1.Exploring Chemical Constituent Distribution in Blood/Brain(Hippocampus) and Emotional Regulatory Effect of Raw and Vinegar-processed Products of Citri Reticulatae Pericarpium Viride
Yi BAO ; Yonggui SONG ; Qianmin LI ; Zhifu AI ; Genhua ZHU ; Ming YANG ; Huanhua XU ; Qin ZHENG ; Yiting HUANG ; Zihan GAO ; Dan SU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):189-197
ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride(CRPV), and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts, as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards, databases, and relevant literature were utilized for compound annotation, with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups, including the blank group, model group, diazepam group(2.5 mg·kg-1), raw CRPV low/high dose groups(0.6, 1.2 g·kg-1), and vinegar-processed CRPV low/high dose groups(0.6, 1.2 g·kg-1), with 10 mice per group. Except for the blank group, all other groups underwent chronic restraint stress(2 h·d-1) for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling, with a total treatment duration of 10 d. Following model-based drug administration, mice underwent open-field, forced swimming, and elevated plus maze tests. After anesthesia with isoflurane, whole brains were collected from each group of mice, and hippocampi were dissected. Reactive oxygen species(ROS) level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei(NeuN) and peroxisome proliferator-activated receptor alpha(PPARα) expressions in hippocampal tissue. Then, pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders, exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV, with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds, including 20 flavonoids, 20 flavonoid glycosides, 3 triterpenes, 3 phenolic acids, 1 alkaloid, and 6 other compounds. Twenty-one components were detected in blood(15 methoxyflavones, 4 flavonoid glycosides, and 2 phenolic acids), with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues(all common to both forms). In regulating emotional disorders, Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology, particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS(P<0.05). ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing, but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway, thereby negatively regulating ROS generation in the hippocampus, reducing oxidative stress, and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards, pharmacodynamic material research, and active drug development of raw and vinegar-processed CRPV.
2.Clinical Efficacy of Qi-regulating and Phlegm-removing Method(Liu Junzitang Combined with Linggang Wuwei Jiangxintang) in Treating AECOPD with Increased EOS
Renjie HUANG ; Wangqin YU ; Wuyinuo TANG ; Hong SONG ; Lyuyuan HE ; Wenbo LIN ; Guanyi WU ; Hang HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):149-156
ObjectiveTo assess the efficacy and safety of the Qi-regulating and phlegm-removing method(Liu Junzitang Combined with Linggang Wuwei Jiangxintang) for treating acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with increased eosinophils (EOS). MethodsSixty-eight AECOPD patients with increased EOS who were hospitalized in the Department of Pulmonary Diseases of Jinhua Traditional Chinese Medicine Hospital from April 2023 to April 2024 were recruited and randomly assigned to an experimental group (EG) or a control group (CG). Both groups received conventional Western medicine, with the EG additionally receiving Liujunzitang and Linggan Wuwei Jiangxintang. The therapeutic efficacy indicators were measured after the treatment. The main therapeutic efficacy indicators included partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2). The secondary efficacy indicators included the TCM symptom scores, the COPD Assessment Test (CAT) score, the Modified Medical Research Council (mMRC) Dyspnea Scale score, and the length of hospital stay. The indicators were measured at baseline and on days 3 and 7 of intervention. The safety was evaluated based on the adverse events. ResultsBaseline characteristics were not statistically different between the two groups. Compared with CG, EG showed no significant difference in PaO2 (P=0.773), PaCO2 (P=0.632) and or CAT score (P=0.336) at on day 3 but better PaO2 (P=0.004), PaCO2 (P=0.008), and CAT score (P=0.013) were significantly better at on day 7. Compared with CGAfter treatment, EG had lower TCM syndrome scores of than CG EG on day 3 (P=0.005) and day 7 were significantly decreased (P0.001). There was no significant difference in mMRC score between the two groups on day 3 (P=0.514) and day 7 (P=0.176) as wasor the length of hospital stay (P=0.915). The generalized linear mixed model (GLMM) showed that compared with CG, EG had significant improvements over time in PaO2, PaCO2, TCM syndrome symptom scores, CAT score, and mMRC score. ConclusionRegulating qi Qi and removing phlegm combined with conventional Western medicine can significantly alleviateimprove the clinical symptoms and improve the lung function of AECOPD patients with increased EOS increased AECOPDwhich has and demonstrates good safety.
