1.Biomimetic dual-cell membrane nanoprobes employed for bimodal fluorescence-MR imaging of pancreatic cancer
Yanqi ZHONG ; Yingying MA ; Wenzheng LU ; Heng ZHANG ; Yuxi GE ; Peng WANG ; Jing ZHAO ; Jianying QIAN ; Jingxiao CHEN ; Shudong HU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(2):88-93
Objective:To construct fused cancer cell/neutrophil membrane-coated polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNP@FMs) and explore the potential for targeted pancreatic cancer fluorescence imaging and MRI.Methods:Cancer cell membranes fused with neutrophil membranes were encapsulated on the surface of polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNPs) to prepare PMNP@FMs. The morphology, structure, and MRI performance of the product were characterized. The cytotoxicity of PMNP@FMs towards human pancreatic cancer cells (PANC-1) and normal human pancreatic ductal epithelial cells (hTERT-HPNE) was evaluated using cell counting kit (CCK)-8, and in vivo toxicity was assessed in healthy mice. PANC-1 pancreatic cancer xenograft nude mouse models were established for in vivo fluorescence imaging and MRI. Data were analyzed using the independent-sample t test, repeated measures analysis of variance and the least significance difference method. Results:PMNP@FMs exhibited a core-shell structure with a diameter of (112.81±8.64) nm, negative surface charge, and good dispersibility. The T 1 relaxivity of PMNPs was 18.81±0.22, which was 4.1 times higher than that of gadopentetate dimeglumine (Gd-DTPA) (4.55±0.24; t=75.54, P<0.001). Co-culture of PMNPs and PMNP@FMs with hTERT-HPNE and PANC-1 cells for 24 h resulted in cell viability above 90% within the concentration range of 0-500 μg/ml. PMNP@FMs did not affect mouse survival and showed no apparent organ damage. In vivo fluorescence imaging and MRI revealed that PMNP@FMs accumulated highly in tumors and reached the peak 24 h post intravenous administration (relative MR signal: 1.35±0.01, fluorescence intensity: (1.20±0.25)×10 10), surpassing the peak observed in the control group (1.22±0.01, (3.87±0.50)×10 9;F values: 11.03-188.01, t values: 18.20, 5.64, all P<0.05), with hepatic metabolism being the primary route of clearance. Conclusion:PMNP@FMs demonstrate a potential for targeted pancreatic cancer fluorescence imaging and MRI, offering promising prospect for precise diagnosis of early-stage pancreatic cancer.
2.NIP7 upregulates the expression of ubiquitin-conjugating enzyme E2 C to promote tumor growth in anaplastic thyroid cancer.
Yingying GONG ; Ziwen FANG ; Yixuan WANG ; Minghua GE ; Zongfu PAN
Journal of Zhejiang University. Medical sciences 2025;54(3):372-381
OBJECTIVES:
To investigate the role of nucleolar pre-rRNA processing protein NIP7 (NIP7) in maintaining the malignant phenotype of anaplastic thyroid cancer (ATC) and its molecular mechanisms.
METHODS:
NIP7 expression in ATC tissues and its gene knock-out effects in ATC cells were analyzed using gene expression microarray (GSE33630), proteome database (IPX0008941000) and the Dependency Map database, respectively. Expression and localization of NIP7 in normal thyroid cells, papillary thyroid cancer cells, and ATC cells were detected by Western blotting. Small interfering RNA (siRNA) was transfected into ATC cells, and the knockdown efficiency of NIP7 was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting. Cell proliferation was assessed by CCK-8 assay, colony formation was evaluated by colony formation assay, and tumor growth was assessed by xenograft tumor model in nude mice. SUnSET (surface sensing of translation) assay combined with co-immunoprecipitation were employed to evaluate the effect of NIP7 silencing on ubiquitin-conjugating enzyme E2 C (UBE2C) translation. Finally, gene set enrichment analysis was used to identify shared pathways of NIP7 and UBE2C, which were validated by qRT-PCR.
