1.Mid-long term follow-up reports on head and neck rhabdomyosarcoma in children
Chao DUAN ; Sidou HE ; Shengcai WANG ; Mei JIN ; Wen ZHAO ; Xisi WANG ; Zhikai LIU ; Tong YU ; Lejian HE ; Xiaoman WANG ; Chunying CUI ; Xin NI ; Yan SU
Chinese Journal of Pediatrics 2025;63(1):62-69
Objective:To analyze the clinical characteristics of children with head and neck rhabdomyosarcoma (RMS) and to summarize the mid-long term efficacy of Beijing Children′s Hospital Rhabdomyosarcoma 2006 (BCH-RMS-2006) regimen and China Children′s Cancer Group Rhabdomyosarcoma 2016 (CCCG-RMS-2016) regimen.Methods:A retrospective cohort study. Clinical data of 137 children with newly diagnosed head and neck RMS at Beijing Children′s Hospital, Capital Medical University from March 2013 to December 2021 were collected. Clinical characteristic of patients at disease onset and the therapeutic effects of patients treated with the BCH-RMS-2006 and CCCG-RMS-2016 regimens were compared. The treatments and outcomes of patients with recurrence were also summarized. Survival analysis was performed by Kaplan-Meier method, and Log-Rank test was used for comparison of survival rates between groups.Results:Among 137 patients, there were 80 males (58.4%) and 57 females (41.6%), the age of disease onset was 59 (34, 97) months. The primary site in the orbital, non-orbital non-parameningeal, and parameningeal area were 10 (7.3%), 47 (34.3%), and 80 (58.4%), respectively. Of all patients, 32 cases (23.4%) were treated with the BCH-RMS-2006 regimen and 105 (76.6%) cases were treated with the CCCG-RMS-2016 regimen. The follow-up time for the whole patients was 46 (20, 72) months, and the 5-year progression free survival (PFS) and overall survival (OS) rates for the whole children were (60.4±4.4)% and (69.3±4.0)%, respectively. The 5-year OS rate was higher in the CCCG-RMS-2016 group than in BCH-RMS-2006 group ((73.0±4.5)% vs. (56.6±4.4)%, χ2=4.57, P=0.029). For the parameningeal group, the 5-year OS rate was higher in the CCCG-RMS-2016 group (61 cases) than in BCH-RMS-2006 group (19 cases) ((57.3±7.6)% vs. (32.7±11.8)%, χ2=4.64, P=0.031). For the group with meningeal invasion risk factors, the 5-year OS rate was higher in the CCCG-RMS-2016 group (54 cases) than in BCH-RMS-2006 group (15 cases) ((57.7±7.7)% vs. (30.0±12.3)%, χ2=4.76, P=0.029). Among the 10 cases of orbital RMS, there was no recurrence. In the non-orbital non-parameningeal RMS group (47 cases), there were 13 (27.6%) recurrences, after re-treatment, 7 cases survived. In the parameningeal RMS group (80 cases), there were 40 (50.0%) recurrences, with only 7 cases surviving after re-treatment. Conclusions:The overall prognosis for patients with orbital and non-orbital non-parameningeal RMS is good. However, children with parameningeal RMS have a high recurrence rate, and the effectiveness of re-treatment after recurrence is poor. Compared with the BCH-RMS-2006 regimen, the CCCG-RMS-2016 regimen can improve the treatment efficacy of RMS in the meningeal region.
