1.Construction of a postoperative mortality risk model for patients with acute aortic dissection based on XGBoost-SHAP method
Xin ZHANG ; Min FANG ; Yi CAO ; Ting-Ting LI ; Xian-Kong LIU ; Jia-Yi DANG ; Xue-Sen ZHAO ; Hong-Qin REN ; Jia-Ze GENG ; Kai-Wen WANG ; Tie-Sheng HAN ; Yong-Bo ZHAO ; Dong MA
Medical Journal of Chinese People's Liberation Army 2025;50(10):1226-1234
Objective To develop a predictive model for postoperative mortality risk in patients with acute aortic dissection(AAD)using the Extreme Gradient Boosting(XGBoost)algorithm combined with Shapley Additive Explanation(SHAP),and to establish a prediction website to serve as a diagnostic and therapeutic support platform for clinicians and patients.Methods A retrospective cohort study design was adopted.Data from 782 AAD patients who underwent surgical treatment at the Fourth Hospital of Hebei Medical University from January 2013 to December 2023 were collected,including basic information and initial serum biomarker test results.Patients were randomly divided into training and test sets at a 7:3 ratio.An external validation set consisting of 313 AAD patients admitted to the Second Hospital of Hebei Medical University from January 2020 to December 2023 was also established for further model validation.Variables were screened using LASSO regression,and an XGBoost machine learning model was constructed and interpreted using SHAP.The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curve analysis.Using the Shiny package,the XGBoost model was deployed to shinyapps.io to create a prediction website for postoperative mortality risk in AAD patients.One patient was selected by simple random sampling from the test set and the external validation set respectively for the prediction example on the Shiny webpage.Results The XGBoost model demonstrated high predictive performance for postoperative mortality in AAD patients,with area under the ROC curve(AUC)values of 0.928(95%CI 0.901-0.956)in the training set,0.919(95%CI 0.891-0.949)in the test set,and 0.941(95%CI 0.915-0.967)in the external validation set.SHAP values indicated the following order of variable importance in the model(from highest to lowest):"lactate dehydrogenase""blood chlorine""multiple organ injury""carbon dioxide combining power""prothrombin time""α-hydroxybutyric acid""creatine kinase isoenzyme""Stanford classification""combined use of bedside blood purification""gender""acute kidney injury""gastrointestinal bleeding""brain injury"and"shock".A risk prediction website for adverse postoperative outcomes in AAD patients was developed using XGBoost-SHAP method(https://dun-dunxiaolu.shinyapps.io/document/)and validated with examples.One randomly selected patient from each of the test and external validation sets was applied:the predicted mortality risk value for patient 1(who died postoperatively)was 0.9539,and that for patient 2(who survived postoperatively)was 0.0206.Conclusions The XGBoost-SHAP model demonstrates high accuracy in predicting postoperative mortality risk for AAD patients.The online prediction tool established based on this model enhances the identification efficiency of high-risk postoperative mortality patients.
2.Cancer cachexia-related monocytic myeloid-derived suppressor cells impair T-cell negative selection and predict immune-related adverse events
Li Wei ; Ya-Qin Sun ; Jian-Hua Ren ; Ze-Xuan Huang ; Yuan Zhang ; Xiu-Qing Pang ; Xiao-Tong Lv ; Xiang-Yuan Wu ; Yan-Fang Xing ; Xing Li
Liver Research 2025;9(4):298-312
Background and aims
Cancer cachexia is prevalent in various cancers and is associated with chemotherapy toxicity. However, limited data exist on the relationship between cachexia and immune-related adverse events (irAEs). The aim of this study is to explore the correlation between cancer cachexia and irAEs and its possible mechanism.
Methods
A murine model of orthotopic hepatocellular carcinoma (HCC) with cachexia was developed to evaluate the impact of T-cell infiltration into multiple tumor-free organs on the occurrence of irAEs. Single-cell RNA sequencing of thymic stromal cells was performed. Additionally, patients with advanced cancers receiving anti-programmed cell death protein 1/ligand 1 (PD-1/L1) antibody treatment were followed to investigate the relationship between cachexia and irAEs.