RESULTS:
Compared with normal tissues and papillary thyroid cancer, NIP7 was significantly upregulated in ATC tissues, and had a gene knock-out fitness effect on different ATC cell lines. The relative protein levels of NIP7 in ATC cells were significantly higher than those in normal thyroid follicular cells, and the protein was mainly expressed in the nucleus. NIP7 silencing significantly inhibited cell proliferation and reduced colony formation. Xenograft tumor model showed that NIP7 knockdown significantly slowed down the growth of ATC xenograft, and the tumor volume and weight were significantly lower than those in the control group (all P<0.05). NIP7 silencing downregulated the protein level of UBE2C, but did not affect the expression of UBE2C mRNA. Compared to the control group, UBE2C silencing significantly inhibited ATC cells proliferation (P<0.01) and colony formation (P<0.05). UBE2C overexpression reversed the proliferation-inhibitory effect induced by NIP7 silencing (P<0.01). Gene set enrichment analysis indicated that NIP7 and UBE2C were both involved in DNA replication. NIP7 or UBE2C silencing could significantly downregulate the expression levels of DNA polymerase epsilon, catalytic subunit 2 and replication factor C4 in DNA replication pathway.
CONCLUSIONS
NIP7 promotes ATC tumor growth by upregulating UBE2C to mediate DNA replication.
Humans
;
Ubiquitin-Conjugating Enzymes/genetics*
;
Thyroid Neoplasms/genetics*
;
Thyroid Carcinoma, Anaplastic/genetics*
;
Animals
;
Mice, Nude
;
Mice
;
Cell Line, Tumor
;
Cell Proliferation
;
Up-Regulation
;
RNA, Small Interfering/genetics*
;
Nuclear Proteins/metabolism*
;
Gene Expression Regulation, Neoplastic
3.The bridging role of programmed cell death in association between periodontitis and rheumatoid arthritis
GE Ruiyang ; ZHOU Yingying ; MAO Haowei ; HAN Lei ; CUI Di ; YAN Fuhua
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(6):457-465
Periodontitis and rheumatoid arthritis (RA) are chronic inflammatory diseases that share similar inflammatory mechanisms and characteristics. Programmed cell death (PCD) has recently garnered attention for its crucial role in regulating inflammation and maintaining tissue homeostasis, as well as for its potential to link these two diseases. The various forms of PCD--including apoptosis, pyroptosis, and necroptosis--are closely controlled by signaling pathways such as Toll-like receptor 4 (TLR4) /NF-κB and MAPK. These pathways determine cell fate and influence inflammatory responses, tissue destruction, and repair, and they both play important roles in the pathogenesis of RA and periodontitis. In periodontitis, periodontal pathogens such as Porphyromonas gingivalis (P. gingivalis) and its virulence factors, including lipopolysaccharide (LPS), induce pyroptosis and necroptosis in immune cells such as macrophages via the TLR4/NF-κB pathway, which leads to an excessive release of pro-inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Concurrently, these pathogens inhibit the normal apoptotic process of immune cells, such as neutrophils, prolonging their survival, exacerbating immune imbalance, and aggravating periodontal tissue destruction. Similarly, in RA synovial tissue, fibroblast-like synoviocytes (FLS) acquire apoptosis resistance through signaling pathways such as the Bcl-2 family, JAK/STAT, and NF-κB, allowing for the consistent proliferation and secretion of matrix metalloproteinases and pro-inflammatory cytokines. Meanwhile, the continuous activation of pyroptotic pathways in neutrophils and macrophages results in the sustained release of IL-1β, further exacerbating synovial inflammation and bone destruction. Notably, dysregulated PCD fosters inter-organ crosstalk through shared inflammatory mediators and metabolic networks. Damage-associated molecular patterns (DAMPs) and cytokines that originate from periodontal lesions can spread systemically, influencing cell death processes in synovial and immune cells, thereby aggravating joint inflammation and bone erosion. By contrast, systemic inflammation in RA can upregulate osteoclastic activity or interfere with the normal apoptosis of periodontal cells via TNF-α and IL-6, ultimately intensifying periodontal immune imbalance. This review highlights the pivotal bridging role of PCD in the pathogenesis of both periodontitis and RA, providing a reference for therapeutic strategies that target cell death pathways to manage and potentially mitigate these diseases.
