1.Mechanism of Fresh Cutting of Traditional Chinese Medicine: Discussion on Integration of Traditional Wisdom and Modern Technology
Wenjie BAO ; Lingyun ZHONG ; Wenhua WU ; Congmin LIU ; Zixin CHEN ; Xingmei LU ; Hengli TONG ; Yi HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):282-290
Fresh-cut processing constitutes a pivotal technique in the origin processing of Chinese medicinal materials, with a long history documented in multiple materia medica. In recent years, it has garnered national policy support for its ability to prevent component loss and low processing efficiency associated with traditional drying-before-cutting methods. As of August 2025, 26 provinces and municipalities nationwide have cumulatively published 789 species for fresh-cut processing. Among these, 78 were included in the 2025 edition of the Pharmacopoeia of the People's Republic of China. However, the practice continues to face common challenges and difficulties, including ambiguous scientific understanding, fragmented standards, limited quality control approaches, and poor process stability. Based on this, this paper synthesises years of research findings to systematically elucidate the core mechanisms of fresh-cut processing. These encompass alterations to herbal tissue structure during cutting, post-processing changes in constituents, and physiological-biochemical processes such as plant stress responses and shifts in endogenous enzyme activity. It also summarises influencing factors, including inherent herbal properties, cutting timing and methods, and environmental conditions like temperature, humidity, and microbial presence. Based on this overview of fresh-cutting mechanisms, subsequent research should advance in four directions:Clarifying the scientific principles of fresh-cutting, overcoming technical bottlenecks, upgrading intelligent equipment, and establishing quality standards and evaluation systems. This study provides a theoretical foundation and scientific basis for future research on fresh-cutting in traditional Chinese medicine(TCM), promoting its deeper practical application within the industry and contributing to the high-quality development of TCM industry and the modernization of TCM.
2.Effect of tirofiban on prognosis in acute anterior circulation large vessel occlusion stroke patients with unsuccessful recanalization after endovascular treatment
Anyu LIAO ; Minxing ZHAO ; Kang YUAN ; Kangmo HUANG ; Zhiliang GUO ; Xianjun HUANG ; Zhenhui DUAN ; Rui LIU ; Guodong XIAO ; Wenhua LIU ; Zhiming ZHOU ; Wusheng ZHU
Chinese Journal of Cerebrovascular Diseases 2025;22(8):515-523,578
Objective To analyze the effects of intravenous tirofiban following endovascular treatment on the prognosis of patients with acute anterior circulation large vessel occlusion stroke who did not achieve successful recanalization.Methods This retrospective study included consecutive patients with acute anterior circulation ischemic stroke who underwent endovascular treatment but did not achieve successful recanalization.These patients were retrospectively enrolled from the Department of Neurology at Nanjing Jinling Hospital,Affiliated Hospital of Medical School,Nanjing University,the Second Affiliated Hospital of Soochow University,Wuhan No.1 Hospital,and Yijishan Hospital of Wannan Medical College(the First Affiliated Hospital of Wannan Medical College)between January 2015 and April 2023.Baseline and clinical data were collected including age,sex,medical history(hypertension,diabetes,atrial fibrillation,hyperlipidemia),personal history(smoking and drinking),National Institutes of Health stroke scale(NIHSS)score at admission,trial of Org 10172 in acute stroke treatment(TOAST)classification(large artery atherosclerosis,cardioembolism,or other types),Alberta stroke program early CT score(ASPECTS)on admission,intravenous thrombolysis,onset-to-puncture time(OTP),collateral circulation status(poor collaterals:American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASTIN/SIR]score 0-2;good collateral:ASTIN/SIR score 3-4),procedure duration(from femoral or radial artery puncture to device removal),occlusion site,number of passes for thrombus retrieval,and post-procedural modified thrombolysis in cerebral infarction(mTICI)grade.Patients were divided into a tirofiban group and a non-tirofiban group based on whether they received post-procedural intravenous tirofiban.The primary outcome is a favorable functional outcome at 90-day since onset(modified Rankin scale[mRS]score ≤ 3).Safety outcomes included mortality at 90-day since onset(mRS score 6),any intracranial hemorrhage within 24 h post-procedure,and symptomatic intracranial hemorrhage within 24 h post-procedure.1∶1 propensity score matchings using the nearest neighbor method was performed based on variables with P<0.05 in the comparison between the tirofiban and non-tirofiban groups.Differences in primary and safety outcomes between the matched groups were compared.Univariate and multivariate Logistic regression analyses were conducted with favorable outcomes at 90 days as the dependent variable to evaluate the effect of intravenous tirofiban administration after endovascular therapy on 90-day prognosis in patients without successful recanalization.Results A total of 356 patients without successful recanalization after endovascular treatment were included,comprising 195 males and 161 females,with a median age of 70(61,78)years(32-92 years).Among them,76 and 280patients were assigned to the tirofiban and non-tirofiban groups,respectively.At 90 days,114 patients had favorable outcomes,while 242 had unfavorable outcomes.