1.Mechanism of Ellagic Acid in Ameliorating Bleomycin-induced Lung Injury
Li SHAO ; Ke TAO ; Li WEI ; Juanli LI ; Zhizhi SHI ; Shugui QIAO ; Shaokang WANG
Journal of Sun Yat-sen University(Medical Sciences) 2026;47(3):496-508
ObjectiveTo investigate the protective effect of ellagic acid (EA) against bleomycin (BLM)-induced pulmonary fibrosis and associated pulmonary function impairment in mice, and to elucidate its relationship with the regulation of the interleukin(IL)-17/ nuclear factor (NF)-κB/ matrix metalloproteinase (MMP)9 signaling axis. MethodsA pulmonary fibrosis model was established in male C57BL/6J mice via intratracheal BLM injection. Interventions included IL-17 neutralizing antibody, Ixekizumab, SB-3CT, PDTC, or EA were used to modulate the IL-17/NF-κB/MMP9 signaling axis. Pathological changes in lung tissue were observed via HE, Masson, and Sirius red staining. Pulmonary function was assessed using a pulmonary function test (PFT). Western blot and qRT-PCR were employed to detect related protein and gene expression. Network pharmacology was utilized to predict the potential targets of EA. A protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape. Molecular docking was performed to validate the binding capability of EA to core targets. ResultsBLM successfully induced obvious pulmonary fibrosis and lung dysfunction in mice, significantly elevating the level of the pro-inflammatory cytokine IL-17. This was associated with the activation of the transcription factor NF-κB p65, leading to the upregulation of the pro-fibrotic factor MMP9. Inhibition of the IL-17/NF-κB/MMP9 signaling axis markedly alleviated the degree of pulmonary fibrosis. EA intervention significantly suppressed the BLM-induced increase in IL-17, blocked the activation of the NF-κB/MMP9 pathway, and consequently reduced lung fibrotic lesions and improved pulmonary function. ConclusionEA may effectively ameliorate BLM-induced pulmonary fibrosis and lung dysfunction in mice, likely by inhibiting the inflammatory and fibrotic responses mediated through the IL-17/NF-κB/MMP9 signaling pathway.
2.Protective effect and mechanism of trophoblast-derived mesenchymal stem cells against liver injury in a mouse model of autoimmune hepatitis
Long XU ; Wanwan SHI ; Jiandan QIAN ; Shiyun KE ; Yusheng HE ; Xiaofang WANG ; Guiqiang WANG
Journal of Clinical Hepatology 2026;42(9):2116-2125
ObjectiveTo investigate the effect of trophoblast-derived mesenchymal stem cell (T-MSC) on concanavalin A (Con A)-induced immune-mediated liver injury in mice, as well as its association with the changes in inflammatory response. MethodsMorphological assessment, flow cytometry, and tri-lineage differentiation assay were used to observe the biological characteristics of T-MSC. In the pilot experiment, mice were divided into PBS group, T-MSC monotherapy group, and Con A groups at a concentration of 10, 15, or 20 mg/kg to evaluate the safety of T-MSC monotherapy on liver function and determine the appropriate dose for modeling. In the formal experiment, mice were divided into healthy control group (HC group), Con A group, and Con A+T-MSC group, with 5 mice in each group. The mice were given injection of Con A (15 mg/kg) via the caudal vein to establish a mouse model of immune-mediated liver injury, while the mice in the T-MSC monotherapy group were given transfusion of 1×106 T-MSCs via the caudal vein at 3 hours after modeling, and samples were collected 12 hours later. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were measured; liver histopathological changes were observed, and Ishak inflammatory activity score and inflammatory necrosis area were assessed; the serum levels of inflammatory cytokines were measured; transcriptome sequencing, immunofluorescence assay, and Western blot were used to measure the changes in inflammation-related molecules in liver tissue. The Shapiro-Wilk test was used to assess the normality of continuous data, and the homogeneity of variance test was also performed; a one-way analysis of variance was used for comparison of normally distributed data with homogeneity of variance between multiple groups, and the Tukey’s post-hoc test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed data with