1.Liraglutide may alleviate acetaminophen-induced liver injury by enhancing autophagy
Guo-jing XING ; Wen-bin LI ; Long-long LUO ; Li-fei WANG ; Yuan DENG ; Zhen WANG ; Zhao-jie ZHANG ; Xiao-hui YU ; Jiu-cong ZHANG
Chinese Pharmacological Bulletin 2025;41(10):1867-1875
Aim To investigate the protective effect of liraglutide(LIRA)on acetaminophen(APAP)-in-duced hepatotoxicity at the in vivo level and to reveal the underlying mechanism.Methods Forty SPF grade male C57BL/6J mice were randomly divided into the Control,LIRA(200 μg·kg-1),APAP(500 mg·kg-1),LIRA+APAP,LIRA+APAP+3-methylade-nine(3-MA,30 mg·kg-1)groups,with eight mice in each group.The mice were administered for three con-secutive days,and the materials were taken after 24 h.The general condition and body weight of mice in each group were recorded,and liver morphology was ob-served.Serum ALT and AST levels,as well as SOD ac-tivity,MDA,and GSH content in liver homogenates,were measured using biochemical assay kits.The levels of inflammatory cytokines IL-6,TNF-α,and IL-1β in serum were detected by ELISA.Liver pathological changes were assessed by HE staining,while mitochon-drial and autophagosome structures in liver tissues were observed using transmission electron microscopy.The number of PCNA-positive cells in liver tissues was e-valuated using immunohistochemical staining.The pro-tein expression levels of LC3Ⅱ,p62,Bax,Bcl-2,PC-NA,and CyclinD1 in liver tissues were determined by Western blot.Results LIRA pretreatment can im-prove the general condition of mice with acetamino-phen-induced liver injury(AILI),reduce serum ALT and AST levels,and effectively ameliorate the appear-ance and morphology of the liver as well as the patho-logical damage to liver tissue.Simultaneously,the lev-els of inflammatory cytokines IL-6,TNF-α,and IL-1βare significantly decreased;SOD activity and GSH con-tent are significantly increased,while MDA content is significantly reduced.Transmission electron microsco-py observations reveal the presence of numerous auto-phagosomes in the cytoplasm of liver tissue.Immuno-histochemical staining results indicate a significant in-crease in the number of PCNA-positive cells.Further-more,the expression of LC3Ⅱ,Bcl-2,PCNA,and Cy-clinD1 proteins in liver tissue is significantly upregulat-ed,while the expression of p62 and Bax proteins is significantly downregulated.However,after interven-tion with the autophagy inhibitor 3-MA,the aforemen-tioned protective effects of LIRA are significantly.Conclusions LIRA pretreatment can significantly im-prove liver injury in AILI mice.Its protective mecha-nism may be related to enhancing autophagy in hepato-cytes,thereby reducing oxidative stress,inflammatory response and apoptosis in liver of AILI mice.
2.A comparative analysis of the effects of metaraminol and norepi-nephrine on sublingual microcirculation in patients experiencing sep-tic shock at high altitudes
Zongzhao HE ; Hao WANG ; Xing ZHENG ; Bin SUN ; Li DENG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(9):1200-1207
AIM:To compare the effects and effi-cacy of methoxyamine and norepinephrine on sub-lingual microcirculation in patients with high-alti-tude septic shock.METHODS:A total of forty-six patients with septic shock from the Xining area of Qinghai Province were randomized into two groups:the M-hydroxylamine group(Group M,n=22)and the norepinephrine group(Group N,n=24).Baseline data as well as the incidence of acute kid-ney injury(AKI),distal limb necrosis/ischemia,and 28-day survival rates were documented.Sublingual microcirculation parameters were monitored and recorded at four time points:before treatment(T0),24 hours post-treatment(T1),48 hours post-treatment(T2),and 72 hours post-treatment(T3)using side-flow dark-field(SDF)imaging.The pa-rameters included total vascular density(TVD),per-fused vascular density(PVD),perfused vessel ratio(PPV),microvascular flow index(MFI),and hetero-geneity index(HI).Additionally,changes in heart rate(HR),mean arterial pressure(MAP),blood urea nitrogen(BUN),serum creatinine(Cr),and lac-tate(Lac)levels were also recorded.RESULTS:There were no significant differences between the two groups in terms of baseline data,incidence of AKI,distal limb necrosis/ischemia,and 28-day sur-vival rate.Additionally,there were no significant differences in HR,MAP,and Lac indices between the two groups at any time point.However,within-group comparisons showed that HR,MAP,and Lac indices improved over the course of treatment,with statistically significant differences.The BUN level at the T3 time point was significantly lower in the mehydroxyamine group compared to the nor-epinephrine group(P<0.05).Similarly,Cr levels were significantly lower at both T2 and T3 time points(P<0.05).There were no significant differenc-es in sublingual microcirculation indices between the two groups at any time point.However,TVD,PVD,PPV,MIF,and HI in both groups improved over the course of treatment,with statistically sig-nificant differences.CONCLUSION:Both methoxy-amine and norepinephrine can enhance both the macrocirculation and sublingual microcirculation in patients with septic shock at high altitudes.Addi-tionally,methoxyamine leads to a faster recovery of creatinine levels within 72 hours.
