1.Expert consensus on the prevention and treatment of adverse reactions in subcutaneous immunotherapy(2023, Chongqing).
Yu Cheng YANG ; Yang SHEN ; Xiang Dong WANG ; Yan JIANG ; Qian Hui QIU ; Jian LI ; Shao Qing YU ; Xia KE ; Feng LIU ; Yuan Teng XU ; Hong Fei LOU ; Hong Tian WANG ; Guo Dong YU ; Rui XU ; Juan MENG ; Cui Da MENG ; Na SUN ; Jian Jun CHEN ; Ming ZENG ; Zhi Hai XIE ; Yue Qi SUN ; Jun TANG ; Ke Qing ZHAO ; Wei Tian ZHANG ; Zhao Hui SHI ; Cheng Li XU ; Yan Li YANG ; Mei Ping LU ; Hui Ping YE ; Xin WEI ; Bin SUN ; Yun Fang AN ; Ya Nan SUN ; Yu Rong GU ; Tian Hong ZHANG ; Luo BA ; Qin Tai YANG ; Jing YE ; Yu XU ; Hua Bin LI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(7):643-656
2.Predictive model of curative effect of mite subcutaneous immunotherapy in 5-18 years of age patients with allergic asthma.
Qing Ning DUAN ; De Yu ZHAO ; Min YAN ; Feng LIU ; Ming Xia CHEN ; Ling Hui YANG
Chinese Journal of Pediatrics 2022;60(4):291-296
		                        		
		                        			
		                        			Objective: To analyze the factors affecting the efficacy of mite subcutaneous immunotherapy (SCIT) in allergic asthma patients aged 5-18 years, and to find the best predictive model for the curative effect. Methods: The data of 688 patients aged 5-18 years with allergic asthma who completed more than 3 years of mite SCIT from December 2006 to November 2021 in the Department of Respiratory Medicine, Children's Hospital Affiliated to Nanjing Medical University were retrospectively analyzed. Male, results of skin prick test (SPT), age, daily medication score (DMS), visual analogue scale (VAS) score, and enrollment season were defined as independent variables. R language models, including Logistic regression model, random forest model and extreme gradient boosting (XGboost) model, were used to analyze the impact of these independent variables on the outcomes. The receiver operating characteristic curve was applied to compare the predictive ability of the models. Hypothesis testing of the area under curve (AUC) of the 3 models was performed using DeLong test. Results: There were 435 males and 253 females in the 688 patients. There were 349 patients aged 5-<8 years, 240 patients aged 8-<11 years, and 99 patients aged 11-18 years. SPT showed that 429 cases (62.4%) were only allergic to mite, and 259 cases (37.7%) were also allergic to other allergens. According to the efficacy after 3 years of SCIT, 351 cases (51.0%) discontinued the treatment and 337 cases (49.0%) required continued treatment. The DMS was 4 (3, 6) at initiation, 3 (2, 5) at 3 months, 3 (2, 5) at 4 months, 2 (1, 3) at 12 months, and 0 (0, 1) at 3 years of SCIT treatment. The VAS was 3.5 (2.5, 5.2) at initiation, 3.2 (2.2, 4.8) at 3 months, 2.6 (1.4, 4.1) at 4 months, 1.0 (0.6, 1.8) at 12 months, and 0.5 (0, 1.2) at 3 years of treatment. At 3, 4, and 12 months, the rate of decline in DMS was 0 (0, 20%), 16.7% (0, 33.3%), and 50.0% (31.0%, 75.0%), respectively; and the VAS decreased by 7.1% (3.2%,13.8%), 27.6% (16.7%,44.4%), and 70.2% (56.1%, 82.3%), respectively. Regarding the enrollment season, 99 cases were in spring, 230 cases in summer, 171 cases in autumn, and 188 cases in winter. The R language Logistic regression model found that DMS>3 points at 3 months (OR=-3.5, 95%CI:-4.3--2.7, P<0.01), male (OR=-1.7, 95%CI:-2.3--1.0), P<0.01), DMS decline rate>16.7% at 4 months (OR=-1.6, 95%CI:-2.3--0.8, P<0.01) and DMS decline rate>0 at 3 months (OR=-0.7, 95%CI:-1.3--0.2, P<0.05) had higher possibility of drug discontinuation; whereas, the decline rate of DMS at 12 months>50.0% (OR=0.7, 95%CI: 0.1-1.3, P<0.05), VAS at 12 months>1.0 points (OR=0.9, 95%CI: 0.3-1.6, P<0.05), and initial VAS<4.0 points (OR=1.0, 95%CI: 0.4-1.6, P<0.01) had lower possibility of drug discontinuation. Both the random forest model and the XGboost model showed that DMS>3 points at 3 months (mean decrease accuracy=30.9, importance=0.45) had the greatest impact on drug discontinuation. The AUC of the random forest model was the largest at 0.900, with an accuracy of 78.2% and a sensitivity of 84.5%. Logistic regression model had AUC of 0.891, accuracy of 80.0%, and sensitivity of 80.0%; XGboost model had AUC of 0.886, accuracy of 76.9%, and sensitivity of 84.5%. The AUC of the pairwise comparison model by DeLong test found that all three models could be used for the prediction of this data set (all P>0.05). Conclusions: The more drugs used to control the primary disease, and the more careful reduction of the control medicine after starting SCIT treatment, the more favorable it is to stop all drugs after 3 years. The random forest model is the best predictive model for the efficacy of mite SCIT in asthmatic children.
		                        		