2.Potential of new self-crosslinked hyaluronic acid gel on the recovery of endometrium after artificial abortion: a multicenter, prospective randomized controlled trial
Chunying LI ; Lirong TENG ; Qing LIN ; Liping ZHAO ; Yunxia ZHU ; Xin MI ; Zhenna WANG ; Xiaoye WANG ; Lisong ZHANG ; Dan HAN ; Lili MA ; Wenpei BAI ; Jianmei WANG ; Jun NI ; Huiping SHEN ; Qinfang CHEN ; Hongmei XU ; Chenchen REN ; Jing JIANG ; Guanyuan LIU ; Ping PENG ; Xinyan LIU
Chinese Journal of Obstetrics and Gynecology 2024;59(11):864-870
Objective:To evaluate the impact of self-crosslinked hyaluronic acid (SCH) gel on endometrium recovery after artificial abortion.Methods:A multicenter, prospective randomized controlled trial was conducted across 18 hospitals from December 2021 to February 2023, involving 382 women who underwent artificial abortion. Participants were randomly allocated to receive either treatment with SCH gel (SCH group) or no treatment (control group) in a 1∶1 ratio. The primary outcome was endometrium thickness in 14 to 18 days after the first postoperative menstruation. Secondary outcomes included changes in menstrual volume during the first postoperative menstruation, menstruation resumption within 6 postoperative weeks, time to menstruation resumption, duration of the first postoperative menstruation, and incidence of dysmenorrhea.Results:Baseline characteristics of participants were comparable between the two groups (all P>0.05), with 95.3% (182/191) in SCH group and 92.7% (177/191) in the control group completed the study. The postoperative endometrial thickness in SCH group was significantly greater than that in the control group [(9.78±3.15) vs (8.95±2.32) mm; P=0.005]. SCH group also had significantly fewer participants with reduced menstrual volume [23 cases (12.6%, 23/182) vs 31 cases (17.5%, 31/177); P=0.038]. Although SCH group experienced less dysmenorrhea during the first postoperative menstrual period, this difference was not statistically significant [28.5% (51/179) vs 37.1% (65/175); P=0.083]. Outcomes were similar between SCH group and the control group regarding the proportion of participants who resumed menstruation within 6 weeks postoperatively, time to menstruation resumption, and duration of the first postoperative menstruation ( P=0.792, 0.485, and 0.254, respectively). No serious adverse events were observed during the study period, and no adverse events were attributed to SCH gel treatment. Conclusion:The application of SCH gel after artificial abortion is safe and might aid in the recovery of the endometrium.
3.Expression changes of RNA m6A regulators in mouse cerebellum affected by hypobaric hypoxia stimulation
Lingfeng XIAO ; Chunhui MA ; Shunli ZHAO ; Qing LI ; Chunying LIU ; Yamei NIU ; Weimin TONG
Chinese Journal of Pathology 2024;53(5):452-457
Objective:To investigate the role of RNA m6A methylation in mediating cerebellar dysplasia through analyzing the phenotypes of the mouse cerebella and the expression of several key m6A regulators upon hypobaric hypoxia treatment.Methods:Five-day old C57/BL6 mice were exposed to hypobaric hypoxia for 9 days. The status of mouse cerebellar development was analyzed by comparing the body weights, brain weights and histological features. Immunostaining of cell-type-specific markers was performed to analyze the cerebellar morphology. Real-time PCR, Western blot and immunohistochemical staining were performed to detect the expression of key m6A regulators in the mouse cerebella.Results:Compared with the control, the body weights, brain weights and cerebellar volumes of hypobaric hypoxic mice were significantly reduced ( P<0.01). The expression of specific markers in different cells, including NeuN (mature neuron), Calbindin-D28K (Purkinje cell) and GFAP (astrocyte), was decreased in hypobaric hypoxic mouse cerebella ( P<0.01), accompanied with disorganized cellular structure. The expression of methyltransferase METTL3 was significantly down-regulated in the cerebella of hypobaric hypoxic mice ( P<0.05). Conclusions:Hypobaric hypoxia stimulation causes mouse cerebellar dysplasia, with structural abnormalities in mature granular neurons, Purkinje cells and astrocytes. Expression of METTL3 is decreased in hypobaric hypoxic mice cerebellum compared with that of normobaric normoxic mice, suggesting that its mediated RNA m6A methylation may play an important role in hypobaric hypoxia-induced mouse cerebellar dysplasia.
