1.Analysis of blood entry component of Yinchenhao decoction in vivo and study on the anti-hepatocellular carcinoma mechanism by network pharmacology
Linfeng ZHANG ; Yuheng SUN ; Dongyao WANG ; Dan LI ; Yan CAO ; Diya LYU
Journal of Pharmaceutical Practice and Service 2026;44(4):200-208
Objective To improve the analysis method of the blood components of Yinchenhao decoction (YCHD) in vivo and explore its anti-hepatocellular carcinoma mechanism. Methods Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to collect and analyze blood samples from mice. The mice were given a single dose of YCHD with a concentration of 0.1 g/ml and a dose of 25 ml/kg, and then the samples were collected 2 h post–administration, which was to systematically study the chemical components of YCHD in vivo. Network pharmacological methods were used to screen the components and targets of YCHD, and the targets of hepatocellular carcinoma; The common targets of YCHD and hepatocellular carcinoma were identified for GO enrichment and KEGG enrichment. Molecular docking was performed on the main targets to verify the binding ability between the active ingredients and the core targets. The relative mRNA expression levels of serine/threonine-protein kinase(AKT1) and tumor protein p53(TP53) in liver tissues were analyzed via qPCR, including the following mouse groups: mice with concanavalin A(Con-A)-induced acute liver injury without preventive administration, mice with Con-A-induced acute liver injury that received 14 d preventive oral administration of YCHD, and untreated control mice. Results ①The active ingredients of YCHD in the blood were identified by retrieving the data from the in vitro component analysis. They were chrysophanol, herniarin, aloe-emodin, and monotropein. ②The mechanism of action of the blood components against hepatocellular carcinoma (HCC) was further analyzed using network pharmacological methods, and a total of 30 components of YCHD were screened for 213 targets and 215 HCC targets. ③There were 17 intersection targets between YCHD and hepatocellular carcinoma, including AKT1, TP53, receptor tyrosine-protein kinase erbB-2 (ERBB2), myelocytomatosis oncogene (MYC), interleukin-1β (IL-1β), etc. The GO enrichment results indicated that these components were primarily involved in DNA replication,chromosome segregation,leukocyte mediated immunity,leukocyte cell-cell adhesion. The KEGG enrichment results demonstrated that these components were predominantly associated with diverse cancer pathways. Additionally, the results indicated involvement in the citrate cycle (TCA cycle), pyruvate metabolism, and p53 signaling pathway, ect. ④The results of molecular docking showed that chrysophanol, herniarin, and aloe - emodin had strong binding abilities with AKT1, TP53, ERBB2, MYC, and IL-1β. ⑤The relative expression of AKT1 and TP53 mRNA was significantly higher in the modelling group than in the control group. The relative expression of AKT1 and TP53 mRNA was significantly lower in the drug administration group than in the modelling group. Conclusion There were 4 blood components in YCHD, among which chrysophanol, herniarin, and aloe-emodin may act on AKT1, TP53, ERBB2, MYC, IL-1β and then participated in the regulation of cancer signaling pathways and p53 signaling pathway to play a role in the treatment of HCC.
