1.Research progress on effects of orexin and its receptor antagonists on epilepsy
Chen-shuo JIA ; Yuan-yuan LIU ; Jing ZHANG ; Ai-ping ZHENG ; Zeng-ming WANG ; Qiao WANG
Chinese Pharmacological Bulletin 2025;41(10):1823-1830
Epilepsy is a chronic neurological disorder caused by an imbalance between excitation and inhibition in the central nervous system.Recently,the role of the orexin system in the pathogenesis of epilepsy has garnered significant attention.Orex-in primarily regulates arousal states and enhances neuronal excit-ability through activation of OX1-R/OX2-R receptors.Studies have shown that elevated orexin levels lower the seizure thresh-old,while orexin receptor antagonists(ORAs)exhibit potential antiepileptic effects.ORAs suppress epileptiform discharges by reducing glutamate release,enhancing GABAergic inhibitory effects,and modulating the thalamocortical circuit.Animal ex-periments and preliminary clinical studies demonstrate that OX1R antagonists decrease excitatory synaptic transmission,whereas OX2 R antagonists primarily strengthen GABA-mediated inhibition.With the widespread application of ORAs in sleep disorders,exploring their clinical value as antiepileptic drugs will become a key focus for future research.This review summa-rizes the role of the orexin system in epileptogenesis and discus-ses the research progress and future directions of ORAs as poten-tial antiepileptic agents.
2.Application of voice training in the treatment of speech disorders in patients with Parkinson′s disease
Xingxing AI ; Ziwen WANG ; Xiaoling LIN ; Yinglian LI ; Tianning LIU ; Xianghua YUAN ; Jiewei HUANG
Chinese Journal of Practical Nursing 2025;41(15):1196-1201
This article summarized the overview of voice training, common training forms, and the application effect of voice training in the treatment of speech disorders in Parkinson′s disease patients, analyzed the shortcomings of its application and put forward prospects for future research, aiming to provide valuable references for both patients and healthcare workers.
3.Acupuncture inhibites hippocampal inflammation in rats with cerebral ischemia-reperfusion injury by regulating PPARβ/δ
Jia YUAN ; Yao WANG ; Xiaoyue LIU ; Litong CHEN ; Kun AI ; Haomei TIAN ; Canming XIE ; Chutao CHEN
Chinese Journal of Neuroanatomy 2025;41(4):486-492
Objective:To explore the role of the expression of peroxisome proliferator-activated receptor β/δ(PPARβ/δ)in the anti-inflammatory mechanism of acupuncture(AC)against cerebral ischemia-reperfusion injury(CIRI)in rat hippocampal tissue.Methods:A total of 60 SD rats were randomly divided into Sham group,CIRI group,CIRI+AC group and CIRI+AC+PPARβ/δsiRNA group.The CIRI rat model was prepared by the method of middle cerebral artery occlusion,and acupuncture treatment was used for intervention.The neurological function of rats was assessed by the modified neurological severity score(mNSS)method after 72 hours of intervention.The brain in-farction volume ratio was observed by 2,3,5-triphenyltetrazolium chloride(TTC)staining method.The pathological morphological changes of brain tissue were observed by hematoxylin-eosin(HE)staining.The expression levels of PPARβ/δ,IL-1β,and IL-10 mRNA in the hippocampal region were detected by RT-qPCR.Results:Compared with the Sham group,the mNSS scores and the brain infarction volume ratio in all modeling groups were significantly in-creased.Compared with the CIRI group,the mNSS scores and the brain infarction volume ratio in the CIRI+AC group were significantly reduced.The expression levels of PPARβ/δ and IL-10 in the hippocampus were significantly upregu-lated,while the expression level of IL-1β was significantly downregulated(P<0.01),with scattered inflammatory cell infiltration observed.Compared with the CIRI+AC group,there was no significant difference in the mNSS scores and the brain infarction volume ratio in the CIRI+AC+PPARβ/δsiRNA group.The expression level of PPARβ/δ in the hippocampus was significantly downregulated(P<0.01),while no significant difference was found in the expression level of IL-10 and IL-1β mRNA,with a small amount of inflammatory cell infiltration observed.Conclusion:Acupunc-ture ameliorates the recovery of neurological function and the ratio of cerebral infarction volume in rats with CIRI,and its mechanism may be associated with the upregulation of PPARβ/δ expression,thereby reducing inflammatory respon-ses and exerting neuroprotective effects.