Results
Inflammatory cell infiltration was observed in multiple tumor-free organs of cachexic HCC mice but not in non-cachexic controls. Immunofluorescence confirmed that the infiltrating cells included CD4+ and CD8+ T cells. Morphological assessment and hematoxylin–eosin staining revealed thymic atrophy in cachexic HCC mice. Single-cell RNA sequencing of thymic stromal cells showed a reduction in medullary thymic epithelial cells (mTECs) II and III in cachexic mice. Autoimmune regulator (Aire) downregulation was accompanied by decreased expression of tissue-restricted antigens in mTECs. T cells from cachexic HCC mice induced organ-specific inflammation and T-cell infiltration in multiple organs of tumor-free mice. Following anti-mouse PD-1 antibody treatment, the incidence of inflammation in multiple organs markedly increased in cachexic HCC mice and in tumor-free mice that had received T cells from the cachexic HCC mice. Flow cytometry and immunofluorescence analyses revealed enrichment of thymic monocytic myeloid-derived suppressor cells (M-MDSCs) in cachexic HCC mice. M-MDSCs infiltrated the thymus in cachexic mice with cancer, and they induced apoptosis of mTECs from tumor-free mice in vitro via nitric oxide production. Transfer of M-MDSCs led to inflammatory cell infiltration in multiple organs and thymic involution in tumor-free mice without affecting body weight. Sixty-four patients with advanced cancer receiving anti-PD-1/L1 therapy were enrolled. Patients who developed irAEs had higher levels of circulating M-MDSCs than those who did not. Moreover, patients with cachexia (body mass index (BMI) < 20 kg/m2 or ≥5% weight loss over the past 6 months) had elevated M-MDSC levels. Patients with both high M-MDSC levels and low BMI or weight loss ≥5% experienced more irAEs (hazard ratio: 2.333; 95% confidence interval: 1.231–4.423).
Conclusions
M-MDSCs in cachexic mice induced mTEC apoptosis through nitric oxide production, impairing T-cell negative selection and promoting autoimmune T-cell infiltration into tumor-free organs. Cancer cachexia-related M-MDSCs may serve as predictive biomarkers for irAEs in patients with advanced cancer.
Graphical abstract
3.Relationship between the Height of Alveolar Bone Resorption and Sex and Age in Adolescents.
Jing-Jing MA ; Min SHANG ; Da-Wei QIN ; Wen-Zhao REN ; Jia-Yin SHI ; Xiao-Yun ZHAO ; Ze-Wei YAO ; Fan LI
Journal of Forensic Medicine 2022;38(5):589-594
OBJECTIVES:
To explore the relationship between the height of alveolar bone resorption and sex and age in the adolescent dentition.
METHODS:
Multi-slice computed tomography (MSCT) was used to measure the height of alveolar bone resorption at labial, lingual, mesial and distal sites of teeth in 149 adolescents aged from 10 to 20 years. SPSS 25.0 software was used to analyze the relationship between the height of alveolar bone resorption and sex and age.
RESULTS:
There was no significant difference in the height of alveolar bone resorption between sex (P>0.05). The height of alveolar bone resorption was positively correlated with age in all types of teeth. The model constructed by combining the alveolar bone resorption height data of four sites (y=2.569x1+3.106x2+4.108x3+1.451x4-0.082, R2max=0.756)had a better ability to infer age than that of combining two sites (y=5.942x1+4.489x2+0.612, R2max=0.706) and a single site (R2max=0.638).
CONCLUSIONS
The height of alveolar bone resorption is positively correlated with the age of adolescents. The combination of four sites has a stronger ability to infer the relationship between the height of alveolar bone resorption and age in adolescents and has higher accuracy in practical application.
Humans
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Adolescent
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Child
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Young Adult
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Adult
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Alveolar Process/diagnostic imaging*
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Cone-Beam Computed Tomography
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Bone Resorption/diagnostic imaging*
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Tomography, X-Ray Computed
4.Effect of KIF22 on promoting proliferation and migration of gastric cancer cells via MAPK-ERK pathways.
Ze-Yuan YU ; Xiang-Yan JIANG ; Rong-Rong ZHAO ; Jun-Jie QIN ; Chang-Jiang LUO ; Yan-Xian REN ; Wen REN ; Zhi-Jian MA ; Zuo-Yi JIAO
Chinese Medical Journal 2020;133(8):919-928
BACKGROUND:
Gastric cancer (GC) is one of the most globally prevalent cancers in the world. The pathogenesis of GC has not been fully elucidated, and there still lacks effective targeted therapeutics. The influence of altered kinesin superfamily protein 22 (KIF22) expression in GC progression is still unclearly. The aim of this study was to investigate the KIF22 effects on GC and related mechanisms.