		                        		
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Allergens
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Asthma/therapy*
		                        			;
		                        		
		                        			Child
		                        			;
		                        		
		                        			Child, Preschool
		                        			;
		                        		
		                        			Desensitization, Immunologic/methods*
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Immunotherapy/methods*
		                        			;
		                        		
		                        			Injections, Subcutaneous
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Mites
		                        			;
		                        		
		                        			Retrospective Studies
		                        			
		                        		
		                        	
3.Systemic reactions to subcutaneous immunotherapy for bronchial asthma and/or allergic rhinitis in children and their risk factors.
Wang LIAO ; Liang CHEN ; Jun BAI
Chinese Journal of Contemporary Pediatrics 2020;22(11):1204-1208
		                        		
		                        			OBJECTIVE:
		                        			To investigate the incidence of systemic reactions (SR) to subcutaneous immunotherapy (SCIT) for bronchial asthma and/or allergic rhinitis in children and their risk factors.
		                        		
		                        			METHODS:
		                        			A retrospective analysis was performed on 198 children with bronchial and/or allergic rhinitis. According to the presence or absence of SR and local reactions (LR) during SCIT, the patients were divided into two groups: SR (with SR and LR, n=31) and control (without SR or LR, n=142). A multivariate logistic regression analysis was used to determine the risk factors associated with SR.
		                        		
		                        			RESULTS:
		                        			Among the 198 patients who received 8 157 injections of SCIT, 25 (12.6%) experienced SR (31 times, 0.38%), including grade I SR (18 times, 58%), grade II SR (10 times, 32%), grade III SR (3 times, 10%), and no grade IV SR. The multivariate logistic regression analysis showed that multiple sensitization with both food and inhaled allergens, specific IgE to dust mites (grade 6), total IgE (grade 6), and a history of LR were independent risk factors for SR (P<0.05).
		                        		
		                        			CONCLUSIONS
		                        			SCIT is a safe treatment for bronchial asthma and/or allergic rhinitis in children, with a low incidence of SR. Children with multiple sensitization with both food and inhaled allergens, a hypersensitive state (specific IgE to dust mites, grade 6; total IgE, grade 6), and a history of LR have an increased risk of SR to SCIT.
		                        		