3.Chemical constituents from salt-processed Litchi Semen and their antioxidant activities
Rui YIN ; Xing YANG ; Wei-mao DONG ; Xu-li DENG ; Yi-mou WANG ; Hong-chuan ZHANG ; Kui-lin ZHU ; Zhang-xian CHEN ; Hong-ping HE ; Fa-wu DONG
Chinese Traditional Patent Medicine 2025;47(2):480-486
AIM To study the chemical constituents from salt-processed Litchi Semen and their antioxidant activities.METHODS The 85%ethanol extract from salt-processed Litchi Semen was isolated and purified by silica gel,Sephadex LH-20,MCI,ODS and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.DPPH and ABTS+free radical scavenging method were used to evaluate their antioxidant activities.RESULTS Fifteen compounds were isolated and identified as dehydrocostuslactone(1),ananosmoside A(2),funingensin A(3),(2S)-pinocembrin-7-O-(6-O-α-L-rhamnopyranosyl-β-D-glucopyranoside)(4),liquiritienin(5),quercetin(6),rutin(7),isorhamnetin-3-O-β-rutinoside(8),procyanidin A2(9),procyanidin A1(10),ethyl protocatechuate(11),5-hydroxymethylfurfural(12),di(2-ethyl-hexyl)phthalate(13),nicotinamide(14),(10E,15Z)-9,12,13-trihydroxyoctadeca-10,15-dienoic acid(15).Compounds 6-7,9-10 exhibited scavenging activities against DPPH radicals with IC50 values of(12.929±1.232),(14.104±0.946),(10.417±1.736),(6.944±0.030)μmol/L,respectively.Compounds 6-10 exhibited scavenging activities against ABTS+radicals with IC50 values of(21.952±0.577),(25.683±0.625),(22.970±1.336),(20.210±1.435),(18.725±0.324)μmol/L,respectively.CONCLUSION Compounds 1,5,14-15 are isolated from Litchi genus for the first time.Compounds 6-7,9-10 have strong in vitro antioxidant activities.