3.Clinical Efficacy of Qi-regulating and Phlegm-removing Method(Liu Junzitang Combined with Linggang Wuwei Jiangxintang) in Treating AECOPD with Increased EOS
Renjie HUANG ; Wangqin YU ; Wuyinuo TANG ; Hong SONG ; Lyuyuan HE ; Wenbo LIN ; Guanyi WU ; Hang HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):149-156
ObjectiveTo assess the efficacy and safety of the Qi-regulating and phlegm-removing method(Liu Junzitang Combined with Linggang Wuwei Jiangxintang) for treating acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with increased eosinophils (EOS). MethodsSixty-eight AECOPD patients with increased EOS who were hospitalized in the Department of Pulmonary Diseases of Jinhua Traditional Chinese Medicine Hospital from April 2023 to April 2024 were recruited and randomly assigned to an experimental group (EG) or a control group (CG). Both groups received conventional Western medicine, with the EG additionally receiving Liujunzitang and Linggan Wuwei Jiangxintang. The therapeutic efficacy indicators were measured after the treatment. The main therapeutic efficacy indicators included partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2). The secondary efficacy indicators included the TCM symptom scores, the COPD Assessment Test (CAT) score, the Modified Medical Research Council (mMRC) Dyspnea Scale score, and the length of hospital stay. The indicators were measured at baseline and on days 3 and 7 of intervention. The safety was evaluated based on the adverse events. ResultsBaseline characteristics were not statistically different between the two groups. Compared with CG, EG showed no significant difference in PaO2 (P=0.773), PaCO2 (P=0.632) and or CAT score (P=0.336) at on day 3 but better PaO2 (P=0.004), PaCO2 (P=0.008), and CAT score (P=0.013) were significantly better at on day 7. Compared with CGAfter treatment, EG had lower TCM syndrome scores of than CG EG on day 3 (P=0.005) and day 7 were significantly decreased (P0.001). There was no significant difference in mMRC score between the two groups on day 3 (P=0.514) and day 7 (P=0.176) as wasor the length of hospital stay (P=0.915). The generalized linear mixed model (GLMM) showed that compared with CG, EG had significant improvements over time in PaO2, PaCO2, TCM syndrome symptom scores, CAT score, and mMRC score. ConclusionRegulating qi Qi and removing phlegm combined with conventional Western medicine can significantly alleviateimprove the clinical symptoms and improve the lung function of AECOPD patients with increased EOS increased AECOPDwhich has and demonstrates good safety.
4.Advances in the application of machine learning in the prediction of adverse drug reactions
Mengjia XU ; Lin SONG ; Tingting YANG ; Chenrong HUANG
China Pharmacy 2026;37(1):105-110
Adverse drug reactions (ADRs) refer to harmful or unintended reactions unrelated to the intended purpose of medication administration, which can lead to various issues such as accelerated disease progression and prolonged hospitalization. Traditional ADRs monitoring systems (such as spontaneous reporting systems) suffer from limitations such as low reporting rates and inconsistent data quality, which hinder the early prevention and control of ADRs. With the rapid development of information technology, machine learning has emerged as a powerful tool for management and decision-making of ADRs by leveraging its strengths in feature extraction and dynamic temporal pattern analysis. By reviewing relevant literature at home and abroad in recent years, this paper summarizes the progress in the application of machine learning for ADRs prediction. It is found that machine learning has gradually been applied to the early warning and risk prediction of ADRs in target organs such as the kidneys, liver, heart and bone marrow (such as acute kidney injury, drug-induced liver injury, and so on). Although machine learning demonstrates significant application potential in the field of ADRs prediction, it still faces limitations such as inadequate quality control of clinical data, lack of standardized criteria for model performance evaluation, insufficient model interpretability and difficulties in clinical translation. In the future, the development trend of machine learning in the field of ADRs prediction should follow a “technology-validation-integration” pathway to systematically promote the practical implementation of models.