2.Anti-tumor Mechanism of Traditional Chinese Medicine with Effect of Softening Hardness and Dissipating Mass: A Review
Yue HU ; Linfeng WANG ; Yue LI ; Rui LIU ; Baojin HUA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):276-286
The global burden of malignant tumors keeps increasing, and the increased morbidity and mortality make malignant tumors one of the major challenges to global health. Currently, malignant tumors are mainly managed by surgical resection, radiotherapy, chemotherapy, targeted therapy, and immunotherapy, which, however, usually cause serious adverse reactions, such as tissue damage, immune function inhibition, and multidrug resistance, affecting the prognosis and quality of life of the patients. Traditional Chinese medicine with low toxic and side effects and multi-target, multi-system, and multi-pathway therapeutic effects has shown positive therapeutic potential in cancer treatment. In particular, the traditional Chinese medicine with the effects of softening hardness and dissipating mass, which contains a variety of active ingredients, have shown strong inhibitory effects on tumor cells. Such medicine can not only directly attack tumor cells and inhibit their proliferation and invasion but also exert therapeutic effects by inducing apoptosis, blocking tumor-related signaling pathways, and inhibiting tumor angiogenesis. In addition, traditional Chinese medicine can improve the overall efficacy of cancer treatment by regulating the immune status of the body and reversing the drug resistance of tumor cells. Traditional Chinese medicine can exert the anti-tumor effect by regulating intracellular signaling pathways, which is one of the research hotspots in this field. Signaling pathways such as signal transducer and activator of transcription 3 (STAT3), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), and mitogen-activated protein kinase (MAPK) play a key role in the formation and development of tumors. Traditional Chinese medicine can regulate the growth, apoptosis, and metabolic process of tumor cells by affecting the activity of these signaling pathways, thus exerting the therapeutic effects on tumors. Based on these mechanisms, a large number of experimental studies and clinical trials have proved that traditional Chinese medicine has broad prospects in anti-tumor treatment. To further verify these research results and provide a basis for the clinical application of traditional Chinese medicine and the development of new drugs, a systematic review and integrated analysis of the research reports on the anti-tumor effect of traditional Chinese medicine was carried out to summarize the anti-tumor mechanisms of traditional Chinese medicine. This review is expected to promote the wide application of traditional Chinese medicine in anti-tumor treatment worldwide and bring more hope and possibility to cancer patients.
3.Construction of a Nomogram risk prediction model for deep vein thrombosis in patients with knee osteoarthritis after artificial total knee arthroplasty
Peng LIU ; Xiaopeng WANG ; Linfeng HU
Journal of Shenyang Medical College 2025;27(1):55-60
Objective:To investigate the factors influencing the occurrence of deep vein thrombosis(DVT)in patients with knee osteoarthritis after artificial total knee arthroplasty(TKA)and to construct a nomogram prediction model.Methods:A total of 120 patients with knee osteoarthritis underwent TKA from Dec 2020 to Dec 2022 were selected.The patients were divided into DVT group(n=20)and non-DVT group(n=100)according to whether DVT occurred after surgery.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of each influencing factor to the occurrence of DVT.Multivariable logistic regression was used to analyze the factors affecting the occurrence of DVT.The nomogram prediction model of DVT was constructed by the R software 4.0"rms"package.The calibration and decision curves were used to internally validate and clinically assess the predictive efficacy of the nomogram prediction model.Results:There were significant differences between DVT group and non-DVT group in age,body mass index(BMI),diabetes mellitus,hyperlipidaemia,plasma D-dimer level,operative time,intraoperative haemorrhage,post-operative bedrest,and anaesthesia modality(P<0.05).ROC curve showed that the AUC for age,BMI,plasma D-dimer,operative time,intraoperative haemorrhage,and postoperative bedrest were 0.663,0.678,0.985,0.856,0.925 and 0.925,respectively.Multivariable logistic regression analysis showed that age≥71 years old,BMI≥25.47 kg/m2,diabetes mellitus,hyperlipidaemia,plasma D-dimer level≥0.69 mg/L,and general anaesthesia were independent risk factors for postoperative DVT(P<0.05).The calibration curve of the nomogram prediction model was close to the original and ideal curves,with a C-index of 0.813(0.721-0.905),indicating a high degree of fit.The threshold value of the nomogram prediction model was>0.17,which could provide a net clinical benefit.And its net clinical benefit was higher than age,BMI,diabetes mellitus,hyperlipidemia,plasma D-dimer,and anaesthesia mode.Conclusions:The factors affecting the occurrence of DVT in patients with knee osteoarthritis after TKA are age,BMI,diabetes mellitus,hyperlipidaemia,plasma D-dimer level,operative time,intraoperative haemorrhage,postoperative bedtrest,and anaesthesia mode.The personalized neomorph prediction model constructed by these predictive factors can help to predict and evaluate whether DVT will be occurred in patients with knee osteoarthritis after TKA,so as to intervene early,reduce the incidence and improve the prognosis.