4.Analysis of infection status and genetic evolution of B2L and F1L genes in epidemic orf virus isolates from primary goat and sheep-producing areas in Anhui Province from 2021 to 2023
Liujun ZHANG ; Jiale CHEN ; Xing FENG ; Weizhen CHEN ; Yafei DENG ; Bo WANG ; Guolin ZUO ; Shaojun HE ; Honglei XIN ; Deyi LIU
Chinese Journal of Zoonoses 2025;41(7):697-703
This study was aimed at investigating the infection status of orf virus(ORFV)and the genetic evolution characteristics of epidemic ORFV isolates from Anhui province.A total of 303 clinical samples collected from major meat sheep breeding cities in An-hui during 2021-2023 were subjected to ORFV detection with fluorescence quantitative PCR(qPCR).The full-length B2L and F1L genes of ORFV in the positive samples were amplified through conventional PCR and sequenced.Genetic evolution analysis of the B2L and F1L genes was conducted after sequencing.The qPCR results indicated a total ORFV positivity rate in the clinical samples of 48.8%(148/303).Multiple sequence comparisons indicated that the B2L genes of 56 sample isolates shared 96.7%-100.0%DNA and 97.4%-100.0%amino acid sequence identity.Moreover,the F2L genes of 56 sample isolates shared 95.1%-100.0%DNA and 95.0%-100.0%amino acid sequence identity.The genetic evolution tree constructed with the B2L gene DNA sequences indicated sample iso-lates and 21 reference strains located in subgroup 1,and 26 sheep-derived sample isolates and 17 reference strains located in sub-group 2.Among them,the goat-derived sample isolate FY-TYA was located in the same sub-branch as the human-derived reference strain Gansu,whereas the goat-derived sample isolate FY-XQC was located in the same sub-branch as the reference strains China Vaccine and OV-HLJ-04.The genetic evolution tree constructed with the F1L gene DNA sequences showed,the goat sample isolates FY-XQA and FY-XQC were located in the same sub-branch as the sheep-derived reference strain Xinjiang.ORFV infection was rela-tively widespread in the major meat sheep breeding areas of Anhui province,and the DNA and amino acid sequences of the B2L and F1L genes of current circulating ORFV isolates showed different degrees of genetic variation,among which F1L gene had a high de-gree of variation.Furthermore,some goat-derived sample isolates were closely related to human,vaccine,and sheep-derived refer-ence strains.These results may serve as a reference for the prevention and control of ORFV infection in Anhui province.
5.The roles of eosinophils in different liver diseases
Guojing XING ; Yuan DENG ; Lifei WANG ; Longlong LUO ; Zhen WANG ; Zhaojie ZHANG ; Meixia YANG ; Ting ZHANG ; Xiaohui YU ; Jiucong ZHANG
Journal of Clinical Hepatology 2025;41(7):1456-1460
Liver diseases have a high prevalence rate worldwide with relatively poor long-term clinical outcomes and have become one of the leading causes of disease burden and death around the world,which poses significant challenges to public health.Eosinophils(Eos)are a class of highly conserved multifunctional immune cells that play critical effector roles in allergic diseases.In recent years,an increasing amount of evidence has shown that Eos plays an important role in the pathogenesis of liver diseases,exerting a protective or harmful effect in different liver diseases,which has become a research hotspot in this field.This article elaborates on the role and potential mechanism of action of Eos in liver diseases,in order to provide a new perspective for in-depth research on the pathogenesis of liver diseases and lay the foundation for developing therapeutic strategies targeting Eos.
6.Analysis of infection status and genetic evolution of B2L and F1L genes in epidemic orf virus isolates from primary goat and sheep-producing areas in Anhui Province from 2021 to 2023
Liujun ZHANG ; Jiale CHEN ; Xing FENG ; Weizhen CHEN ; Yafei DENG ; Bo WANG ; Guolin ZUO ; Shaojun HE ; Honglei XIN ; Deyi LIU
Chinese Journal of Zoonoses 2025;41(7):697-703
This study was aimed at investigating the infection status of orf virus(ORFV)and the genetic evolution characteristics of epidemic ORFV isolates from Anhui province.A total of 303 clinical samples collected from major meat sheep breeding cities in An-hui during 2021-2023 were subjected to ORFV detection with fluorescence quantitative PCR(qPCR).The full-length B2L and F1L genes of ORFV in the positive samples were amplified through conventional PCR and sequenced.Genetic evolution analysis of the B2L and F1L genes was conducted after sequencing.The qPCR results indicated a total ORFV positivity rate in the clinical samples of 48.8%(148/303).Multiple sequence comparisons indicated that the B2L genes of 56 sample isolates shared 96.7%-100.0%DNA and 97.4%-100.0%amino acid sequence identity.Moreover,the F2L genes of 56 sample isolates shared 95.1%-100.0%DNA and 95.0%-100.0%amino acid sequence identity.The genetic evolution tree constructed with the B2L gene DNA sequences indicated sample iso-lates and 21 reference strains located in subgroup 1,and 26 sheep-derived sample isolates and 17 reference strains located in sub-group 2.Among them,the goat-derived sample isolate FY-TYA was located in the same sub-branch as the human-derived reference strain Gansu,whereas the goat-derived sample isolate FY-XQC was located in the same sub-branch as the reference strains China Vaccine and OV-HLJ-04.The genetic evolution tree constructed with the F1L gene DNA sequences showed,the goat sample isolates FY-XQA and FY-XQC were located in the same sub-branch as the sheep-derived reference strain Xinjiang.ORFV infection was rela-tively widespread in the major meat sheep breeding areas of Anhui province,and the DNA and amino acid sequences of the B2L and F1L genes of current circulating ORFV isolates showed different degrees of genetic variation,among which F1L gene had a high de-gree of variation.Furthermore,some goat-derived sample isolates were closely related to human,vaccine,and sheep-derived refer-ence strains.These results may serve as a reference for the prevention and control of ORFV infection in Anhui province.
