1.Acute Inflammatory Pain Induces Sex-different Brain Alpha Activity in Anesthetized Rats Through Optically Pumped Magnetometer Magnetoencephalography
Meng-Meng MIAO ; Yu-Xuan REN ; Wen-Wei WU ; Yu ZHANG ; Chen PAN ; Xiang-Hong LIN ; Hui-Dan LIN ; Xiao-Wei CHEN
Progress in Biochemistry and Biophysics 2025;52(1):244-257
ObjectiveMagnetoencephalography (MEG), a non-invasive neuroimaging technique, meticulously captures the magnetic fields emanating from brain electrical activity. Compared with MEG based on superconducting quantum interference devices (SQUID), MEG based on optically pump magnetometer (OPM) has the advantages of higher sensitivity, better spatial resolution and lower cost. However, most of the current studies are clinical studies, and there is a lack of animal studies on MEG based on OPM technology. Pain, a multifaceted sensory and emotional phenomenon, induces intricate alterations in brain activity, exhibiting notable sex differences. Despite clinical revelations of pain-related neuronal activity through MEG, specific properties remain elusive, and comprehensive laboratory studies on pain-associated brain activity alterations are lacking. The aim of this study was to investigate the effects of inflammatory pain (induced by Complete Freund’s Adjuvant (CFA)) on brain activity in a rat model using the MEG technique, to analysis changes in brain activity during pain perception, and to explore sex differences in pain-related MEG signaling. MethodsThis study utilized adult male and female Sprague-Dawley rats. Inflammatory pain was induced via intraplantar injection of CFA (100 μl, 50% in saline) in the left hind paw, with control groups receiving saline. Pain behavior was assessed using von Frey filaments at baseline and 1 h post-injection. For MEG recording, anesthetized rats had an OPM positioned on their head within a magnetic shield, undergoing two 15-minute sessions: a 5-minute baseline followed by a 10-minute mechanical stimulation phase. Data analysis included artifact removal and time-frequency analysis of spontaneous brain activity using accumulated spectrograms, generating spectrograms focused on the 4-30 Hz frequency range. ResultsMEG recordings in anesthetized rats during resting states and hind paw mechanical stimulation were compared, before and after saline/CFA injections. Mechanical stimulation elevated alpha activity in both male and female rats pre- and post-saline/CFA injections. Saline/CFA injections augmented average power in both sexes compared to pre-injection states. Remarkably, female rats exhibited higher average spectral power 1 h after CFA injection than after saline injection during resting states. Furthermore, despite comparable pain thresholds measured by classical pain behavioral tests post-CFA treatment, female rats displayed higher average power than males in the resting state after CFA injection. ConclusionThese results imply an enhanced perception of inflammatory pain in female rats compared to their male counterparts. Our study exhibits sex differences in alpha activities following CFA injection, highlighting heightened brain alpha activity in female rats during acute inflammatory pain in the resting state. Our study provides a method for OPM-based MEG recordings to be used to study brain activity in anaesthetized animals. In addition, the findings of this study contribute to a deeper understanding of pain-related neural activity and pain sex differences.
2.Effects of Kidney-Tonifying and Blood-Activating Acupuncture on Mitochondrial Membrane Potential and SIRT1/PGC-1α Axis in Hippocampal Tissue of SAMP8 Mice
Dan REN ; Ting ZHANG ; Jiangxi XU ; Hong ZHU ; Ruomeng LI
Journal of Traditional Chinese Medicine 2025;66(13):1378-1385
ObjectiveTo explore the potential mechanisms of kidney-tonifying and blood-activating acupuncture for Alzheimer's disease. MethodsMale SAMP8 mice were randomly divided into a model group, acupuncture group, non-acupoint group, and donepezi group, with 10 mice in each group, and 10 SAMR1 mice as normal group. The acupuncture group received acupuncture at Baihui (GV 20), Xuehai (SP 10), Shenshu (BL 23), and Geshu (BL 17). Xuehai (SP 10), Shenshu (BL 23), and Geshu (BL 17) were stimulated on the left side first and then on the right side alternately, once a day. The non-acupoint group received acupuncture at fixed bilateral non-meridian, non-acupoint points under the ribs, once a day. The model and normal groups underwent equivalent handling and restraint stress without acupuncture. The donepezi group received 1 mg/kg donepezil via gastric gavage daily. All groups were treated for 4 weeks. After treatment, Morris water maze tests (to record orientation sailing latency, number of traverses through the platform quadrant) and open field (to record distance travelled) were used to evaluate learning and memory abilities; hippocampal neuronal damage was analyzed via HE and Nissl staining; mitochondrial membrane potential and reactive