1.Effect and mechanism of Prunus mume against hepatic fibrosis
Feng HAO ; Ji LI ; Jing DU ; Yuchen OUYANG ; Yichun CUI ; Shuang WEI
China Pharmacy 2025;36(2):172-178
OBJECTIVE To explore the effect and mechanism of Prunus mume against hepatic fibrosis (HF). METHODS Male SD rats were randomly divided into normal control group (n=10) and modeling group (n=50). The modeling group established HF model using carbon tetrachloride. The modeled rats were randomly divided into model group (normal saline), positive control group [colchicine, 0.09 mg/(kg·d)], and P. mume low-dose, medium-dose and high-dose groups [1.35, 2.70, 5.40 g/(kg·d)], with 9 rats in each group. They were given the corresponding drug/normal saline intragastrically, once a day, for 8 consecutive weeks. After the last medication, the liver index was calculated, while liver function indexes, liver fiber indexes, oxidative stress indicators and inflammatory factors of rats were measured. HE staining was used to observe the pathological changes in liver tissue of rats; Masson staining was used to observe the degree of HF in liver tissue of rats; transmission electron microscopy was used to observe the ultrastructure of liver tissue in rats; TUNEL staining was used to detect liver cell apoptosis in each group of rats. Western blot method was used to detect the protein expressions of transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) in liver tissue of rats. RESULTS Compared with normal control group, the levels of alanine transaminase, alkaline phosphatase, aspartate transaminase, total bilirubin, malondialdehyde, procollagen type Ⅲ protein, Ⅳ-type pre collagenase, laminin, hyaluronic acid, interleukin-6, tumor necrosis factor-α, as well as the protein expressions of TGF-β1 and PDGF in model group were increased significantly, while the levels of superoxide dismutase and glutathione peroxidase were significantly reduced (P<0.01); the HE, Masson staining and transmission electron microscopy observation results showed obvious HF characteristics in rats of model group. Compared with model group, varying degrees of improvement in above indexes were observed in P. mume groups, and the above 2021BSZR011) indicators of rats in P. mume medium-dose and high-dose groups were reversed significantly (P<0.05 or P<0.01). CONCLUSIONS P. mume has an anti-HF effect, which may be achieved through mechanisms such as antioxidation, anti-inflammation, reduction of collagen production, inhibition of PDGF protein expression, and regulation of TGF- β1 signaling pathway.
2.Effect and mechanism of Prunus mume against hepatic fibrosis
Feng HAO ; Ji LI ; Jing DU ; Yuchen OUYANG ; Yichun CUI ; Shuang WEI
China Pharmacy 2025;36(2):172-178
OBJECTIVE To explore the effect and mechanism of Prunus mume against hepatic fibrosis (HF). METHODS Male SD rats were randomly divided into normal control group (n=10) and modeling group (n=50). The modeling group established HF model using carbon tetrachloride. The modeled rats were randomly divided into model group (normal saline), positive control group [colchicine, 0.09 mg/(kg·d)], and P. mume low-dose, medium-dose and high-dose groups [1.35, 2.70, 5.40 g/(kg·d)], with 9 rats in each group. They were given the corresponding drug/normal saline intragastrically, once a day, for 8 consecutive weeks. After the last medication, the liver index was calculated, while liver function indexes, liver fiber indexes, oxidative stress indicators and inflammatory factors of rats were measured. HE staining was used to observe the pathological changes in liver tissue of rats; Masson staining was used to observe the degree of HF in liver tissue of rats; transmission electron microscopy was used to observe the ultrastructure of liver tissue in rats; TUNEL staining was used to detect liver cell apoptosis in each group of rats. Western blot method was used to detect the protein expressions of transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) in liver tissue of rats. RESULTS Compared with normal control group, the levels of alanine transaminase, alkaline phosphatase, aspartate transaminase, total bilirubin, malondialdehyde, procollagen type Ⅲ protein, Ⅳ-type pre collagenase, laminin, hyaluronic acid, interleukin-6, tumor necrosis factor-α, as well as the protein expressions of TGF-β1 and PDGF in model group were increased significantly, while the levels of superoxide dismutase and glutathione peroxidase were significantly reduced (P<0.01); the HE, Masson staining and transmission electron microscopy observation results showed obvious HF characteristics in rats of model group. Compared with model group, varying degrees of improvement in above indexes were observed in P. mume groups, and the above 2021BSZR011) indicators of rats in P. mume medium-dose and high-dose groups were reversed significantly (P<0.05 or P<0.01). CONCLUSIONS P. mume has an anti-HF effect, which may be achieved through mechanisms such as antioxidation, anti-inflammation, reduction of collagen production, inhibition of PDGF protein expression, and regulation of TGF- β1 signaling pathway.
