1.Mechanism by which Huangqintang regulates intestinal flora for treatment of intestinal acute graft-versus-host disease in mice
Mengting XIA ; Runjie SUN ; Jiaqi FU ; Suzhen LI ; Manya YU ; Xing CUI
Chinese Journal of Tissue Engineering Research 2025;29(1):95-102
BACKGROUND:Intestinal acute graft-versus-host disease is one of the most aggressive complications after allogeneic hematopoietic stem cell transplantation with high lethality.How to improve intestinal inflammation and regulate autophagy by applying traditional Chinese medicine in order to treat intestinal acute graft-versus-host disease is a worthwhile research issue nowadays. OBJECTIVE:To investigate the mechanism of Huangqintang modulating intestinal flora for the treatment of intestinal acute graft-versus-host disease. METHODS:CB6F1 mice were irradiated with 60Co X radiation at a total dose of 8 Gy,and then single nucleated cell suspensions(bone marrow cells+splenocytes)from Balb/c H-2d mice were injected into the tail vein in order to prepare a model of intestinal acute graft-versus-host disease.These samples were randomly divided into the model group and the high-,moderate-,and low-dose Huangqintang groups.After modeling,the model,high-,moderate-,and low-dose groups received different doses of Huangqintang or an equal volume of saline by continuous gavage for 14 days.Clinical acute graft-versus-host disease grading,and survival time was recorded.Small intestinal tissues from each group were stained with hematoxylin and eosin for small intestinal mucosal pathology scoring.The intestinal flora of mice in each group was detected using 16S rDNA sequencing.Autophagy-related markers were detected using immunofluorescence,immunohistochemistry,and PCR. RESULTS AND CONCLUSION:(1)Compared with the model group,the survival time of mice was significantly prolonged(P<0.01);the clinical acute graft-versus-host disease scores were significantly reduced(P<0.01);the pathological grading scores of the small intestinal mucosa were significantly diminished(P<0.01);the levels of the small intestinal tissue inflammatory factors tumor necrosis factor-α,interleukin-1β,and interleukin-6,were significantly decreased(P<0.01);the structural integrity of the small intestinal mucosal epithelium was partially restored in mice after the intervention of moderate and high-dose Huangqintang.(2)The study of intestinal flora found that compared with the model group,the pro-inflammatory strain Enterococcus was significantly reduced(P<0.05),while beneficial bacteria such as Clostridium_innocuum and Rhodococcus,a pro-autophagy bacterium,were significantly elevated(P<0.05)in the moderate-dose Huangqintang group.(3)Compared with the model group,the autophagy markers were significantly elevated in the moderate-dose Huangqintang group(P<0.05);under transmission electron microscopy,the number of autophagic vacuoles of moderate-dose Huangqintang group increased significantly.(4)The results showed that Huangqintang significantly reduced the abundance of conditionally pathogenic bacteria and the level of inflammatory factors in small intestinal tissues,and increased the relative abundance of beneficial bacteria and promoted the expression of autophagy in the small intestinal mucosa,which resulted in a significant improvement of intestinal symptoms in mice with acute graft-versus-host disease.
2.Research progresses of endogenous vascular calcification inhibitor BMP-7
Xin ZHOU ; Lu XING ; Peng-Quan LI ; Dong ZHAO ; Hai-Qing CHU ; Chun-Xia HE ; Wei QIN ; Hui-Jin LI ; Jia FU ; Ye ZHANG ; Li XIAO ; Hui-Ling CAO
Chinese Pharmacological Bulletin 2024;40(7):1226-1230
Vascular calcification is a highly regulated process of ectopic calcification in cardiovascular system while no effective intervention can be clinically performed up to date.As vascular calcification undergoes a common regulatory mechanism within bone formation,bone morphogenetic protein 7(BMP-7)main-tains contractile phenotype of vascular smooth muscle cells and further inhibits vascular calcification via promoting the process of osteoblast differentiation,reducing ectopic calcification pressure by increasing bone formation and reducing bone resorption.This work systematically reviews the role of BMP-7 in vascular calcifi-cation and the possible mechanism,and their current clinical application as well.The current proceedings may help develope early diagnostic strategy and therapeutic treatment with BMP-7 as a new molecular marker and potential drug target.The expec-tation could achieve early prevention and intervention of vascular calcification and improve poor prognosis on patients.