(1)Before the 1∶1 propensity score matching,significant differences were observed between the tirofiban and non-tirofiban groups in terms of admission NIHSS score,ASPECTS,good collateral circulation,intravenous thrombolysis,and mTICI grade(all P<0.05).After 1∶1 propensity score matching,66 matched pairs(132 patients)were obtained.No significant differences in the baseline and clinical characteristics were found between the two groups after matching(all P>0.05).(2)After 1∶1 matching,a significant difference was observed in the rate of favorable outcomes at 90 days between the two groups(48.5%[32/66]vs.30.3%[20/66],P=0.033)after propensity score matching,while no significant differences were found in 90-day mortality,intracranial hemorrhage within 24h,or symptomatic intracranial hemorrhage within 24h(all P>0.05).(3)Univariate analysis after 1∶1 matching indicated that age,atrial fibrillation,smoking history,admission NIHSS score,M2 segment middle cerebral artery occlusion,good collateral circulation,number of passes for thrombus retrieval,and tirofiban treatment were factors influencing favorable outcomes at 90 days.Multivariate Logistic regression analysis showed that younger age(aOR,0.942,95%CI 0.906-0.978,P=0.002),lower admission NIHSS score(aOR,0.855,95%CI 0.777-0.941,P=0.001),good collateral circulation(aOR,5.534,95%CI 2.141-14.301,P<0.01),tirofiban treatment(aOR,2.774,95%CI 1.092-7.046,P=0.032),and M2 segment MCA occlusion(reference:internal carotid artery occlusion;aOR,4.874,95%CI 1.428-16.632,P=0.011)were independent predictors of favorable outcomes at 90 days.Conclusions Intravenous tirofiban administration after endovascular therapy may improve 90-day neurological outcomes in patients with acute anterior circulation large vessel occlusion stroke who did not achieve successful recanalization without increasing the risk of hemorrhage.Further large-scale randomized controlled trials are warranted to validate these findings.
3.Medication pattern and mechanism of marine traditional Chinese medicine in the treatment of osteoporosis
Yue LAI ; Xuan LIN ; Miao XU ; Huan LIU ; Jianlin SHEN ; Wenhua HUANG
Chinese Journal of Tissue Engineering Research 2025;29(17):3713-3723
BACKGROUND:Marine traditional Chinese medicine offers a potentially effective and less adverse treatment for osteoporosis.OBJECTIVE:To explore the pharmacological regulations and procedures of traditional Chinese medicine in treating osteoporosis through data mining and network pharmacology techniques.METHODS:Data mining and network pharmacology methods were used to study the medication pattern and mechanism of marine Chinese medicine patented prescriptions approved by China National Intellectual Property Administration for the treatment of osteoporosis,and special attention was paid to the core Chinese medicine constituents of these prescriptions.The core constituents of the compound drug group composed of oyster-Dipsacus asper-epimedium were comprehensively identified and analyzed by using ultra-high-performance liquid chromatography tandem mass spectrometry.RESULTS AND CONCLUSION:(1)We collected 381 authorized compound patents for the treatment of osteoporosis from the database inception to April 1,2024.Among these,48 patent groups utilized marine traditional Chinese medicine.These prescriptions contained 183 Chinese herbal medicines,of which 13 marine traditional Chinese medicines were used 574 times in total,and the number of flavors used in a single patented formula ranged from 2 to 41.(2)Oyster was the most frequently used marine ingredient,while Dipsacus asper,epimedium,Rehmannia glutinosa,Eucommia ulmoides Oliv.were the most frequent non-marine components.Association rule analysis identified oyster,Dipsacus asper,and epimedium as the core drug group.Network pharmacology analysis revealed that the core targets of this group for the treatment of osteoporosis included ALB,AKT1,TP53,PPARG,and SRC.Sitosterol,liquiritigenin,japonine,luteolin,and kaempferol were identified as the core components within the marine traditional Chinese medicine prescriptions.(3)The GO and KEGFG enrichment analyses suggested a potential association between the mechanism of the core drug group and the rap1/mapk signaling pathway in the treatment of osteoporosis.(4)The molecular docking verified the beneficial interactions between core components and core targets.(5)The ultra-high-performance liquid chromatography tandem mass spectrometry analysis of the compound medicine confirmed the presence of luteolin,sitosterol,kaempferol,and other components,aligning with the drug components identified by network pharmacology.Quantitative analysis indicated that flavonoids,terpenes,and alkaloids constituted a significant proportion of the compound medicine's components.