4.Electroacupuncture Modulates Alveolar Macrophage Polarization via the Vagus Nerve to Alleviate Pulmonary Inflammation in a Mouse Model of Chronic Obstructive Pulmonary Disease
Na LIU ; Linfeng WANG ; Yifan LI ; Shuwen XU ; Xinfang ZHANG ; Shuiying XIANG ; Heren GAO ; Zibing LIU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(10):1356-1364
OBJECTIVE To investigate the anti-inflammatory effect of electroacupuncture in mice with chronic obstructive pul-monary disease(COPD)and its underlying mechanisms.METHODS Forty C57BL/6 mice were randomly divided into normal group,model group,electroacupuncture(EA)group,vagotomy group,and vagotomy+EA group,with 8 mice in each group.Except for the normal group,all groups were exposed to cigarette smoke for 12 weeks to establish a COPD model.After model establishment,the vagotomy group and the vagotomy+EA group underwent left cervical vagotomy before EA.EA treatment was performed at the Feishu(BL13)and Zusanli(ST36)acupoints once daily for 20 minutes for a total of 14 days.After EA,the pulmonary ventilation function of the mice was detected by a pulmonary function analysis system;lung tissue pathology was observed by HE staining;the levels of inter-leukin(IL)-6,tumor necrosis factor-α(TNF-α),IL-10,and transforming growth factor-β(TGF-β)in lung tissue were detected by ELISA;the expression of CD86 and CD206 proteins in lung tissue was detected by Western blot;the distribution of F4/80+CD86+(M1 type)and F4/80+CD206+(M2 type)cells in lung tissue was determined by flow cytometry;the expression of CD86 and CD206 in lung tissue was observed by immunofluorescence.RESULTS Compared with the normal group,the model group showed significantly decreased lung function(P<0.01),obvious lung pathological damage,increased M1 proportion,IL-6,TNF-α,CD86 content and expression(P<0.05,P<0.01),and decreased M2 proportion,IL-10,TGF-β,CD206 content and expression(P<0.01).Compared with the model group,the EA group showed varying degrees of improvement in lung function and pathology;the M1 proportion,IL-6,TNF-α,and CD86 were reduced(P<0.05,P<0.01),while the M2 proportion,IL-10,TGF-β,and CD206 were increased(P<0.05,P<0.01).The vagotomy group showed worsened lung function and pathology,increased IL-6,TNF-α,and CD86 content and expression(P<0.05,P<0.01),and decreased IL-10,TGF-β,and CD206 content and expression(P<0.05,P<0.01).Compared with the EA group,the vagotomy+EA group showed increased M1 proportion,IL-6,TNF-α,and CD86 content and expression(P<0.01),and decreased M2 proportion,IL-10,TGF-β,and CD206 content and expression(P<0.05,P<0.01).CONCLUSION EA at Feishu(BL13)and Zusanli(ST36)acupoints can improve lung function and pulmonary inflammation in COPD mice,promoting the polarization of alveolar macrophages from M1 to M2,which is mediated by the vagus nerve.
