1.Current Research Status of Digital Technology in the Rehabilitation of Rare Neurological and Muscular Diseases
Yixuan GUO ; Yi GAO ; Yiyang YAO ; Zhuoyue QIN ; Yaofang ZHANG ; Jiaqi JING ; Jing XIE ; Jian GUO ; Shuyang ZHANG
JOURNAL OF RARE DISEASES 2025;4(1):122-131
To review the randomized controlled trials (RCTs) at home and abroad on digital intelligence (DI)-driven rehabilitation in patients of neuromuscular disease, compare the effects of DI-driven rehabilitation with traditional rehabilitation, summarize the special needs and challenges faced by patients in rehabilitation of rare neuromuscular diseases, and provide evidence for the development and quality improvement of rehabilitation for rare neuromuscular diseases. We searched PubMed, Web of Science, Embase, CNKI, VIP, and Wanfang databases for literature on neuromuscular diseases, rare diseases, digital and intelligent technologies, and rehabilitation published from the inception of the databases to June 2024. Basic and research-related information from the retrieved literature was extracted and analyzed. A total of 43 RCTs in English from 14 countries were included. The most studied diseases were Parkinson′s disease and multiple sclerosis. The application of DI-driven technologies in rehabilitation of rare neuromuscular diseases was still limited. The commonly used technologies were virtual reality (VR) games, intelligent treadmill assistance, gait training robots, hybrid assistive limb (HAL), wearable sensors and tele-rehabilitation (TR) systems. These technologies were applied in patients′ homes or rehabilitation service centers. The VR games significantly improved both static/dynamic balance functions and cognitive functions. The intelligent treadmill assistance significantly enhanced gait speed and stride length. The gait training robots significantly improved balance, gait speed and stride length of patients. The wearable exoskeletons significantly enhanced walking ability. DI-driven rehabilitation measures have great value and potential in the field of neuromuscular disease rehabilitation. Their advantages and characteristics can meet the diverse needs of rare disease patients. In the future, a hierarchical and collaborative rehabilitation service system should be established to meet the urgent needs of the rehabilitation of rare neuromuscular diseases. Combining the advantages of digitization and intelligence will provide standardized, scientific, convenient and affordable rehabilitation services to patients.
2.The Application of Digital Intelligence Technology in the Management of Non-Hospitalized Patients with Rare Diseases
Yiyang YAO ; Yi GAO ; Yixuan GUO ; Zhuoyue QIN ; Yaofang ZHANG ; Jiaqi JING ; Jing XIE ; Jian GUO ; Shuyang ZHANG
JOURNAL OF RARE DISEASES 2025;4(1):46-53
To provide references to and give suggestions to the development and optimiza-tion of Digital Intelligence (DI) technology in management of non-hospitalized patients by systematical review the application of digital technology in non-hospital settings. We designed the search strategy and used the words " rare diseases"" patient management"" non-hospitalized management"" community management"" digital intelligence"" big data"" telemedicine" as MESH terms or free words. We searched the database of PubMed, Science-Direct, Web of Science, CNKI, Wanfang and VIP from the beginning of the database to July 2024 and used computer retrieval to get the literatures on the application of DI technology in the management of patients with rare diseases in non-hospital setting. We extracted the information of the first author, country or region, publication time, research participants, DI technology application, and application effect for summary analysis. A total of 13 articles were included in this study, which were from 8 countries or regions. We found that DI technologies used were in the following forms: Internet information platform, wearable devices, telemedicine management platform and electronic database. The DI technology was used by the patients with rare diseases, patient caregivers and professional medical staffs. The application of all the forms above in different populations had good effect. The Internet information platform helped patients and their caregivers learn more about the disease and improved their self-management ability. The wearable device helped monitor the health status of patients in real time and predict the risk of emergent events. The telemedicine management platform facilitated to optimize the allocation of medical resources and strengthen doctor-patient communication. The electronic health database promoted the interconnection of data inside and outside the hospital and improved the accuracy of decision-making through data sharing. The application of DI technology in the management of patients with rare diseases in non-hospitalized settings has shown positive results. In the future, it is necessary to correct the shortcomings and to deal with the challenges in terms of accuracy, readiness, applicability, and privacy protection. Besides, the DI can be integrated into the tri-level management system of patients known as the "patient-community-hospital". It is advisable to take the advantages of digital intelligence technology to improve the efficiency and quality of management of patients in non-hospitalized settings.