3.Functional Studies on the Regulation of Flowering by PfFT3,a Member of the Perilla PEBP Gene Family
Qi-Feng WANG ; Xiao-Yan FENG ; Hui LI ; Fu-Peng HOU ; Xi GUO ; Jun-Xing LU ; Jian HU ; Tao ZHANG
Chinese Journal of Biochemistry and Molecular Biology 2024;40(8):1173-1184
Perilla frutescens,a short-day plant,is rich in biologically active substances and nutrients.Current research on Perilla frutescens focuses on agronomic traits such as yield and fatty acid accumula-tion,with limited exploration of the flowering process and floral organ development.The molecular regu-latory mechanisms underlying these aspects remain unclear.FLOWERING LOUC T(FT)is a florigen in Arabidopsis,plays critical roles in floral transition.PfFT3 is unannotated by genome but annotated by transcriptomics data to the FT-like subfamily.Its function in controlling flowering is yet to be explored.Here subcellular localization analysis showed that PfFT3 is localized in the nucleus and cytoplasm.The plant over-expression vector pCAMBIAI1303-PfFT3 was constructed and transformed into wild-type(Col-0)and mutant fd-2,fd-3,and ft-10 plants by agrobacterium-mediated inflorescence infiltration as a means of obtaining genetically stable and pure overexpression and backfill transgenic lines in Arabidopsis,respectively.Analysis of the results showed that overexpression of PfFT3 significantly promoted early flowering in Arabidopsis and rescued the late-flowering phenotype of the mutants fd-2,fd-3,and ft-10,and that expression of the exogenous PfFT3 promoted the expression of the downstream endogenous flow-ering genes AtSOC1,AtAP1,AtFUL,and AtLFY.This study demonstrates the positive role of PfFT3 in promoting flowering,providing a foundation for further investigation of PfPEBP function and advancing the breeding of early-flowering Perilla frrutescens cultivars.
4.Correlation Between Hyperbaric Oxygen Therapy Course and Reduction of Clonazepam in Patients with Paroxysmal Sympathetic Hyperactivity: A Retrospective Cohort Study
Sujuan LIU ; Yong WANG ; Ran LI ; Haidong LI ; Jie LIU
Medical Journal of Peking Union Medical College Hospital 2024;16(2):386-392
To analyze the correlation between the duration of hyperbaric oxygen (HBO) therapy and oral medication clonazepam reduction in patients with paroxysmal sympathetic hyperactivity (PSH). Clinical data of patients with secondary PSH after severe brain injury at Capital Medical University Affiliated Fuxing Hospital from September 2017 to July 2023 were retrospectively included, covering general information, etiology, lesion location, comorbidities, vital signs at admission, PSH attack characteristics, HBO treatment frequency, PSH treatment drugs and dosage. According to the number of HBO treatments, PSHpatients were divided into HBO short course group (10 treatments) and HBO long course group (>10 treatments). Multiple logistic regression and rank correlation analysis were used to investigate the correlation between the duration/frequency of HBO treatment and the reduction of clonazepam. A total of 75 PSH patients who met the inclusion and exclusion criteria were selected, including 38 cases (50.7%) who received reduced doses of clonazepam. There were 32 cases (42.7%) in the HBO short course group and 43 cases (52.3%) in the HBO long course group. The reduction rate of clonazepam in the HBO short course group was lower than that in the HBO long course group[31.3% (10/32) vs.65.1% (28/43), crude Long course HBO treatment was positively correlated with oral reduction of clonazepam in PSH patients, which may help reduce the side effects caused by clonazepam and become a non- pharmacological treatment option for PSH.