oxygen species (ROS) were measured using assay kits; Western blot and qRT-PCR were performed to detect silencing information regulator 1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and mRNA expression levels. ResultsCompared with the normal group, mice in the model group and non-acupoint group showed elevated orientation sailing latency and relative multiplicity of ROS in hippocampal tissues, and reduced number of traverses through the platform quadrant, distance of movement in the open-field experiment, number of Nissl-staining-positive cells in the hippocampal tissues, mitochondrial membrane potential, and protein levels and mRNA expression of SIRT1, PGC-1α (P<0.01); HE staining showed that the hippocampal tissues of the mice was loosely arranged, with reduced number of neurons and vacuolar degeneration; Nissl staining showed that pyramidal neurons in the hippocampal region were not neatly arranged, and the number of Nissl bodies in the cytoplasm was less and the staining was lighter. Compared with the model group, mice in the acupuncture group and donepezil group had lower orientation sailing latency and relative multiplicity of ROS in the hippocampal tissue, higher number of traverses through the platform quadrant, distance of movement in the open-field experiment, number of Nissl-stained positive cells in the hippocampal tissue, mitochondrial membrane potential, and protein levels and mRNA expression of SIRT1 and PGC-1α (P<0.01), and HE staining and Nissl staining showed significant improvement in hippocampal histopathological damage. Compared with the donepezil group, the orientation sailing latency shortened in the acupuncture group of mice (P<0.01). ConclusionKidney-tonifying and blood-activating acupuncture method can alleviate the SIRT1/PGC-1α signalling pathway in the hippocampal tissue and improve the mitochondrial function, thus alleviating the neuronal damage, which is one of the possible mechanisms for its treatment of Alzheimer's disease.
3.Effects of total saponins of Trillium tschonoskii Maxim on cognitive function and neurovascular unit in 2-VO model rats
Dan YANG ; Li-Jun YANG ; Xian-E TANG ; Gang WANG ; Ren-Ze DUAN ; Xian-Bing CHEN
Medical Journal of Chinese People's Liberation Army 2024;49(3):316-322
Objective To observe the effects of total saponins of Trillium tschonoskii Maxim(TST)on vascular cognitive impairment(VCI),neurovascular units(NVUs),and neural circuit integrity in rats.Methods Forty-eight male Sprague-Dawley(SD)rats were randomly divided into sham-operated group,model group,TST group(intragastric administration,100 mg/kg),and donepezil group(intragastric administration,0.45 mg/kg),and then subjected to ischemic stroke by 2-VO method(bilateral common carotid artery ligation)or sham surgery.After 28 days of intragastric administration,Mirros water maze test was performed to evaluate the spatial learning and memory abilities of rats in each group.HE and Nissl staining were used to observe the pathological changes of brain tissue in rats.The expression of synuclein(SYN)in rat hippocampus was observed by immunohistochemical staining.Changes in dendritic spines in rat's hippocampal neurons were observed by Golgi staining.Western blotting was used to detect the expression levels of IL-1β,IL-10,vascular endothelial growth factor A(VEGFA),postsynaptic density protein 95(PSD95),and growth associated protein 43(GAP43)in rat's hippocampus in each group.Results In Mirros water maze test,rats in model group showed significant prolonged escape latency(P<0.05),and a significant reduction in the number of crossing platforms and the percentage of activity time in the target quadrant(P<0.05)than those in sham-operated group;while rats in TST group and donepezil group showed significant shortened escape latency(P<0.01),and significant increase of the number of times of crossing platforms and the percentage of activity time in the target quadrant(P<0.05)than those in model group.Compared of sham-operated group,model group showed a decrease in the expression of SYN and the number of neurons,Nissl bodies,and dendritic spines in the CA1 region of the hippocampus(P<0.05).Compared with model group,TST group and donepezil group showed an increase in the expression of SYN and the number of neurons,Nissl bodies,and dendritic spines in the CA1 region of the hippocampus(P<0.05).Western blotting showed a significant increase in the expression of IL-1β and VEGF(P<0.05),and a decrease in the expression of IL-10,PSD95,and GAP43(P<0.01)in rat's hippocampus of model group than those in sham-operated group.Compared with model group,TST group and donepezil group showed a significant decrease in the expression of IL-1β(P<0.05),and an increase in the expression of VEGFA,IL-10,and GAP43(P<0.05).Conclusions TST could alleviate cognitive impairment through promoting synaptic plasticity and neurovascular unit remodeling in 2-VO model rats,suggesting its significance as a potential drug for apoplexy.