3.Principles, technical specifications, and clinical application of lung watershed topography map 2.0: A thoracic surgery expert consensus (2024 version)
Wenzhao ZHONG ; Fan YANG ; Jian HU ; Fengwei TAN ; Xuening YANG ; Qiang PU ; Wei JIANG ; Deping ZHAO ; Hecheng LI ; Xiaolong YAN ; Lijie TAN ; Junqiang FAN ; Guibin QIAO ; Qiang NIE ; Mingqiang KANG ; Weibing WU ; Hao ZHANG ; Zhigang LI ; Zihao CHEN ; Shugeng GAO ; Yilong WU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(02):141-152
With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.
4.Mechanism of Xielitang Against Ulcerative Colitis in Mice Based on "Intestinal Flora-bile Acid" Axis
Xiaotian WANG ; Yaning BIAO ; Yixin ZHANG ; Jian CHEN ; Ya GAO ; Yufang ZHANG ; Muqing ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):30-38
ObjectiveTo investigate the protective effect of Xielitang on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice and its possible mechanism. MethodsDSS was used to establish UC model. Sixty mice were randomly divided into a normal group, a model group, a sulfasalazine group (0.6 g·kg-1), and low-, medium-, and high-dose Xielitang groups (1.67, 3.34, 6.68 g·kg-1). After treatment for 42 d, the colon length was recorded, and the disease activity index (DAI) score was calculated. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10). Hematoxylin-eosin (HE) staining was used to observe the pathomorphological changes of colon. Western blot was used to detect the protein expression of farnesoid X receptor (FXR), small heterodimer partner (SHP), liver receptor homolog-1 (LRH-1), cholesterol 7α-hydroxylase (CYP7A1), and fibroblast growth factor receptor 4 (FGFR4) in liver and FXR, sodium-dependent bile acid transporter (ASBT), and fibroblast growth factor 15 (FGF15) in ileum. 16S rRNA sequencing was used to analyze the intestinal flora. Moreover, ultra-high performance liquid chromatography–tandem mass spectrometry was used to detect the bile acid content. ResultsCompared with the normal group, the model group showed significantly decreased colon length, IL-10 content, α-diversity index, abundance of Firmicutes and Lactobacillus, and content of deoxycholic acid (DCA) and lithocholic acid (LCA) (P<0.01), significantly increased DAI score, IL-6 and TNF-α content, abundance of Bacteroidetes, and the content of cholic acid (CA), chenodeoxycholic acid (CDCA), and taurocholic acid (TCA) (P<0.05, P<0.01), significantly down-regulated protein expression of FXR, SHP, and FGFR4 in liver and FXR, ASBT, and FGF15 in ileum (P<0.01), and significantly up-regulated protein expression of LRH-1 and CYP7A1 in liver (P<0.01). In addition, the structure of colonic mucosa was destroyed, and inflammatory cells infiltrated in the model group. Compared with the model group, Xielitang could significantly increase the colon length, IL-10 content, α-diversity index, the abundance of Firmicutes and Lactobacillus, and DCA and LCA content (P<0.05, P<0.01), decrease DAI score, abundance of Bacteroidetes, and the content of IL-6, TNF-α, CA, CDCA, and TCA (P<0.01), up-regulate the protein expression of FXR, SHP, and FGFR4 in liver and FXR, ASBT, and FGF15 in ileum (P<0.01), and down-regulate the protein expression of LRH-1 and CYP7A1 in liver (P<0.01). The pathological damage of colonic mucosa was obviously alleviated. ConclusionXielitang protects against UC probably by regulating the "intestinal microbiota-bile acid" axis, regulating intestinal flora imbalance, and maintaining bile acid homeostasis.