3.Mechanism of Ferroptosis in Cerebral Ischemia-reperfusion and Interventional Mechanism of Huoxue Huayu Jiedu Prescription Based on "Blood Stasis and Toxin" Pathogenesis
Jiayue HAN ; Danyi PAN ; Jiaxuan XIAO ; Yuchen LIU ; Jiyong LIU ; Yidi ZENG ; Jinxia LI ; Caixing ZHENG ; Hua LI ; Wanghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):51-60
ObjectiveTo explore the material basis of the "interaction of blood stasis and toxin" mechanism in cerebral ischemia-reperfusion injury, as well as the protective role of Huoxue Huayu Jiedu prescription (HXHYJDF) against ferroptosis. MethodsSixty SPF-grade male SD rats were randomly divided into six groups: sham group, model group, deferoxamine (DFO) group (100 mg·kg-1), low-dose HXHYJDF group (4.52 g·kg-1), medium-dose HXHYJDF group (9.04 g·kg-1), and high-dose HXHYJDF group (18.07 g·kg-1), with ten rats in each group. Except for the sham group, the other groups were used to replicate the model of focal cerebral ischemia-reperfusion in the middle cerebral artery of rats by the reforming Longa method. Neurological function was assessed at 1st, 3rd, 5th, and 7th days post-reperfusion using the modified neurological severity scores (m-NSS). Brain tissue pathology and the morphology of mitochondria were observed using hematoxylin-eosin (HE) staining and transmission electron microscopy. The contents of malondialdehyde (MDA), glutathione (GSH), divalent iron ions (Fe2+), and reactive oxygen species (ROS) in the ischemic cerebral tissue were detected using enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry and Western blot (WB) were used to detect the expression of iron death marker proteins glutathione peroxidase 4 (GPX4), ferroportin-1 (FPN1), transferrin receptor protein 1 (TfR1), and ferritin mitochondrial (FtMt) in brain tissue. ResultsCompared with the sham group, the mNSS score of the model group was significantly increased (P<0.01). HE staining showed that the number of neurons in the cortex of brain tissue was seriously reduced, and the intercellular space was widened. The nucleus was fragmented, and the cytoplasm was vacuolated. The results of transmission electron microscopy showed that the mitochondria in the cytoplasm contracted and rounded, and the mitochondrial cristae decreased. The matrix was lost and vacuolated, and the density of the mitochondrial bilayer membrane increased. The results of ELISA showed that the content of GSH decreased significantly (P<0.01), and the contents of MDA, Fe2+, and ROS increased significantly (P<0.01). The results of immunohistochemistry and WB showed that the expression of GPX4 and FPN1 proteins was significantly decreased (P<0.01), and the expression of FtMt and TfR1 proteins was significantly increased (P<0.01). Compared with those of the model group, the m-NSS scores of the high-dose and medium-dose HXHYJDF groups began to decrease on the 3rd and 5th days, respectively (P<0.05, P<0.01). The results of HE and transmission electron microscopy showed that the intervention of HXHYJDF improved the pathological changes of neurons and mitochondria. The results of ELISA showed that the content of GSH in the medium-dose and high-dose HXHYJDF groups increased significantly (P<0.01), and the contents of MDA, Fe2+, and ROS decreased significantly (P<0.05, P<0.01). The content of GSH in the low-dose HXHYJDF group increased significantly (P<0.01), and the contents of MDA and ROS decreased significantly (P<0.01). The results of immunohistochemistry showed that the expression of GPX4 and FPN1 in the high-dose HXHYJDF group increased significantly (P<0.01), and the expression of FtMt and TfR1 decreased significantly (P<0.01). The expression of GPX4 and FPN1 in the medium-dose HXHYJDF group increased significantly (P<0.05), and the expression of TfR1 decreased significantly (P<0.01). WB results showed that the expression levels of FPN1 and GPX4 proteins in the high-dose, medium-dose, and low-dose HXHYJDF groups were significantly up-regulated (P<0.01), and the expression levels of FtMt and TfR1 proteins were significantly down-regulated (P<0.01). ConclusionHXHYJDF can significantly improve neurological dysfunction symptoms in rats with cerebral ischemia-reperfusion injury, improve the pathological morphology of the infarcted brain tissue, and protect the brain tissue of rats with cerebral ischemia-reperfusion injury to a certain extent. Neuronal ferroptosis is involved in cerebral ischemia-reperfusion injury, with increased levels of MDA, Fe2+, ROS, and TfR1 and decreased levels of FtMt, FPN1, GPX4, and GSH potentially constituting the material basis of the interaction of blood stasis and toxin mechanism in cerebral ischemia-reperfusion injury. HXHYJDF may exert brain-protective effects by regulating iron metabolism-related proteins, promoting the discharge of free iron, reducing brain iron deposition, alleviating oxidative stress, and inhibiting ferroptosis.