5.Effect of finite element method in treatment of developmental dysplasia of the hip in children
Xiaojun SUN ; Huaming WANG ; Dehong ZHANG ; Xuewen SONG ; Jin HUANG ; Chen ZHANG ; Shengtai PEI
Chinese Journal of Tissue Engineering Research 2025;29(9):1897-1904
BACKGROUND:Developmental dysplasia of the hip often leads to limb deformities in children,and the research related to its diagnosis and treatment has been gradually clarified.Recently,the finite element method has been paid attention to by scholars in the research related to developmental dysplasia of the hip because of its advantages. OBJECTIVE:Through literature search and review of the relevant research progress of finite element method in children's developmental dysplasia of the hip and treatment,analyze and summarize its advantages and disadvantages,and explore the direction of further research in the future. METHODS:PubMed,SCI,CBM,and CNKI were searched for relevant articles published from January 2014 to November 2023 with the key words of"developmental dysplasia(dislocation)of the hip,dysplasia of the hip,finite element analysis(method),pavlik harness,fixation in herringbone position,biomechanics,pelvic osteotomies,pemberton,salter,dega,periacetabular osteotomy,children"in Chinese and English.A small number of long-term articles were included,and 62 articles were finally included for analysis through screening. RESULTS AND CONCLUSION:(1)The mechanical environment of hip joint in children with developmental dysplasia of the hip was abnormal.The pressure in acetabulum was uneven.The stress increased and concentrated;the joint contact area decreased,and the local stress concentrated in femoral neck.(2)In the Pavlik sling and herringbone fixation,the mechanical environment of the hip was improved;the concentrated high stress area disappeared and the joint contact area increased,but the excessive abduction angle led to the increase of stress in the acetabulum and the lateral femoral head.(3)After pelvic osteotomy,the stress environment of hip joint and sacroiliac joint was improved.There was no single hinge in the three kinds of osteotomy,and the stress load position was different according to the age of the children.(4)After peri-acetabular osteotomy,the joint contact pressure was close to normal,but it was difficult to recover in patients with non-spherical femoral head.(5)The postoperative X-ray film findings could not show that the joint contact mechanics was the best.(6)It is indicated that the information that cannot be measured in the body can be obtained by using the finite element method,which can be operated in a virtual environment without the limitation of time and ethics.It can directly see the stress change area of normal and developmental dysplasia of the hip,explain the effectiveness of treatment from the point of view of mechanics,establish a specific finite element model and tailor-made operation plan for patients who need osteotomy.There is no standard or unified standard for the finite element modeling of developmental dysplasia of the hip and the material characteristic parameters of children's hip joint.Due to the inherent limitations of finite element method,it is impossible to analyze the model that contains bone,cartilage,ligament,muscle and other elements at the same time.The operation of finite element analysis is difficult,although it has advantages,it is not universal,and the current research sample size is small,which needs to be further expanded and verified.
6.Inhibitory effect of hydroxy safflower yellow A on neuronal pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation treatment
Zeqian WANG ; Yanzhe DUAN ; Yige WU ; Dong MA ; Jianjun HUANG ; Yuqing YAN ; Lijuan SONG
Chinese Journal of Tissue Engineering Research 2025;29(19):4044-4051
BACKGROUND:Hydroxy safflower yellow A has anti-ischemia,anti-oxidation,anti-thrombotic and anti-inflammatory effects.Whether it affects neuronal pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation is still unclear. OBJECTIVE:To investigate the protective effect of hydroxy safflower yellow A on neuronal pyroptosis and its mechanism. METHODS:HT22 cells in logarithmic growth phase were randomly divided into five groups:normal group,model group,hydroxy safflower yellow A group,colivelin group,and colivelin+hydroxy safflower yellow A group.HT22 cells were treated with glucose-oxygen deprivation/reglucose-reoxygenation to establish neuronal pyroptosis model,and then treated with STAT3 agonist Colivelin and hydroxy safflower yellow A.JC-1 probe was employed to assess changes in mitochondrial membrane potential.Reactive oxygen species kit was used to determine the content of reactive oxygen species in cells.GSDMD/TUNEL staining was conducted to observe cell pyroptosis.Immunofluorescence analysis was performed to detect STAT3 and GSDMD protein expression.RT-PCR was utilized for assessing mRNA expression levels of STAT3,NLRP3,and Caspase-1.Western blot assay was utilized to measure the protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β. RESULTS AND CONCLUSION:(1)Compared with the normal group,the number of pyroptotic cells increased in HT22 cells in the model group along with a significant increase in protein expression levels of p-STAT3,NLRP3,Cleaved-caspase-1,GSDMD,and interleukin-1β.Compared with the model group,the number of pyroptotic cells reduced,and the expression of pyroptosis-related proteins significantly decreased in the hydroxy safflower yellow A group.(2)In comparison with the model group,pyroptosis worsened in the colivelin group where mitochondrial membrane potential decreased along with elevated reactive oxygen species content and increased mRNA expression levels of STAT3,NLRP3,and Caspase-1,as well as increased protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β.Compared with the Colivelin group,above indexes were improved in the colivelin+hydroxy safflower yellow A group.These results suggest that hydroxy safflower yellow A plays a neuroprotective role through STAT3 signaling pathway to inhibit HT22 pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation treatment.