heterogeneity of variance between multiple groups, and the Wilcoxon test was used for further comparison between two groups. ResultsT-MSC had a long spindle shape, showed the characteristics of fibroblast-like morphology and adherent growth, and possessed the osteogenic, chondrogenic, and adipogenic differentiation abilities. Flow cytometry showed high expression levels of CD90, CD105, and CD73 in T-MSC, with a positive rate of 96.8%, 99.0%, and 99.9%, respectively, while there was low or no expression of CD31, human leukocyte antigen DR, CD45, and CD34, with a positive rate of 0.120%, 0, 0.061%, and 0, respectively. Administration of T-MSC alone did not cause obvious abnormalities in ALT, AST, or LDH. Con A at the concentrations of 10, 15, and 20 mg/kg all increased the serum levels of biochemical parameters for liver injury in a dose-dependent manner, with mortality observed in the 20 mg/kg group. In the formal experiment, compared with the HC group, the Con A group had significant increases in the serum levels of ALT, AST, and LDH (P<0.01), and after T-MSC treatment, there were significant reductions in these markers compared with the Con A group (P<0.01). HE staining showed that the Con A group had disordered structure of the liver, accompanied by marked inflammatory cell infiltration and focal/patchy necrosis, and these pathological changes were alleviated after T-MSC treatment. Compared with the HC group, the Con A group had significant increases in Ishak score and the percentage of inflammatory necrosis area (P<0.001), while there were significant reductions in these indicators after T-MSC treatment compared with the Con A group (P<0.01). ELISA showed that compared with the HC group, the Con A group had significant increases in the serum levels of interleukin-21 (IL-21), interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-17A (IL-17A), and tumor necrosis factor-α (TNF-α) (P<0.05), and there were significant reductions in these markers after T-MSC treatment compared with the Con A group (P<0.05), with no significant differences in IL-21, IL-1β, IL-17A, and TNF-α compared with the HC group (P>0.05); although there was a significant reduction in the level of IL-2, the Con A+T-MSC group still had a significantly higher level of IL-2 than the HC group (P=0.001). In contrast, compared with the HC group, the Con A group had a significant increase in IL-10 (P<0.05), with a further increase after T-MSC treatment (P<0.05). The transcriptome analysis showed that T-MSC treatment downregulated the expression of the inflammation- and chemokine-related genes including Ccl2, Cxcl10, Il-21, and Il-6 and inhibited the inflammation-related pathways such as TNF, IL-17, nuclear factor-κB, and JAK-STAT. Immunofluorescence assay showed that compared with the HC group, the Con A group had a significant increase in the expression of IL-21 in the liver (P<0.001), and there was a significant reduction in IL-21 after T-MSC treatment compared with the Con A group (P<0.001); the results of Western blot showed the same trend. ConclusionT-MSC can alleviate Con A-induced immune-mediated liver injury in mice, as evidenced by the improvement in liver biochemical parameters, the alleviation of histopathological damage, and the overall downregulation of inflammation-related molecules. T-MSC exerts marked anti-inflammatory and immunomodulatory effects in this model, and IL-21 shows a significant change in inflammatory response and can be used as a candidate molecule for further investigation.
3.The multi-center mid-term clinical outcomes of combined complete preservation of chordal structure mitral valve replacement with total anatomic complete arterial myocardial revascularization for coronary patients with moderate-to-severe or severe ischemic mitral regurgitation
Ke GUO ; Xujun CHEN ; Baoshi ZHENG ; Chao SHI ; Keli HUANG ; Yong CAO ; Chengquan LIAO ; Jingwei CHEN ; Yu LIN ; Chengxin LIU ; Quansheng CAO ; Lin SHEN ; Zhendong WANG
Chinese Journal of Surgery 2025;63(1):58-67
