1.Association Between the Red Blood Cell Distribution Width and 30-Day Mortality in Intensive Care Patients Undergoing Cardiac Surgery: A Retrospective Observational Study Based on the Medical Information Mart for Intensive Care-IV Database
Weiqiang CHEN ; Peiling YU ; Chao CHEN ; Shaoyan CAI ; Junheng CHEN ; Chunqin ZHENG ; Chaojin CHEN ; Liangjie ZHENG ; Chunming GUO
Annals of Laboratory Medicine 2024;44(5):401-409
Background:
Millions of patients undergo cardiac surgery each year. The red blood cell distribution width (RDW) could help predict the prognosis of patients who undergo percutaneous coronary intervention or coronary artery bypass surgery. We investigated whether the RDW has robust predictive value for the 30-day mortality among patients in an intensive care unit (ICU) after undergoing cardiac surgery.
Methods:
Using the Medical Information Mart for Intensive Care-IV Database, we retrieved data for 11,634 patients who underwent cardiac surgery in an ICU. We performed multivariate Cox regression analysis to model the association between the RDW and 30-day mortality and plotted Kaplan–Meier curves. Subgroup analyses were stratified using relevant covariates. Receiver operating characteristic (ROC) curves were used to determine the predictive value of the RDWs.
Results:
The total 30-day mortality rate was 4.2% (485/11,502). The elevated-RDW group had a higher 30-day mortality rate than the normal-RDW group (P < 0.001). The robustness of our data analysis was confirmed by performing subgroup analyses. Each unit increase in the RDW was associated with a 17% increase in 30-day mortality when the RDW was used as a continuous variable (adjusted hazard ratio = 1.17, 95% confidence interval, 1.10–1.25). Our ROC results showed the predictive value of the RDW.
Conclusions
An elevated RDW was associated with a higher 30-day mortality in patients after undergoing cardiac surgery in an ICU setting. The RDW can serve as an efficient and accessible method for predicting the mortality of patients in ICUs following cardiac surgery.
2.Association Between the Red Blood Cell Distribution Width and 30-Day Mortality in Intensive Care Patients Undergoing Cardiac Surgery: A Retrospective Observational Study Based on the Medical Information Mart for Intensive Care-IV Database
Weiqiang CHEN ; Peiling YU ; Chao CHEN ; Shaoyan CAI ; Junheng CHEN ; Chunqin ZHENG ; Chaojin CHEN ; Liangjie ZHENG ; Chunming GUO
Annals of Laboratory Medicine 2024;44(5):401-409
Background:
Millions of patients undergo cardiac surgery each year. The red blood cell distribution width (RDW) could help predict the prognosis of patients who undergo percutaneous coronary intervention or coronary artery bypass surgery. We investigated whether the RDW has robust predictive value for the 30-day mortality among patients in an intensive care unit (ICU) after undergoing cardiac surgery.
Methods:
Using the Medical Information Mart for Intensive Care-IV Database, we retrieved data for 11,634 patients who underwent cardiac surgery in an ICU. We performed multivariate Cox regression analysis to model the association between the RDW and 30-day mortality and plotted Kaplan–Meier curves. Subgroup analyses were stratified using relevant covariates. Receiver operating characteristic (ROC) curves were used to determine the predictive value of the RDWs.
Results:
The total 30-day mortality rate was 4.2% (485/11,502). The elevated-RDW group had a higher 30-day mortality rate than the normal-RDW group (P < 0.001). The robustness of our data analysis was confirmed by performing subgroup analyses. Each unit increase in the RDW was associated with a 17% increase in 30-day mortality when the RDW was used as a continuous variable (adjusted hazard ratio = 1.17, 95% confidence interval, 1.10–1.25). Our ROC results showed the predictive value of the RDW.
Conclusions
An elevated RDW was associated with a higher 30-day mortality in patients after undergoing cardiac surgery in an ICU setting. The RDW can serve as an efficient and accessible method for predicting the mortality of patients in ICUs following cardiac surgery.