5.Right ventricular-pulmonary artery connection for palliative treatment of pulmonary atresia with ventricular septal defect in children: A single-center retrospective study
Shuai ZHANG ; Jianrui MA ; Hailong QIU ; Xinjian YAN ; Wen XIE ; Qiushi REN ; Juemin YU ; Tianyu CHEN ; Yong ZHANG ; Xiaohua LI ; Furong LIU ; Shusheng WEN ; Jian ZHUANG ; Qiang GAO ; Jianzheng CEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(03):366-371
Objective To compare the benefits and drawbacks of primary patch expansion versus pericardial tube right ventricular-pulmonary artery connection in patients diagnosed with pulmonary atresia with ventricular septal defect (PA/VSD). Methods A retrospective study was conducted on patients diagnosed with PA/VSD who underwent primary right ventricular-pulmonary artery connection surgery at our center between 2010 and 2020. Patients were categorized into two groups based on the type of right ventricular-pulmonary artery connection: a pericardial tube group and a patch expansion group. Clinical data and imaging findings were compared between the two groups. Results A total of 51 patients were included in the study, comprising 31 males and 20 females, with a median age of 12.57 (4.57, 49.67) months. The pericardial tube group included 19 patients with a median age of 17.17 (7.33, 49.67) months, while the patch expansion group consisted of 32 patients with a median age of 8.58 (3.57, 52.72) months. In both groups, the diameter of pulmonary artery, McGoon index, and Nakata index significantly increased after treatment (P<0.001). However, the pericardial tube group exhibited a longer extracorporeal circulation time (P<0.001). The reoperation rate was notably high, with 74.51% of patients requiring further surgical intervention, including 26 (81.25%) patients in the patch expansion group and 12 (63.16%) patients in the pericardial tube group. No statistical differences were observed in long-term cure rates or mortality between the two groups (P>0.005). Conclusion In patients with PA/VSD, both patch expansion and pericardial tube right ventricular-pulmonary artery connection serve as effective initial palliative treatment strategies that promote pulmonary vessel development and provide a favorable foundation for subsequent radical operations. However, compared to the pericardial tube approach, the patch expansion technique is simpler to perform and preserves some intrinsic potential for pulmonary artery development, making it the preferred procedure.
6.LC-MS-based phosphoproteomic profiling of the acute phase of myocardial infarction in mice
Yang GAO ; Jian ZHANG ; Shiyu HU ; Jingpu WANG ; Yiwen WANG ; Jiatian CAO ; Feng ZHANG
Chinese Journal of Clinical Medicine 2025;32(3):392-402
Objective To investigate dynamic changes in myocardial protein phosphorylation during the acute phase of myocardial infarction (MI) in mice. Methods Six 8-week-old C57BL/6J mice were randomly assigned to MI model (n=3) or sham-operated control (n=3) groups. Cardiac tissues were harvested 72 hours post-intervention for proteomic analysis. Phosphorylation modifications were systematically characterized using liquid chromatography-mass spectrometry (LC-MS). Bioinformatics analyses included differential phosphorylation screening, functional enrichment, hierarchical clustering, and protein-protein interaction network. Results LC-MS identified 1 921 differentially phosphorylated sites (20 tyrosine and 1 901 serine/threonine sites) across 851 proteins. Compared with controls, MI hearts exhibited significant phosphorylation upregulation at 1 545 sites and downregulation at 376 sites (P<0.05). Conclusions This study delineates MI-associated phosphorylation dynamics, providing mechanistic insights and potential therapeutic targets for acute MI intervention.
7.Implications of left atrial volume index in patients with three-vessel coronary disease: A 6.6-year follow-up cohort study
Ru LIU ; Lei SONG ; Ce ZHANG ; Lin JIANG ; Jian TIAN ; Lianjun XU ; Xinxing FENG ; Linyuan WAN ; Xueyan ZHAO ; Ou XU ; Chongjian LI ; Runlin GAO ; Rutai HUI ; Wei ZHAO ; Jinqing YUAN
Chinese Medical Journal 2024;137(4):441-449
Background::Risk assessment and treatment stratification for three-vessel coronary disease (TVD) remain challenging. This study aimed to investigate the prognostic value of left atrial volume index (LAVI) with the Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score II, and its association with the long-term prognosis after three strategies (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], and medical therapy [MT]) in patients with TVD.Methods::This study was a post hoc analysis of a large, prospective cohort of patients with TVD in China, that aimed to determine the long-term outcomes after PCI, CABG, or optimal MT alone. A total of 8943 patients with TVD were consecutively enrolled between 2004 and 2011 at Fuwai Hospital. A total of 7818 patients with available baseline LAVI data were included in the study. Baseline, procedural, and follow-up data were collected. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was a composite of all-cause death, myocardial infarction (MI), and stroke. Secondary endpoints included all-cause death, cardiac death, MI, revascularization, and stroke. Long-term outcomes were evaluated among LAVI quartile groups. Results::During a median follow-up of 6.6 years, a higher LAVI was strongly associated with increased risk of MACCE (Q3: hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.06-1.37, P = 0.005; Q4: HR 1.85, 95%CI 1.64-2.09, P <0.001), all-cause death (Q3: HR 1.41, 95% CI 1.17-1.69, P <0.001; Q4: HR 2.54, 95%CI 2.16-3.00, P <0.001), and cardiac death (Q3: HR 1.81, 95% CI 1.39-2.37, P <0.001; Q4: HR 3.47, 95%CI 2.71-4.43, P <0.001). Moreover, LAVI significantly improved discrimination and reclassification of the SYNTAX score II. Notably, there was a significant interaction between LAVI quartiles and treatment strategies for MACCE. CABG was associated with lower risk of MACCE than MT alone, regardless of LAVI quartiles. Among patients in the fourth quartile, PCI was associated with significantly increased risk of cardiac death compared with CABG (HR: 5.25, 95% CI: 1.97-14.03, P = 0.001). Conclusions::LAVI is a potential index for risk stratification and therapeutic decision-making in patients with three-vessel coronary disease. CABG is associated with improved long-term outcomes compared with MT alone, regardless of LAVI quartiles. When LAVI is severely elevated, PCI is associated with higher risk of cardiac death than CABG.