5.Nafamostat Mesylate Alleviates Renal Ischemia-Reperfusion Injury in a Rat Model Through HMGB1 Modulation:An Omics Analysis-Based Study of the Protective Effect and the Mechanisms Involved
Yuxuan WU ; Hongqian LI ; Linfeng LIU ; Yu WANG ; Bo CHEN ; Jiang LIU ; Jianhua QIN ; Santao OU ; Weihua WU
Journal of Sichuan University (Medical Sciences) 2025;56(1):175-182
Objective To investigate the organ protective role and the underlying mechanism of nafamostat mesylate(NM)in a renal ischemia-reperfusion injury(RIRI)model.Methods A total of 21 healthy male Sprague-Dawley(SD)rats were randomly assigned to 3 groups(n=7 in each group),including the sham operation group(Sham group),the RIRI group,and the NM intervention group(NM group).The RIRI and NM groups underwent ischemia-reperfusion injury(IRI)modeling.The NM group was given an intraperitoneal injection of NM at 0.75 mg/kg before modeling.Venous blood and renal tissue samples were then collected from the rats 24 hours after modeling.The levels of serum creatinine,cystatin C,and serum inflammatory factors were determined using the serum samples.Hematoxylin-eosin(HE)staining and TUNEL stainings were performed on the renal tissues to evaluate the damage of the renal tissues.The localization and expression of HMGB1 were analyzed by immunofluorescence and Western blotting,respectively.Single-cell RNA sequencing of the nuclei was performed to obtain the single-cell transcriptome of the kidneys from the rats in the RIRI and the NM groups and to acquire the RIRI cell profile.The cells were annotated according to the cell marker genes to explore the cell type composition in the disease model and the functional status of immune cells between the groups.Results 1)Compared with those of the Sham group,the levels of cystatin C,creatinine,and inflammatory factors in the RIRI and NM groups were significantly increased,and the expression levels in the NM group were lower than those in the RIRI group(P<0.05).Compared with those of the RIRI group,the tubular injury score and apoptosis rate in the NM group were significantly decreased(P<0.05),but those of both the NM and RIRI groups were higher than those of the sham group.Compared with that in the RIRI group,the expression of HMGB1 in the NM group was significantly decreased(P<0.05),but the expression levels in both the RIRI and NM groups were higher than that in the sham group.Immunofluorescence showed that there was increased cytoplasmic expression of HMGB1 in both the NM and RIRI groups,with the increase being more prominent in the RIRI group.2)A total of 13 major cell populations were identified through the single-nucleus sequencing results.The proportion of tubular cells in the NM group was higher,with the HMGB1 gene being highly expressed in the damaged proximal convoluted tubular cells.The proportion of the polarized Macro3 cell subpopulation in the macrophages in the NM group was lower compared to that in the RIRI group.Conclusion NM may play a protective role in a rat model of RIRI,and its underlying mechanisms may be related to the regulation of the functional abnormalities of HMGB1-mediated macrophages.
6.Preparation of nano BaTiO 3@Au Schottky junction coatings on titanium implant and the influence on osteogenic properties of rat bone marrow stem cells
Xiaoling GUO ; Danhe SUN ; Luying LI ; Linfeng ZHONG ; Xiaoyan WANG ; Quan ZHOU ; Lingzhou ZHAO
Chinese Journal of Stomatology 2025;60(11):1264-1273
Objective:To prepare a nano-barium titanate@gold Schottky junction (nano-BaTiO 3@Au) coating and investigate its effects on the adhesion, proliferation, and osteogenic differentiation of bone marrow stem cells (BMSCs), aiming to explore a titanium surface modification strategy with superior osteogenic activity. Methods:Pure titanium specimens served as the control group (Ti group). Titanium dioxide coatings were prepared on their surfaces via anodic oxidation. Nano-barium titanate (nBTO group) was further synthesized using the hydrothermal method. Gold nanoparticles were grown in situ on the nano-BaTiO 3 via high-temperature reduction of chloroauric acid using sodium citrate, yielding the nano-barium titanate@gold Schottky junction coating (nBTO@Au group). Surface morphology was observed by scanning electron microscopy (SEM). Elemental composition was analyzed using X-ray energy dispersive spectrum (EDS) and X-ray photoelectron spectroscopy (XPS). Crystal structure was analyzed using X-ray diffraction (XRD) and Raman spectroscopy. Hydrophilicity was assessed via water contact angle measurement. Specimens were co-cultured with BMSCs to evaluate biocompatibility and osteogenic properties. Cell proliferation on days 1, 3, 5, and 