1.Inhibition of HDAC3 Promotes Psoriasis Development in Mice Through Regulating Th17
Fan XU ; Xin-Rui ZHANG ; Yang-Chen XIA ; Wen-Ting LI ; Hao CHEN ; An-Qi QIN ; Ai-Hong ZHANG ; Yi-Ran ZHU ; Feng TIAN ; Quan-Hui ZHENG
Progress in Biochemistry and Biophysics 2025;52(4):1008-1017
ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4+ T lymphocytes, CD8+ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4+ T lymphocytes. Additionally, spleen CD4+ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4+ and CD8+ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4+ and CD8+ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4+ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4+ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.
2.Progress in the application of poloxamer in new preparation technology
Xue QI ; Yi CHENG ; Nan LIU ; Zengming WANG ; Hui ZHANG ; Aiping ZHENG ; Dongzhou KANG
China Pharmacy 2025;36(5):630-635
Poloxamer, as a non-ionic surfactant, exhibits a unique triblock [polyethylene oxide-poly (propylene oxide)-polyethylene oxide] structure, which endows it with broad application potential in various fields, including solid dispersion technology, nanotechnology, gel technology, biologics, gene engineering and 3D printing. As a carrier, it enhances the solubility and bioavailability of poorly soluble drugs. In the field of nanotechnology, it serves as a stabilizer etc., enriching preparation methods. In gel technology, its self-assembly behavior and thermosensitive properties facilitate controlled drug release. In biologics, it improves targeting efficiency and reduces side effects. In gene engineering, it enhances delivery efficiency and expression levels. In 3D printing, it provides novel strategies for precise drug release control and the production of high-quality biological products. As a versatile material, poloxamer holds promising prospects in the pharmaceutical field.
3.Bioinformatics analysis of efferocytosis-related genes in diabetic kidney disease and screening of targeted traditional Chinese medicine.
Yi KANG ; Qian JIN ; Xue-Zhe WANG ; Meng-Qi ZHOU ; Hui-Juan ZHENG ; Dan-Wen LI ; Jie LYU ; Yao-Xian WANG
China Journal of Chinese Materia Medica 2025;50(14):4037-4052
This study employed bioinformatics to screen the feature genes related to efferocytosis in diabetic kidney disease(DKD) and explores traditional Chinese medicine(TCM) regulating these feature genes. The GSE96804 and GSE30528 datasets were integrated as the training set, and the intersection of differentially expressed genes and efferocytosis-related genes(ERGs) was identified as DKD-ERGs. Subsequently, correlation analysis, protein-protein interaction(PPI) network construction, enrichment analysis, and immune infiltration analysis were performed. Consensus clustering was conducted on DKD patients based on the expression levels of DKD-ERGs, and the expression levels, immune infiltration characteristics, and gene set variations between different subtypes were explored. Eight machine learning models were constructed and their prediction performance was evaluated. The best-performing model was evaluated by nomograms, calibration curves, and external datasets, followed by the identification of efferocytosis-related feature genes associated with DKD. Finally, potential TCMs that can regulate these feature genes were predicted. The results showed that the training set contained 640 differentially expressed genes, and after intersecting with ERGs, 12 DKD-ERGs were obtained, which demonstrated mutual regulation and immune modulation effects. Consensus clustering divided DKD into two subtypes, C1 and C2. The support vector machine(SVM) model had the best performance, predicting that growth arrest-specific protein 6(GAS6), S100 calcium-binding protein A9(S100A9), C-X3-C motif chemokine ligand 1(CX3CL1), 5'-nucleotidase(NT5E), and interleukin 33(IL33) were the feature genes of DKD. Potential TCMs with therapeutic effects included Astragali Radix, Trionycis Carapax, Sargassum, Rhei Radix et Rhizoma, Curcumae Radix, and Alismatis Rhizoma, which mainly function to clear heat, replenish deficiency, activate blood, resolve stasis, and promote urination and drain dampness. Molecular docking revealed that the key components of these TCMs, including β-sitosterol, quercetin, and sitosterol, exhibited good binding activity with the five target genes. These results indicated that efferocytosis played a crucial role in the development and progression of DKD. The feature genes closely related to both DKD and efferocytosis, such as GAS6, S100A9, CX3CL1, NT5E, and IL33, were identified. TCMs such as Astragali Radix, Trionycis Carapa, Sargassum, Rhei Radix et Rhizoma, Curcumae Radix, and Alismatis Rhizoma may provide a new therapeutic strategy for DKD by regulating efferocytosis.