		                        		
		                        		
		                        			Allergens
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Asthma/drug therapy*
		                        			;
		                        		
		                        			Child
		                        			;
		                        		
		                        			Desensitization, Immunologic
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Injections, Subcutaneous
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Rhinitis, Allergic/therapy*
		                        			;
		                        		
		                        			Risk Factors
		                        			
		                        		
		                        	
4.Consideration of Application of Insulin Pen Needles and Supervision.
Chinese Journal of Medical Instrumentation 2019;43(1):63-64
		                        		
		                        			
		                        			With the increasing incidence of diabetes mellitus in China, hypodermic injection of artificial insulin to control blood sugar has been popularized. Insulin pen needles are widely used in hospitals, communities and families. This article attempts to explore and think about the harm and countermeasures brought about by the reuse of insulin pen needles from the perspective of medical device supervision.
		                        		
		                        		
		                        		
		                        			China
		                        			;
		                        		
		                        			Diabetes Mellitus, Type 1
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hypoglycemic Agents
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			Injections, Subcutaneous
		                        			;
		                        		
		                        			instrumentation
		                        			;
		                        		
		                        			Insulin
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			Needles
		                        			
		                        		
		                        	
5.Incidence and Risk of Peripheral Neuropathy Caused by Intravenous and Subcutaneous Injection of Bortezomib.
Zhi-Qiang LIU ; Hai-Long XIA ; Cheng-Jun LI ; Lei XIA
Journal of Experimental Hematology 2019;27(5):1654-1663
		                        		
		                        			OBJECTIVE:
		                        			To compare the effects of intravenous and subcutaneous injection of bortezomib on incidence and relative risk of peripheral neuropathy in patients with multiple myeloma(MM).
		                        		
		                        			METHODS:
		                        			The electronic database of PubMed, Embase, Cochrance library, CNKI and related meeting records were searched by computers. The data were derived all from a matched randomized controlled studies. The incidence, relative risk(RR) and 95% confidence interval of peripheral neuropathy caused by intravenous and subcustaneous injections were calculated by the statistical methods.
		                        		
		                        			RESULTS:
		                        			Four RCT studies were selected for meta-analysis, with a total of 911 patients (479 cases and 432 cases in the subcutaneous injection and intravenous injection groups, respectively). The incidence of peripheral neuropathy in the intravenous injection group was 41.4% (95% CI=0.137-0.692, P=0.003), and the incidence of >2 grade of peripheral neuropathy was 15.6% (95% CI=0.005-0.308, P=0.043). The corresponding incidence rates of the subcutaneous injection group were 16% (95% CI=0.021-0.299, P=0.024) and 3.4% (95% CI=-0.011-0.080, P=0.141) respectively. Compared with the intravenous injection group, the RR of peripheral neuropathy and the relative risk of peripheral neuropathy above grade 2 were 0.525, 95% CI=0.297-0.928 (P=0.027) and 0.376, 95% CI=0.196-0.722 (P=0.003) respectively.
		                        		
		                        			CONCLUSION
		                        			Subcutaneous injection of bortezomib at therapeutic doses significantly reduces the incidence of peripheral neuropathy compared with intravenous injection.
		                        		
		                        		
		                        		
		                        			Antineoplastic Agents
		                        			;
		                        		
		                        			Bortezomib
		                        			;
		                        		
		                        			adverse effects
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Incidence
		                        			;
		                        		
		                        			Injections, Subcutaneous
		                        			;
		                        		
		                        			Multiple Myeloma
		                        			;
		                        		
		                        			Peripheral Nervous System Diseases
		                        			;
		                        		
		                        			chemically induced
		                        			
		                        		
		                        	
6.Safety of Ultra-rush Schedule of Subcutaneous Allergen Immunotherapy With House Dust Mite Extract Conducted in an Outpatient Clinic in Patients With Atopic Dermatitis and Allergic Rhinitis
So Hee LEE ; Myoung Eun KIM ; Yoo Seob SHIN ; Young Min YE ; Hae Sim PARK ; Dong Ho NAHM
Allergy, Asthma & Immunology Research 2019;11(6):846-855
		                        		