Objective:To evaluate the clinical outcomes of combined complete preservation of chordal structure mitral valve replacement (C-MVR) with total anatomical arterial myocardial revascularization (TACR) in coronary patients with moderate-to-severe or severe ischemic mitral regurgitation (IMR).Methods:This is a retrospective multi-center case series study. Data were retrospectively collected from 127 patients with coronary artery disease with moderate to severe or severe IMR who received TACR with C-MVR from July 2015 to April 2024 in 13 hospitals in China. There were 90 males and 37 females, aged (56.5±10.7) years (range: 33 to 74 years). Perioperative data and follow-up data including left ventricular ejection fraction, left ventricular end-diastolic diameter, and patency rate of arterial grafts of patients were collected. Comparisons were made using paired sample t-test or χ2 test. Results:In this cohort of 127 patients, 67 underwent concurrent tricuspid valve repair. During surgery, 113 grafts of the left internal mammary artery (LIMA), 127 grafts of the left radial artery, 80 grafts of the right radial artery, and 110 grafts of the right internal mammary artery (RIMA) were harvested. The number of the distal anastomosis was 4.2±0.4 (range: 3 to 5). The aortic cross-clamp time and cardiopulmonary bypass time were (97.5±23.4) minutes (range: 90 to 161 minutes) and (145.4±19.2) minutes (range: 101 to 210 minutes), respectively. There was one operative death. Intraoperative placement of an intra-aortic balloon pump was performed in 21 patients to improve the left ventricular ejection. No sternal ischemic occurred. All patients completed follow-up, with a mean follow-up period of (64.3±7.5) months (range: 4 to 110 months). No major cerebrovascular events occurred during the follow-up period, and all patients survived. Left ventricular ejection fraction improved postoperatively (55.0%±5.3% vs. 41.0%±15.3%, t=17.23, P<0.01). The proportion of patients with New York Heart Association functional class ≤2 increased postoperatively (23.6% (30/127) vs. 87.3% (110/126), χ2=103.77, P<0.01). The proportion of patients with Canadian Cardiovascular Society Angina Classification ≤3 decreased postoperatively (4.8% (6/126) vs. 78.7% (100/127), χ2=142.19, P<0.01). The left ventricular end-diastolic diameter decreased postoperatively ((5.70±4.50) cm vs. (6.10±0.23) cm, t=12.15, P<0.01). Coronary multi-detector computed tomography angiography (MDCTA) follow-up was conducted for (60.5±11.7) months (range: 6 to 109 months) postoperatively. MDCTA confirmed the patency rates of the grafts: 96.4% (108/112) for the LIMA grafts, 88.9% (112/126) for the left radial artery grafts, 93.7% (74/79) for the right radial artery grafts, and 90.9% (100/110) for the free RIMA grafts. No significant differences in graft patency rates were observed between the arterial grafts ( χ2=5.24, P=0.155). Conclusion:The results of this multi-centre study demonstrate satisfactory mid-term results of C-MVR with TACR for the treatment of coronary artery disease with moderate to severe or severe IMR.
4.The multi-center mid-term clinical outcomes of combined complete preservation of chordal structure mitral valve replacement with total anatomic complete arterial myocardial revascularization for coronary patients with moderate-to-severe or severe ischemic mitral regurgitation
Ke GUO ; Xujun CHEN ; Baoshi ZHENG ; Chao SHI ; Keli HUANG ; Yong CAO ; Chengquan LIAO ; Jingwei CHEN ; Yu LIN ; Chengxin LIU ; Quansheng CAO ; Lin SHEN ; Zhendong WANG
Chinese Journal of Surgery 2025;63(1):58-67
Objective:To evaluate the clinical outcomes of combined complete preservation of chordal structure mitral valve replacement (C-MVR) with total anatomical arterial myocardial revascularization (TACR) in coronary patients with moderate-to-severe or severe ischemic mitral regurgitation (IMR).Methods:This is a retrospective multi-center case series study. Data were retrospectively collected from 127 patients with coronary artery disease with moderate to severe or severe IMR who received TACR with C-MVR from July 2015 to April 2024 in 13 hospitals in China. There were 90 males and 37 females, aged (56.5±10.7) years (range: 33 to 74 years). Perioperative data and follow-up data including left ventricular ejection fraction, left ventricular end-diastolic diameter, and patency rate of arterial grafts of patients were collected. Comparisons were made using paired sample