7.Effect of Different Time Interventions of Yangxin Tongmai Formula (养心通脉方) on DNA Methylation in Rat Models of Premature Coronary Heart Disease with Blood Stasis Syndrome
Xing CHEN ; Zixuan YU ; Shumeng ZHANG ; Yanjuan LIU ; Shuangyou DENG ; Ying WANG ; Lingli CHEN ; Jie LI
Journal of Traditional Chinese Medicine 2025;66(11):1165-1173
ObjectiveTo observe the effect of Yangxin Tongmai Formula (养心通脉方) by midnight-noon ebb-flow administration method for rat models of premature coronary heart disease (PCHD) with blood stasis syndrome, and to explore the possible mechanism of action from the perspective of DNA methylation differential gene expression. MethodsThere were 3 SD rats in each of the blank group, model group and Yangxin Tongmai Formula group, and the rats in the model group and Yangxin Tongmai Formula group were fed with high-fat chow plus vitamin D3 by gavage plus isoproterenol hydrochloride by subcutaneous injection to construct rat models of PCHD with blood stasis syndrome. After successful modelling, rats in Yangxin Tongmai Formula group were gavaged with 18 g/(kg‧d) of Yangxin Tongmai Formula, and rats in blank group and the model group were gavaged with 4 ml/(kg‧d) of 0.9% NaCl solution, and serum samples of rats in each group were collected for DNA methylation sequencing after 3 weeks to screen for the relevant DNA methylation differentiation genes. In addition, rats with successful modelling of PCHD with blood stasis were randomly divided into model group, Yangxin Tongmai Formula with midnight-noon ebb-flow administration method group [18 g/(kg‧d) of Yangxin Tongmai Formula was gavaged twice in the heart channel period (12:00) and pericardium channel period (20:00)], the Yangxin Tongmai Formula control group [18 g/(kg‧d) of Yangxin Tongmai Formula was gavaged twice at 8:00 and 18:00] and the Atorvastatin Calcium group [atorvastatin calcium tablets solution 1.8 mg/(kg‧d) at the same intervention time as that in Yangxin Tongmai Formula control group], and set up a blank group of 8 rats in each group. The model group and blank group were gavaged with 0.9% NaCl solution 4 ml/(kg‧d) for the same time as the Yangxin Tongmai Formula control group. After 3 weeks of gavage, the blood lipids [including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL)] levels of rats in each group were detected; the HE staining of myocardial tissues and thoracic aorta was used to observe the pathomorphological changes; the levels of serum inflammation indexes [tumour necrosis factor alpha (TNF-alpha), lipopolysaccharide (LPS), and interleukin 10 (IL-10)] were detected; immunoprecipitation-realtime fluorescence quantitative PCR was used to detect the relative expression of cardiac tissue screening differential genes. ResultsThe genes screened for differentially methylated regions were calmodulin 2 (Calm2), calcium voltage-gated channel subunit α1s (Cacna1s), and phospholipase Cβ1 (Plcb1). Compared with the blank group, rats in the model group showed elevated levels of TC, LDL, TNF-α and LPS, and decreased levels of HDL and IL-10 (P<0.05 or P<0.01); HE staining showed obvious swelling of myocardial fibres, accompanied by a large number of inflammatory cell infiltration, and thickening of the inner wall of the aortic vessels with internal wall damage, which was visible as a large number of lipid cholesterol crystals and obvious inflammatory cell infiltration. Compared with the model group, the TC, LDL, TNF-α and LPS contents of rats in the Yangxin Tongmai Formula with midnight-noon ebb-flow administration method group, the Yangxin Tongmai Formula control group, and the atorvastatin calcium group all reduced, and the contents of HDL and IL-10 all elevated (P<0.05), with the improvement of myocardial tissue damage and the reduction of inflammatory infiltration, and the improvement of the damage of the inner lining of the thoracic aorta and the reduction of lipid infiltration. Compared with Yangxin Tongmai Formula control group, LDL, TNF-α and LPS contents reduced, and IL-10 contents increased in the midnight-noon ebb-flow administration method group (P<0.05). Compared with the model group, the relative expression of Calm2 and Plcb1 genes decreased and the relative expression of Cacna1s gene increased in Yangxin Tongmai Formula control group and the midnight-noon ebb-flow administration method group (P<0.05); compared with the Yangxin Tongmai Formula control group, the relative expression of Calm2 gene decreased and the relative expression of Cacna1s gene increased in the midnight-noon ebb-flow administration method group (P<0.05). ConclusionThe intervention of Yangxin Tongmai Formula in the heart channel period (12:00) and pericardium channel period (20:00) was more effective in improving the blood lipid level, inhibiting inflammation, and improving myocardial tissue damage in rats of PCHD with blood stasis syndrome, and Calm2 and Cacna1s genes may be the key targets of Yangxin Tongmai Formula in intervening the blood stasis syndrome of PCHD.