8.Expression and significance of ABCC4 and miR-125b-5p in prostate cancer tissue
Jian GAO ; Yuan ZHANG ; Lei LI
International Journal of Surgery 2024;51(6):382-387
Objective:To detect the expression of ABC transporter family 4(ABCC4) and miR-125b-5p in prostate cancer tissues, and analyze their relationship with the prognosis of prostate cancer.Methods:From May 2019 to May 2021, 60 patients with prostate cancer diagnosed by pathological diagnosis admitted to Qinhuangdao Hospital of Traditional Chinese Medicine were selected. All fresh tissue samples of prostate cancer were obtained from prostate cancer surgery and divided into prostate cancer group (cancer tissue) and control group (adjacent tissue). Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of ABCC4 mRNA and miR-125b-5p in the cancer tissue and adjacent tissue. Immunohistochemistry was used to detect the expression of ABCC4 in paraffin sections of tissues, and to analyze the relationship between the expression levels of ABCC4 and miR-125b-5p and clinicopathological features, prognosis of patients with prostate cancer, and the influencing factors of poor prognosis of prostate cancer. The measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used for comparison between groups; Chi-square test was used to compare the count data between groups. Pearson method was used to analyze the correlation between ABCC4 mRNA and miR-125b-5p levels in prostate cancer. Kaplan-Meier method was used to analyze the relationship between the expression levels of ABCC4 and miR-125b-5p and prognosis, and Log-rank test was used to compare the survival rates. Univariate and multivariate COX regression analysis was used to evaluate the influencing factors of poor prognosis of prostate cancer. Results:The results of RT-qPCR showed that the expression level of ABCC4 mRNA in prostate cancer group was higher than that in control group ( P<0.05), and the expression level of miR-125b-5p was lower than that in control group ( P<0.05). Immunohistochemistry showed that the positive rate of ABCC4 in prostate cancer tissues was higher than that in adjacent tissues ( P<0.05). Pearson correlation analysis showed that the expression level of ABCC4 mRNA was negatively correlated with miR-125b-5p ( r=-0.687, P<0.05). The expression level of ABCC4 and miR-125b-5p in patients with prostate cancer was related to tumor stage, serum prostate-specific antigen, Gleason score and tumor metastasis ( P<0.05). Kaplan-Meier analysis showed that the 3-year cumulative survival rate of ABCC4-positive patients was lower than that of negative patients ( P<0.05), and the 3-year cumulative survival rate of patients with high-expression of miR-125b-5p was higher than that of patients with low-expression ( P<0.05). Multivariate COX regression analysis showed that the low level of miR-125b-5p and the high level of ABC-C4 were the risk factors for the poor prognosis of prostate cancer ( HR=2.685, 3.461, P<0.05). Conclusion:The high-expression of ABCC4 and the low-expression of miR-125b-5p in prostate cancer tissues are related to many clinicopathological features and prognosis of prostate cancer, which are risk factors for poor prognosis of prostate cancer patients.