4.Biomimetic dual-cell membrane nanoprobes employed for bimodal fluorescence-MR imaging of pancreatic cancer
Yanqi ZHONG ; Yingying MA ; Wenzheng LU ; Heng ZHANG ; Yuxi GE ; Peng WANG ; Jing ZHAO ; Jianying QIAN ; Jingxiao CHEN ; Shudong HU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(2):88-93
Objective:To construct fused cancer cell/neutrophil membrane-coated polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNP@FMs) and explore the potential for targeted pancreatic cancer fluorescence imaging and MRI.Methods:Cancer cell membranes fused with neutrophil membranes were encapsulated on the surface of polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNPs) to prepare PMNP@FMs. The morphology, structure, and MRI performance of the product were characterized. The cytotoxicity of PMNP@FMs towards human pancreatic cancer cells (PANC-1) and normal human pancreatic ductal epithelial cells (hTERT-HPNE) was evaluated using cell counting kit (CCK)-8, and in vivo toxicity was assessed in healthy mice. PANC-1 pancreatic cancer xenograft nude mouse models were established for in vivo fluorescence imaging and MRI. Data were analyzed using the independent-sample t test, repeated measures analysis of variance and the least significance difference method. Results:PMNP@FMs exhibited a core-shell structure with a diameter of (112.81±8.64) nm, negative surface charge, and good dispersibility. The T 1 relaxivity of PMNPs was 18.81±0.22, which was 4.1 times higher than that of gadopentetate dimeglumine (Gd-DTPA) (4.55±0.24; t=75.54, P<0.001). Co-culture of PMNPs and PMNP@FMs with hTERT-HPNE and PANC-1 cells for 24 h resulted in cell viability above 90% within the concentration range of 0-500 μg/ml. PMNP@FMs did not affect mouse survival and showed no apparent organ damage. In vivo fluorescence imaging and MRI revealed that PMNP@FMs accumulated highly in tumors and reached the peak 24 h post intravenous administration (relative MR signal: 1.35±0.01, fluorescence intensity: (1.20±0.25)×10 10), surpassing the peak observed in the control group (1.22±0.01, (3.87±0.50)×10 9;F values: 11.03-188.01, t values: 18.20, 5.64, all P<0.05), with hepatic metabolism being the primary route of clearance. Conclusion:PMNP@FMs demonstrate a potential for targeted pancreatic cancer fluorescence imaging and MRI, offering promising prospect for precise diagnosis of early-stage pancreatic cancer.
5.Establishment of life cycle management system of equipment in medical laboratories of public hospitals
Lili WU ; Yongmei JIANG ; Xia WANG ; Yingying LI ; Ge ZHANG ; Caiqin JIANG
Modern Hospital 2024;24(5):722-725
Objective This paper aims to address the challenges of hospital equipment management by implementing the life cycle management system in the medical laboratories of public hospitals.Methods Based on the three principles of standard-ization,refinement,and dynamism,this paper conducted data tracking and managed equipment analysis with specifications dur-ing the processes of planning,discussion,procurement,acceptance,operation,maintenance,performance evaluation,scrap-ping,and updating.Results After implementing life cycle management,the average risk level significantly decreased compared to pre-implementation(P<0.05).Budget implementation efficiency increased by 14.53%from 2019 to 2023.The investment payback period was controlled within 2 years.Conclusion The application of the life cycle management system to equipment management in medical laboratories of public hospitals is of great significance for the high-quality development of hospitals.