4.Isolation,identification,homology and biological characteristics of Escherichia co-li from chicken
Jiayu WANG ; Xiaojing HAO ; Meiling SUN ; Wenhua LIU
Chinese Journal of Veterinary Science 2025;45(5):948-953
In order to understand the infection status of Escherichia coli(E.coli)in different popu-lations of chickens,E.coli was isolated and identified from 1-day-old chickens,dead embryos,clini-cal dead chickens from 3 hatcheries and 9 broiler farms in Yantai area,and 1 950 samples from e-liminated breeder chickens;the homology of the isolated strains was analyzed by pulsed field gel e-lectrophoresis;virulence genes and serotypes were identified by PCR;pathogenicity was determined by challenge chicken embryos.Drug resistance of the strain was determined by drug sensitivity test.Results showed that a total of 116 strains of E.coli were isolated,of which 97 strains were successfully classified into 66 band types,15 virulence genes and 5 serotype were detected by PCR,and 56,32 and 28 strains were divided into high,medium and low pathogenic strains by chicken embryo challenge test.Results indicated that E.coli from clinically dead chickens and eliminated breeder chickens had higher pathogenicity and drug resistance.This study provides a reference ba-sis for the prevention and control of colibacillosis in chicken farms.
5.Isolation,identification,homology and biological characteristics of Escherichia co-li from chicken
Jiayu WANG ; Xiaojing HAO ; Meiling SUN ; Wenhua LIU
Chinese Journal of Veterinary Science 2025;45(5):948-953
In order to understand the infection status of Escherichia coli(E.coli)in different popu-lations of chickens,E.coli was isolated and identified from 1-day-old chickens,dead embryos,clini-cal dead chickens from 3 hatcheries and 9 broiler farms in Yantai area,and 1 950 samples from e-liminated breeder chickens;the homology of the isolated strains was analyzed by pulsed field gel e-lectrophoresis;virulence genes and serotypes were identified by PCR;pathogenicity was determined by challenge chicken embryos.Drug resistance of the strain was determined by drug sensitivity test.Results showed that a total of 116 strains of E.coli were isolated,of which 97 strains were successfully classified into 66 band types,15 virulence genes and 5 serotype were detected by PCR,and 56,32 and 28 strains were divided into high,medium and low pathogenic strains by chicken embryo challenge test.Results indicated that E.coli from clinically dead chickens and eliminated breeder chickens had higher pathogenicity and drug resistance.This study provides a reference ba-sis for the prevention and control of colibacillosis in chicken farms.