4.Changes of D-dimer, cTnI and VIS after Stanford type A aortic dissection and their predictive effect on death outcome
Li TANG ; Wensu LI ; Qingjuan CHEN ; Xiaolan ZHAO ; Shuwen SUN ; Chunying ZHANG ; Teng CAI
Journal of Chinese Physician 2023;25(3):374-377,381
Objective:To investigate the change of D-Dimer (D-D), cardiac troponin I (cTnI) and vasoactive-inotropic score (VIS) after Stanford type A aortic dissection (TAAD) and thier predictive effect on death outcome.Methods:120 patients with TAAD who were treated in the Affiliated Hospital of Jining Medical College from January 2019 to January 2022 were retrospectively selected and divided into death group ( n=17) and survival group ( n=103) according to the 28-day survival after operation. The difference of clinical data between the two groups was compared, and the influencing factors of postoperative death in TAAD patients were analyzed by logistic regression method. Results:The age, deep hypothermic circulatory arrest time, D-D and cTnI of the patients in the death group were (60.50±5.42)years old, (30.40±9.92)min, (15.65±5.52)g/L and (3.32±0.82)mg/L, respectively, which were significantly higher than those in the survival group (all P<0.05). The VIS score and change of VIS score in the death group at 24 hours after operation were (9.66±1.10)points and (4.50±0.91)points respectively, which were significantly higher than those in the survival group (all P<0.05). Logistic regression analysis showed that age, D-D, cTnI and change of VIS score were the influencing factors of death after TAAD (all P<0.05). The area under the receiver operating characteristic (ROC) curve predicted by the D-D, cTnI and change of VIS score for death in TAAD patients was 0.718, 0.691 and 0.789 respectively (all P<0.05). Conclusions:Postoperative death of TAAD patients is affected by their age, D-D, cTnI and change of VIS score. The D-D, cTnI and change of VIS score have certain application value in predicting postoperative death of patients.
5.Effect of comprehensive intervention on the incidence of lactation galactostasis during breasefeeding of pregnant and delivery women
Feng WANG ; Jiandong WANG ; Baofeng GUO ; Xuexia GU ; Ping LI ; Guanrong GAO ; Chunying ZHAO
Shanghai Journal of Preventive Medicine 2023;35(5):448-452
ObjectiveTo observe the effect of comprehensive intervention on the incidence of lactation galactostasis in communities from the perspective of preventive medicine, so as to prevent the occurrence of the mammary ducts obstruction disease. MethodsA total of 400 women in the early stage of pregnancy were selected from four communities. Those in two communities were set up as the intervention group. Comprehensive intervention for the prevention and treatment of mammary ducts obstruction disease during pregnancy and "Six-step recanalization manual therapy" practical guidance were conducted on the intervention group. The pregnant women from the other two communities were the control group, who received no intervention or guidance training. The two groups were followed up at 1 month, 3 months and 5 months postpartum, and the occurrence of mammary ducts obstruction disease was investigated and interventions were carried out. ResultsThe incidence of galactostasis in the intervention group was 26.0%, 10.6% and 5.1%, respectively at 1, 3 and 5 months after delivery, and the incidence of galactostasis in the control group was 38.0%, 22.2% and 8.3%, respectively. The incidence of galactostasis at 1 month and3 months after delivery was statistically different (P<0.05), while the incidence of galactostasis 5 months after delivery was not statistically different (P>0.05). The protection rates of comprehensive intervention on galactostasis were 31.58%, 52.25% and 38.55%, respectively. ConclusionPublicity and education work of prevention and control of the mammary ducts obstruction disease and "Six-step recanalization manual therapy" practical guidance can effectively reduce the occurrence of plugged mammary ducts, and therefore should be promoted.