6.Mechanism of Elesclomol Induced Cuproptosis in Endometrial Cancer Cells
Shasha ZHANG ; Yingying SHI ; Chunxiang WU ; Ning GE
Herald of Medicine 2024;43(9):1393-1397
Objective To investigate the mechanism of copper ionophore elesclomol induced cuproptosis in endometrial cancer cells.Methods HEC-1-A cells were treated with different concentrations of copper ion carrier elesclomol and copper chloride.Cell proliferation was detected using a cell counting kit(CCK-8)assay.Enzyme-linked immunosorbent assay(ELISA)detected mitochondrial respiratory chain complexesⅠ,Ⅱ,Ⅲ,and IV.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect mRNA expression.Western blotting and immunohistochemistry were used to detect protein expression.Results Adding elesclomol or copper chloride alone to HEC-1-A cells did not affect cell survival.However,the simultaneous addition of 50 nmol·L-1 elesclomol and 1 μmol·L-1 copper ions caused a significant decrease in cell survival(P<0.01).Elesclomol-induced HEC-1-A cell death does not involve the apoptosis mechanism.After treatment with 50 nmol·L-1 elesclomol and 1 μmol·L-1 copper ions in HEC-1-A cells,the levels of mitochondrial respiratory chain complexes Ⅰ,Ⅱ,and Ⅲsignificantly increased.After knocking down ferredoxin 1(FDX1),the cuproptosis in HEC-1-A cells was significantly inhibited(P<0.01).In addition,FDX1 was under-expressed in endometrial cancer tissues.Conclusion Elesclomol may promote cuproptosis in endometrial cancer cells through the FDX1/mitochondrial respiratory pathway.
7.Analysis of the efficacy and influencing factors after the First 131Ⅰ treatment after surgery for differentiated thyroid cancer
Shaoneng TAO ; Junliang GE ; Jiwen YANG ; Xiaolei CHEN ; Weili YIN ; Yingying WANG ; Xiaocen LIU
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(12):1435-1440
AIM:To explore the therapeutic effica-cy and influencing factors of differentiated thyroid cancer(DTC)after the first postoperative 131Ⅰ treat-ment.METHODS:We retrospectively analyzed the clinical data of 116 DTC patients treated with 131Ⅰfor the first time after thyroid cancer surgery in the Department of Nuclear Medicine of the First Affili-ated Hospital of Wannan Medical College,analysed their therapeutic efficacy,and Univariate and multi-variate Logistic analyses were performed for the factors that may affect the efficacy of the treat-ment,respectively,and established ROC curves to analyse the diagnostic and ER efficacy of those with psTg and TTR that had a significant effect on the multifactorial Logistic analyses.RESULTS:In DTC patients who were followed up 3-9 months af-ter the first postoperative 131Ⅰ treatment,69.0%(80/116)achieved ER.Univariate analysis revealed no statistical significance between ER and NER groups in terms of age,gender,TSH,TgVR,maximum tu-mour diameter,presence of lymph node metasta-sis,bilaterality of tumour,multifocality and clinical stage(P>0.05).While 131Ⅰ dose,nsTg,psTg,TgV and TTR(Tg/TSH ratio)were statistically significant(P<0.05).The results of multifactorial Logistic analysis showed that psTg and TTR were independent risk factors for the first 131Ⅰ treatment after DTC,with a psTg OR of 5.950(95%CI 1.437-24.639,P<0.05)and a TTR OR of 4.137(95%CI 1.073-15.947,P<0.05).The best threshold value of psTg for ROC curve analysis to predict the efficacy of the first postoperative 131Ⅰ treatment for DTC was 8.935 μg/L,with a sensitivity of 80.6%,a specificity of 83.6%,and a Yuden's index of 0.64.And the best threshold value of TTR for predicting the efficacy of the first postoperative 131Ⅰ treatment for DTC was 125.72 ng/mIU,with a sensitivity,specificity of 80.6%and 91.2%,and the Yuden index was 0.618.psTg and TTR areas under the curve were 0.839 and 0.833,respectively.psTg<8.935 μg/L patients achieved ER after 3-9 months of follow-up in DTC patients(67/74,90.5%).psTg>8.935 μg/L patients achieved ER(13/42,30.95%).Correspondingly TTR<125.72 ng/mIU achieved ER(65/72,90.2%).psTg>125.72 ng/mIU achieved ER(15/44,34.1%).CONCLUSION:The efficacy of the first 131Ⅰ treatment after surgery for differentiated thyroid cancer is significant.psTg and TTR are independent risk factors for the first 131Ⅰ treatment after DTC and have an important predictive value of efficacy.