METHODS:
Gastric carcinoma tissues and matching non-cancerous tissues were collected from patients with GC who have accepted a radical gastrectomy in Lanzhou University Second Hospital from May 2013 to December 2014. The expression of KIF22 was examined in GC of 67 patients and 20 para-carcinoma tissues by immunochemical staining. The relationship between the expression of KIF22 and clinicopathologic characteristics was next investigated in the remaining 52 patients except for 15 patients who did not complete follow-up for 5 years. Cell viability was performed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test and colony formation assay in the MGC-803 and BGC-823 GC cells. Cell scratch and trans-well invasion assay was performed to assess migration ability in the MGC-803 and BGC-823 GC cells. Gene set enrichment analysis (GSEA) pathway enrichment analysis was performed to explore the potential functions. Cell cycle was detected by flow cytometry. In addition, the two GC cell lines were used to elucidate the underlying mechanism of KIF22 in GC in vitro via assessing the effects on mitogen-activated protein kinase and extracellular regulated protein kinases (MAPK/ERK) signal transduction pathway-related expressions by Western blotting assays. The differences were compared by t tests, one-way analysis of variance, and Chi-squared tests.
RESULTS:
The study showed that KIF22 was up-regulated in GC, and KIF22 high expression was significantly related to differentiation degree (χ = 12.842, P = 0.002) and poorly overall survivals. GSEA pathway enrichment analysis showed that KIF22 was correlated with the cell cycle. Silence of KIF22 decreased the ability of the proliferation and migration in gastric cells, induced G1/S phase cell cycle arrest via regulating the MAPK-ERK pathways.
CONCLUSIONS
KIF22 protein level was negatively correlated with prognosis. KIF22 knockdown might inhibit proliferation and metastasis of GC cells via the MAPK-ERK signaling pathway.
5.HBsAg Levels Normalized to the Same Hepatic Parenchyma Cell Volume Is Correlated with Pathological Progression but Not HBeAg Status
Lei TAN ; Tao WU ; Yan LV ; Wei-li WANG ; Jie REN ; Rong-qin ZHENG ; Ze-qian WU
Journal of Sun Yat-sen University(Medical Sciences) 2019;40(5):747-753
【Objective】To study retrospectively the serum hepatitis B surface antigen(HBsAg)and HBsAg normal⁃
ized to the same hepatic parenchyma cell volume(HPCV),namely,the same hepatic cell quantities,between HBeAg-
positive and HBeAg-negative chronic hepatitis B(CHB).【Methods】A total of 168 CHB patients who had undergone liv⁃
er biopsy and test of serum HBsAg levels due to their disease in the Third Affiliated Hospital of SunYat-sen University
were selected as the study subjects. The serum HBsAg levels,as well as HBsAg levels normalized to HPCV(hepatic cell
quantities)were compared between HBeAg-positive and HBeAg-negative CHB,respectively.【Results】There was statis⁃
tically significant difference in serum HBsAg levels between HBeAg-positive and HBeAg-negative CHB(P = 0.028),
while there was no statistical difference in HBsAg normalized to HPCV(P = 0.073). There were no correlations between
serum HBsAg and liver inflammation grades(HBeAg-positive:r s = 0.020,P = 0.876 & HBeAg-negative:r s = 0.037,P =0.711). Similarly,there were no correlations between HBsAg and hepatic fibrosis stages(HBeAg-positive:r s = 0.087,
P = 0.488 & HBeAg-negative:r s = 0.144,P = 0.148). Nevertheless,statistically significant positive correlations were
shown between HBsAg normalized to HPCV and liver inflammation grades(HBeAg-positive:r s = 0.309,P = 0.012 &
HBeAg-negative:r s = 0.389,P < 0.001). Similarly,the HBsAg normalized to HPCV and hepatic fibrosis stages were
shown to be statistically significantly correlated(HBeAg-positive:r s = 0.490,P < 0.001 & HBeAg-negative:r s = 0.599,
P < 0.001).【Conclusions】Serum HBsAg normalized to HPCV but not HBsAg levels,is correlated with liver inflamma⁃
tion grades as well as hepatic fibrosis stages positively in both HBeAg-positive and HBeAg-negative CHB. But there is
no difference in serum HBsAg levels normalized to HPCV between HBeAg-positive and HBeAg-negative CHB.