3.Association Between the Red Blood Cell Distribution Width and 30-Day Mortality in Intensive Care Patients Undergoing Cardiac Surgery: A Retrospective Observational Study Based on the Medical Information Mart for Intensive Care-IV Database
Weiqiang CHEN ; Peiling YU ; Chao CHEN ; Shaoyan CAI ; Junheng CHEN ; Chunqin ZHENG ; Chaojin CHEN ; Liangjie ZHENG ; Chunming GUO
Annals of Laboratory Medicine 2024;44(5):401-409
Background:
Millions of patients undergo cardiac surgery each year. The red blood cell distribution width (RDW) could help predict the prognosis of patients who undergo percutaneous coronary intervention or coronary artery bypass surgery. We investigated whether the RDW has robust predictive value for the 30-day mortality among patients in an intensive care unit (ICU) after undergoing cardiac surgery.
Methods:
Using the Medical Information Mart for Intensive Care-IV Database, we retrieved data for 11,634 patients who underwent cardiac surgery in an ICU. We performed multivariate Cox regression analysis to model the association between the RDW and 30-day mortality and plotted Kaplan–Meier curves. Subgroup analyses were stratified using relevant covariates. Receiver operating characteristic (ROC) curves were used to determine the predictive value of the RDWs.
Results:
The total 30-day mortality rate was 4.2% (485/11,502). The elevated-RDW group had a higher 30-day mortality rate than the normal-RDW group (P < 0.001). The robustness of our data analysis was confirmed by performing subgroup analyses. Each unit increase in the RDW was associated with a 17% increase in 30-day mortality when the RDW was used as a continuous variable (adjusted hazard ratio = 1.17, 95% confidence interval, 1.10–1.25). Our ROC results showed the predictive value of the RDW.
Conclusions
An elevated RDW was associated with a higher 30-day mortality in patients after undergoing cardiac surgery in an ICU setting. The RDW can serve as an efficient and accessible method for predicting the mortality of patients in ICUs following cardiac surgery.
4.Association Between the Red Blood Cell Distribution Width and 30-Day Mortality in Intensive Care Patients Undergoing Cardiac Surgery: A Retrospective Observational Study Based on the Medical Information Mart for Intensive Care-IV Database
Weiqiang CHEN ; Peiling YU ; Chao CHEN ; Shaoyan CAI ; Junheng CHEN ; Chunqin ZHENG ; Chaojin CHEN ; Liangjie ZHENG ; Chunming GUO
Annals of Laboratory Medicine 2024;44(5):401-409
Background:
Millions of patients undergo cardiac surgery each year. The red blood cell distribution width (RDW) could help predict the prognosis of patients who undergo percutaneous coronary intervention or coronary artery bypass surgery. We investigated whether the RDW has robust predictive value for the 30-day mortality among patients in an intensive care unit (ICU) after undergoing cardiac surgery.
Methods:
Using the Medical Information Mart for Intensive Care-IV Database, we retrieved data for 11,634 patients who underwent cardiac surgery in an ICU. We performed multivariate Cox regression analysis to model the association between the RDW and 30-day mortality and plotted Kaplan–Meier curves. Subgroup analyses were stratified using relevant covariates. Receiver operating characteristic (ROC) curves were used to determine the predictive value of the RDWs.
Results:
The total 30-day mortality rate was 4.2% (485/11,502). The elevated-RDW group had a higher 30-day mortality rate than the normal-RDW group (P < 0.001). The robustness of our data analysis was confirmed by performing subgroup analyses. Each unit increase in the RDW was associated with a 17% increase in 30-day mortality when the RDW was used as a continuous variable (adjusted hazard ratio = 1.17, 95% confidence interval, 1.10–1.25). Our ROC results showed the predictive value of the RDW.
Conclusions
An elevated RDW was associated with a higher 30-day mortality in patients after undergoing cardiac surgery in an ICU setting. The RDW can serve as an efficient and accessible method for predicting the mortality of patients in ICUs following cardiac surgery.