4.Association of monocyte/high-density lipoprotein cholesterol ratio with periodontitis: a cross-sectional study based on the NHANES database
HU Zhiqiang ; ZHANG Qi ; LI Xinpeng ; CUI Yuchen ; YUAN Jiamin ; ZHU Xianchun
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(3):212-220
Objective:
To investigate the association between monocyte to high-density lipoprotein cholesterol ratio (MHR) and periodontitis and to provide new epidemiologic evidence on the factors affecting periodontitis.
Methods:
Data on MHR, periodontitis, and other covariates were selected from the NHANES(National Health and Nutrition Examination) database for 3 cycles of subjects in 2009-2010, 2011-2012, and 2013-2014, and a total of 8 456 study subjects were included. The study participants were grouped according to the prevalence of periodontitis (presence or absence), and three regression models (unadjusted covariates, partially adjusted covariates, and fully adjusted covariates) were constructed to analyze the relationship between MHR and periodontitis by using a weighted logistic regression method with stepwise adjustment for confounders. MHR was divided into four groups from Q1 to Q4 according to quartiles from small to large for weighted trend analysis, and the nonlinear relationship between MHR (continuous) and periodontitis was analyzed using a restricted cubic spline with subgroup analysis and sensitivity analysis.
Results:
All three logistic regression models showed a positive association between MHR and periodontitis (OR = 2.92, 95%CI: 2.14-3.99, P<0.001 (not adjusted); OR = 1.97, 95%CI: 1.39-2.78, P<0.001 (partially adjusted); OR = 1.62, 95%CI: 1.10-2.39, P = 0.017 (fully adjusted)). Trend analysis showed a significantly higher risk of developing periodontitis in the Q4 group compared with the Q1 group in both single (OR = 1.92, 95% CI: 1.58-2.33, P<0.001) and multifactorial analyses (OR = 1.30, 95% CI: 1.03-1.64, P = 0.029). Restricted cubic spline results did not support a nonlinear relationship between MHR and periodontitis (P for nonlinear>0.05), subgroup analysis showed no significant interaction between the covariates and MHR (P>0.05), and sensitivity analysis also showed a positive correlation between MHR and periodontitis (OR = 1.67, 95%CI: 1.31-2.14, P<0.001).
Conclusion
MHR is positively associated with the risk of developing periodontitis.