6.Patient and Care Delays of Breast Cancer in China
Yue Lin LI ; Ya Chao QIN ; Lu Ying TANG ; Yu Huang LIAO ; Wei ZHANG ; Xiao Ming XIE ; Qiang LIU ; Ying LIN ; Ze Fang REN
Cancer Research and Treatment 2019;51(3):1098-1106
PURPOSE: This study differentiates patient and care delays of breast cancer and explores the related factors as well as the associations with the prognosis in Guangzhou, a southern city of China. METHODS: A cohort of female incident breast cancer patients (n=1,551) was recruited from October 2008 to March 2012 and followed up until January 1, 2016 (n=1,374) in the affiliated hospitals of Sun Yat-sen University. The factors associated with patient and care delays were analyzed with multivariable logistic models. Cox proportional hazards regression models were constructed to estimate the impacts of the delays on the prognosis. RESULTS: There were 40.4% patient delay (≥3 months) and 15.5% care delay (≥1 month). The patient delay, but not the care delay, was significantly related to the clinical stage and consequently worsened the prognosis of breast cancer (hazard ratio, 1.45; 95% confidence interval, 1.09 to 1.91 for progression-free survival). The factors related to an increased patient delay included premenopausal status, history of benign breast disease, and less physical examination. CONCLUSION: Patient delay was the main type of delay in Guangzhou and resulted in higher clinical stage and poor prognosis of breast cancer. Screening for breast cancer among premenopausal women may be an effective way to reduce this delay.
Breast Diseases
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Breast Neoplasms
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Breast
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China
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Cohort Studies
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Female
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Humans
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Logistic Models
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Mass Screening
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Physical Examination
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Prognosis
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Solar System
7.Down-regulation of HDAC6 Expression Promotes Apoptosis of Human Leukemia K562 Cells.
Ze-Hong LIU ; Bing GUO ; Guan-Hai QIN ; Ying YUAN ; Yu-Dong WANG ; Yi-Ren ZHOU ; Shi-Qing SONG ; Yan-Hua HOU
Journal of Experimental Hematology 2018;26(6):1626-1631
OBJECTIVE:
To study the promoting-apoptosis effect of HDAC6 on the human leukemia cells and its mechanism.
METHODS:
The siRNA interference technology was used to inhibit the expression of HDAC6 gene, the RT-PCR and Western blot were used to detect the expression of HDAC6 and related signal pathway proteins respectively, the flow cytometry and Hoechest staining were used to detect the apoptosis and morphology changes of K562 cells.
RESULTS:
Compared with the periphal blood monocyte and bone marrow stromal cells of healthy volunteers, the expression level of HDAC6 in leukemia cell lines was up-regulated significantly(P<0.05); the flow cytometry and Hoechest staining showed that after interference of HDAC6 gene, the apoptosis of K562 cells increased, moreover the cell morphology was changed; the Western blot detection showed that the interfering HDAC6 increased BAX/BCL-2 ratio and cleaved caspase 3 expression, and activated the MAPK, ATK, ERK signaling pathway.
CONCLUSION
The interferance of HDAC6 can promote the K562 cell apoptosis, its mechanism may relate with activation of MAPK signaling pathway.
Apoptosis
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Cell Proliferation
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Down-Regulation
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Histone Deacetylase 6
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Humans
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K562 Cells
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Leukemia
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RNA, Small Interfering
8.Relationship between two blood stasis syndromes and inflammatory factors in patients with acute coronary syndrome.
Cai-Yun MA ; Jing-Hua LIU ; Jian-Xun LIU ; Da-Zhuo SHI ; Zhen-Ye XU ; Shao-Ping WANG ; Min JIA ; Fu-Hai ZHAO ; Yue-Rong JIANG ; Qin MA ; Hong-Yu PENG ; Yuan LU ; Ze ZHENG ; Feng-Xue REN
Chinese journal of integrative medicine 2017;23(11):845-849
OBJECTIVETo investigate the relationship between inflammatory factors and two Chinese medicine (CM) syndrome types of qi stagnation and blood stasis (QSBS) and qi deficiency and blood stasis (QDBS) in patients with acute coronary syndrome (ACS).
METHODSSixty subjects with ACS, whose pathogenesis changes belongs to qi disturbance blood stasis syndrome, were divided into 2 groups: 30 in the QSBS group and 30 in the QDBS group. The comparative analysis on them was carried out through comparing general information, coronary angiography and inflammatory factors including intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40) and lipoprotein-associated phospholipase A2 (Lp-PLA2).
RESULTSCompared with the QSBS group, Lp-PLA2 and YKL-40 levels in the QDBS group showed no-significant difference (P>0.05); ICAM-1 was significantly higher in the QDBS group than in the QSBS group in the pathological processes of qi disturbance and blood stasis syndrome of ACS (P<0.05).
CONCLUSIONSInflammatory factor ICAM-1 may be an objective basis for syndrome typing of QSBS and QDBS, which provides a research direction for standardization research of CM syndrome types.
9.Identification of cattail pollen (puhuang), pine pollen (songhuafen) and its adulterants by ITS2 sequence.