5.Expression and prognostic factors analysis of CYFRA21-1, CEA, and Ki67 in non-small cell lung cancer
Jianyun PAN ; Yien HUANG ; Shujun HONG ; Shaohan FANG ; Jingwei LIU ; Weiqiang CHEN ; Gaojian PAN ; Jie JIANG ; Guojun GENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(05):682-688
Objective To explore the value of preoperative detection of soluble fragments of cytokeratin-19 (CYFRA21-1), carcinoembryonic antigen (CEA), and postoperative detection of nuclear proliferation associated antigen Ki67 in prognostic evaluation of non-small cell lung cancer patients. Methods The clinicopathological data and follow-up results of patients with non-small cell lung cancer treated in the Department of Thoracic Surgery of the First Affiliated Hospital of Xiamen University in 2017 were collected. CYFRA21-1>3.39 ng/mL was defined as positive, and CEA>5 ng/mL was defined as positive. The receiver operating characteristic curve (ROC curve) of Ki67 expression level was drawn. The maximum area under the curve (AUC) was the cutoff value of Ki67 expression level, and the Ki67 expression level greater than its cutoff value was defined as positive. Cox regression analysis was used to determine the independent risk factors for poor prognosis in patients with non-small cell lung cancer. Results Finally 248 patients were collected, including 125 males and 123 females, with a median age of 61 years (ranging from 30 to 81 years) at the time of surgery. Univariate analysis showed that positive CYFRA21-1, high expression of Ki67, positive CEA, age≥60 years at operation, distant metastasis, lymph node metastasis, maximum tumor diameter>3 cm, and TNM stage Ⅲ were associated with poor prognosis in patients with non-small cell lung cancer. When combined detection of preoperative tumor markers and postoperative Ki67, the prognosis of all negative patients was the best, and that of all positive patients was the worst. Cox regression analysis showed that positive CEA+positive CYFRA21-1+high expression of Ki67 was an independent risk factor for poor prognosis in patients with non-small cell lung cancer (P<0.05). Conclusion The combined detection of preoperative serum CYFRA21-1, CEA, and postoperative Ki67 has important value in evaluating the prognosis of non-small cell lung cancer patients.
6.Role of inflammatory factors in diabetic ulcers and prospects of traditional Chinese medicine intervention
Yuchang ZHANG ; Xiang CHEN ; Bo HE ; Shenghua LI ; Xiangqian MU ; Weiqiang SUN ; Li ZHANG ; Jie CHEN
Chinese Journal of Tissue Engineering Research 2024;28(34):5544-5551
BACKGROUND:Diabetic ulcers are a common complication of diabetes mellitus,which is manifested as foot ulcers complicated with infection,long treatment cycle,high disability rate and mortality rate,and brings a heavy burden to patients and social care. OBJECTIVE:To review the mechanism of action and the latest treatment progress of traditional Chinese medicine(TCM)in the treatment of diabetic ulcers,and to provide a basis for further theoretical research and clinical application. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature using the keywords of"diabetic ulcer,medicinal herb,inflammation,interleukin-1β,interleukin-6,tumor necrosis factor,hypersensitive C-reactive protein,γ-interferon,interleukin-4,interleukin-10"in Chinese and English,respectively.The relevant literature in recent years was searched,and finally 75 articles were included for review. RESULTS AND CONCLUSION:The high glucose environment of the body will increase the level of pro-inflammatory cytokines,so that diabetic ulcer wounds are in a state of chronic inflammatory response for a long time,and difficult to heal or even not heal.TCM has summed up a lot of experience in the long-term struggle with diabetic ulcer.At present,TCM divides diabetic ulcers into four syndrome types:dampness and heat poison syndrome,blood and blood stasis obstruction pattern,heat poison injury Yin pattern,and Qi and blood deficiency syndrome,as well as representative prescriptions for treatment.According to their clinical characteristics,diabetic ulcers can be also divided into three stages:primary,middle and late stages.Different treatment methods are proposed:"clear method,""warm and clear combined use"and"maintenance method."Under the guidance of dialectical typing and staging of TCM,TCM monomers,extracts and compounds inhibit the inflammatory response and promote the healing of diabetic ulcers by down-regulating the expression of pro-inflammatory factors and/or up-regulating the expression of anti-inflammatory factors.Compared with modern medicine,TCM has significant advantages in the treatment of diabetic ulcers.There are many TCM monomers,extracts and compounds for the treatment of diabetic ulcers,such as angelica,curcumin,improved Chonghe ointment,Sanhuang blood exhaustion prescription and sore-ulcer I.formula,etc.It has been found that TCM for the treatment of diabetic ulcers is mainly heat-clearing and detoxifying,invigorating blood circulation and removing blood stasis,and amassing sores and muscle-building drugs,and the frequency of use,treatment scope and therapeutic effect of TCM compounds are obviously better than those of TCM monomers and extracts.Among them,the most commonly used are the Sanhuang blood exhaustion prescription and the sore-ulcer I as well as prescription for the treatment of damp heat toxicity syndrome and Zizhu ointment for the treatment of non-ischemic diabetic ulcers.However,there are also some shortcomings in the treatment of diabetic ulcers with TCM.First,there are few clinical syndrome studies on diabetic ulcers.Secondly,there are a wide variety of TCM monomers,extracts and compounds for the treatment of diabetic ulcers,and the relevant research is insufficiently in-depth.Finally,the research on the mechanism underlying TCM treatment of diabetic ulcers is still in the preliminary exploration stage,and the mechanism of action still needs to be further explored.In the future,it is necessary to strengthen the research on the pharmacology of TCM and the clinical syndrome of diabetic ulcers,analyze the potential targets and related signaling pathways of TCM in the treatment of diabetic ulcers,give full play to the therapeutic advantages of TCM with multiple targets,multiple pathways,multiple levels and multiple systems,and develop TCM with significant efficacy,active ingredients and clear targets.