5.Research progress on impact of micro/nanoplastics exposure on reproductive health
Yan HUANG ; Yuanyuan HUANG ; Yanxi ZHUO ; Yiqin LIN ; Qipeng LI ; Xiaofeng ZHENG ; Wenxiang WANG ; Yuchen LI ; Wenya SHAO ; Henggui CHEN
Journal of Environmental and Occupational Medicine 2025;42(4):490-496
Micro/nanoplastics (MNPs), recognized as emerging environmental pollutants, are widely distributed in natural environments. Due to their small particle size and significant migratory capacity, MNPs can infiltrate diverse environmental matrices, then invade and accumulate in the organism via the skin, respiration, and digestion. Recently, concerns have grown over the detrimental effects and potential toxicity of MNPs on reproductive health. This review summarized published epidemiological and toxicological studies related to MNPs exposure and their effects on reproductive health. Firstly, this review critically examined the current landscape of epidemiological evidence and found that MNPs (e.g., polystyrene, polypropylene, polyvinyl chloride, polyethylene, etc.) are present in various biological specimens from both males and females, and their presence may be associated with an increased risk of reproductive disorders. Secondly, extensive toxicological studies revealed that MNPs exposure induces reproductive health damage through mechanisms such as disrupting the microstructure of reproductive organs and altering molecular-level expressions. Oxidative stress, inflammatory responses, and apoptosis are identified as potential links between MNPs exposure and reproductive damage. Finally, this review addressed the prevalent shortcomings in existing studies and proposed future directions to tackle the challenges posed by MNPs-induced reproductive harm. These insights aim to inform strategies for safeguarding public reproductive health and ecological security, providing a scientific foundation for mitigating risks associated with MNPs pollution.
6.Research progress of internal limiting membrane peeling in the treatment of rhegmatogenous retinal detachment
Yuchen ZHANG ; Kejun LI ; Zhiyang JIA
International Eye Science 2025;25(6):933-937
Rhegmatogenous retinal detachment(RRD)is a vision-threatening ocular emergency with the potential risk of blindness. Pars plana vitrectomy(PPV)is the treatment of choice for RRD, especially for complex retinal detachments such as posterior pole retinal tears, grade B or higher proliferative vitreoretinopathy, and concomitant choroidal detachment. Although most patients achieve good anatomical restoration after surgery, some patients may still experience postoperative symptoms such as distorted vision, abnormal color perception, and lack of improvement in corrected visual acuity. Epiretinal membranes(ERM), as one of the most common complications after RRD, occur in 4% to 13% of cases, which not only affect the recovery of patients' postoperative vision, but also are frequently associated with visual distortion. In severe cases, a second surgical intervention may be required. In recent years, internal limiting membrane peeling(ILMP)has been introduced as an adjunctive procedure in the treatment of RRD, to facilitate retinal reorientation, reduce postoperative complications, and improve patients' postoperative visual quality and quality of life. However, previous studies on the effects of combined intraoperative ILMP on retinal anatomy and visual function recovery are limited. Therefore, this article reviews the mechanism, clinical application, challenges and research progress of ILMP in RRD, providing a reference for surgical decision making, disease assessment, and prognosis evaluation.
7.Relationship between physical activity and sarcopenia among elderly people in ten provinces (autonomous regions) of China, 2022—2023
Yuchen WANG ; Huijun WANG ; Yuna HE ; Chang SU ; Jiguo ZHANG ; Wenwen DU ; Xiaofang JIA ; Feifei HUANG ; Li LI ; Jing BAI ; Yanli WEI ; Xiaofan ZHANG ; Fangxu GUAN ; Yifei OUYANG
Journal of Environmental and Occupational Medicine 2025;42(6):661-667
Background The decline of physical activity in the elderly due to aging may increase the risk of sarcopenia. Currently, there is a lack of evidence from large natural populations on the relationship between PA and sarcopenia. Objective To explore the relationship between PA and sarcopenia in the elderly aged 60 years and above in 10 provinces (autonomous regions) of China. Methods Data were retrieved from the 2022—2023 round of the China Development and Nutrition Health Impact Cohort. Personal basic information and PA data were collected by questionnaire survey. Skeletal muscle mass was measured by bio-electrical impedance analysis, muscle strength was measured using a grip dynamometer, and physical performance was reflected by 6-meter walk speed. The Asian Working Group for Sarcopenia (AWGS) 2019 criteria were used to diagnose sarcopenia. Light physical activity (LPA) duration, moderate-to-vigorous physical activity (MVPA) duration, and total physical activity volume were calculated. A total of