8.Liraglutide may alleviate acetaminophen-induced liver injury by enhancing autophagy
Guo-jing XING ; Wen-bin LI ; Long-long LUO ; Li-fei WANG ; Yuan DENG ; Zhen WANG ; Zhao-jie ZHANG ; Xiao-hui YU ; Jiu-cong ZHANG
Chinese Pharmacological Bulletin 2025;41(10):1867-1875
Aim To investigate the protective effect of liraglutide(LIRA)on acetaminophen(APAP)-in-duced hepatotoxicity at the in vivo level and to reveal the underlying mechanism.Methods Forty SPF grade male C57BL/6J mice were randomly divided into the Control,LIRA(200 μg·kg-1),APAP(500 mg·kg-1),LIRA+APAP,LIRA+APAP+3-methylade-nine(3-MA,30 mg·kg-1)groups,with eight mice in each group.The mice were administered for three con-secutive days,and the materials were taken after 24 h.The general condition and body weight of mice in each group were recorded,and liver morphology was ob-served.Serum ALT and AST levels,as well as SOD ac-tivity,MDA,and GSH content in liver homogenates,were measured using biochemical assay kits.The levels of inflammatory cytokines IL-6,TNF-α,and IL-1β in serum were detected by ELISA.Liver pathological changes were assessed by HE staining,while mitochon-drial and autophagosome structures in liver tissues were observed using transmission electron microscopy.The number of PCNA-positive cells in liver tissues was e-valuated using immunohistochemical staining.The pro-tein expression levels of LC3Ⅱ,p62,Bax,Bcl-2,PC-NA,and CyclinD1 in liver tissues were determined by Western blot.Results LIRA pretreatment can im-prove the general condition of mice with acetamino-phen-induced liver injury(AILI),reduce serum ALT and AST levels,and effectively ameliorate the appear-ance and morphology of the liver as well as the patho-logical damage to liver tissue.Simultaneously,the lev-els of inflammatory cytokines IL-6,TNF-α,and IL-1βare significantly decreased;SOD activity and GSH con-tent are significantly increased,while MDA content is significantly reduced.Transmission electron microsco-py observations reveal the presence of numerous auto-phagosomes in the cytoplasm of liver tissue.Immuno-histochemical staining results indicate a significant in-crease in the number of PCNA-positive cells.Further-more,the expression of LC3Ⅱ,Bcl-2,PCNA,and Cy-clinD1 proteins in liver tissue is significantly upregulat-ed,while the expression of p62 and Bax proteins is significantly downregulated.However,after interven-tion with the autophagy inhibitor 3-MA,the aforemen-tioned protective effects of LIRA are significantly.Conclusions LIRA pretreatment can significantly im-prove liver injury in AILI mice.Its protective mecha-nism may be related to enhancing autophagy in hepato-cytes,thereby reducing oxidative stress,inflammatory response and apoptosis in liver of AILI mice.
9.Minimally invasive reduction of ulnar bicortex angulation and intramedullary fixation in the treatment of Bado typeⅠchildren with Monteggia fracture.