4.The effects of acupuncture on the expression of circRNA_017109 and miR-138-5p in rat hippocampus post ischemia-reperfusion injury
Litong CHEN ; Canming XIE ; Yao WANG ; Jia YUAN ; Xiaoyue LIU ; Haomei TIAN ; Chutao CHEN ; Kun AI
Chinese Journal of Neuroanatomy 2025;41(4):445-451
Objective:To investigate the effects of acupuncture intervention on the expression of circRNA_017109 and miR-138-5p in the hippocampal region of rats with cerebral ischemia-reperfusion injury(CIRI),and to explore the potential mechanism of acupuncture in treating CIRI.Methods:Forty-five Sprague-Dawley(SD)rats were divided into sham group,middle cerebral artery occlusion/reperfusion(MCAO/R)group,and acupuncture(MCAO/R+AC)group.The MCAO/R and MCAO/R+AC groups were subjected to the modified Longa suture method to establish the MCAO/R model.The MCAO/R+AC group received acupuncture at the"Dazhui","Renzhong",and"Baihui"acu-points.Neurological impairment was assessed via the modified neurological severity score(mNSS).while cerebral infarct volume was assessed through TTC staining.Histological alterations in brain tissue were examined via HE stai-ning,and the expression of circRNA_017109 and miR-138-5p in the hippocampal area were determined using RT-qPCR.Results:The mNSS scores and cerebral infarct volume ratios in the model groups were markedly higher than those in the sham group(P<0.01),but these were significantly reduced in MCAO/R+AC group compared to the MCAO/R group(P<0.01).HE staining showed severe necrosis and inflammation in the MCAO/R group's hippocam-pus,while the MCAO/R+AC group had minimal necrosis and scattered inflammation.RT-qPCR results indicated that the expression of circRNA_017109 and miR-138-5p was downregulated in the MCAO/R group,while MCAO/R+AC group upregulated the expression of circRNA_017109 and miR-138-5p(P<0.05,P<0.01).Conclusion:Acupunc-ture can improve neurological deficits,reduce cerebral infarction volume,and alleviate inflammatory cell infiltration in CIRI rats by upregulating the expression of circRNA_017109 and miR-138-5p,thereby exerting neuroprotective effects.
5.Study on performance evaluation method for lubricating coatings of intravascular catheters
Hong-jian CHEN ; Chong-chong AI ; Yuan-yu LI ; Li-ping HUANG ; Jia-qi NIE ; Chang-bin WANG ; Qian YANG ; Yu-xin BI ; Wen-bo LU
Chinese Medical Equipment Journal 2025;46(1):66-72
Three evaluation methods were recommended for the key properties of the intravascular catheter lubricating coating such as stability,lubricity and integrity,including insoluble particle test method,friction test procedure and appearance detection method.Fifteen batches of microcatheters produced by different manufacturers were selected for testing to clarify the three methods in test principle,step,result,characteristic.References were provided for the design,production,evaluation and regulation of intravascular catheters with lubricant coatings.[Chinese Medical Equipment Journal,2025,46(1):66-72]
6.Acupuncture inhibites hippocampal inflammation in rats with cerebral ischemia-reperfusion injury by regulating PPARβ/δ
Jia YUAN ; Yao WANG ; Xiaoyue LIU ; Litong CHEN ; Kun AI ; Haomei TIAN ; Canming XIE ; Chutao CHEN
Chinese Journal of Neuroanatomy 2025;41(4):486-492