5.Evaluation of the efficacy and safety of intravenous infusion of ferric derisomaltose in the treatment of iron deficiency anemia: a single-center retrospective analysis
Shaoxue DING ; Yihui ZHAO ; Ting WANG ; Jing GUAN ; Limin XING ; Hong LIU ; Guojin WANG ; Xiaoming WANG ; Yuhong WU ; Wen QU ; Jia SONG ; Huaquan WANG ; Lijuan LI ; Zonghong SHAO ; Rong FU
Chinese Journal of Hematology 2024;45(2):178-183
Objective:To investigate the clinical efficacy and safety of ferric derisomaltose injection versus iron sucrose injection in the treatment of iron deficiency anemia (IDA) .Methods:A total of 120 patients with iron deficiency anemia admitted from June 2021 to March 2023 were given intravenous iron supplementation with ferric derisomaltose to assess the efficacy and safety of hemoglobin (HGB) elevation before and after treatment. Simultaneously, the clinical effects of iron supplementation with iron sucrose were compared to those of inpatient patients during the same period.Results:Baseline values were comparable in both groups. Within 12 weeks of treatment, the elevated HGB level in the ferric derisomaltose group was higher than that of the iron sucrose group, with a statistical difference at all time points, and the proportion of HGB increased over 20 g/L in the patients treated for 4 weeks was higher (98.7%, 75.9% ). During the treatment with ferric derisomaltose and iron sucrose, the proportion of mild adverse reactions in the ferric derisomaltose group was slightly lower than that of the iron sucrose group, and neither group experienced any serious adverse reactions. The patients responded well to the infusion treatment, with no reports of pain or pigmentation at the injection site.Conclusion:The treatment of IDA patients with ferric derisomaltose has a satisfactory curative effect, with the advantages of rapidity, accuracy, and safety. Therefore, it is worthy of widespread clinical use.
6.Efficacy and safety of eltrombopag in the treatment of primary immune thrombocytopenia: real-world data from a single medical center
Xifeng DONG ; Yalan LI ; Nianbin LI ; Weinan LIN ; Ting WANG ; Huaquan WANG ; Lijuan LI ; Wen QU ; Limin XING ; Hong LIU ; Yuhong WU ; Guojin WANG ; Jia SONG ; Jing GUAN ; Xiaoming WANG ; Zonghong SHAO ; Rong FU
Chinese Journal of Hematology 2024;45(3):271-276
Objective:This study aimed at investigating the efficacy and safety of eltrombopag in the treatment of adult primary immune thrombocytopenia (ITP) and evaluated the factors influencing its efficacy and side effects.Methods:A total of 198 patients with adult ITP who were admitted to Tianjin Medical University General Hospital between January 2018 and March 2022 were retrospectively analyzed. The efficacy of each starting dose of eltrombopag was evaluated, and adverse events were analyzed. The factors influencing efficacy were investigated, including sex, age, adult ITP type, platelet antibodies, and combined drug treatments.Results:Of the 198 patients, 70 males and 128 females with a median age of 45 years (18-88 years) were included; 130 (65.7%) had newly diagnosed adult ITP, 25 (12.6%) had persistent adult ITP, and 43 (21.7%) had chronic adult ITP. The bleeding event scores at baseline were assessed; 84.3% had scores of<4 and 15.7% had scores of ≥4. The eltrombopag response rate (initial response) at 6 weeks was 78.8% (complete response [CR]: 49.0%; CR1: 14.6%; CR2: 15.2%). The median response time to eltrombopag was 7 (7, 14) days. The initial response rates to 25, 50, and 75 mg eltrombopag were 74.1%, 85.9%, and 60.0%, respectively ( P=0.031). The initial response rate to the 50 mg dose was significantly higher than that of the 25-mg and 75-mg doses. Two patients received 100 mg as the starting dose, and their initial response was 0. Regarding dose adjustment, 70.7% of the patients remained on the starting dose, 8.6% underwent dose adjustment to 50 mg, and 6.1% underwent dose adjustment to 75 mg. Another two patients underwent dose adjustment to 100 mg. After dose adjustment, the persistent response rates were 83.6%, 85.3%, and 85.7% for the 25-, 50-, and 75-mg doses, respectively, with no significant difference. After dose adjustment, the sustained efficacy rate for the 100-mg dose (4 patients) was 100.0%. After 6 weeks of treatment with eltrombopag, the overall bleeding score of patients with ITP decreased. The number of patients with a score of ≥4 decreased to 0, the number of patients with a score of<4 decreased, and there was no significant change in the number of patients with a score of 1-2. The most common adverse event associated with eltrombopag was impaired liver function (7.7%). No thrombosis events or other adverse events were observed. ITP type and number of megakaryocytes significantly affected the initial response to eltrombopag. The initial response rates to eltrombopag for newly diagnosed adult ITP, persistent adult ITP, and chronic adult ITP were 85.3%, 56.0%, and 76.2%, respectively ( P=0.003). For megakaryocytes, the initial response rates were 61.8%, 87.1%, and 84.3% ( P=0.009) for the decreased, normal, and increased megakaryocyte groups, respectively. Conclusion:Eltrombopag, as a second-line or higher treatment for adult ITP, has a rapid onset of action and good safety. The initial response rate is significantly higher with a dose of 50 mg than with a dose of 25 mg. Patients with newly diagnosed ITP and those with normal or increased megakaryocyte numbers have a higher initial response rate to eltrombopag.