6.Qualitative Analysis of Metabolites of Aristolochiae Fructus Aqueous Extract in Rats
Fang WANG ; Chunying LI ; Yan YI ; Suyan LIU ; Yong ZHAO ; Jing MENG ; Jingzhuo TIAN ; Lianmei WANG ; Jiayin HAN ; Chen PAN ; Yushi ZHANG ; Chenyue LIU ; Shasha QIN ; Dunfang WANG ; Zhong XIAN ; Xuan TANG ; Meiting LIU ; Aihua LIANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(13):112-121
ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MSE) technique, we identified qualitatively the metabolites of aristolochic acid(AAs) in rat in order to analyze the metabolic differences between water extract of Aristolochiae fructus(AFE) and Aristolochic acid Ⅰ(AAⅠ). MethodSD rats were selected and administered AFE(110 g·kg-1·d-1) or AAⅠ(5 mg·kg-1·d-1) by oral for 5 days, respectively. Serum, urine and feces were collected after administration. Through sample pretreatment, ACQUITY UPLC BEH C18 column(2.1 mm×100 mm, 1.7 μm) was used with the mobile phase of 0.01% formic acid methanol(A)-0.01% formic acid water(B, containing 5 mmol·L-1 ammonium acetate) for gradient elution(0-1 min, 10%B; 1-7 min, 10%-75%B; 7-7.2 min, 75%-95%B; 7.2-10.2 min, 95%B; 10.2-10.3 min, 95%-10%B; 10.3-12 min, 10%B) at a flow rate of 0.3 mL·min-1. Positive ion mode of electrospray ionization(ESI+) was performed in the scanning range of m/z 100-1 200. In combination with UNIFI 1.9.4.053 system, the Pathway-MSE was used to qualitatively analyze and identify the AAs prototype and related metabolites in biological samples(serum, urine and feces), and to compare the similarities and differences of metabolites in rats in the subacute toxicity test between AFE group and AAⅠ group. ResultCompared with AAⅠ group, 6, 10, 13 common metabolites and 14, 20, 30 unique metabolites were identified in biological samples(serum, urine and feces) of AFE group, respectively. Moreover, the main AAs components always followed the metabolic processes of demethylation, nitrate reduction and conjugation. Compared with common metabolites in AAⅠ group, prototype components of AAⅠ in serum and most metabolic derivatives of AAⅠ[AAⅠa, aristolochic lactam Ⅰ(ALⅠ)a, 7-OHALⅠ and its conjugated derivatives] in biological samples were significantly increased in AFE group(P<0.05, P<0.01), except that the metabolic amount of ALⅠ in feces of AFE group was remarkably lowed than that of AAⅠ group(P<0.01). In addition, a variety of special ALⅠ efflux derivatives were also identified in the urine and feces of the AFE group. ConclusionAlthough major AAs components in AFE all show similar metabolic rules as AAⅠ components in vivo, the coexistence of multiple AAs components in Aristolochiae Fructus may affect the metabolism of AAⅠ, and achieve the attenuating effect by increasing the metabolic effection of AAⅠ and ALⅠ.
7.Mechanism of Chenpi Huoxiangtang Against Diarrhea: Based on Network Pharmacology and Experimental Verification
Zhe LI ; Na LI ; Xiaoyan CUI ; Qingqing ZHAO-LAN ; Yongzhou YU ; Chunying ZHAO ; Hui XIONG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(23):79-86
ObjectiveTo explore the mechanism of Chenpi Huoxiangtang against diarrhea based on network pharmacology and experimental verification. MethodThe active components and targets of Chenpi Huoxiangtang were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and targets related to diarrhea from GeneCards and Online Mendelian Inheritance in Man (OMIM). Thereby, the common targets were screened out. The component-target-disease network and protein-protein interaction (PPI) network were constructed with Cytoscape 3.7.1 and STRING. Bioconductor and R language were employed for gene ontology (GO) term enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment of core targets, and AutoDockTools 1.5.6 and AutoDockVina 1.1.2 for molecular docking. Finally, animal experiment was carried out for verification. ResultA total of 51 active components 226 targets of Chenpi Huoxiangtang and 37 common targets of the medicine and the disease were screened out. The core targets were involved in 1 249 GO terms (P<0.05) and 110 KEGG pathways (P<0.05), mainly the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), Janus kinase (JAK)/signal transducer and activator of transcription (STAT), hypoxia inducible factor (HIF)-1, and mitogen-activated protein kinase (MAPK) pathways. Molecular docking suggested that hesperidin and Akt1 showed the highest binding affinity. Animal experiment demonstrated that Chenpi Huoxiangtang significantly alleviated the diarrhea symptoms. The diarrhea index on the first day of administration decreased to 0.92, which was statistically different from that (1.24) of the model group (P<0.05). The intestinal ink propulsion rate was 70.36%, higher than that (58.20%) in the model group (P<0.01). Moreover, intestinal peristalsis was improved by the decoction. Enzyme-linked immunosorbent assay (ELISA) indicated the decrease in the levels of interleukin-6 (IL-6) and interleukin-1β (IL-1β) (P<0.05) and increase in the levels of Akt1, epidermal growth factor (EGF), and epidermal growth factor receptor (EGFR) (P<0.05). ConclusionThe active components of Chenpi Huoxiangtang mainly regulate PI3K/Akt, MAPK, and other signaling pathways through Akt1, IL-6, IL-1β, EGF, EGFR, and other core targets, thereby relieving diarrhea. This study is expected to lay a basis for the research on the pharmacological mechanism of Citri Reticulatae Pericarpium-Pogostemonis Herba combination and the scientific connotation of their compatibility.