		                        			
		                        			PURPOSE: Ultra-rush schedule of subcutaneous allergen immunotherapy (UR-SCIT) administering maximum maintenance dose of allergen extract within one day can save time and effort for allergen immunotherapy in patients with allergic disease. However, UR-SCIT is associated with an increased risk of systemic reaction (SR) and typically has been conducted in a hospital admission setting. To overcome disadvantages of UR-SCIT, we evaluated the safety of UR-SCIT conducted in an outpatient clinic in patients with atopic dermatitis (AD) and allergic rhinitis (AR). METHODS: UR-SCIT was performed in 538 patients with AD and/or AR sensitized to house dust mite (HDM). A maximum maintenance dose of tyrosine-adsorbed HDM extract (1 mL of maintenance concentration) was divided into 4 increasing doses (0.1, 0.2, 0.3, and 0.4 mL) and administered to the patients by subcutaneous injection at 2-hour intervals for 8 hours in an outpatient clinic. SRs associated with UR-SCIT were classified according to the World Allergy Organization grading system. RESULTS: SR was observed in 12 of 538 patients (2.2%) with AD and/or AR during UR-SCIT. The severity grades of the observed SRs were mild-to-moderate (grade 1 in 7 patients, grade 2 in 4 patients, and grade 3 in 1 patient). The scheduled 4 increasing doses of HDM extract could be administered in 535 of 538 patients (99.4%) except 3 patients who experienced SR before administration of the last scheduled dose. SR was observed within 2 hours in 11 patients after administration of the scheduled doses of HDM extract except one patient who experienced a grade 2 SR at 5.5 hours after administration of the last scheduled dose. CONCLUSIONS: UR-SCIT with tyrosine-adsorbed HDM extract conducted in an outpatient clinic was tolerable in patients with AD and AR. UR-SCIT can be a useful method to start a SCIT in patients with AD and AR.
		                        		
		                        		
		                        		
		                        			Ambulatory Care Facilities
		                        			;
		                        		
		                        			Appointments and Schedules
		                        			;
		                        		
		                        			Dermatitis, Atopic
		                        			;
		                        		
		                        			Desensitization, Immunologic
		                        			;
		                        		
		                        			Dust
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hypersensitivity
		                        			;
		                        		
		                        			Injections, Subcutaneous
		                        			;
		                        		
		                        			Methods
		                        			;
		                        		
		                        			Outpatients
		                        			;
		                        		
		                        			Pyroglyphidae
		                        			;
		                        		
		                        			Rhinitis, Allergic
		                        			
		                        		
		                        	
7.Respiratory syncytial virus increases eosinophil extracellular traps in a murine model of asthma
Josiane Silva SILVEIRA ; Géssica Luana ANTUNES ; Rodrigo Benedetti GASSEN ; Ricardo Vaz BREDA ; Renato Tetelbom STEIN ; Paulo Márcio PITREZ ; Aline Andrea DA CUNHA
Asia Pacific Allergy 2019;9(4):e32-
		                        		
		                        			
		                        			BACKGROUND: Respiratory viral infections are the leading cause of asthma exacerbations. Eosinophil activation results in the formation of eosinophil extracellular traps (EETs), which release web-like structures of DNA and proteins that bind, disarm and extracellularly kill pathogens. OBJECTIVE: We investigated whether the respiratory syncytial virus (RSV) in vitro could induce EETs in bronchoalveolar lavage fluid eosinophils in a murine model of asthma. METHODS: BALB/cJ mice (6–8 weeks old) were sensitized with 2 subcutaneous injections of ovalbumin (20 μg) on days 0 and 7, followed by three intranasal challenges with ovalbumin (100 μg) on days 14, 15, and 16 of the protocol. The control group received Dulbecco's phosphate-buffered saline. Bronchoalveolar lavage fluid eosinophils of ovalbumin group or control group were stimulated with RSV (103 PFU/mL) in vitro for 3 hours. After that, culture supernatant was collected to perform the analyses proposed in this study. RESULTS: We verified an increase in extracellular DNA concentration in bronchoalveolar lavage fluid eosinophils from ovalbumin group stimulated with RSV (10³ PFU/mL) in vitro, which was confirmed by confocal microscopy. We demonstrated that most cells are negative for annexin V and propidium iodide in all groups evaluated. Also, RSV in vitro decreased interferon-ɣ in culture supernatant when compared to the ovalbumin group. CONCLUSION: In this study, we demonstrated for the first time that RSV in vitro induces EETs formation in eosinophils from asthmatic mice.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Annexin A5
		                        			;
		                        		