7.A single-center analysis of pathogenic bacteria distribution and drug resistance in bacterial bloodstream infections among patients with hematological diseases
Mengting CHE ; Chaomeng WANG ; Hui LIU ; Haifang KONG ; Lijuan LI ; Jia SONG ; Huaquan WANG ; Guojin WANG ; Yuhong WU ; Jing GUAN ; Limin XING ; Wen QU ; Hong LIU ; Xiaoming WANG ; Zhidong HU ; Zonghong SHAO ; Rong FU
Chinese Journal of Hematology 2024;45(10):937-943
Objective:To analyze the distribution and drug resistance of pathogens of bacterial bloodstream infection in patients with hematological diseases in the Department of Hematology of Tianjin Medical University General Hospital, and to provide etiological data for clinical empirical anti-infection treatment.Methods:A retrospective analysis was conducted on the general clinical information, pathogenic bacteria and drug susceptibility test results of patients with hematological diseases diagnosed with bacterial bloodstream infection by menstrual blood culture in our center from January 2016 to December 2022.Results:Patients included 498 inpatients, with a total of 639 bacterial strains. Among the patients, 86.9% patients had malignancies, and 76.7% had agranulocytosis. Symptoms of concurrent infections, including those of the respiratory tract, oral mucosa, skin and soft tissues, and abdominal sources were observed in 68.3% patients. Gram-negative bacteria (G -) accounted for 79.0% of the isolated bacteria, and gram-positive bacteria (G +) accounted for 21.0%. The top five isolated pathogens were Klebsiella pneumoniae (22.5%), Escherichia coli (20.8%), Pseudomonas aeruginosa (15.0%), Enterococcus faecium (5.5%), and Stenotrophomonas maltophilum (5.0%). Escherichia coli exhibited a decreasing trend of resistance to quinolones, cephalosporins, and carbapenems. Klebsiella pneumoniae exhibited increasing rates of resistance to quinolones and cephalosporins between 2016 and 2018, but the rated decreased after 2019. The resistance rate to carbapenems exhibited by Pseudomonas aeruginosa was approximately 20%. Carbapenem-resistant strains of Pseudomonas aeruginosa strains were first detected in 2017, with a peak resistance rate of 35.7%, detected in 2019. A 60.0% resistance rate to methicillin was observed in methicillin-resistant coagulase-negative staphylococci (MRCNS), and one case of linezolid-resistant MRCNS was detected. Conclusions:Pathogenic bacteria of bacterial bloodstream infections were widely distributed in our center, and precautions are warranted against carbapenem resistant P. aeruginosa and Klebsiella pneumoniae.