9.Study on anti-myocardial ischemia active components and mechanism of Xinkeshu tablets based on network pharmacology and zebrafish model
Lin-Hua HOU ; Hua-Zheng ZHANG ; Shuo GAO ; Yun ZHANG ; Qiu-Xia HE ; Ke-Chun LIU ; Chen SUN ; Jian-Heng LI ; Qing XIA
Chinese Pharmacological Bulletin 2024;40(5):964-974
Aim To study the active ingredients and mechanism of action of Xinkeshu tablets against myo-cardial ischemia by network pharmacology and ze-brafish model.Methods The anti-myocardial ische-mia activity of Xinkeshu tablets was evaluated by iso-prenaline hydrochloride(ISO)-induced zebrafish myo-cardial ischemia model and H2O2-induced H9c2 dam-age model.The active ingredients of Xinkeshu tablets were retrieved using databases such as TCMSP.The potential targets were predicted by PharmaMapper data-base.Myocardial ischemic disease targets were searched by OMIM database.The potential therapeutic targets of Xinkeshu tablets against myocardial ischemia were analyzed.GO and KEGG enrichment analysis were conducted on core targets.The active ingredients were verified by zebrafish and cell model.qRT-PCR was used to detect the expression of key targets.Re-sults Xinkeshu tablets could significantly alleviate ISO-induced pericardial edema and bradycardia.It al-so could increase sinus venous-bulb aortic(SV-BA)distance and improve the cell viability.The 30 poten-tial active ingredients of Xinkeshu tables mainly acted on 30 core targets,including ALB,AKT1 and MAPK1,to regulate 627 GO items,including protein phosphorylation,negative regulation of apoptosis and positive regulation of PI3K signal transduction.KEGG results showed that 117 signaling pathways,including PI3K/Akt,FOXO and Ras,exerted anti-myocardial ischemia effect.Salvianolic acid A,lithospermic acid,rosmarinic acid,salvianolic acid D,salvianolic acid B,ginsenoside Rg2,hyperoside,3'-methoxypuerarin,3'-hydroxypuerarin and ginsenoside Rg1 could alleviate ISO-induced zebrafish myocardial ischemia and im-prove the cell viability.Xinkeshu tablets could upregu-late the expression of genes such as ras and akt1,and downregulate the expression of genes such as mapk1 and mapk8.Conclusion The active ingredients,in-cluding salvianolic acid A in Xinkeshu tablets,exert anti-myocardial ischemia effects by targeting targets,such as AKT1,MAPK1,and regulating signaling path-ways,such as PI3K/Akt,MAPK and Ras.
10.Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract improves radiation-induced pulmonary fibrosis in rats by regulating NLRP3/caspase-1/GSDMD pyroptosis pathway
Chun-Zhen REN ; Jian-Fang YUAN ; Chun-Ling WANG ; Xiao-Dong ZHI ; Qi-Li ZHANG ; Qi-Lin CHEN ; Xin-Fang LYU ; Xiang GAO ; Xue WU ; Xin-Ke ZHAO ; Ying-Dong LI
Chinese Pharmacological Bulletin 2024;40(11):2124-2131
Aim To investigate the mechanism of py-roptosis mediated by the NLRP3/caspase-1/GSDMD signaling pathway and the intervention effect of Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract(RAS-RA)in radiation-induced pulmonary fi-brosis.Methods Fifty Wistar rats were randomly di-vided into five groups,with ten rats in each group.Ex-cept for the blank control group,all other groups of rats were anesthetized and received a single dose of 40 Gy X-ray local chest radiation to establish a radiation-in-duced pulmonary fibrosis rat model.After radiation,the rats in the RAS-RA intervention groups were orally administered doses of 0.12,0.24 and 0.48 g·kg-1 once a day for 30 days.The average weight and lung index of the rats were observed after 30 days of contin-uous administration.Hydroxyproline(HYP)content in lung tissue was determined by hydrolysis method.The levels of IL-18 and IL-1 β in serum were detected by ELISA.Lung tissue pathological changes were ob-served by HE and Masson staining.Ultrastructural changes in lung tissue were observed by transmission e-lectron microscopy.The expression levels of NLRP3/caspase-1/GSDMD pyroptosis pathway-related proteins and fibrosis-related proteins in lung tissue were detec-ted by Western blot.Results Compared with the blank group,the HYP content in lung tissue and the levels of IL-18 and IL-1 β in serum significantly in-creased in the model group(P<0.01).HE and Mas-son staining showed inflammatory cell infiltration and collagen fiber deposition.Transmission electron mi-croscopy revealed increased damaged mitochondria,disordered arrangement,irregular morphology,shallow matrix,outer membrane rupture,mostly fractured and shortened cristae,mild expansion,increased electron density of individual mitochondrial matrix,mild sparse structure of lamellar bodies,partial disorder,unclear organelles,and characteristic changes of pyroptosis.Western blot analysis showed increased expression of caspase-1,GSDMD,NLRP3,CoL-Ⅰ,α-SMA,and CoL-Ⅲ proteins(P<0.01).Compared with the model group,the RAS-RA intervention group showed signifi-cant improvement in body mass index and lung index of rats,decreased levels of IL-18 and IL-1 β inflammatory factors(P<0.01),improved mitochondrial structure,reduced degree of fibrosis,and decreased expression of caspase-1,GSDMD,NLRP3,COL-Ⅰ,COL-Ⅲ,and α-SMA proteins in lung tissue(P<0.01).Conclusion RAS-RA has an inhibitory effect on radiation-in-duced pulmonary fibrosis,and its mechanism may be related to the inhibition of pyroptosis through the regu-lation of the NLRP3/caspase-1/GSDMD signaling pathway.

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