4.Pyroptosis-related genes defines the progression and im-mune tolerance microenvironment of hepatocellular carcino-ma
Xiao-Dong HAO ; Yi-Dan REN ; Mao-Xiao FENG ; Yun-Shan WANG
Chinese Journal of Current Advances in General Surgery 2024;27(2):98-104
Objective:To explore the expression pattern of pyroptosis-related genes(PRGs)in hepatocellular carcinoma(HCC),and analyze the relationship between its expression and tumor prog-nosis and immune microenvironment.Methods:TCGA database was used to analyze the genetic changes and expression patterns of PRGs in primary HCC cells,and cluster analysis was used to i-dentify the pyrogenic subtypes of HCC.To compare the difference of prognosis and immune mi-croenvironment among HCC pyrodeath subtypes.Scorch death score quantified the comprehensive expression of PRGs in each sample,and analyzed the correlation between scorch death score and each immune score.Results:Two pyroptosis-associated subtypes of primary HCC were identi-fied,and the expression pattern of PRGs is closely related to the prognosis of cancer patients and the tumor microenvironment.The subtype with high expression of PRGs had a poor prognosis,and functional enrichment analysis found that some tumor-promoting pathways and PD-1 checkpoint pathways were significantly enriched in this subtype.And various cells and immune checkpoints re-lated to immunosuppression were also enriched in this subtype.By constructing PYROPTO-SIS_score to quantify the comprehensive expression of pyroptosis-related genes in each sample,it was found that PYROPTOSIS_score was significantly positively correlated with tumor-infiltrating macrophages,myeloid-derived suppressor cells,and Treg cells.Conclusion:These results sug-gest that pyroptosis may play a tumor-promoting as well as immunosuppressive role in HCC,pro-viding new insights into the assessment of tumor patient prognosis and the immune microenviron-ment.
5.Clinical observation of Van Herick method for evaluating anterior chamber angle width
Peng ZHANG ; Lifang WANG ; Yanzheng WANG ; Kunling HAN ; Zhaoyang REN ; Yanling WANG
International Eye Science 2024;24(1):136-139
AIM: To explore a more convenient and accurate method for evaluating the anterior chamber angle width based on the Van Herick method.METHODS:A total of 58 patients(69 eyes)with age-related cataract who visited our hospital between January and December 2021 were included. They were divided into the chamber angle width ≥1/2 corneal thickness(CT)group(44 eyes of 37 cases)and <1/2CT group(25 eyes of 21 cases)according to the Van Herick method. The central anterior chamber depths and the peripheral anterior chamber angle degrees were measured by ultrasound biomicroscopy.RESULTS: There were statistically significant differences in central anterior chamber depth between the two groups(2.64±0.27 mm vs. 2.23±0.29 mm, P<0.01), and the differences of chamber angle degrees of quadrants of superior, temporal, inferior and nasal compared between two groups were all statistically significant(P<0.01). The difference of chamber angle degrees of quadrants of superior and inferior in chamber angle width ≥1/2CT group was not statistically significant(P>0.05), while the differences of chamber angle degrees of other quadrants were all statistically significant(P<0.05). The differences of chamber angle degrees of quadrants of superior and nasal, temporal and the chamber angle degrees of quadrants of inferior and temporal were all statistically significant in chamber angle width <1/2CT group(P<0.05).CONCLUSION: In the overall evaluation of the anterior chamber angle, it would be more simple, fast and accurate when evaluating the temporal chamber angle width and inferior quadrant of chamber angle width by using the Van Herick method under silt lamp.
6.Effects of Sijunzi decoction on the regulation of autophagy proteins by inflammatory factors based on TNF-α/NF-κB in hippocampal neurons of SAMP8 mice
Xudong LIU ; Songnan WANG ; Dan MA ; Dehong SHAN ; Lu REN
Immunological Journal 2024;40(1):53-58
This study was designed to investigate the effect of Sijunzi decoction(SJZD)on the expression of inflammatory factors and autophagic proteins in the hippocampus of senescence-accelerated mouse prone 8(SAMP8)mice and its mechanism.SAMR1 mice were used as control group,and 32 SAMP8 mice were divided into model group,donepezil group,SJZD low and SJZD high dose treatment groups.Y-maze experiment was performed to detect changes in mouse memory function;the expression of NF-κB was detected by immunohistochemistry;the levels of TNF-α,IL-1β,IL-6 were detected by ELISA;the expression of A[3,caspse-1,beclin-1 and LC3-Ⅱproteins in hippocampal tissue were detected by Western blotting.Compared with the control group,the model group mice showed a decrease in total number of entries and alternations,an elevation in the levels of TNF-α,IL-1β,IL-6,Aβ protein and caspse-1 protein,and downregulation in the expression of beclin-1 and LC3-Ⅱ proteins.Both donepezil and SJZD(low-dose group and high-dose group)can reverse these changes in model mice.In conclusion,the mechanism of SJZD in treating Alzheimer's disease may relate to the correction of central hippocampal inflammatory factors and autophagy dysfunction.