t-test or χ2 test. Results:In this cohort of 127 patients, 67 underwent concurrent tricuspid valve repair. During surgery, 113 grafts of the left internal mammary artery (LIMA), 127 grafts of the left radial artery, 80 grafts of the right radial artery, and 110 grafts of the right internal mammary artery (RIMA) were harvested. The number of the distal anastomosis was 4.2±0.4 (range: 3 to 5). The aortic cross-clamp time and cardiopulmonary bypass time were (97.5±23.4) minutes (range: 90 to 161 minutes) and (145.4±19.2) minutes (range: 101 to 210 minutes), respectively. There was one operative death. Intraoperative placement of an intra-aortic balloon pump was performed in 21 patients to improve the left ventricular ejection. No sternal ischemic occurred. All patients completed follow-up, with a mean follow-up period of (64.3±7.5) months (range: 4 to 110 months). No major cerebrovascular events occurred during the follow-up period, and all patients survived. Left ventricular ejection fraction improved postoperatively (55.0%±5.3% vs. 41.0%±15.3%, t=17.23, P<0.01). The proportion of patients with New York Heart Association functional class ≤2 increased postoperatively (23.6% (30/127) vs. 87.3% (110/126), χ2=103.77, P<0.01). The proportion of patients with Canadian Cardiovascular Society Angina Classification ≤3 decreased postoperatively (4.8% (6/126) vs. 78.7% (100/127), χ2=142.19, P<0.01). The left ventricular end-diastolic diameter decreased postoperatively ((5.70±4.50) cm vs. (6.10±0.23) cm, t=12.15, P<0.01). Coronary multi-detector computed tomography angiography (MDCTA) follow-up was conducted for (60.5±11.7) months (range: 6 to 109 months) postoperatively. MDCTA confirmed the patency rates of the grafts: 96.4% (108/112) for the LIMA grafts, 88.9% (112/126) for the left radial artery grafts, 93.7% (74/79) for the right radial artery grafts, and 90.9% (100/110) for the free RIMA grafts. No significant differences in graft patency rates were observed between the arterial grafts ( χ2=5.24, P=0.155). Conclusion:The results of this multi-centre study demonstrate satisfactory mid-term results of C-MVR with TACR for the treatment of coronary artery disease with moderate to severe or severe IMR.
5.Chemical consitituents and hypoglycemic activity of Qinhuai No. 1 Rehmannia glutinosa
Meng YANG ; Zhi-you HAO ; Xiao-lan WANG ; Chao-yuan XIAO ; Jun-yang ZHANG ; Shi-qi ZHOU ; Xiao-ke ZHENG ; Wei-sheng FENG
Acta Pharmaceutica Sinica 2025;60(1):205-210
Eight compounds were isolated and purified from the ethyl acetate part of 70% acetone extract of
6.Effect of intestinal flora and metabolites on the development and progression of acute-on-chronic liver failure
Ke SHI ; Qun ZHANG ; Xianbo WANG ; Ying FENG
Journal of Clinical Hepatology 2025;41(3):568-573
Acute-on-chronic liver failure (ACLF) is a dangerous disease with severe conditions, rapid progression, and high short-term mortality. Intestinal flora and metabolites are closely associated with the development, progression, and pathogenesis of ACLF. During the development of ACLF, the destruction of intestinal integrity and the dysregulation of intestinal microecology and its metabolites mediate immune disturbance and thus aggravate systemic inflammatory response. This article elaborates on the role of intestinal flora and metabolites in the development and progression of ACLF and related therapeutic strategies.
7.Expert consensus on intraoperative repositioning for patients with spine fracture and dislocation (version 2025)
Dongmei BIAN ; Ke SUN ; Ningbo CHEN ; Caixia BAI ; Miao WANG ; Yafeng QIAO ; Fei WANG ; Hong WANG ; Feng TIAN ; Mei YAN ; Meng BAI ; Linjuan ZHANG ; Liyan ZHAO ; Yaqing CUI ; Xue JIANG ; Leling FENG ; Ning NING ; Junqin DING ; Lan WEI ; Yonghua ZHAI ; Yu ZENG ; Zengmei ZHANG ; Jiqun HE ; Fenggui BIE ; Hong CHEN ; Zengyan WANG ; Li LI ; Li ZHANG ; Yaying ZHOU ; Bing SHAO ; Ying WANG ; Caixia XIE ; Yanfeng YAO ; Jingjing AN ; Wen SHI ; Xiongtao LIU ; Xiaoyan AN ; Ning NAN ; Lan LI ; Xiaohui GOU ; Qiaomei LI ; Xiuting WU ; Yuqin ZHANG ; Jing LIU ; Fusen XIANG ; Xu XU ; Na MEI ; Jiao ZHOU ; Shan FAN ; Qian WANG ; Shuixia LI
Chinese Journal of Trauma 2025;41(2):138-147
Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.