Xiao-Xi MA ; Wei SUN ; Wei-Chao REN ; Li XIANG ; Bo ZHAO ; Ya-Qin ZHANG ; Ming SONG ; Ze-Jing MU ; Shi-Lin CHEN
China Journal of Chinese Materia Medica 2014;39(12):2189-2193
DNA barcoding method was conducted for the authentication of pollen materials due to difficulty of discriminating pollen materials bearing morphological similarity. In this study, a specific focus was to identify cattail pollen (Puhuang) and pine pollen (Songhuafen) samples from their adulterants which are frequently mixed-together. Regions of the internal transcribed spacer (ITS2) from 60 samples were sequenced, and new primers for cattail pollen were designed according to the sequence information. The results from the NJ trees showed that the species of pine pollen, Puhuang and their adulterants can be classified as obvious monophyly. Therefore, we propose to adapt DNA barcoding methodology to accurately distinguish cattail pollen, pine pollen and their adulterant materials. It is a great help for drug regulatory agency to supervise the quality of medicinal materials.
China
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DNA Barcoding, Taxonomic
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methods
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DNA, Plant
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genetics
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DNA, Ribosomal Spacer
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genetics
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Drug Contamination
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prevention & control
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Drugs, Chinese Herbal
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chemistry
;
classification
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Molecular Sequence Data
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Phylogeny
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Pinus
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classification
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genetics
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Pollen
;
classification
;
genetics
;
Quality Control
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Typhaceae
;
classification
;
genetics
10.Influence of depth on liver stiffness measurement with real-time shear wave elastography
Jian, ZHENG ; Jie, ZENG ; Rong-qin, ZHENG ; Ze-ping, HUANG ; Jie, REN ; Cong-zhi, WANG ; Hai-rong, ZHENG
Chinese Journal of Medical Ultrasound (Electronic Edition) 2013;(8):647-651
Objective To assess the inlfuence of depth on liver stiffness measurement with real-time shear wave elastography (SWE) and determine the optimal depth for SWE in liver. Methods SWE of liver was performed on 89 healthy volunteers between May 2012 and November 2012. The depths of each liver were varied from 0 cm to 7 cm (from the liver capsule) in 1 cm increment and there were 8 depth groups in total. Then the elastic modulus of liver in each depth group were measured three times by SWE. The body mass index (BMI) and the distance from body surface to liver capsule were documented. The success rates and the mean elastic modulus of each group were calculated. Results The success rates of 0-7 cm were 0, 98.9%(88/89), 98.9%(88/89), 98.9%(88/89), 71.9%(64/89), 24.7%(22/89), 3.4%(3/89) and 0, respectively. The success rates were highest in 1 cm, 2 cm and 3 cm groups but signiifcant decreased with the increasement of depths in 4 cm, 5 cm and 6 cm groups ( 3 cm vs 4 cm, χ2=25.94, P<0.001; 4 cm vs 5 cm, χ2=39.68, P<0.001;5 cm vs 6 cm,χ2=16.79, P<0.001). The mean elastic modulus of 1 cm, 2 cm, 3 cm, 4 cm and 5 cm groups were (4.77±0.99), (4.68±0.99), (4.76±0.95), (5.19±1.10) and (5.41±0.95) kPa, respectively. The mean elastic modulus of 4 cm and 5 cm groups were signiifcant higher than those of 1 cm, 2 cm, 3 cm groups (4 cm vs 1 cm, t=-2.85, P=0.005;4 cm vs 2 cm, t=-3.49, P=0.001;4 cm vs 3 cm, t=-2.76, P=0.006;5 cm vs 1 cm, t=-3.13, P=0.002;5 cm vs 2 cm, t=-3.66, P=0.000;5 cm vs 3 cm, t=-3.05, P=0.003). In the group of 4 cm, the BMI and the distance from body surface to liver capsule of the volunteers performed successfully and unsuccessfully were (20.70±2.87), (22.07±2.42) kg/m2 and (1.45±0.25 ), (1.60±0.29) cm, respectively. In the group of 5 cm, the BMI and the distance from body surface to liver capsule of the volunteers performed successfully and unsuccessfully were (19.82±2.76), (21.49±2.72) kg/m2 and (1.35±0.21), (1.54±0.26) cm respectively. The BMI had no signiifcant difference between the successful and unsuccessful groups (t=-2.83, P=0.108 for 4 cm;t=0.77, P=0.709 for 5 cm), but the distance from body surface to liver capsule was signiifcantly different (t=26.51, P=0.012 for 4 cm;t=79.57, P=0.004 for 5 cm). Conclusions The success rates and elastic modulus were different at different depths. SWE should be performed at the depths of 1-3 cm from the liver capsule.


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