8. Correlation between cytokine levels and liver function damage in patients with occupational medicamentosa-like dermatitis due to trichloroethylene
Chunying ZHU ; Na ZHAO ; Hongling LI ; Xinxiang QIU ; Qifeng WU ; Lihua XIA ; Xinhua ZHAO ; Hailan WANG
China Occupational Medicine 2020;47(02):162-167
OBJECTIVE: To investigate the correlation between plasma cytokine levels and liver functions in patients with occupational medicamentosa-like dermatitis due to trichloroethylene(OMDT). METHODS: A total of 22 OMDT patients were selected as research subjects using judgment sampling method. Blood samples were collected from patients on the 1 st, 2 nd, 3 rd, 4 th, and 5 th week of admission and the day of hospital discharge. The automatic biochemical instrument was used for detecting the index of serum liver function. The levels of cytokines including tumor necrosis factor-α(TNF-α), interferon-γ(IFN-γ), interleukin(IL)-5, IL-6, and IL-10 in plasma were measured by enzyme-linked immunosorbent assay. The Spearman correlation analysis was performed to analyze the correlation between cytokines and liver function in 15 patients with exfoliative dermatitis. RESULTS: The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TBIL), direct bilirubin(DBIL), glutamyl transpeptidase(GGT), and total bile acid(TBA) of OMDT patients on the 1 st week of admission increased(P<0.05), while total protein(TP) and albumin(ALB) decreased(P<0.05) compared with the results at discharge(a stage of recovery). The correlation analysis results of patients with exfoliative dermatitis showed that: the levels of TNF-α, IFN-γ and IL-6 were negatively correlated with the levels of TP and ALB respectively(P<0.05), the level of IL-5 was negatively correlated with TBIL(P<0.05), and the level of IL-10 was negatively correlated with ALB(P<0.05) in the 1 st week. The level of IL-6 was positively correlated with ALT(P<0.05) in the 2 nd week. The level of TNF-α was positively correlated with TBIL(P<0.05), the level of IL-10 was positively correlated with AST(P<0.05) in the 3 rd week. The levels of TNF-α and IL-10 were positively correlated with AST and ALT respectively(P<0.05), the level of IFN-γ was positively correlated with AST(P<0.05) in the 4 th week. The levels of IL-6 and IL-10 were positively correlated with ALT and GGT(P<0.05), and the levels of TNF-α and IFN-γ were positively correlated with AST(P<0.05) in the 5 th week. The level of TNF-α was negatively correlated with DBIL(P<0.05) and was positively correlated with TBA(P<0.05) at discharge.CONCLUSION:s Patients with OMDT are frequently accompanied with severe liver function damage at the early stage. The level of plasma cytokines(TNF-α, IFN-γ, IL-6 and IL-10) might correlate with the severity of liver dysfunction.