7.Effects of Naringenin on Myocardial Fibrosis and Activin A/follistatin System in Rats with Chronic Heart Failure
Dan RUAN ; Lei HUANG ; Fengjuan REN ; Bo LUO
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(3):751-757
Objective To study the effect of naringenin(NAR)on myocardial fibrosis in rats with chronic heart failure(CHF)and its mechanism.Methods The rat model of CHF was established and randomly divided into CHF model group(CHF),NAR low dose group(L-NAR),medium dose group(M-NAR)and high dose group(H-NAR),with 10 rats in each group.In addition,sham operation group(Sham)was set up.The cardiac function of rats was detected by ultrasonic electrocardiogram.HE staining and Masson staining were used to observe the pathological changes of myocardium.The content of hydroxyproline(HYP)in myocardium was determined by alkaline hydrolysis method,and the content of collagen was calculated.The mRNA expression levels of activin A(Act A)and follistatin(FS)in myocardium were detected by qRT-PCR.The protein expression levels of Act A,FS,Collagen Ⅰ,Collagen Ⅲ,Smad2,Smad3,p-Smad2 and p-Smad3 were detected by Western blot.Results Compared with Sham group,the arrangement of muscle fibers in CHF group was disordered,cells were swollen,and the degree of fibrosis was higher.The left ventricular end diastolic dimension(LVEDD),left ventricular end systolic dimension(LVESD),collagen content,and the expression levels of Act A,Collagen I,Collagen Ⅲ,p-Smad2/Smad2,and p-Smad3/Smad3 ratios were significantly increased(P<0.05),The left ventricular ejection fraction(LVEF)and FS expression level were significantly decreased(P<0.05).Compared with CHF group,the pathological changes and fibrosis degree of myocardial tissue in M-NAR group and H-NAR group were improved.LVEDD,LVESD,collagen content and the expression levels of Act A,Collagen Ⅰ,Collagen Ⅲ,p-Smad2/Smad2,and p-Smad3/Smad3 ratios were significantly decreased(P<0.05),while LVEF and FS expression levels were significantly increased(P<0.05).Compared with L-NAR group,medium and high-dose NAR intervention was more effective in improving myocardial fibrosis and Act A/FS system disorder in CHF rats(P<0.05).Conclusion NAR can inhibit myocardial fibrosis in CHF rats,and its mechanism may be related to the regulation of Act A/FS system.
8.Research Progress of Di-Huang-Yin-Zi Decoction in the Treatment of Alzheimer's Disease and Parkinson's Disease
Jinfeng REN ; Xiaoyu LIU ; Luyan YOU ; Yuanjun QU ; Dan CHEN ; Hao ZHANG ; Sheng WEI ; Xiwen GENG
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(8):2069-2075
Neurodegenerative diseases are a type of disease characterized by specific types of neuronal loss and progressive progression,mainly represented by Alzheimer's disease and Parkinson's disease.This type of disease,due to its intractable and irreversible symptoms,brings great physical and psychological burden to patients,which is seriously disturbing their normal life.In terms of treatment,there is currently no specific treatment for Alzheimer's disease in clinical practice,and first-line treatment drugs for Parkinson's disease also have great limitations.In traditional Chinese medicine,kidney governs bone,generates marrow,and connects to the brain.In clinical evidence typing,premature aging,fatigue and forgetfulness,and tremor of limbs caused by kidney deficiency and medullary reduction are considered to be the main pathologies of these diseases.Di-Huang-Yin-Zi decoction which is derived from the"General Records of Holy Universal Relief",is recorded as a good formula for nourishing kidney yin and filling kidney yang.Clinical data shows that this formula has significant therapeutic effects in treating neurodegenerative diseases caused by kidney essence deficiency.Modern research results indicate that its mechanism of action involves inhibiting inflammatory reactions,regulating mitochondrial autophagy,reversing The hypothalamic-pituitary-adrenal axis abnormalities,and neuroprotection.The main effective ingredients in this formula include loganin,echinarin,and schisandrin A.This article aims to summarize and analyze the clinical efficacy,mechanism of action,and active ingredients of Di-Huang-Yin-Zi decoction in the treatment of Alzheimer's and Parkinson's disease in recent years,in order to clarify the research status of Di-Huang-Yin-Zi decoction in the neurodegenerative disease and provide reference for further research.