7 was assessed using the cell counting kit-8 (CCK-8) assay. Cytotoxicity towards BMSCs was assessed using live/dead cell staining. Cell morphology and adhesion were observed using cytoskeleton staining. Alkaline phosphatase (ALP) expression in BMSCs after 7 days was quantified using an ALP activity assay and ALP staining. Extracellular matrix mineralization after 7 days was evaluated using alizarin red staining and quantification assay. Each experiment was performed using three specimens per group. Results:Scanning electron microscopy revealed that gold nanoparticles with the diameter of(14.838±0.718) nm, uniform in size and homogeneously distributed, were successfully grown in situ on the surface of the nBTO coating. EDS and XPS confirmed the presence of Ba, Ti, O, and Au elements in the nBTO@Au composite coating. XRD and Raman spectroscopy analysis indicated that the nanostructured barium titanate (nBTO) coating was synthesized via a hydrothermal method.Water contact angle measurements showed that the contact angle was 66.8°± 0.45° for the control group, 22.55°±0.42° for the nBTO group, and 26.78°±1.15° for the nBTO@Au group, indicating good hydrophilicity of both nBTO and nBTO@Au coatings. On day 1 and day 3 of culture, the cell proliferation in the nBTO group was significantly lower than that in the control group ( P<0.05). In contrast, no significant differences were observed between the nBTO@Au group and either the control group or the nBTO group (all P>0.05). By day 5, the cell proliferation of nBTO@Au groups was significantly lower than that of the control group ( P<0.05), and the cell proliferation of nBTO group was significantly lower than that of the control group and that of the nBTO@Au group ( P<0.05). By day 7, there were no statistically significant differences in cell proliferation among all experimental groups ( F=1.62, P>0.05).Live/dead cell staining demonstrated that the cell survival rate exceeded 90% in all groups, with normal morphology and few dead cells, indicating good biocompatibility of the nBTO@Au coating. Compared to the control group, both nBTO and nBTO@Au groups promoted cell adhesion and spreading, although no significant difference in cell morphology was noted between the two modified groups. ALP staining revealed a larger stained area and deeper coloration in the nBTO@Au group. Quantitative results showed that ALP activity in the nBTO@Au group was significantly higher than that in both the nBTO and control groups ( P<0.05), and the nBTO group also exhibited significantly higher activity than the control group( P<0.05). Alizarin red staining indicated the deepest coloration in the nBTO@Au group, followed by the nBTO group, and the lightest in the control group. Quantitative analysis further confirmed that the amount of calcium nodule deposition in the nBTO@Au group was significantly greater than that in the other two groups ( P<0.05), and the nBTO group also showed significantly more deposition than the control group( P<0.05). Conclusions:This study successfully prepared an nBTO@Au coating possessing good biocompatibility and enhanced osteogenic properties.
7.Efficacy assessment of an intelligent blood transfusion system in intraoperative red blood cell transfusion
Linfeng CHEN ; Yu FENG ; Zongmei TIAN ; Yan WANG ; Wei ZHOU ; Qingqing YANG ; Yang YU ; Deqing WANG
Chinese Journal of Blood Transfusion 2025;38(11):1495-1501
Objective: To evaluate the long-term effectiveness of an intelligent blood transfusion system in intraoperative blood management by comparing its performance with clinicians' decisions. Methods: A retrospective analysis of 26 760 surgical cases (2017-2024) was conducted, comparing pre- and post-implementation (2017-2019 vs 2020-2024) metrics, including transfusion prediction accuracy, rationality of blood use, and clinical outcomes. The system, powered by XGBoost, integrated patient demographics, laboratory results, and surgical data to predict red blood cell transfusion needs. Results: The intelligent blood transfusion systems achieved an accuracy of 80.62% in predicting transfusion necessity, significantly outperforming clinicians (24.83%, P<0.001). Its blood-use rationality rate was 83.92% vs 18.02% for clinicians (P<0.001). Post-implementation, major surgeries (grades Ⅲ-Ⅳ) increased while the requested blood units decreased. High physician compliance (>75%) correlated with 88.18% rationality. Conclusion: The intelligent blood transfusion system significantly improves the accuracy of transfusion decision-making, reduces excessive red blood cell use, optimizes perioperative transfusion management, and enhances the utilization of blood medical resources.