Objective:To explore the role of the expression of peroxisome proliferator-activated receptor β/δ(PPARβ/δ)in the anti-inflammatory mechanism of acupuncture(AC)against cerebral ischemia-reperfusion injury(CIRI)in rat hippocampal tissue.Methods:A total of 60 SD rats were randomly divided into Sham group,CIRI group,CIRI+AC group and CIRI+AC+PPARβ/δsiRNA group.The CIRI rat model was prepared by the method of middle cerebral artery occlusion,and acupuncture treatment was used for intervention.The neurological function of rats was assessed by the modified neurological severity score(mNSS)method after 72 hours of intervention.The brain in-farction volume ratio was observed by 2,3,5-triphenyltetrazolium chloride(TTC)staining method.The pathological morphological changes of brain tissue were observed by hematoxylin-eosin(HE)staining.The expression levels of PPARβ/δ,IL-1β,and IL-10 mRNA in the hippocampal region were detected by RT-qPCR.Results:Compared with the Sham group,the mNSS scores and the brain infarction volume ratio in all modeling groups were significantly in-creased.Compared with the CIRI group,the mNSS scores and the brain infarction volume ratio in the CIRI+AC group were significantly reduced.The expression levels of PPARβ/δ and IL-10 in the hippocampus were significantly upregu-lated,while the expression level of IL-1β was significantly downregulated(P<0.01),with scattered inflammatory cell infiltration observed.Compared with the CIRI+AC group,there was no significant difference in the mNSS scores and the brain infarction volume ratio in the CIRI+AC+PPARβ/δsiRNA group.The expression level of PPARβ/δ in the hippocampus was significantly downregulated(P<0.01),while no significant difference was found in the expression level of IL-10 and IL-1β mRNA,with a small amount of inflammatory cell infiltration observed.Conclusion:Acupunc-ture ameliorates the recovery of neurological function and the ratio of cerebral infarction volume in rats with CIRI,and its mechanism may be associated with the upregulation of PPARβ/δ expression,thereby reducing inflammatory respon-ses and exerting neuroprotective effects.
7.The effects of acupuncture on the expression of circRNA_017109 and miR-138-5p in rat hippocampus post ischemia-reperfusion injury
Litong CHEN ; Canming XIE ; Yao WANG ; Jia YUAN ; Xiaoyue LIU ; Haomei TIAN ; Chutao CHEN ; Kun AI
Chinese Journal of Neuroanatomy 2025;41(4):445-451
Objective:To investigate the effects of acupuncture intervention on the expression of circRNA_017109 and miR-138-5p in the hippocampal region of rats with cerebral ischemia-reperfusion injury(CIRI),and to explore the potential mechanism of acupuncture in treating CIRI.Methods:Forty-five Sprague-Dawley(SD)rats were divided into sham group,middle cerebral artery occlusion/reperfusion(MCAO/R)group,and acupuncture(MCAO/R+AC)group.The MCAO/R and MCAO/R+AC groups were subjected to the modified Longa suture method to establish the MCAO/R model.The MCAO/R+AC group received acupuncture at the"Dazhui","Renzhong",and"Baihui"acu-points.Neurological impairment was assessed via the modified neurological severity score(mNSS).while cerebral infarct volume was assessed through TTC staining.Histological alterations in brain tissue were examined via HE stai-ning,and the expression of circRNA_017109 and miR-138-5p in the hippocampal area were determined using RT-qPCR.Results:The mNSS scores and cerebral infarct volume ratios in the model groups were markedly higher than those in the sham group(P<0.01),but these were significantly reduced in MCAO/R+AC group compared to the MCAO/R group(P<0.01).HE staining showed severe necrosis and inflammation in the MCAO/R group's hippocam-pus,while the MCAO/R+AC group had minimal necrosis and scattered inflammation.RT-qPCR results indicated that the expression of circRNA_017109 and miR-138-5p was downregulated in the MCAO/R group,while MCAO/R+AC group upregulated the expression of circRNA_017109 and miR-138-5p(P<0.05,P<0.01).Conclusion:Acupunc-ture can improve neurological deficits,reduce cerebral infarction volume,and alleviate inflammatory cell infiltration in CIRI rats by upregulating the expression of circRNA_017109 and miR-138-5p,thereby exerting neuroprotective effects.