8.Antimicrobial resistance of bacteria from blood specimens:surveillance re-port from Hunan Province Antimicrobial Resistance Surveillance System,2012-2021
Hong-Xia YUAN ; Jing JIANG ; Li-Hua CHEN ; Chen-Chao FU ; Chen LI ; Yan-Ming LI ; Xing-Wang NING ; Jun LIU ; Guo-Min SHI ; Man-Juan TANG ; Jing-Min WU ; Huai-De YANG ; Ming ZHENG ; Jie-Ying ZHOU ; Nan REN ; An-Hua WU ; Xun HUANG
Chinese Journal of Infection Control 2024;23(8):921-931
Objective To understand the change in distribution and antimicrobial resistance of bacteria isolated from blood specimens of Hunan Province,and provide for the initial diagnosis and treatment of clinical bloodstream infection(BSI).Methods Data reported from member units of Hunan Province Antimicrobial Resistance Survei-llance System from 2012 to 2021 were collected.Bacterial antimicrobial resistance surveillance method was imple-mented according to the technical scheme of China Antimicrobial Resistance Surveillance System(CARSS).Bacteria from blood specimens and bacterial antimicrobial susceptibility testing results were analyzed by WHONET 5.6 soft-ware and SPSS 27.0 software.Results A total of 207 054 bacterial strains were isolated from blood specimens from member units in Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021,including 107 135(51.7%)Gram-positive bacteria and 99 919(48.3%)Gram-negative bacteria.There was no change in the top 6 pathogenic bacteria from 2012 to 2021,with Escherichia coli(n=51 537,24.9%)ranking first,followed by Staphylococcus epidermidis(n=29 115,14.1%),Staphylococcus aureus(n=17 402,8.4%),Klebsiella pneu-moniae(17 325,8.4%),Pseudomonas aeruginosa(n=4 010,1.9%)and Acinetobacter baumannii(n=3 598,1.7%).The detection rate of methicillin-resistant Staphylococcus aureus(MRSA)decreased from 30.3%in 2015 to 20.7%in 2021,while the detection rate of methicillin-resistant coagulase-negative Staphylococcus(MRCNS)showed an upward trend year by year(57.9%-66.8%).No Staphylococcus was found to be resistant to vancomy-cin,linezolid,and teicoplanin.Among Gram-negative bacteria,constituent ratios of Escherichia coli and Klebsiella pneumoniae were 43.9%-53.9%and 14.2%-19.5%,respectively,both showing an upward trend(both P<0.001).Constituent ratios of Pseudomonas aeruginosa and Acinetobacter baumannii were 3.6%-5.1%and 3.0%-4.5%,respectively,both showing a downward trend year by year(both P<0.001).From 2012 to 2021,resistance rates of Escherichia coli to imipenem and ertapenem were 1.0%-2.0%and 0.6%-1.1%,respectively;presenting a downward trend(P<0.001).The resistant rates of Klebsiella pneumoniae to meropenem and ertapenem were 7.4%-13.7%and 4.8%-6.4%,respectively,presenting a downward trend(both P<0.001).The resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannii to carbapenem antibiotics were 7.1%-15.6%and 34.7%-45.7%,respectively.The trend of resistance to carbapenem antibiotics was relatively stable,but has de-creased compared with 2012-2016.The resistance rates of Escherichia coli to the third-generation cephalosporins from 2012 to 2021 were 41.0%-65.4%,showing a downward trend year by year.Conclusion The constituent ra-tio of Gram-negative bacillus from blood specimens in Hunan Province has been increasing year by year,while the detection rate of carbapenem-resistant Gram-negative bacillus remained relatively stable in the past 5 years,and the detection rate of coagulase-negative Staphylococcus has shown a downward trend.
9.Antimicrobial resistance of bacteria from cerebrospinal fluid specimens:surveillance report from Hunan Province Antimicrobial Resistance Survei-llance System,2012-2021
Jun LIU ; Li-Hua CHEN ; Chen-Chao FU ; Chen LI ; Yan-Ming LI ; Xing-Wang NING ; Guo-Min SHI ; Jing-Min WU ; Huai-De YANG ; Hong-Xia YUAN ; Ming ZHENG ; Nan REN ; An-Hua WU ; Xun HUANG ; Man-Juan TANG
Chinese Journal of Infection Control 2024;23(8):932-941