Humans
;
Computational Biology
;
Diabetic Nephropathies/physiopathology*
;
Protein Interaction Maps
;
Medicine, Chinese Traditional
;
Drugs, Chinese Herbal
;
Phagocytosis/genetics*
;
Efferocytosis
4.Biomechanical study and clinical application of two osteotomy guide methods in media open wedge high tibial osteotomy operation.
Chao QI ; Xiao-Ming LI ; Dong-Hui GUO ; Qiu-Ling SHI ; Yun-Chao ZHAO ; Jun DONG ; Zheng-Xin MENG ; Xing-Yue WANG
China Journal of Orthopaedics and Traumatology 2025;38(7):698-704
OBJECTIVE:
To explore the effectiveness and feasibility of two osteotomy guides in medial open wedge high tibial osteotomy (MOWHTO).
METHODS:
Clinical data of 103 patients who underwent routine MOWHTO surgery between January 2020 and December 2022 were collected for retrospective analysis. The patients were divided into two groups based on the method of osteotomy guide plate. The control group of 51 patients received traditional osteotomy guide plate technique, including 17 males and 34 females, aged from 48 to 68 years old with an average of(57.93±4.82) years old, with a disease duration ranged from 1 to 8 years with an average of (4.89±1.49) years. The observation group of 52 patients received personalized osteotomy guide plate technique, including 23 males and 29 females, aged from 48 to 69 with an average of (58.22±5.10) years, with a disease duration ranged from 1 to 9 years with an average of(5.10±1.55) years. The perioperative indicators, complications, and knee joint recovery rate were statistically analyzed for both groups, as well as the preoperative and postoperative coagulation function, fibrinogen (FIB), D-dimer (D-D), gait parameters (step frequency, step length, step speed), biomechanical indicators, weight bearing line (WBL), medial proximal tibial angle (MPTA), joint line conergence angle (JLCA), and anterior cruciate ligament (ACL) function (body width, tibial anterior displacement).
RESULTS:
All patients were followed up for 6 months. The intraoperative blood loss, operation time, and number of fluoroscopic views in the observation group were (358.58±93.76) ml, (84.42±8.17) min, and (2.00±0.44) times, respectively, which were all less than those in the control group (465.55±105.38) ml, (96.53±10.51) min, and (6.31±0.58) times (P<0.05). Three days after surgery, the FIB and D-D levels in the observation group were (4.21±0.48) g·L-1 and (204.47±35.59) μg·L-1, respectively, which were both lower than those in the control group (5.56±0.57) g·L-1 and (311.12±42.23) μg·L-1 (P<0.05). Three months after surgery, the step frequency, step length, and step speed in the observation group were (1.89±0.23) steps·s-1, (0.57±0.15) m, and (0.99±0.11) m·s-1, respectively, which were all higher than those in the control group (1.80±0.18) steps·s-1, (0.50±0.14) m, and (0.95±0.09) m·s-1 (P<0.05). Three months after surgery, the WBL and MPTA in the observation group were (45.53±4.41)% and (87.03±8.15)°, respectively, which were both higher than those in the control group (38.38±4.36)% and (83.68±8.50)°, and the JLCA was (2.36±0.24)°, which was lower than that in the control group (2.61±0.33)° (P<0.05). The ACL body width during internal fixation removal was (5.60±0.51) mm, which was greater than that in the control group (5.08±0.56) mm, and the tibial migration was (5.70±0.42) mm, which was less than that in the control group (6.33±0.48) mm (P<0.05). There was no significant difference in the incidence of complications between the two groups (P>0.05). Six months after surgery, there was no significant difference in the recovery rate of knee joint between the two groups (P>0.05).
CONCLUSION
The application of personalized osteotomy guide technique in MOWHTO can help improve knee biomechanics and ACL function, and has less effect on coagulation function and no increase in complications.