8.Analysis of the efficacy and influencing factors after the First 131Ⅰ treatment after surgery for differentiated thyroid cancer
Shaoneng TAO ; Junliang GE ; Jiwen YANG ; Xiaolei CHEN ; Weili YIN ; Yingying WANG ; Xiaocen LIU
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(12):1435-1440
AIM:To explore the therapeutic effica-cy and influencing factors of differentiated thyroid cancer(DTC)after the first postoperative 131Ⅰ treat-ment.METHODS:We retrospectively analyzed the clinical data of 116 DTC patients treated with 131Ⅰfor the first time after thyroid cancer surgery in the Department of Nuclear Medicine of the First Affili-ated Hospital of Wannan Medical College,analysed their therapeutic efficacy,and Univariate and multi-variate Logistic analyses were performed for the factors that may affect the efficacy of the treat-ment,respectively,and established ROC curves to analyse the diagnostic and ER efficacy of those with psTg and TTR that had a significant effect on the multifactorial Logistic analyses.RESULTS:In DTC patients who were followed up 3-9 months af-ter the first postoperative 131Ⅰ treatment,69.0%(80/116)achieved ER.Univariate analysis revealed no statistical significance between ER and NER groups in terms of age,gender,TSH,TgVR,maximum tu-mour diameter,presence of lymph node metasta-sis,bilaterality of tumour,multifocality and clinical stage(P>0.05).While 131Ⅰ dose,nsTg,psTg,TgV and TTR(Tg/TSH ratio)were statistically significant(P<0.05).The results of multifactorial Logistic analysis showed that psTg and TTR were independent risk factors for the first 131Ⅰ treatment after DTC,with a psTg OR of 5.950(95%CI 1.437-24.639,P<0.05)and a TTR OR of 4.137(95%CI 1.073-15.947,P<0.05).The best threshold value of psTg for ROC curve analysis to predict the efficacy of the first postoperative 131Ⅰ treatment for DTC was 8.935 μg/L,with a sensitivity of 80.6%,a specificity of 83.6%,and a Yuden's index of 0.64.And the best threshold value of TTR for predicting the efficacy of the first postoperative 131Ⅰ treatment for DTC was 125.72 ng/mIU,with a sensitivity,specificity of 80.6%and 91.2%,and the Yuden index was 0.618.psTg and TTR areas under the curve were 0.839 and 0.833,respectively.psTg<8.935 μg/L patients achieved ER after 3-9 months of follow-up in DTC patients(67/74,90.5%).psTg>8.935 μg/L patients achieved ER(13/42,30.95%).Correspondingly TTR<125.72 ng/mIU achieved ER(65/72,90.2%).psTg>125.72 ng/mIU achieved ER(15/44,34.1%).CONCLUSION:The efficacy of the first 131Ⅰ treatment after surgery for differentiated thyroid cancer is significant.psTg and TTR are independent risk factors for the first 131Ⅰ treatment after DTC and have an important predictive value of efficacy.
9.Clinical analysis of 402 patients with dental trauma
GE Yang ; SHI Shanwei ; WANG Yingying ; XING Yundi ; CHEN Lei
Journal of Prevention and Treatment for Stomatological Diseases 2023;31(1):28-33
Objective :
To study the clinical characteristics of dental trauma and provide data support for clinical work and health education, the clinical data of patients in the Guangzhou area were reviewed.
Methods :
The clinical data of patients attending the general Emergency Department of Stomatological Hospital of Southern Medical University from January 2017 to January 2022 were analyzed according to gender, age, trauma cause, trauma type, tooth position and trauma duration, and postoperative time of trauma.
Results:
The ratio of males to females was 1.07:1, and the ratio of patients aged 10-19 years was 2.76:1. Falls and collisions were the main causes of the trauma. Concussion and uncomplicated crown fracture were the most frequent subcategories of dental trauma. For tooth position, the upper maxillary middle incisors had the highest rate of trauma, followed by the maxillary lateral incisors. January and December were the two months with the highest incidence of trauma, while the rate of dental trauma on weekends was slightly higher than on weekdays, and 77.81% of patients visited within 24 h after the trauma.
Conclusion
Dental trauma commonly occurs in the adolescent maxillary incisors, and crown fracture and concussion are the main types of injury. The major causes are falls and collisions. The general population should pay more attention to strengthening the protection of teeth during outdoor activities and learn emergency dental treatment methods. At the same time, dentists should be more skilled in the treatment of dental trauma, and uncommon types of dental trauma should be given more attention to avoid poor outcomes.