Objective To investigate changes in the distribution and antimicrobial resistance of bacteria isolated from cerebrospinal fluid(CSF)specimens in Hunan Province,and provide reference for correct clinical diagnosis and rational antimicrobial use.Methods Data reported by member units of Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021 were collected according to China Antimicrobial Resistance Surveillance Sys-tem(CARSS)technical scheme.Data of bacteria isolated from CSF specimens and antimicrobial susceptibility tes-ting results were analyzed with WHONET 5.6 and SPSS 20.0 software.Results A total of 11 837 bacterial strains were isolated from CSF specimens from member units of Hunan Province Antimicrobial Resistance Surveillance Sys-tem from 2012 to 2021.The top 5 strains were coagulase-negative Staphylococcus(n=6 397,54.0%),Acineto-bacter baumannii(n=764,6.5%),Staphylococcus aureus(n=606,5.1%),Enterococcus faecium(n=465,3.9%),and Escherichia coli(n=447,3.8%).The detection rates of methicillin-resistant coagulase-negative Staphyloco-ccus(MRCNS)and methicillin-resistant Staphylococcus aureus(MRSA)were 58.9%-66.3%and 34.4%-62.1%,respectively.No Staphylococcus spp.were found to be resistant to vancomycin,linezolid,and teicoplanin.The de-tection rate of Enterococcus faecium was higher than that of Enterococcus faecalis,and the resistance rates of En-terococcus f aecium to penicillin,ampicillin,high concentration streptomycin and levofloxacin were all higher than those of Enterococcus faecalis(all P=0.001).Resistance rate of Streptococcus pneumoniae to penicillin was 85.0%,at a high level.Resistance rate of Escherichia coli to ceftriaxone was>60%,while resistance rates to enzyme inhibitors and carbapenem antibiotics were low.Resistance rate of Klebsiella pneumoniae to ceftriaxone was>60%,to en-zyme inhibitors piperacillin/tazobactam and cefoperazone/sulbactam was>30%,to carbapenem imipenem and me-ropenem was about 30%.Resistance rates of Acinetobacter baumannii to most tested antimicrobial agents were>60%,to imipenem and meropenem were 59.0%-79.4%,to polymyxin B was low.Conclusion Among the bac-teria isolated from CSF specimens,coagulase-negative Staphylococcus accounts for the largest proportion,and the overall resistance of pathogenic bacteria is relatively serious.Bacterial antimicrobial resistance surveillance is very important for the effective treatment of central nerve system infection.
10.Antimicrobial resistance of bacteria from intensive care units:surveillance report from Hunan Province Antimicrobial Resistance Surveillance Sys-tem,2012-2021
Li-Hua CHEN ; Chen-Chao FU ; Chen LI ; Yan-Ming LI ; Jun LIU ; Xing-Wang NING ; Guo-Min SHI ; Jing-Min WU ; Huai-De YANG ; Hong-Xia YUAN ; Ming ZHENG ; Nan REN ; Xun HUANG ; An-Hua WU ; Jian-Dang ZHOU
Chinese Journal of Infection Control 2024;23(8):942-953
Objective To investigate the distribution and antimicrobial susceptibility of clinically isolated bacteria from intensive care units(ICUs)in hospitals of Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021.Methods According to China Antimicrobial Resistance Surveillance System,data of clinically isolated bacterial strains and antimicrobial susceptibility testing results of bacteria from ICUs reported by all member units of Hunan Province Antimicrobial Resistance Surveillance System were analyzed with WHONET 2022 software.Results From 2012 to 2021,the total number of bacteria isolated from ICUs of member units of the Hunan Province Antimi-crobial Resistance Surveillance System was 5 777-22 369,with Gram-negative bacteria accounting for 76.1%-78.0%annually.Staphylococcus aureus ranked first among isolated Gram-positive bacteria each year.The top 5 bacteria among Gram-negative bacteria were Acinetobacter baumannii,Klebsiella pneumoniae,Escherichia coli,Pseudo-monas aeruginosa,and Stenotrophomonas maltophilia.Detection rate of methicillin-resistant Staphylococcus aureus showed a downward trend year by year.No Staphylococcus spp.were found to be resistant to vancomycin,teico-planin and linezolid.Detection rates of vancomycin-resistant Enterococcus faecalis and vancomycin-resistant Entero-coccus faecium were 0.6-1.1%and 0.6%-2.2%,respectively.Resistance rates of Escherichia coli and Kleb-siella pneumoniae to imipenem were 3.1%-5.7%and 7.7%-20.9%,respectively.Resistance rates of Pseudo-monasaeruginosa and Acinetobacter baumannii to imipenem were 24.6%-40.1%and 76.1%-80.9%,respective-ly.Detection rates of carbapenem-resistant Pseudomonas aeruginosa declined year by year.Acinetobacter baumannii maintained high susceptibility to polymyxin B,with resistance rate<10%.Conclusion Antimicrobial resistance of bacteria from ICUs is serious.Carbapenem-resistant Enterobacteriales has an upward trend after 2019.It is nece-ssary to strengthen the surveillance of bacterial resistance and carry out multidisciplinary collaboration.

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