7.Analysis of clinical characteristics of persistent HBeAg positivity in patients with chronic hepatitis B treated with nucleos(t)ide analogues
Liangpen PENG ; Weiqiang GAN ; Yubao ZHENG ; Youming CHEN ; Jing LIU ; Zhebin WU ; Zhiliang GAO
Chinese Journal of Hepatology 2024;32(3):193-200
Objective:To explore the clinical characteristics of persistent HBeAg positivity in patients with chronic hepatitis B treated with nucleos(t)ide analogues.Methods:A retrospective analysis was performed according to different data types. An independent sample t-test, Mann-Whitney U test, chi-square test, or Fisher's exact probability method were used. Chronic hepatitis B patients followed up for four years were collected from the follow-up case database of the Department of Infectious Diseases of Zhongshan Third Hospital from January 2009 to December 2018 and were divided into two groups, A and B, with 87 and 145 cases respectively, according to the duration of HBeAg-negativity≤ 3 and persistent positivity >3 years. Statistical analysis was conducted on the age, gender, family history, baseline, follow-up visit duration, liver function, and other data among the two patient groups.Results:There were no statistically significant differences in gender, age, family history of liver cirrhosis, family history of liver cancer, liver cirrhosis condition before treatment, fatty liver disease combined condition before treatment, baseline HBsAg, anti-HBc, alanine aminotransferase, albumin, or total bilirubin between the two groups of patients ( P ?>?0.05). HBV DNA and HBeAg were significantly higher in group B than those in group A at baseline, with P≤0.001. Aspartate aminotransferase and γ-glutamyl transferase were significantly higher in group A than those in group B at baseline. The proportion of family history of hepatitis B was significantly higher in group B (69.0%) than that in group A (50.6%) among the two groups of patients, and the difference was statistically significant ( P ?=?0.005). The proportion of mothers with hepatitis B was significantly higher in group B (25.5%) than in group A (11.5%), P ?=?0.010. During the treatment process, the HBV DNA quantification was significantly higher in group B than that in group A at 0.5 and 1 years (P≤0.002). The proportion of HBV DNA <100IU/ml was also significantly different at six months and one year (χ 2=30.327, P ?0.001 and χ 2=11.779, P ?=?0.001). The HBsAg level was higher in group B than that of group A in the second and fourth years, P ?0.05. During the entire treatment process, the HBeAg level was significantly higher in group B than that in group A ( P ?0.001). A total of seven cases developed liver cirrhosis or cancer during follow-up, including three cases in group A and four cases in group B ( P ?>?0.05). Conclusion:HBeAg-positive patients with chronic hepatitis B have persistent HBeAg positivity when treated with long-term nucleos(t)ide analogues. Accordingly, a greater proportion of this kind of patient family and mothers have a remarkable history of hepatitis B and a reduced HBV DNA relapse rate in the early stages (within a year or less).