10.Influence of airway mucus plugs on patients with bronchial asthma and its management
Kexin LIU ; Yingying GE ; Ying SHANG ; Meijiao LI ; Lina SUN ; Zhu SONG ; Chun CHANG
Chinese Journal of Health Management 2023;17(1):29-35
Objective:To explore the influence of airway mucus plugs on patients with bronchial asthma and its management.Methods:In this cross-sectional study, from January 2020 to June 2022, 100 patients who were diagnosed with asthma and underwent chest CT examination in the Outpatient Department of Peking University Third Hospital were included. The chest CT results and medical history, pulmonary function, fractional exhaled nitric oxide (FeNO), blood routine, total allergen IgE, Aspergillus fumigatus M3 allergen-specific IgE antibody test results were collected. According to the results of chest CT, the asthma patients were divided into group with mucus plugs and those without mucus plugs. Distribution of airway mucus plugs and the mucus plug scores based on lung segments were calculated. The relationships of mucus plugs with medical history, pulmonary function [These included before and after the bronchodilation test, forced vital capacity percent of predicted value (FVC%pred), forced expiratory volume in one second percent of predicted value (FEV 1%pred), FEV 1/FVC, peak expiratory flow percent of predicted value (PEF%pred), maximal mid-expiratory flow percent of predicted value (MMEF%pred), maximal expiratory flow at 25%, 50%, 75% of vital capacity remaining percent of predicted value (MEF 25%pred, MEF 50%pred, MEF 75%pred)], FeNO, and peripheral blood eosinophil (Eos) counts were analyzed. The logistic regression model was used to analyze whether airway mucus plug was a risk factor for asthma exacerbation, and the corresponding intervention strategies were explored. Results:Among the 100 patients with asthma, 24 cases were in the mucus plug group and 76 cases were in the non-mucus plug group. The distribution of mucus plug was more common in the lower lungs (30.53% and 9.16% in the lower and upper lobe of left lung, respectively; 29.01%, 14.50% and 16.80% in the lower, middle and upper lobe of right lung, respectively). The average score of mucus plug was (4.42±3.12) points. The body mass index (BMI), the number of visits to a doctor due to asthma exacerbations, FeNO, peripheral blood Eos counts in the mucus plug group were higher than those in the non-mucus plug group [(24.95±4.34) vs (23.22±2.91) kg/m 2, 0(0, 1) vs 0(0, 0), 97(37, 169) vs 31(18, 59) ppb (1 ppb=1×10 -9), 0.41(0.15, 0.70) vs 0.18(0.09, 0.37)×10 9/L](all P<0.05), and FVC%pred, FEV 1%pred, FEV 1/FVC, PEF%pred, MEF 50%pred, MEF 25%pred, MMEF%pred, MEF 75%pred were lower than those in the non-mucus plug group [(87.49±19.32)% vs (97.34±14.24)%, (76.49±19.58)% vs (91.07±18.33)%, (72.44±10.91)% vs (79.48±8.13)%, (82.36±24.46)% vs (93.83±18.27)%, (53.03±24.81)% vs (75.75±27.15)%, (46.47±22.92)% vs (64.09±25.90)%, (50.28±23.73)% vs (74.53±26.80)%, (71.30±27.55)% vs (89.92±26.82)%] (all P<0.05). In the group with mucus plug, the airway mucus plug score was positively correlated with the patient′s body weight and the number of peripheral blood Eos counts at enrollment ( r=0.413, 0.478; all P<0.05), and negatively correlated with FVC%pred and FEV 1%pred ( r=-0.576, -0.465; all P<0.05). Logistic regression analysis showed that airway mucus plug score was a risk factor for acute asthma attack ( OR=1.269, 95% CI: 1.031-1.562; P=0.024). Conclusions:Asthma patients have a high incidence of airway mucus plug, which is related to the level of Eos inflammation and body size. Airway mucus plugs can promote airflow obstruction and acute exacerbation of asthma. In clinical practice, appropriate asthma management policies can be formulated for airway mucus plugs to delay the progression of asthma and reduce the number of acute attacks.


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