staining revealed that during the acute phase of thrombus formation(within 24 hours after surgery),red blood cells were the predominant component initially,but after this period,fibrin and collagen fibers became the main components.(3)The detection results of MO macrophages showed that 24 hours after surgery,MO macrophages in the thrombus were not evenly distributed throughout the thrombus,but mainly gathered at the thrombus edge;at 1 week after surgery,the positive area percentage of MO macrophage in the thrombus increased compared with 24 hours after surgery(thrombus edge:[41.7±27.0]％vs.[24.6±16.7]％,thrombus core:[35.7±19.6]％vs.[11.1±10.4]％,all P＜0.001),and evenly distributed within the thrombus;at 4 weeks after surgery,MO macrophages in the thrombus decreased compared with 1 week after surgery(thrombosis edge:[10.7±6.1]％vs.[41.7±27.0]％,thrombus core:[12.1±8.5]％vs.[35.7±19.6]％,all P＜0.001),the differences were statistically significant.At 4,8,and 12 weeks after surgery,MO macrophages within the thrombus did not change significantly with time(thrombus edge:[10.7±6.1]％,[8.0±7.7]％,and[8.9±5.3]％;thrombus core:[12.1±8.5]％,[9.5±4.2]％,and[15.7±11.0]％),and the differences were not statistically significant(all P＞0.05).In addition,at 12 weeks after surgery,MO macrophages at the thrombus edge was less than the thrombus core([8.9+5.3]％vs.[15.7±11.0]％,P＜0.01).The detection results of M2 macrophages showed that 24 hours after surgery,M2 macrophages in the thrombus were widely distributed throughout the thrombus;at 1 week after surgery,the positive area percentage of M2 macrophages in the thrombus increased compared with 24 hours after surgery(thrombus edge:[22.1±11.3]％vs.[11.4±8.7]％,P＜0.001;thrombus core:[24.5±9.8]％vs.[7.6±6.0]％,P＜0.001);at 4 weeks after surgery,M2 macrophage in the thrombus decreased compared with 1 week after surgery(thrombosis edge:[10.6±3.7]％vs.[22.1±11.3]％,P＜0.001;thrombus core:[9.2±4.3]％vs.[24.5±9.8]％,P＜0.001);at 8 weeks after surgery,M2 macrophages in the thrombus increased compared with 4 weeks after surgery([17.9±8.8]％vs.[9.2±4.3]％,P＜0.001),and the differences were statistically significant.However,M2 macrophages in the thrombus did not change significantly from 8 weeks to 12 weeks after surgery(thrombus edge:[9.4±6.3]％vs.[8.5±5.3]％,P＞0.05;thrombus core:[17.9±8.8]％vs.[14.4±10.0]％,P＞0.05).In addition,at 8 and 12 weeks after surgery,M2 macrophages in the thrombus core was greater than the thrombus edge(8 weeks after surgery:[17.9±8.8]％vs.[9.4±6.3]％,P＜0.001;12weeks after surgery:[14.4±10.0]％vs.[8.5±5.3]％,P＜0.001).Conclusions This study successfully established an ACTO animal model and demonstrated for the first time the dynamic evolution of macrophages within 12 weeks post-thrombus formation.Macrophages may played a significant role in both thrombus formation and fibrinolysis,as well as in the promotion of thrombus dissolution and the formation of new blood vessels within the thrombus which may potentially promote the spontaneous reperfusion of the occluded vessels.The results of this study need further verification.

AIM To evaluate the quality of Yanyangke Mixture.METHODS The HPLC fingerprints were established,after which cluster analysis,principal component analysis and partial least squares discriminant analysis were performed.The contents of liquiritin,rosmarinic acid,sheganoside,irisgenin,honokiol,monoammonium glycyrrhizinate,irisflorentin,isoliquiritin and magnolol were determined,the analysis was performed on a 35 ℃ thermostatic Agilent ZORBAX SB-C18 column(5 μm,250 mmx4.6 mm),with the mobile phase comprising of 0.1％phosphoric acid-acetonitrile flowing at 1 mL/min in a gradient elution manner,and multi-wavelength detection was adopted.RESULTS There were ten common peaks in the fingerprints for twelve batches of samples with the similarities of more than 0.9.Various batches of samples were clustered into three types,three principal components displayed the acumulative variance contribution rate of 87.448％,peaks 5、14(honokiol),3(liquiritin),11(monoammonium glycyrrhizinate)and 15(asarinin)were quality markers.Nine constituents showed good linear relationships within their own ranges(r＞0.999 0),whose average recoveries were 98.5％-103.6％with the RSDs of 0.92％-1.7％.CONCLUSION This stable and reliable method can provide a basis for the quality control of Yanyangke Mixture.

Diabetes mellitus erectile dysfunction(DMED)is a common diabetic-related vascular,endo-crine and neuropathy in clinical practice,and patients with DMED often present with symptoms such as difficulty in erection,prolonged erection time,poor hardness,and short sexual intercourse.The etiological mechanism is complex,and it is often closely related to many factors such as oxidative stress(OS),inflammatory response,and neurological and endocrine lesions,which often cross-react and promote the progression of DMED lesions.In recent years,relevant studies have shown that OS and ferroptosis play a key role in DMED:OS can cause neuro-logical and Abnormal endocrine function,decreased synthesis or bioavailability of penile vascular endothelium,spongy endothelial cell dysfunction and decreased smooth muscle diastolic function,resulting in penile erectile dysfunction,and ferroptosis has also been confirmed to be closely related to DMED,controlling OS and ferroptosis to improve erectile function in diabetic patients is a reasonable and effective treatment pathway,but the mechanism of action of ferroptosis leading to DMED needs to be further studied.Therefore,this article reviews the latest infor-mation on the correlation between OS and ferroptosis and DMED,aiming to provide a useful reference for exploring the mechanism of DMED,clinical prevention and treatment of DMED,and providing potential directions for future research in this field.