8.Research progress on effects of orexin and its receptor antagonists on epilepsy
Chen-shuo JIA ; Yuan-yuan LIU ; Jing ZHANG ; Ai-ping ZHENG ; Zeng-ming WANG ; Qiao WANG
Chinese Pharmacological Bulletin 2025;41(10):1823-1830
Epilepsy is a chronic neurological disorder caused by an imbalance between excitation and inhibition in the central nervous system.Recently,the role of the orexin system in the pathogenesis of epilepsy has garnered significant attention.Orex-in primarily regulates arousal states and enhances neuronal excit-ability through activation of OX1-R/OX2-R receptors.Studies have shown that elevated orexin levels lower the seizure thresh-old,while orexin receptor antagonists(ORAs)exhibit potential antiepileptic effects.ORAs suppress epileptiform discharges by reducing glutamate release,enhancing GABAergic inhibitory effects,and modulating the thalamocortical circuit.Animal ex-periments and preliminary clinical studies demonstrate that OX1R antagonists decrease excitatory synaptic transmission,whereas OX2 R antagonists primarily strengthen GABA-mediated inhibition.With the widespread application of ORAs in sleep disorders,exploring their clinical value as antiepileptic drugs will become a key focus for future research.This review summa-rizes the role of the orexin system in epileptogenesis and discus-ses the research progress and future directions of ORAs as poten-tial antiepileptic agents.
9.Association of Co-Exposure to Polycyclic Aromatic Hydrocarbons and Metal(loid)s with the Risk of Neural Tube Defects: A Case-Control Study in Northern China.
Xiao Qian JIA ; Yuan LI ; Lei JIN ; Lai Lai YAN ; Ya Li ZHANG ; Ju Fen LIU ; Le ZHANG ; Linlin WANG ; Ai Guo REN ; Zhi Wen LI
Biomedical and Environmental Sciences 2025;38(2):154-166
OBJECTIVE:
Exposure to polycyclic aromatic hydrocarbons (PAHs) or metal(loid)s individually has been associated with neural tube defects (NTDs). However, the impacts of PAH and metal(loid) co-exposure and potential interaction effects on NTD risk remain unclear. We conducted a case-control study in China among population with a high prevalence of NTDs to investigate the combined effects of PAH and metal(loid) exposures on the risk of NTD.
METHODS:
Cases included 80 women who gave birth to offspring with NTDs, whereas controls were 50 women who delivered infants with no congenital malformations. We analyzed the levels of placental PAHs using gas chromatography and mass spectrometry, PAH-DNA adducts with 32P-post-labeling method, and metal(loid)s with an inductively coupled plasma mass spectrometer. Unconditional logistic regression was employed to estimate the associations between individual exposures and NTDs. Least absolute shrinkage and selection operator (LASSO) penalized regression models were used to select a subset of exposures, while additive interaction models were used to identify interaction effects.
RESULTS:
In the single-exposure models, we found that eight PAHs, PAH-DNA adducts, and 28 metal(loid)s were associated with NTDs. Pyrene, selenium, molybdenum, cadmium, uranium, and rubidium were selected through LASSO regression and were statistically associated with NTDs in the multiple-exposure models. Women with high levels of pyrene and molybdenum or pyrene and selenium exhibited significantly increased risk of having offspring with NTDs, indicating that these combinations may have synergistic effects on the risk of NTDs.
CONCLUSION
Our findings suggest that individual PAHs and metal(loid)s, as well as their interactions, may be associated with the risk of NTDs, which warrants further investigation.
Humans
;
Neural Tube Defects/chemically induced*
;
Polycyclic Aromatic Hydrocarbons/adverse effects*
;
Female
;
Case-Control Studies
;
China/epidemiology*
;
Adult
;
Pregnancy
;
Environmental Pollutants
;
Maternal Exposure/adverse effects*
;
Metals/toxicity*
;
Young Adult
;
Risk Factors
10.Astragaloside IV Alleviates Podocyte Injury in Diabetic Nephropathy through Regulating IRE-1α/NF-κ B/NLRP3 Pathway.
Da-Lin SUN ; Zi-Yi GUO ; Wen-Yuan LIU ; Lin ZHANG ; Zi-Yuan ZHANG ; Ya-Ling HU ; Su-Fen LI ; Ming-Yu ZHANG ; Guang ZHANG ; Jin-Jing WANG ; Jing-Ai FANG
Chinese journal of integrative medicine 2025;31(5):422-433
OBJECTIVE:
To investigate the effects of astragaloside IV (AS-IV) on podocyte injury of diabetic nephropathy (DN) and reveal its potential mechanism.