9. Analysis on dynamic change of cytokines in patients with occupational trichloroethylene-induced medicamentosa-like dermatitis
Hongling LI ; Chunying ZHU ; Na ZHAO ; Lihua XIA ; Jiabin CHEN ; Xinxiang QIU ; Ying ZHENG ; Laiyu LI ; Hanlin HUANG ; Hailan WANG
China Occupational Medicine 2020;47(06):705-710
OBJECTIVE: To analysis the dynamic change of cytokines in patients with occupational trichloroethylene-induced medicamentosa-like dermatitis(OMDT) at the initial stage of treatment. METHODS: Twenty-two cases of early onset OMDT with no glucocorticoid treatment history were selected as the research subjects by judgment sampling method. Blood samples were collected on the 1 st, 2 nd, 3 rd, 4 th and 5 th weeks after admission and on the day of hospital discharge. The levels of tumor necrosis factor-α(TNF-α), interferon-γ(IFN-γ), interleukin(IL)-5, IL-6 and IL-10 in plasma samples were measured by the enzyme linked immunosorbent assay. RESULTS: The five cytokines in patients with exfoliative dermatitis showed an increasing trend at the initial stage of treatment. Among them, the levels of TNF-α, IL-5 and IL-10 reached a peak and then dropped rapidly to form a plateau, and the levels of IFN-γ and IL-6 were slightly increased and the duration of increase was shorter than that of other cytokines. The levels of TNF-α, IFN-γ, IL-5 and IL-6 in patients with erythema multiforme remained within the detection limits in the detection process. Only a few patients showed a short-term increase, the IL-10 level showed a slight increase at the initial stage and then decreased to the plateau stage. The levels of TNF-α, IFN-γ and IL-6 in patients with bullous epidermal necrolysis increased rapidly at the initial detection stage for a short period of time, and then decreased sharply. The level of IL-5 remained at the detection limit, and the IL-10 level showed alternative rising and falling pattern. Part of the dynamic change of cytokines in patients with exfoliative dermatitis and bullous epidermal necrolysis was similar. CONCLUSION: The levels of TNF-α, IFN-γ, IL-5, IL-6, and IL-10 in OMDT patients changed with the progression of the disease at the early treatment stage, and the degree of change was related to the type of rash. Among them, the levels of TNF-α and IL-10 showed dynamic changes due to the progression of the disease, which could be considered as effect biomarkers to evaluate the severity and progression of the disease, and provide a reference for the rational treatment of patients.
10.Clinical observation of decitabine combined with low-dose cytarabine in treatment of high-risk myelodysplastic syndrome
Yujiao CUI ; Xindong ZHAO ; Shaoling WU ; Chunying DUAN ; Haifeng YUAN ; Qiao SONG
Journal of Leukemia & Lymphoma 2020;29(5):279-283
Objective:To observe the clinical efficacy and safety of decitabine combined with low-dose cytarabine in treatment of high-risk myelodysplastic syndrome.Methods:The data of 47 newly treated MDS patients who had high-risk or above scores according to revised international prognostic scoring system (IPSS-R) in the Affiliated Hospital of Qingdao University from January 2016 to September 2018 were retrospectively analyzed. The patients were divided into decitabine combined with low-dose cytarabine group (15 cases) and decitabine group (32 cases). The clinical efficacy and adverse reactions in two groups were compared.Results:After 4 courses of treatment, the bone marrow remission rate, partial remission rate and hematologic remission rate was 20.0% (3/15), 6.7% (1/15), and 13.3% (2/15), respectively in decitabine combined with low-dose cytarabine group, and was 28.1% (9/32), 3.1% (1/32), and 9.4% (3/32), respectively in decitabine group, and there were no statistically differences of both groups (both P > 0.05). The overall response rate in decitabine combined with low-dose cytarabine group was higher than that in decitabine group [93.3% (14/15) vs. 62.5% (20/32), P = 0.037], and the complete remission rate in decitabine combined with low-dose cytarabine group was higher than that in decitabine group [53.3% (8/15) vs. 21.9% (7/32), P = 0.046]. The 1-year overall survival (OS) rate of decitabine combined with low-dose cytarabine group was 86%; and the median OS time of decitabine combined with low-dose cytarabine group was 24 months (95% CI 15.5-32.5 months), which was higher than that of decitabine group (20 months), but there was no statistically significant difference ( χ2 = 0.058, P = 0.810). The incidence of grade Ⅲ-Ⅳ bone marrow suppression and infection in decitabine combined with low-dose cytarabine group was higher than that in decitabine group, but there were no statistically significant differences of both groups (both P > 0.05). Grade Ⅲ-Ⅳ bone marrow suppression and infection were commonly found within the first 2 courses of treatment in decitabine combined with low-dose cytarabine group, and the adverse reactions gradually decreased in the subsequent treatment. Conclusions:Decitabine combined with low-dose cytarabine can achieve better remission rate and prolong survival time for MDS patients with high-risk and above. There is no significant increase in the incidence of grade Ⅲ-Ⅳ bone marrow suppression and infection. For high-risk MDS patients who are not suitable or unable to receive hematopoietic stem cell transplantation, it can be the preferred option.

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