Chuan-Wei ZHANG ; Deng-Shan CHEN ; Lei WANG ; Xing-Po DING
China Journal of Orthopaedics and Traumatology 2025;38(4):415-419
OBJECTIVE:
To evaluate the effectiveness of minimally invasive reduction and ulna bicortical angulation intramedullary fixation in the management of Bado typeⅠMonteggia fracture in pediatric patients.
METHODS:
Between August 2018 and August 2020, the clinical data of 15 pediatric patients diagnosed with Bado typeⅠfresh Monteggia fracture were retrospectively analyzed. There were 11 males and 4 females. The left side was implicated in 5 cases, while the right side was involved in 10 cases. The age ranged from 4 to 12 years old. There were a total of 10 cases of upper ulna fractures and 5 cases of middle ulna fractures. Among these, the ulnar fracture line presented as transverse or short oblique in 9 cases, and long oblique or spiral in 6 cases. The pediatric patients underwent treatment utilizing minimally invasive reduction and ulna bicortical angulation intramedullary fixation. The effectiveness of the treatment was assessed based on the Mayo elbow scoring system.
RESULTS:
The follow-up period for all 15 cases ranged from 6 to 24 months. Among them, the occurrence of needle tail irritation was observed in 3 cases, all of which exhibited satisfactory healing following routine disinfection and dressing change. The other children had no re dislocation of the radial capitulum, no epiphyseal injury, no osteofascial compartment syndrome, elbow instability and other complications. The degree of limitation of daily life, range of motion of joints, pain level and appearance of limbs were recorded at the last follow-up. According to Mayo elbow scoring system, 12 cases were excellent and 3 cases were good.
CONCLUSION
The minimally invasive reduction and ulna bicortical angulation intramedullary fixation technique is a simple and effective treatment for Bado typeⅠfresh Monteggia fractures in children.
Humans
;
Male
;
Female
;
Child
;
Monteggia's Fracture/surgery*
;
Child, Preschool
;
Minimally Invasive Surgical Procedures/methods*
;
Fracture Fixation, Intramedullary/methods*
;
Retrospective Studies
10.Ultrasound-guided closed reduction and internal fixation using Kirschner wire for the treatment of olecranon fractures of the ulna in children.
Deng-Shan CHEN ; Chuan-Wei ZHANG ; Lei WANG ; Xing-Po DING ; Jian-Ping YANG
China Journal of Orthopaedics and Traumatology 2025;38(7):743-746
OBJECTIVE:
To investigate the clinical efficacy and safety of ultrasound-guided closed reduction and internal fixation using Kirschner wire for the treatment of olecranon fractures of the ulna in children.
METHODS:
Between January 2019 and January 2021, 13 children with olecranon fracture were treated with ultrasound-guided closed reduction and percutaneous Kirschner wire internal fixation, including 10 males and 3 females. The age ranged from 3 to 14 years old. Children with ulnar olecranon fractures were evaluated using the Gicquel scoring system. The clinical evaluation encompassed postoperative pain, functional status, and range of motion, with a maximum score of 15 points. The radiological assessment contributed an additional 4 points. A cumulative score of more than 18 scores was classified as excellent, more than 17 scores as good, more than16 scores as fair, and less than 16 scores as poor. Clinical assessment:A score of 14 indicates excellent performance, a score of 13 reflects good performance, a score of 12 denotes fair performance, and a score of less than 11 signifies poor performance.
RESULTS:
A total of 13 patients were followed up, with a duration ranging from 6 to 12 months. According to the Gicquel scoring criteria, the comprehensive evaluation of clinical and radiographic findings yielded 10 excellent and 3 good outcomes. Evaluation based solely on clinical findings resulted in 13 excellent outcomes.
CONCLUSION
Ultrasound-guided percutaneous cross Kirschner wire fixation for children's olecranon fracture has the advantages of less trauma, rapid recovery, less fluoroscopy, and good recovery of elbow function. The clinical effect is satisfactory.
Humans
;
Child
;
Male
;
Female
;
Fracture Fixation, Internal/instrumentation*
;
Ulna Fractures/physiopathology*
;
Bone Wires
;
Child, Preschool
;
Adolescent
;
Olecranon Process/surgery*
;
Ultrasonography
;
Closed Fracture Reduction/methods*
;
Olecranon Fracture

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