7.Differentiation and Treatment of Lipid Turbidity Disease Based on Theory of "Spleen Ascending and Stomach Descending"
Yun HUANG ; Wenyu ZHU ; Wei SONG ; Xiaobo ZHANG ; Xin ZHOU ; Lele YANG ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):244-252
Lipid turbidity disease is a metabolic disease featuring lipid metabolism disorders caused by many factors such as social environment, diet, and lifestyle, which is closely related to many diseases in modern medicine, such as hyperlipidemia, obesity, fatty liver, atherosclerosis, metabolic syndrome, and cardiovascular and cerebrovascular diseases, with a wide range of influence and far-reaching harm. According to the Huangdi Neijing, lipid turbidity disease reflects the pathological change of the body's physiologic grease. Grease is the thick part of body fluids, which has the function of nourishing, and it is the initial state and source of important substances in the human body such as brain, marrow, essence, and blood. Once the grease of the human body is abnormal, it can lead to lipid turbidity disease. The Huangdi Neijing also points out the physiological relationship between the transportation and transformation of body fluids and the rise and fall of the spleen and stomach, which can deduce the pathological relationship between the occurrence of lipid turbidity disease and the abnormal rise and fall of the spleen and stomach functions. Lipid turbidity disease is caused by overconsumption of fatty and sweet foods or insufficient spleen and stomach endowments, leading to disorders of the function of promoting clear and reducing turbidity in the spleen and stomach. This leads to the transformation of thick grease in body fluids into lipid turbidity, which accumulates in the body's meridians, blood vessels, skin pores, and organs, forming various forms of metabolic diseases. The research team believed that the pathological basis of lipid turbidity disease was the abnormal rise and fall of the spleen and stomach and the obstruction of the transfer of grease. According to the different locations where lipid turbidity stays, it was divided into four common pathogenesis types: ''inability to distinguish between the clear and turbid, turbid stagnation in the Ying blood'', ''spleen not rising clear, turbid accumulation in the vessels'', ''spleen dysfunction, lipid retention in the pores'', ''spleen failure to transportation and transformation, and grease accumulation in the liver''. According to the pathogenesis, it could be divided into four common syndromes, namely, turbid stagnation in the Ying blood, turbid accumulation in the vessels, lipid retention in the pores, and grease accumulation in the liver, and the corresponding prescriptions were given for syndrome differentiation and treatment, so as to guide clinical differentiation and treatment of the lipid turbidity disease.
8.Treatment Effect on Structure and Function of Submandibular Gland in Sjögren's Syndrome Model Mice by Artemisinin
Ziwei HUANG ; Qian HE ; Jiahe LIAO ; Xinbo YU ; Jing LUO ; Weijiang SONG ; Qingwen TAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):158-165
ObjectiveTo investigate the effects of artemisinin (ART) on histopathological damage and salivary secretion in the submandibular gland (SMG) of mice with Sjögren's syndrome (SS) model,and on the expression of aquaporin 5 (AQP5) in SMG cells. MethodsThe NOD/Ltj mice were used as a model of SS and randomly divided into the SS model group,the ART group,and the hydroxychloroquine sulfate (HCQ) group,with six mice per group. Another 6 female BALB/c mice at the same week were selected as the control group. Mice in the ART group was fed with the ART solution daily in the dosage of 50 mg·kg-1,and mice in the HCQ group was given with the HCQ solution (1 300 mg·kg-1). Mice in the SS model and control groups were given saline daily. The treatment lasted for 8 weeks. The 24-hour average water intake,salivary flow rate,SMG pathology scores of mice in each group were measured,as well as the expression levels of AQP5 protein and gene in the SMG tissues. ResultsCompared with the control group,the 24-hour average water intake of mice in the model group was significantly increased (P<0.01),and the saliva flow rate was significantly decreased (P<0.01). Compared to the SS model group,the 24-hour average water intake of mice in the ART and HCQ groups was significantly reduced (P<0.01),and the salivary flow rate was significantly increased in the ART group(P<0.01),comparisons between groups showed that the ART was superior to the HCQ in reducing water intake and improving saliva flow rate in SS model mice (P<0.05). The HE staining results showed that,compared with the normal group,the number of lymphocyte infiltration foci in SMG tissue in the model group increased,and the pathological score increased (P<0.01). Compared to the SS model group,after the intervention of the ART and HCQ,the number of lymphocytic infiltration foci in the SMG tissue decreased,the area of the lymphocytic infiltration foci was reduced,and the pathology score of the SMG tissues was lowered in the ART group(P<0.01). However,there was no difference in pathological scores between the ART and HCQ groups . The results of IHC,Western blot,and Real-time PCR showed that,compared with the normal group,the expression levels of AQP5 protein and gene in SMG tissue in the model group significantly decreased (P<0.05). Comparing with the SS model group,the ART and HCQ groups could significantly up-regulated the expression levels of AQP5 protein and mRNA in the SMG tissue,and the treatment effect was better than that of HCQ. ConclusionART was able to ameliorate SMG structural damage and salivary secretion function in SS model mice,and its mechanism of action may be related to the up-regulation of AQP5 protein and gene expression levels in SMG cells.