8.Health economic evaluation of minimally invasive surgery in treatment of digestive tract cancers: a Meta-analysis
Xiaoyue YIN ; Ning ZHOU ; Xueli YANG ; Zhuoyu SUN ; Yinghui BAO ; Shengshu WANG ; Ke HAN ; Jing LONG ; Min ZHAO ; Haowei LI ; Rongrong LI ; Shimin CHEN ; Junhan YANG ; Huaihao LI ; Yueting SHI ; Guoning ZHU ; Jianhua WANG ; Shanshan YANG ; Boyan LI ; Wenchang WANG ; Shengyan DU ; Yao HE ; Enqiang LING-HU ; Huikai LI ; Miao LIU ; Juan XIE
Chinese Journal of Epidemiology 2025;46(1):154-165
Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.
9.Mycolicibacterium wolinskyi pulmonary disease:a case report and literature review
Jun-ke MA ; Jun-wei CUI ; Shi-yan WANG ; Jing ZHANG ; Yong-liang WANG ; Hong-fei DUAN
Chinese Journal of Zoonoses 2025;41(4):403-412
We reported the clinical manifestations,radiographic characteristics and prognosis of 1 case with Mycolicibacterium wolinskyi pulmonary disease,and provided a comprehensive literature review on this disease.Using"M.wolinskyi"OR"Mycobacterium wolinskyi"OR"Mycolicibacterium wolinskyi"as search term in PubMed database,CNKI and Wanfang database up to August 26 2023,40 reports were retrieved.32 cases from the literature and 1 case of our institution were used for review.A 59-year-old female presented intermittent hemoptysis since 2015.She was diagnosed with tuberculosis and clinical symptoms continued after anti-tuberculosis treatment.After multiple cultures of mycobacterium sputum and species identification in our hospital,M.wolinskyi was finally identified.She was diagnosed with M.Wolinski pulmonary disease according to clinical symptoms,computed tomography findings as well as bacteriological examinations.Combination therapy with Azithromycin,Moxifloxacin hydrochloride and Amikacin were administered based on antimicrobial susceptibility testing.Mycobacterium sputum culture became negative after 1 month treatment and kept negative,and the patient continued this combination therapy for 12 months after first culture negative.M.wolinskyi disease is exceedingly rare in medical institutions,and clinical symptoms are different depending on different location.Most cases were infected with skin,soft tissue or bone tissue infection after trauma or surgery,and a few cases were bloodstream infection.Most patients could have a good prognosis after proper treatment.M.wolinskyi disease is rare and clinically atypical,which may lead to long-term misdiagnosis.With the increase of aged or immunosuppressed population,the diagnosis and treatment of these rare non-tuberculous mycobacterial infections deserve more attention.
10.Effects of TREM2 on synaptic plasticity induced by cocaine addiction
Rui-ke XU ; Zhi-wen WANG ; Jiao-jiao OUYANG ; Qi DU ; Li-hua LI ; Shi-jun HONG ; Yan-xia PENG ; Gen-meng YANG
Chinese Pharmacological Bulletin 2025;41(12):2341-2347
Aim To investigate the role of triggering receptor expressed on myeloidcells 2(TREM2)in syn-aptic plasticity induced by cocaine addiction.Methods C57BL/6J mice and Trem2 knockout mice were uti-lized in this study to evaluate the alterations in postsyn-aptic density protein 95(PSD-95)and synapsin 1(SYN1)within the cortex and hippocampus of co-caine-addicted mice by using immunological tech-niques.Results HE staining and Nissl staining showed increased neuronal damage in the hippocampus and cortex of mice after cocaine addiction.The results of immunohistochemistry and fluorescence of PSD-95 and SYN1 were consistent with the expression trend of Western blot.In the wild type mouse model,the ex-pression level of PSD-95 in the hippocampus and cortex was lower than that in the saline group,and the ex-pression of SYN1 was higher than that in the saline group.In the knockout mouse model,the expression levels of PSD-95 and SYN1 in the hippocampus and cortex were significantly higher than those in the saline group after cocaine addiction.The expression levels of PSD-95 and SYN1 in the hippocampus and cortex of cocaine knockout mice were higher than those of co-caine wild type mice.Conclusion Cocaine addiction can change the synaptic plasticity,and TREM2 plays a regulatory role in the synaptic plasticity of hippocampus and cortex in mice with cocaine injury.TREM2 is ex-pected to be a new target for studying the mechanism of cocaine addiction.

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