8.Exploring the causality between intestinal flora and hyperplastic scars of human based on two-sample Mendelian randomization analysis
Wentao CHEN ; Xiaoxiang WANG ; Wenlian ZHENG ; Weiqiang ZHANG ; Lujia MAO ; Jianan ZHUO ; Sitong ZHOU ; Ronghua YANG
Chinese Journal of Burns 2024;40(4):333-341
Objective:To investigate the causality between intestinal flora and hypertrophic scars (HS) of human.Methods:This study was a study based on two-sample Mendelian randomization (TSMR) analysis. The data on intestinal flora ( n=18 473) and HS ( n=208 248) of human were obtained from the genome-wide association study database. Genetically variable genes at five levels (phylum, class, order, family, and genus) of known intestinal flora, i.e., single nucleotide polymorphisms (SNPs), were extracted as instrumental variables for linkage disequilibrium (LD) analysis. Human genotype-phenotype association analysis was performed using PhenoScanner V2 database to exclude SNPs unrelated to HS in intestinal flora and analyze whether the selected SNPs were weak instrumental variables. The causal relationship between intestinal flora SNPs and HS was analyzed through four methods of TSMR analysis, namely inverse variance weighted (IVW), MR-Egger regression, weighted median, and weighted mode. Scatter plots of significant results from the four aforementioned analysis methods were plotted to analyze the correlation between intestinal flora SNPs and HS. Both IVW test and MR-Egger regression test were used to assess the heterogeneity of intestinal flora SNPs, MR-Egger regression test and MR-PRESSO outlier test were used to assess the horizontal multiplicity of intestinal flora SNPs, and leave-one-out sensitivity analysis was used to determine whether HS was caused by a single SNP in the intestinal flora. Reverse TSMR analyses were performed for HS SNPs and genus Intestinimonas or genus Ruminococcus2, respectively, to detect whether there was reverse causality between them. Results:A total of 196 known intestinal flora, belonging to 9 phyla, 16 classes, 20 orders, 32 families, and 119 genera, were obtained, and multiple SNPs were obtained from each flora as instrumental variables. LD analysis showed that the SNPs of the intestinal flora were consistent with the hypothesis that genetic variation was strongly associated with exposure factors, except for rs1000888, rs12566247, and rs994794. Human genotype-phenotype association analysis showed that none of the selected SNPs after LD analysis was excluded and there were no weak instrumental variables. IVW, MR-Egger regression, weighted median, and weighted mode of TSMR analysis showed that both genus Intestinimonas and genus Ruminococcus2 were causally associated with HS. Among them, forest plots of IVW and MR-Egger regression analyses also showed that 16 SNPs (the same SNPs number of this genus below) of genus Intestinimonas and 15 SNPs (the same SNPs number of this genus below) of genus Ruminococcus2 were protective factors for HS. Further, IVW analysis showed that genus Intestinimonas SNPs (with odds ratio of 0.62, 95% confidence interval of 0.41-0.93, P<0.05) and genus Ruminococcus2 SNPs (with odds ratio of 0.62, 95% confidence interval of 0.40-0.97, P<0.05) were negatively correlated with the risk of HS. Scatter plots showed that SNPs of genus Intestinimonas and genus Ruminococcus2 were protective factors of HS. Both IVW test and MR-Egger regression test showed that SNPs of genus Intestinimonas (with Q values of 5.73 and 5.76, respectively, P>0.05) and genus Ruminococcus2 (with Q values of 13.67 and 15.61, respectively, P>0.05) were not heterogeneous. MR-Egger regression test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity (with intercepts of 0.01 and 0.06, respectively, P>0.05); MR-PRESSO outlier test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity ( P>0.05). Leave-one-out sensitivity analysis showed that no single intestinal flora SNP drove the occurrence of HS. Reverse TSMR analysis showed no reverse causality between HS SNPs and genus Intestinimonas or genus Ruminococcus2 (with odds ratios of 1.01 and 0.99, respectively, 95% confidence intervals of 0.97-1.06 and 0.96-1.04, respectively, P>0.05). Conclusions:There is a causal relationship between intestinal flora and HS of human, in which genus Intestinimonas and genus Ruminococcus2 have a certain effect on inhibiting HS.