8.Correlation Between Cardiovascular Events and Traditional Chinese Medicine Syndrome in Patients with Rheumatoid Arthritis:A Cross-Sectional Study
Fuyuan ZHANG ; Quan JIANG ; Jun LI ; Yuchen YANG ; Xieli MA ; Tian CHANG ; Congmin XIA ; Jian WANG ; Xun GONG
Journal of Traditional Chinese Medicine 2025;66(15):1572-1578
ObjectiveTo explore the correlation between the occurrence of cardiovascular events in rheumatoid arthritis(RA) and traditional Chinese medicine(TCM) syndrome. MethodsThe cross-sectional study selected 6713 RA patients from 122 centres nationwide, in which general information such as name, gender, age, height, body weight, and course of disease were collected by completing a questionnaire; patients were classified into eight types of syndrome according to the information of their four examinations,i.e. wind-dampness obstruction syndrome, cold-dampness obstruction syndrome, dampness-heat obstruction syndrome, phlegm-stasis obstruction syndrome, stasis-blood obstructing collateral syndrome, qi-blood deficiency syndrome, liver-kidney insufficiency syndrome, and qi-yin deficiency syndrome. According to the occurrence of cardiovascular events, they were divided into the occurrence group and the non-occurrence group, and the condition assessment data and laboratory examination indexes were recorded. The test of difference between groups was used to analyse the possible risk factors for the occurrence of RA cardiovascular events, and binary logistic regression was used to analyse the correlation between TCM syndromes and RA cardiovascular events. ResultsA total of 6713 RA patients were included, including 256 cases in occurrence group and 6457 in non-occurrence group. There was no statistically significant difference between groups in terms of height, gender, insomnia, appetite, white blood cell(WBC), hemoglobin(HGB), platelets(PLT), rheumatoid factor(RF), anti-cyclic peptide containing citrulline(CCP), alanine aminotransferase(ALT), aspartate aminotransferase(AST), γ-glutamyl transpeptidase(GGT), urea creatinine(CREA), and glucose(GLU)(P>0.05). The TCM syndromes between groups showed significant statistic differences(P<0.05). Patients in occurrence group had longer disease duration, heavier body weight, and older age; more severe conditions such as disease activity(DAS-28), number of painful joints(TJC), number of swollen joints(SJC), health questionnaire scores(HAQ), visual analog scores(VAS), restlessness, and fatigue; higher blood sedimentation rate(ESR), low-density lipoprotein(LDL-C), triglyceride(TG), total cholesterol(TC), D-Dimer, and lower high-density lipoprotein(HDL-C)(P<0.05). The distribution of syndrome types showed that dampness-heat obstruction syndrome accounted for the largest proportion of patients in both groups and was higher in RA cardiovascular events. Logistic regression analysis showed that the occurrence of RA cardiovascular events was strongly associated with dampness-heat obstruction syndrome[OR=5.937, 95%CI (4.434, 7.949), P<0.001]. ConclusionThe occurrence of RA cardiovascular events were associated with TCM syndromes, and the probability of cardiovascular events in the RA patients with dampness-heat obstruction syndrome was 5.937 times higher than patients with other TCM syndromes.
9.A 30-year review and outlook on esophageal acid and pressure measurement
Yong JIANG ; Wentao FANG ; Zhigang LI ; Wenhu CHEN ; Wenhu PAN ; Yanfang ZHENG ; Hong ZHANG ; Yuchen SU ; Jie ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(06):766-770
The Department of Thoracic Surgery of Shanghai Chest Hospital has performed esophageal function testing for over 30 years, being the only department of its kind in China with this capability. The pressure testing and 24-hour pH/impedance monitoring of the esophagus is of great help to assist in the diagnosis and treatment of benign and malignant esophageal diseases related to it. Thanks to the esophageal function test, in addition to the routine various endoscopic anti-reflux procedures, our hospital has taken the lead in China in recent years to carry out a series of clinical and research work for benign esophageal diseases, such as the development of magnetic ring, double nedoscopic combination and new anti-reflux endoscopic techniques. In recent years, we have carried out high-resolution esophageal manometry and 24-hour pH/impedance monitoring for patients with interstitial pneumonia and pulmonary fibrosis suspected to be caused by gastroesophageal acid reflux. We can better assess the correlation between gastroesophageal reflux and pulmonary fibrosis, and to provide the different clinical treatments and even surgical interventions. The Bravo capsule is used more often in the United States, and it has obvious advantages over traditional approach for acid measurement. We strongly call for the collaboration between industry and academic institutions in this field, and the development of our own related products with independent intellectual property rights.