8.Screening analyses of tuberculosis infection among primary and secondary school students in Cixi City of Zhejiang Province from 2024 to 2025
Linfeng WANG ; Sinan XU ; Na LI ; Yang CHE
Shanghai Journal of Preventive Medicine 2025;37(10):813-816
ObjectiveTo determine the prevalence and determinants of Mycobacterium tuberculosis latent infection among primary and secondary school students in Cixi City, Zhejiang Province, so as to provide references for the prevention and control of tuberculosis in school settings. MethodsInterferon-γ release assay (IGRA) testing was performed to fourth-grade primary school students , as well as to those grade 7 and grade 10 students of the academic year 2024‒2025 in Cixi City. Individuals tested positive for IGRA were subsequently subjected to chest X-ray examination and sputum tests (including three smear microscopy examinations and one mycobaterial culture), and epidemiological investigations were carried out for confirmed cases. Infection rates were compared across student categories by χ² tests, while factors influencing infection were analysed through multivariate logistic regression. ResultsA total of 36 214 students completed tuberculosis screening, with an infection rate of 0.72% (260/36 214). The tuberculosis infection rates among fourth-grade primary school students, non boarding grade 7 students, boarding grade 7 students, grade 10 students of senior high school and of vocational high school were 0.68% (89/13 139), 0.75% (86/11 501), 0.51% (13/2 553), 0.76% (52/6 819), and 0.91% (20/2 202), respectively. Multivariate logistic regression analyses indicated that students with a history of close contact with tuberculosis patients (OR=21.435, P<0.001) had a higher risk of tuberculosis infection, students with a geographic origin outside Zhejiang Province (OR=1.485, P=0.002) had a higher risk of infection than those within Zhejiang Province. Furthermore, students from ethnic minority classes (OR=4.232, P<0.001) might be high-risk groups for tuberculosis infection in high school settings. One IGRA-positive student was confirmed as bacteriologically positive pulmonary tuberculosis by liquid culture of sputum collected one month later. ConclusionSchools should prioritize tuberculosis screening. Students with a history of close contact, those with a geographic origin outside Zhejiang Province, and those enrolled in minority classes should be taken as priority targets for future tuberculosis screening programmes. A tracking and follow-up system must be established for IGRA-positive students to prevent persistent transmission of Mycobacterium tuberculosis within the school settings.
9.Prevalence of musculoskeletal disorders among bus drivers in a first-tier city and associated influencing factors
Linfeng LUO ; Huining WANG ; Huijie ZHANG ; Baolong LIU ; Tenglong YAN ; Jue LI
Journal of Environmental and Occupational Medicine 2025;42(11):1342-1349
Background During urbanization, the passenger load on urban public transport systems continues to increase, exposing bus drivers to a high risk of musculoskeletal disorders (MSDs). This occupational health issue may also potentially compromise public transport safety. Objective To investigate the prevalence of MSDs among bus drivers in a first-tier city and to explore associated influencing factors. Methods A self-administered questionnaire survey was conducted from December 2024 to March 2025 among
10.Cerebral endothelial 3-mercaptopyruvate sulfurtransferase improves ischemia-induced cognitive impairment via interacting with protein phosphatase 2A.
Li ZHU ; Yi HUANG ; Jing JIN ; Rongjun ZOU ; Rui ZUO ; Yong LUO ; Ziqing SONG ; Linfeng DAI ; Minyi ZHANG ; Qiuhe CHEN ; Yunting WANG ; Wei WANG ; Rongrong HE ; Yang CHEN
Acta Pharmaceutica Sinica B 2025;15(1):314-330
The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H2S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H2S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2AEC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H2S signaling pathway. A robust reduction in endothelial MPST-dependent H2S production followed PP2A deficiency. Exogenous H2S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2AEC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H2S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.

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