9.Applications of Vaterite in Drug Loading and Controlled Release
Xiao-Hui SONG ; Ming-Yu PAN ; Jian-Feng XU ; Zheng-Yu HUANG ; Qing PAN ; Qing-Ning LI
Progress in Biochemistry and Biophysics 2025;52(1):162-181
Currently, the drug delivery system (DDS) based on nanomaterials has become a hot interdisciplinary research topic. One of the core issues is drug loading and controlled release, in which the key lever is carriers. Vaterite, as an inorganic porous nano-material, is one metastable structure of calcium carbonate, full of micro or nano porous. Recently, vaterite has attracted more and more attention, due to its significant advantages, such as rich resources, easy preparations, low cost, simple loading procedures, good biocompatibility and many other good points. Vaterite, gained from suitable preparation strategies, can not only possess the good drug carrying performance, like high loading capacity and stable loading efficiency, but also improve the drug release ability, showing the better drug delivery effects, such as targeting release, pH sensitive release, photothermal controlled release, magnetic assistant release, optothermal controlled release. At the same time, the vaterite carriers, with good safety itself, can protect proteins, enzymes, or other drugs from degradation or inactivation, help imaging or visualization with loading fluorescent drugs in vitro and in vivo, and play synergistic effects with other therapy approaches, like photodynamic therapy, sonodynamic therapy, and thermochemotherapy. Latterly, some renewed reports in drug loading and controlled release have led to their widespread applications in diverse fields, from cell level to clinical studies. This review introduces the basic characteristics of vaterite and briefly summarizes its research history, followed by synthesis strategies. We subsequently highlight recent developments in drug loading and controlled release, with an emphasis on the advantages, quantity capacity, and comparations. Furthermore, new opportunities for using vaterite in cell level and animal level are detailed. Finally, the possible problems and development trends are discussed.
10.Clinical and contrast-enhanced ultrasonographic characteristics of peripheral lung masses in patients infected with human immunodeficiency virus
Lei ZHAO ; Jingjing HUANG ; Xin MA ; Xia SHI ; Dou WU ; Zhi ZHANG ; Fengxiang SONG ; Jianjian LIU
Chinese Journal of Clinical Medicine 2025;32(2):276-282
Objective To evaluate the clinical characteristics of human immunodeficiency virus (HIV) infected patients with peripheral lung masses (PLMs), and to assess the diagnostic utility of contrast-enhanced ultrasound (CEUS) in differentiating benign and malignant PLMs. Methods A retrospective analysis was performed on the clinical data of 69 patients with PLM treated in Shanghai Public Health Clinical Center from January 2020 to December 2023. All patients underwent percutaneous biopsy, and were categorized into benign group (n=36) and malignant group (n=33). 25 patients were HIV-positive and 44 patients were HIV-negative. The clinical features and CEUS parameters in patients were compared across these groups. Results Patients with malignant masses were significantly older than those with benign masses (P<0.05). In the malignant group, HIV-negative patients exhibited significantly larger tumor diameters compared to HIV-positive patients (P<0.05); in the HIV-positive patients, no significant difference in tumor size was observed between benign and malignant masses. 19 patients underwent CEUS. 10 malignant masses, irrespective of HIV status (10 positive and 9 negative), commonly presented with indistinct margins, delayed enhancement, heterogeneous perfusion, and delayed peak enhancement on CEUS. 9 benign masses showed earlier peak enhancement compared to 10 malignant masses (P<0.05); no significant differences were observed in the initiation and washout time of enhancement between benign and malignant masses. In HIV-positive patients, 5 benign masses frequently demonstrated discrepancies between CEUS findings and pathological results. Conclusions The clinical and CEUS characteristics were different between benign and malignant PLMs. However, CEUS shows limited accuracy in distinguishing benign and malignant PLMs, underscoring the need for pathological confirmation.

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