6.Medication pattern and mechanism of marine traditional Chinese medicine in the treatment of osteoporosis
Yue LAI ; Xuan LIN ; Miao XU ; Huan LIU ; Jianlin SHEN ; Wenhua HUANG
Chinese Journal of Tissue Engineering Research 2025;29(17):3713-3723
BACKGROUND:Marine traditional Chinese medicine offers a potentially effective and less adverse treatment for osteoporosis.OBJECTIVE:To explore the pharmacological regulations and procedures of traditional Chinese medicine in treating osteoporosis through data mining and network pharmacology techniques.METHODS:Data mining and network pharmacology methods were used to study the medication pattern and mechanism of marine Chinese medicine patented prescriptions approved by China National Intellectual Property Administration for the treatment of osteoporosis,and special attention was paid to the core Chinese medicine constituents of these prescriptions.The core constituents of the compound drug group composed of oyster-Dipsacus asper-epimedium were comprehensively identified and analyzed by using ultra-high-performance liquid chromatography tandem mass spectrometry.RESULTS AND CONCLUSION:(1)We collected 381 authorized compound patents for the treatment of osteoporosis from the database inception to April 1,2024.Among these,48 patent groups utilized marine traditional Chinese medicine.These prescriptions contained 183 Chinese herbal medicines,of which 13 marine traditional Chinese medicines were used 574 times in total,and the number of flavors used in a single patented formula ranged from 2 to 41.(2)Oyster was the most frequently used marine ingredient,while Dipsacus asper,epimedium,Rehmannia glutinosa,Eucommia ulmoides Oliv.were the most frequent non-marine components.Association rule analysis identified oyster,Dipsacus asper,and epimedium as the core drug group.Network pharmacology analysis revealed that the core targets of this group for the treatment of osteoporosis included ALB,AKT1,TP53,PPARG,and SRC.Sitosterol,liquiritigenin,japonine,luteolin,and kaempferol were identified as the core components within the marine traditional Chinese medicine prescriptions.(3)The GO and KEGFG enrichment analyses suggested a potential association between the mechanism of the core drug group and the rap1/mapk signaling pathway in the treatment of osteoporosis.(4)The molecular docking verified the beneficial interactions between core components and core targets.(5)The ultra-high-performance liquid chromatography tandem mass spectrometry analysis of the compound medicine confirmed the presence of luteolin,sitosterol,kaempferol,and other components,aligning with the drug components identified by network pharmacology.Quantitative analysis indicated that flavonoids,terpenes,and alkaloids constituted a significant proportion of the compound medicine's components.
7.Application and development direction of finite element method in biomechanical analysis of thoracolumbar fractures of the spine
Kai HE ; Wenhua XING ; Feng LI ; Shengxiang LIU ; Xianming BAI ; Chen ZHOU ; Xu GAO ; Yu QIAO ; Qiang HE ; Zhiyu GAO ; Zhen GUO ; Aruhan BAO ; Chade LI
Chinese Journal of Tissue Engineering Research 2025;29(15):3244-3252
BACKGROUND:The highest incidence of spinal fracture is in the thoracolumbar segment,and its symptoms are back pain,posterior convexity deformity,activity limitation,or with spinal cord nerve injury causing lower limb pain,numbness,and even paraplegia and other complications.The finite element method is a digital computer modeling technique,which can simulate the physical model and carry out force analysis realistically.OBJECTIVE:To review the application of finite element method in thoracolumbar spine fractures.METHODS:We searched the Chinese and English literature databases PubMed,Web of Science,and CNKI for relevant literature on the application of the finite element analysis method in spinal thoracolumbar fracture published before March 2024.The search terms in Chinese and English were:finite element analysis methods,biomechanical phenomena,stress analysis,thoracolumbar fractures,spinal fractures.Finally,55 papers were included.RESULTS AND CONCLUSION:(1)The exploration of thoracolumbar fractures caused by different etiologies(osteoporotic,traumatic,and pathological)through the finite element method is conducive to a deeper understanding of the biomechanics of various types of thoracolumbar fractures,and to improve the individualized and fine-tuned treatment of thoracolumbar fractures.(2)The finite element analysis of a single sample or a small number of samples has the chance,and a larger number of samples are required for the future finite element analysis to reduce the chance caused by the sample.(3)The rigid structure of bones alone cannot meet the biomechanical working conditions of the integrity of the physical object,and future finite element models need to incorporate all the structures of the physical object(e.g.,soft tissues,such as muscles and ligaments)as far as possible.(4)The finite element method has been used in more studies on osteoporotic and traumatic thoracolumbar spine fractures,which will need to be more in-depth in the future,and less in the field of pathologic thoracolumbar fractures,which has a wider scope for future research.