10.A Randomized,Double-blind,Multi-center Clinical Trial of Tengfu Jiangya Tablets Combined with Valsartan/Amlodipine in Treatment of Grade 2 Hypertension with Hyperactivity of Liver Yang
Yuchen QI ; Yunlun LI ; Yujie WU ; Haiquan WANG ; Yu WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(9):83-92
ObjectiveTo observe the clinical efficacy and safety of Tengfu Jiangya tablets combined with valsartan/amlodipine in the treatment of grade 2 hypertension with liver Yang hyperactivity syndrome. MethodAccording to a randomized,double-blind,and placebo parallel control method,288 patients with grade 2 hypertension with liver Yang hyperactivity from 7 subcenters were included. They were randomly divided into an observation group (144 cases) and a control group (144 cases),and then treated with Tengfu Jiangya tablets combined with valsartan/amlodipine and placebo combined with valsartan/amlodipine,respectively. The efficacy was evaluated after four weeks of intervention. During the experiment,the safety indicators and adverse reaction events of the subjects were recorded for safety evaluation,and the efficacy indicators and TCM syndrome scores were recorded for effectiveness evaluation. Sensitivity analysis was also conducted on the statistical results of the main efficacy indicators such as blood pressure (BP) compliance rate to ensure the accuracy of the analysis results. 88 groups of blood samples from each of the treatment and control groups were included as test subjects. Fasting blood samples were collected from the patients in the clinical trial on the day before and after medication,and enzyme linked immunosorbent assay (ELISA) was performed on the treated serum. The levels of arachidonic acid (AA),thromboxane B2 (TXB2),and prostaglandin E2 (PGE2) in the serum of the patients before and after treatment were measured to explore the regulation of inflammatory factors in the body by Tengfu Jiangya tablets. ResultA total of 271 patients (133 in the observation group and 138 in the control group) completed the trial. There was no statistically significant difference before and after treatment in such safety indicators as the blood routine (white blood cells,red blood cells,and platelets),urine routine (urinary protein and urinary red blood cells),alanine aminotransferase,aspartate aminotransferase,creatinine,urea,and abnormal electrocardiogram,and no serious adverse reactions were observed. After four weeks,the systolic blood pressure (SBP) difference and diastolic blood pressure (DBP) difference of patients in the observation group were greater than those in the control group(P<0.01). According to the criteria for determining the antihypertensive effect,the overall response rate in the observation group[89.47%(119/133)] was higher than that in the control group[57.97%(80/138)] (Z=2.593,P<0.01). The SBP compliance rate was 61.65%(82/133) and 37.68%(52/138) in the observation group and control group, respectively. The DBP compliance rate in the observation group was 78.20%(104/133),while in the control group it was 55.07%(76/138). The overall BP compliance rate in the observation group was 48.12%(64/133),while in the control group it was 23.19%(32/138). The BP compliance rates in the observation group were all significantly higher than those in the control group(χ2=15.571,16.236,18.404,P<0.01). According to the criteria for evaluating the therapeutic effect of TCM syndrome integration,the overall response rate of the observation group[57.89%(77/133)] was higher than that of the control group[38.41%(53/133)] (Z=-3.172,P<0.01).Compared with those before treatment, the levels of serum AA and TXB2 in the two groups were significantly decreased after treatment (P<0.01), and the level of PGE2 in the observation group was significantly increased (P<0.01). Compared with those of the control group after treatment, the levels of AA and TXB2 in the observation group were significantly decreased, while the level of PGE2 was significantly increased (P<0.01). The results suggest that Tengfu Jiangya tablets can effectively reduce inflammatory factors,reduce the production of inflammatory mediators,and thus prevent the occurrence of inflammatory reactions in the treatment of patients with grade 2 hypertension. ConclusionTengfu Jiangya tablets can more effectively reduce patients' SBP and DBP,improve their BP compliance rates,and improve their TCM syndromes in the treatment of grade 2 hypertension with liver Yang hyperactivity. Its clinical application is safe. Tengfu Jiangya tablets has outstanding clinical efficacy and can be used as an effective intervention method for the treatment of grade 2 hypertension with liver Yang hyperactivity syndrome.


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