		                        			Asthma
		                        			;
		                        		
		                        			Bronchoalveolar Lavage Fluid
		                        			;
		                        		
		                        			DNA
		                        			;
		                        		
		                        			Eosinophil Peroxidase
		                        			;
		                        		
		                        			Eosinophils
		                        			;
		                        		
		                        			Extracellular Traps
		                        			;
		                        		
		                        			In Vitro Techniques
		                        			;
		                        		
		                        			Inflammation
		                        			;
		                        		
		                        			Injections, Subcutaneous
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Microscopy, Confocal
		                        			;
		                        		
		                        			Ovalbumin
		                        			;
		                        		
		                        			Propidium
		                        			;
		                        		
		                        			Respiratory Syncytial Viruses
		                        			
		                        		
		                        	
8.Udenafil Induces the Hair Growth Effect of Adipose-Derived Stem Cells
Biomolecules & Therapeutics 2019;27(4):404-413
		                        		
		                        			
		                        			Udenafil, which is a PDE5 inhibitor, is used to treat erectile dysfunction. However, it is unclear whether udenafil induces hair growth via the stimulation of adipose-derived stem cells (ASCs). In this study, we investigated whether udenafil stimulates ASCs and whether increased growth factor secretion from ASCs to facilitate hair growth. We found that subcutaneous injection of udenafil-treated ASCs accelerated telogen-to-anagen transition in vivo. We also observed that udenafil induced proliferation, migration and tube formation of ASCs. It also increased the secretion of growth factors from ASCs, such as interleukin-4 (IL-4) and IL12B, and the phosphorylation of ERK1/2 and NFκB. Furthermore, concomitant upregulation of IL-4 and IL12B mRNA levels was attenuated by ERK inhibitor or NFκB knockdown. Application of IL-4 or IL12B enhanced anagen induction in mice and increased hair follicle length in organ culture. The results indicated that udenafil stimulates ASC motility and increases paracrine growth factor, including cytokine signaling. Udenafil-stimulated secretion of cytokine from ASCs may promote hair growth via the ERK and NFκB pathways. Therefore, udenafil can be used as an ASC-preconditioning agent for hair growth.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Erectile Dysfunction
		                        			;
		                        		
		                        			Hair Follicle
		                        			;
		                        		
		                        			Hair
		                        			;
		                        		
		                        			Injections, Subcutaneous
		                        			;
		                        		
		                        			Intercellular Signaling Peptides and Proteins
		                        			;
		                        		
		                        			Interleukin-4
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Organ Culture Techniques
		                        			;
		                        		
		                        			Phosphorylation
		                        			;
		                        		
		                        			RNA, Messenger
		                        			;
		                        		
		                        			Stem Cells
		                        			;
		                        		
		                        			Up-Regulation
		                        			
		                        		
		                        	
9.Possibility of Injecting Adipose-Derived Stromal Vascular Fraction Cells to Accelerate Microcirculation in Ischemic Diabetic Feet: A Pilot Study
Kyung Chul MOON ; Ha Yoon CHUNG ; Seung Kyu HAN ; Seong Ho JEONG ; Eun Sang DHONG
International Journal of Stem Cells 2019;12(1):107-113
		                        		