8.Effect of tirofiban on prognosis in acute anterior circulation large vessel occlusion stroke patients with unsuccessful recanalization after endovascular treatment
Anyu LIAO ; Minxing ZHAO ; Kang YUAN ; Kangmo HUANG ; Zhiliang GUO ; Xianjun HUANG ; Zhenhui DUAN ; Rui LIU ; Guodong XIAO ; Wenhua LIU ; Zhiming ZHOU ; Wusheng ZHU
Chinese Journal of Cerebrovascular Diseases 2025;22(8):515-523,578
Objective To analyze the effects of intravenous tirofiban following endovascular treatment on the prognosis of patients with acute anterior circulation large vessel occlusion stroke who did not achieve successful recanalization.Methods This retrospective study included consecutive patients with acute anterior circulation ischemic stroke who underwent endovascular treatment but did not achieve successful recanalization.These patients were retrospectively enrolled from the Department of Neurology at Nanjing Jinling Hospital,Affiliated Hospital of Medical School,Nanjing University,the Second Affiliated Hospital of Soochow University,Wuhan No.1 Hospital,and Yijishan Hospital of Wannan Medical College(the First Affiliated Hospital of Wannan Medical College)between January 2015 and April 2023.Baseline and clinical data were collected including age,sex,medical history(hypertension,diabetes,atrial fibrillation,hyperlipidemia),personal history(smoking and drinking),National Institutes of Health stroke scale(NIHSS)score at admission,trial of Org 10172 in acute stroke treatment(TOAST)classification(large artery atherosclerosis,cardioembolism,or other types),Alberta stroke program early CT score(ASPECTS)on admission,intravenous thrombolysis,onset-to-puncture time(OTP),collateral circulation status(poor collaterals:American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASTIN/SIR]score 0-2;good collateral:ASTIN/SIR score 3-4),procedure duration(from femoral or radial artery puncture to device removal),occlusion site,number of passes for thrombus retrieval,and post-procedural modified thrombolysis in cerebral infarction(mTICI)grade.Patients were divided into a tirofiban group and a non-tirofiban group based on whether they received post-procedural intravenous tirofiban.The primary outcome is a favorable functional outcome at 90-day since onset(modified Rankin scale[mRS]score ≤ 3).Safety outcomes included mortality at 90-day since onset(mRS score 6),any intracranial hemorrhage within 24 h post-procedure,and symptomatic intracranial hemorrhage within 24 h post-procedure.1∶1 propensity score matchings using the nearest neighbor method was performed based on variables with P<0.05 in the comparison between the tirofiban and non-tirofiban groups.Differences in primary and safety outcomes between the matched groups were compared.Univariate and multivariate Logistic regression analyses were conducted with favorable outcomes at 90 days as the dependent variable to evaluate the effect of intravenous tirofiban administration after endovascular therapy on 90-day prognosis in patients without successful recanalization.Results A total of 356 patients without successful recanalization after endovascular treatment were included,comprising 195 males and 161 females,with a median age of 70(61,78)years(32-92 years).Among them,76 and 280patients were assigned to the tirofiban and non-tirofiban groups,respectively.At 90 days,114 patients had favorable outcomes,while 242 had unfavorable outcomes.(1)Before the 1∶1 propensity score matching,significant differences were observed between the tirofiban and non-tirofiban groups in terms of admission NIHSS score,ASPECTS,good collateral circulation,intravenous thrombolysis,and mTICI grade(all P<0.05).After 1∶1 propensity score matching,66 matched pairs(132 patients)were obtained.No significant differences in the baseline and clinical characteristics were found between the two groups after matching(all P>0.05).(2)After 1∶1 matching,a significant difference was observed in the rate of favorable outcomes at 90 days between the two groups(48.5%[32/66]vs.30.3%[20/66],P=0.033)after propensity score matching,while no significant differences were found in 90-day mortality,intracranial hemorrhage within 24h,or symptomatic intracranial hemorrhage within 24h(all P>0.05).(3)Univariate analysis after 1∶1 matching indicated that age,atrial fibrillation,smoking history,admission NIHSS score,M2 segment middle cerebral artery occlusion,good collateral circulation,number of passes for thrombus retrieval,and tirofiban treatment were factors influencing favorable outcomes at 90 days.Multivariate Logistic regression analysis showed that younger age(aOR,0.942,95%CI 0.906-0.978,P=0.002),lower admission NIHSS score(aOR,0.855,95%CI 0.777-0.941,P=0.001),good collateral circulation(aOR,5.534,95%CI 2.141-14.301,P<0.01),tirofiban treatment(aOR,2.774,95%CI 1.092-7.046,P=0.032),and M2 segment MCA occlusion(reference:internal carotid artery occlusion;aOR,4.874,95%CI 1.428-16.632,P=0.011)were independent predictors of favorable outcomes at 90 days.Conclusions Intravenous tirofiban administration after endovascular therapy may improve 90-day neurological outcomes in patients with acute anterior circulation large vessel occlusion stroke who did not achieve successful recanalization without increasing the risk of hemorrhage.Further large-scale randomized controlled trials are warranted to validate these findings.