METHODS:
In in vitro experiment, podocytes were divided into 4 groups, normal, high glucose (HG), inositol-requiring enzyme 1 (IRE-1) α activator (HG+thapsigargin 1 µmol/L), and IRE-1α inhibitor (HG+STF-083010, 20 µmol/L) groups. Additionally, podocytes were divided into 4 groups, including normal, HG, AS-IV (HG+AS-IV 20 µmol/L), and IRE-1α inhibitor (HG+STF-083010, 20 µmol/L) groups, respectively. After 24 h treatment, the morphology of podocytes and endoplasmic reticulum (ER) was observed by electron microscopy. The expressions of glucose-regulated protein 78 (GRP78) and IRE-1α were detected by cellular immunofluorescence. In in vivo experiment, DN rat model was established via a consecutive 3-day intraperitoneal streptozotocin (STZ) injections. A total of 40 rats were assigned into the normal, DN, AS-IV [AS-IV 40 mg/(kg·d)], and IRE-1α inhibitor [STF-083010, 10 mg/(kg·d)] groups (n=10), respectively. The general condition, 24-h urine volume, random blood glucose, urinary protein excretion rate (UAER), urea nitrogen (BUN), and serum creatinine (SCr) levels of rats were measured after 8 weeks of intervention. Pathological changes in the renal tissue were observed by hematoxylin and eosin (HE) staining. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expressions of GRP78, IRE-1α, nuclear factor kappa Bp65 (NF-κBp65), interleukin (IL)-1β, NLR family pyrin domain containing 3 (NLRP3), caspase-1, gasdermin D-N (GSDMD-N), and nephrin at the mRNA and protein levels in vivo and in vitro, respectively.
RESULTS:
Cytoplasmic vacuolation and ER swelling were observed in the HG and IRE-1α activator groups. Podocyte morphology and ER expansion were improved in AS-IV and IRE-1α inhibitor groups compared with HG group. Cellular immunofluorescence showed that compared with the normal group, the fluorescence intensity of GRP78 and IRE-1α in the HG and IRE-1α activator groups were significantly increased whereas decreased in AS-IV and IRE-1α inhibitor groups (P<0.05). Compared with the normal group, the mRNA and protein expressions of GRP78, IRE-1α, NF-κ Bp65, IL-1β, NLRP3, caspase-1 and GSDMD-N in the HG group was increased (P<0.05). Compared with HG group, the expression of above indices was decreased in the AS-IV and IRE-1α inhibitor groups, and the expression in the IRE-1α activator group was increased (P<0.05). The expression of nephrin was decreased in the HG group, and increased in AS-IV and IRE-1α inhibitor groups (P<0.05). The in vivo experiment results revealed that compared to the normal group, the levels of blood glucose, triglyceride, total cholesterol, BUN, blood creatinine and urinary protein in the DN group were higher (P<0.05). Compared with DN group, the above indices in AS-IV and IRE-1α inhibitor groups were decreased (P<0.05). HE staining revealed glomerular hypertrophy, mesangial widening and mesangial cell proliferation in the renal tissue of the DN group. Compared with the DN group, the above pathological changes in renal tissue of AS-IV and IRE-1α inhibitor groups were alleviated. Quantitative RT-PCR and Western blot results of GRP78, IRE-1α, NF-κ Bp65, IL-1β, NLRP3, caspase-1 and GSDMD-N were consistent with immunofluorescence analysis.
CONCLUSION
AS-IV could reduce ERS and inflammation, improve podocyte pyroptosis, thus exerting a podocyte-protective effect in DN, through regulating IRE-1α/NF-κ B/NLRP3 signaling pathway.
Podocytes/metabolism*
;
Animals
;
Diabetic Nephropathies/metabolism*
;
Saponins/therapeutic use*
;
Triterpenes/therapeutic use*
;
Signal Transduction/drug effects*
;
NF-kappa B/metabolism*
;
Protein Serine-Threonine Kinases/metabolism*
;
Male
;
Rats, Sprague-Dawley
;
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
;
Endoribonucleases/metabolism*
;
Endoplasmic Reticulum Chaperone BiP
;
Rats
;
Diabetes Mellitus, Experimental/complications*
;
Endoplasmic Reticulum/metabolism*
;
Multienzyme Complexes

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