		                        			
		                        			BACKGROUND AND OBJECTIVES: Beneficial effects of human adipose-derived stromal vascular fraction (SVF) cell injection on microcirculation have been recently reported in in vitro and in vivo studies. However, no clinical studies have reported its effect in diabetic patients who commonly experience compromised tissue perfusion, regardless of the status of intravascular blood flow. The present piloting study was designed to clinically examine the possibility of SVF cell injection to accelerate microcirculation, particularly in ischemic diabetic feet. METHODS: Ten diabetic feet were included to receive subcutaneous injection of SVF cells around wounds. Transcutaneous partial oxygen pressure (TcPO2) and cutaneous microvascular blood flow were measured before and every four weeks after cell injection until the 12th week visit. RESULTS: TcPO2 values increased from 31.3±7.4 before injection to 46.4±8.2 mmHg at 12 weeks after SVF injection (1.5-fold, p<0.05). Cutaneous microvascular blood flow levels increased from 34.0±21.1 before injection to 76.1±32.5 perfusion unit at 12 weeks after SVF injection (2.2-fold, p<0.05). There were no adverse events related to SVF cell injection. CONCLUSIONS: Results of this study demonstrate that adipose-derived SVF cell injection have the possibility to provide beneficial effects on microcirculation in ischemic diabetic feet.
		                        		
		                        		
		                        		
		                        			Diabetic Foot
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			In Vitro Techniques
		                        			;
		                        		
		                        			Injections, Subcutaneous
		                        			;
		                        		
		                        			Microcirculation
		                        			;
		                        		
		                        			Oxygen
		                        			;
		                        		
		                        			Perfusion
		                        			;
		                        		
		                        			Pilot Projects
		                        			;
		                        		
		                        			Wounds and Injuries
		                        			
		                        		
		                        	
10.Can Three Months of Teriparatide Be One of Treatment Options for Osteoporotic Vertebral Compression Fracture Patients?
Jung Hoon KANG ; Sang Mi YANG ; Soo Bin IM ; Je Hoon JEONG
Korean Journal of Neurotrauma 2019;15(1):19-27
		                        		
		                        			
		                        			OBJECTIVE: Osteoporosis is one of the most common causes of vertebral compression fractures (VCFs). Teriparatide, a recombinant human parathyroid hormone, is the first anabolic agent for the treatment of osteoporosis. The aim of this study was to determine whether 3 months of teriparatide could be effective for patients with osteoporotic VCF at the thoracolumbar spine. METHODS: We reviewed 25 patients with thoracolumbar osteoporotic compression fractures between July 2012 and October 2016 who could be followed up for more than 1 year. Patients were divided into 2 groups depending on the use of teriparatide: 14 patients received teriparatide through subcutaneous injection (group I) and 11 patients did not receive teriparatide (group II). Demographic data, bone mineral density, hospitalization period, changes in the visual analogue scale (VAS) score, body mass index, and medical history such as smoking, alcohol, diabetes, and steroid usage were reviewed. Radiographs were also reviewed to evaluate vertebral body compression percentages and kyphotic angles. RESULTS: Overall changes of VAS score between injury and follow-up were statistically improved in both groups at 2 to 3 weeks post-injury. However, difference in VAS improvement at a specific time between the 2 groups was not statistically significant. Overall kyphotic angle and compression percentage between injury and follow-up time were increased in group II than those in group I, although the difference between the 2 groups was not statistically significant. CONCLUSION: Three-month of teriparatide did not show protective effects on progression of fractured vertebral body collapse or kyphotic changes in patients with osteoporosis.
		                        		
		                        		
		                        		
		                        			Body Mass Index
		                        			;
		                        		
		                        			Bone Density
		                        			;
		                        		
		                        			Follow-Up Studies
		                        			;
		                        		
		                        			Fractures, Compression
		                        			;
		                        		
		                        			Hospitalization
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Injections, Subcutaneous
		                        			;
		                        		
		                        			Osteoporosis
		                        			;
		                        		
		                        			Osteoporotic Fractures
		                        			;
		                        		
		                        			Parathyroid Hormone
		                        			;
		                        		
		                        			Smoke
		                        			;
		                        		
		                        			Smoking
		                        			;
		                        		
		                        			Spine
		                        			;
		                        		
		                        			Teriparatide
		                        			;
		                        		
		                        			Thoracic Vertebrae
		                        			;
		                        		
		                        			Treatment Outcome
		                        			
		                        		
		                        	
            
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