9.Prevalence and risk factors of food allergies among children in North China grassland: a cross-sectional study based on Zhangbei County, Hebei Province
Yang LIU ; Yanlei CHEN ; Yaojun PANG ; Ruijuan ZHANG ; Haiyun SHI ; Weiting JIN ; Wenhua MING ; Ye WANG ; Zilu CHENG ; Tingting MA ; Xueyan WANG
Chinese Journal of Preventive Medicine 2025;59(10):1725-1733
Objective:To determine the prevalence of self-reported food allergies among children in the grasslands of North China and to analyze its associated risk factors.Methods:In this study, a cross-sectional epidemiological survey method was used to select children under 14 years old by multi-stage, stratified and random cluster sampling in the grassland ecological area of Zhangbei County, Hebei Province, China from May to July 2018. Face-to-face questionnaires were administered to gather food allergy-related information from the participants. Multivariate logistic regression analysis was used to analyze the risk factors associated with self-reported food allergy.Results:A total of 2 086 children completed the survey. The prevalence of self-reported food allergies was 22.0%(459/2 086). The prevalence of multiple food allergies (≥3 types) was 3.1%(64/2 086) versus 16.3% (341/2 086) for a single food allergy among all children. Mango allergy (6.1%, 127/2 086) was the most common, followed by peach allergy (4.1%, 85/2 086). Children who reported food allergies had a significantly higher prevalence of all 4 atopic disorders (eczema, asthma, allergic rhinitis, and allergic conjunctivitis than those without food allergies(35.73% vs. 20.65%, 5.88% vs. 2.77%, 17.86% vs. 7.38%, 16.78% vs. 10.45%, χ2 =44.663 1, 10.434 3, 45.038 3, 13.728 4, all P<0.001).Significantly associated risk factors of food allergy were found to be pollen allergy ( OR: 2.29; 95% CI: 1.80-2.92) and drug allergy ( OR: 1.53; 95% CI: 1.12-2.09). Conclusions:The prevalence of self-reported food allergies among children in the Zhangbei County area of the North China Grassland was relatively high. Pollen allergy and drug allergy are major risk factors.
10.Nociceptin/orphanin FQ receptor agonist inhibits heroin relapse in rats via CREB/BDNF pathway in VTA
Shanshan CHEN ; Miaojun LAI ; Yiying ZHOU ; Huizhen LIU ; Fangmin WANG ; Yuting WANG ; Wenhua ZHOU
Chinese Journal of Pharmacology and Toxicology 2025;39(10):721-730
OBJECTIVE To study the effects of Ro 64-6198,a selective nociceptin/orphanin FQ receptor(NOPR)agonist,on heroin self-administration and drug-seeking behavior in rats.METHODS Rats were trained to self-administer heroin intravenously at a dose of 0.05 mg·kg-1 under a fixed ratio 1(FR1)reinforcement schedule.Heroin motivation was assessed using a progressive ratio(PR)schedule.Firstly,a stable heroin self-administered rat model was established before the effects of Ro 64-6198 on heroin rewarding under the FR1 schedule were observed.After three days of self-administration recovery training,the effects of Ro 64-6198 on heroin reward motivation were observed under the PR3-4 schedule.Following extinction,the reinstatement of heroin seeking induced by either conditioned cues or heroin priming was evaluated in rats withdrawn from self-administration.The expressions of cAMP response element-binding protein(CREB)and brain-derived neurotrophic factor(BDNF)in the ventral tegmental area(VTA)were analyzed using Western blotting,while the expression of the NOPR in neurons in the VTA was examined through immunofluorescence staining.RESULTS Pretreatment with 3 mg·kg-1 Ro 64-6198 significantly reduced active responses and heroin infusions during FR1 testing,as well as decreased breakpoints,indicating reduced motivation under the PR schedule.At a dose of 1 mg·kg-1,Ro 64-6198 markedly attenuated the reinstatement of heroin-seeking behavior induced by conditioned cues or heroin priming.Furthermore,the administration of SB-612111,an NOPR antagonist,blocked the inhibitory effects of Ro 64-6198 on cue-induced heroin-seeking,although SB-612111 alone had no effect on heroin-seeking behavior.Ro 64-6198 treatment also suppressed the reduction of both phos-phorylated CREB(p-CREB)and BDNF levels in the VTA and the decreased expression of NOPR and p-CREB in dopaminergic neurons of the VTA.CONCLUSION These results demonstrate that Ro 64-6198 can mitigate heroin-seeking behavior through NOPR activation and CREB/BDNF pathway in the VTA.This study is expected to offer evidence for its potential as a clinical treatment for heroin addiction and relapse.

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