9.Application of limb motor rehabilitation program based on the patient health engagement model in patients with hemorrhagic stroke
Shufang SHI ; Huishu REN ; Hongyan DUAN ; Dan WU ; Yanjun ZHANG ; Mingxia GUO ; Wanling LI
Chinese Journal of Practical Nursing 2024;40(32):2481-2488
Objective:To explore the effectiveness of limb motor rehabilitation program based on patient health engagement (PHE) model in patients with hemorrhagic stroke, and to provide reference for the limb motor rehabilitation management of hemorrhagic stroke patients.Methods:Through literature review and Delphi expert correspondence, a limb motor rehabilitation program for hemorrhagic stroke patients based on the PHE model was constructed. A non-contemporaneous controlled study was conducted, 45 hemorrhagic stroke patients hospitalized in the Department of Neurosurgery of Shanxi Bethune Hospital from March to August 2022 were selected by convenience sampling method as the control group, and routine exercise rehabilitation measure was given, 45 hemorrhagic stroke patients from September 2022 to February 2023 were selected as the intervention group, a limb motor rehabilitation program based on PHE model was implemented on the basis of control group. The functional exercise compliance, limb motor function, daily activity ability, emotional and social dysfunction of patients in the two groups were observed before intervention, 1 and 3 months after intervention respectively.Results:A total of 85 patients with hemorrhagic stroke were included. There were 42 patients in the intervention group, 25 males and 17 females, aged (52.07 ± 9.91) years old, and 43 patients in the control group, 21 males and 22 females, aged (53.93 ± 10.52) years old. There were no significant differences in the functional exercise compliance, limb motor function, daily activity ability, emotional and social dysfunction of patients before intervention between the two groups. At 3 months after intervention, the functional exercise compliance score in the intervention group was (40.83 ± 7.92) points, higher than that in the control group (37.14 ± 6.44) points, and the difference was statistically significant ( t = 2.36, P<0.05). At 1 and 3 months after intervention, the scores of limb motor function and daily activity ability in the intervention group were (27.12 ± 6.74), (33.67 ± 6.54) points and (61.31 ± 6.72), (74.40 ± 8.71) points, which were higher than (24.91 ± 6.03), (27.02 ± 6.59) points and (52.33 ± 9.78), (60.12 ± 10.03) points of the control group, the differences were statistically significant ( t values were 2.06-7.01, all P<0.05), the scores of emotional and social dysfunction were (75.52 ± 22.09) and (58.33 ± 18.88) points, which were lower than (86.02 ± 23.04), (78.51 ± 21.67) points of the control group, and the differences were statistically significant ( t = - 2.14, - 4.57, both P<0.05). Conclusions:The limb motor rehabilitation program based on the PHE model could improve the exercise compliance of patients with hemorrhagic stroke, improve the limb motor function and daily activity ability of patients, alleviate negative emotions, and reduce the level of social dysfunction.
10.Expert consensus on the rational application of the biological clock in stomatology research
Kai YANG ; Moyi SUN ; Longjiang LI ; Zhangui TANG ; Guoxin REN ; Wei GUO ; Songsong ZHU ; Jia-Wei ZHENG ; Jie ZHANG ; Zhijun SUN ; Jie REN ; Jiawen ZHENG ; Xiaoqiang LV ; Hong TANG ; Dan CHEN ; Qing XI ; Xin HUANG ; Heming WU ; Hong MA ; Wei SHANG ; Jian MENG ; Jichen LI ; Chunjie LI ; Yi LI ; Ningbo ZHAO ; Xuemei TAN ; Yixin YANG ; Yadong WU ; Shilin YIN ; Zhiwei ZHANG
Journal of Practical Stomatology 2024;40(4):455-460
The biological clock(also known as the circadian rhythm)is the fundamental reliance for all organisms on Earth to adapt and survive in the Earth's rotation environment.Circadian rhythm is the most basic regulatory mechanism of life activities,and plays a key role in maintaining normal physiological and biochemical homeostasis,disease occurrence and treatment.Recent studies have shown that the biologi-cal clock plays an important role in the development of oral tissues and in the occurrence and treatment of oral diseases.Since there is cur-rently no guiding literature on the research methods of biological clock in stomatology,researchers mainly conduct research based on pub-lished references,which has led to controversy about the research methods of biological clock in stomatology,and there are many confusions about how to rationally apply the research methods of circadia rhythms.In view of this,this expert consensus summarizes the characteristics of the biological clock and analyzes the shortcomings of the current biological clock research in stomatology,and organizes relevant experts to summarize and recommend 10 principles as a reference for the rational implementation of the biological clock in stomatology research.

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