9.SPEEDO:a rapid and accurate Monte Carlo dose calculation program for carbon ion therapy
Jin WU ; Shijun LI ; Yuxin WANG ; Yankui CHANG ; Xi PEI ; Zhi CHEN ; Weiqiang CHEN ; Qiang LI ; George Xie XU
Chinese Journal of Medical Physics 2024;41(10):1189-1198
Objective To develop a rapid and accurate Monte Carlo program(simplified code for dosimetry of carbon ions,SPEEDO)for carbon ion therapy.Methods For electromagnetic process,type Ⅱ condensed history simulation scheme and continuous slowing down approximation were used to simulate energy straggling,range straggling,multiple scattering,and ionization processes.For nuclear interaction,5 types of target nuclei were considered,including hydrogen,carbon,nitrogen,oxygen,and calcium.The produced secondary charged particles followed the same condensed history framework.The study simulated the transport of carbon ions in 4 materials(water,soft tissues,lung,and bone),and the calculated doses were validated against TOPAS(a Monte Carlo simulation software for radiotherapy physics),followed by a comparison with dose measurements in a water phantom from the HIMM-WW(a medical heavy-ion accelerator facility in Wuwei).Results SPEEDO's simulation results showed good consistency with TOPAS.For each material,in the voxel region where the physical dose was greater than 10%of the maximum dose point,the relative maximum dose error of both was less than 2%.At treatment energy of 400 MeV/u,SPEEDO's computation time was significantly less than that of TOPAS(13.8 min vs 105.0 min).SPEEDO's calculation results also showed good agreement with HIMM-WW measurements in terms of lateral dose distribution and integrated dose depth curve.Conclusion SPEEDO program can accurately and rapidly perform Monte Carlo dose calculations for carbon-ion therapy.
10.Comparison of cannulated screws and Kirschner wires in the treatment of pediatric medial malleolar fractures of Salter-Harris types Ⅲ and Ⅳ
Yuancheng PAN ; Fengshan LU ; Tianlai CHEN ; Hong MA ; Yueming GUO ; Weiqiang LI ; Shunyou CHEN
Chinese Journal of Orthopaedic Trauma 2024;26(5):398-403
Objective:To compare the therapeutic effects of cannulated screws and Kirschner wires in the treatment of medial malleolar fractures of Salter-Harris types Ⅲ and Ⅳ in children.Methods:A retrospective study was conducted to analyze the data of 48 and 16 children who had been treated respectively at Department of Pediatric Orthopaedics, Fuzhou Second General Hospital, and Department of Pediatric Orthopaedics, Foshan Hospital of Traditional Chinese Medicine for medial malleolar fractures of Salter-Harris types Ⅲ and Ⅳ from June 2016 to June 2022. There were 32 males and 32 females with an age of 12 (10, 14) years; 31 left and 33 right sides were affected. By the Salter-Harris classification: type Ⅲ in 45 cases, and type Ⅳ in 19 cases. The patients were divided into 2 groups according to their internal fixation methods. Group A (44 cases) was subjected to internal fixation with cannulated screws and group B (20 cases) to internal fixation with Kirschner wires. At the last follow-up, anteroposterior and lateral X-ray films of their ankle joints were taken for imaging evaluation. Functional recovery of the affected limbs was evaluated based on the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scoring, and related complications were recorded.Results:The 2 groups were comparable because there were no significant differences in their preoperative general data except laterality ( P>0.05). All the patients were followed up for (37.3±21.5) months and achieved bony union. At the last follow-up, for groups A and B respectively, the distal lateral angle of the tibia was 89.0° (89.0°, 90.0°) and 89.0° (89.0°, 90.0°), the range of ankle motion was 73.5° (67.8°, 76.0°) and 70.0° (70.0°, 75.0°), and the good and excellent rate by the AOFAS ankle-hindfoot scoring was 97.7% (43/44) and 95.0% (19/20), showing no significant difference between the 2 groups ( P>0.05). There was a significant difference between the 2 groups in the incidence of premature physeal closure [36.4% (16/44) versus 65.0% (13/20)] ( P=0.033). Conclusions:In the treatment of medial malleolar fractures of Salter-Harris types Ⅲ and Ⅳ in children, internal fixation with both cannulated screws and Kirschner wires can lead to comparable efficacy in good functional recovery and imaging evaluation. However, fixation with cannulated screws may be more advantageous in reducing the risk of early closure of the epiphysis.

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