Humans
;
Male
;
Female
;
Osteotomy/methods*
;
Middle Aged
;
Tibia/physiopathology*
;
Aged
;
Biomechanical Phenomena
;
Retrospective Studies
;
Osteoarthritis, Knee/physiopathology*
5.Expert consensus on the diagnosis and treatment of cemental tear.
Ye LIANG ; Hongrui LIU ; Chengjia XIE ; Yang YU ; Jinlong SHAO ; Chunxu LV ; Wenyan KANG ; Fuhua YAN ; Yaping PAN ; Faming CHEN ; Yan XU ; Zuomin WANG ; Yao SUN ; Ang LI ; Lili CHEN ; Qingxian LUAN ; Chuanjiang ZHAO ; Zhengguo CAO ; Yi LIU ; Jiang SUN ; Zhongchen SONG ; Lei ZHAO ; Li LIN ; Peihui DING ; Weilian SUN ; Jun WANG ; Jiang LIN ; Guangxun ZHU ; Qi ZHANG ; Lijun LUO ; Jiayin DENG ; Yihuai PAN ; Jin ZHAO ; Aimei SONG ; Hongmei GUO ; Jin ZHANG ; Pingping CUI ; Song GE ; Rui ZHANG ; Xiuyun REN ; Shengbin HUANG ; Xi WEI ; Lihong QIU ; Jing DENG ; Keqing PAN ; Dandan MA ; Hongyu ZHAO ; Dong CHEN ; Liangjun ZHONG ; Gang DING ; Wu CHEN ; Quanchen XU ; Xiaoyu SUN ; Lingqian DU ; Ling LI ; Yijia WANG ; Xiaoyuan LI ; Qiang CHEN ; Hui WANG ; Zheng ZHANG ; Mengmeng LIU ; Chengfei ZHANG ; Xuedong ZHOU ; Shaohua GE
International Journal of Oral Science 2025;17(1):61-61
Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans
;
Dental Cementum/injuries*
;
Consensus
;
Diagnosis, Differential
;
Cone-Beam Computed Tomography
;
Tooth Fractures/therapy*
6.Biomechanical Evaluation of 2 Endoscopic Spine Surgery Methods for Treating Lumbar Disc Herniation: A Finite Element Study
Yang ZOU ; Shuo JI ; Hui Wen YANG ; Tao MA ; Yue Kun FANG ; Zhi Cheng WANG ; Miao Miao LIU ; Ping Hui ZHOU ; Zheng Qi BAO ; Chang Chun ZHANG ; Yu Chen YE
Neurospine 2024;21(1):273-285
Objective:
This study aimed to evaluate the effects of 2 endoscopic spine surgeries on the biomechanical properties of normal and osteoporotic spines.
Methods:
Based on computed tomography images of a healthy adult volunteer, 6 finite element models were created. After validating the normal intact model, a concentrated force of 400 N and a moment of 7.5 Nm were exerted on the upper surface of L3 to simulate 6 physiological activities of the spine. Five types of indices were used to assess the biomechanical properties of the 6 models, range of motion (ROM), maximum displacement value, intervertebral disc stress, maximum stress value, and articular protrusion stress, and by combining them with finite element stress cloud.
Results:
In normal and osteoporotic spines, there was no meaningful change in ROM or disc stress in the 2 surgical models for the 6 motion states. Model N1 (osteoporotic percutaneous transforaminal endoscopic discectomy model) showed a decrease in maximum displacement value of 20.28% in right lateral bending. Model M2 (unilateral biportal endoscopic model) increased maximum displacement values of 16.88% and 17.82% during left and right lateral bending, respectively. The maximum stress value of L4–5 increased by 11.72% for model M2 during left rotation. In addition, using the same surgical approach, ROM, maximum displacement values, disc stress, and maximum stress values were more significant in the osteoporotic model than in the normal model.
Conclusion
In both normal and osteoporotic spines, both surgical approaches were less disruptive to the physiologic structure of the spine. Furthermore, using the same endoscopic spine surgery, normal spine biomechanical properties are superior to osteoporotic spines.
7.Value of contrast-enhanced ultrasonography in microwave ablation treatment of symptomatic focal uterine adenomyosis
Xiao-Long LI ; Jia-Xin LI ; Song-Yuan YU ; Pei-Li FAN ; Yun-Jie JIN ; Er-Jiao XU ; Sai-Nan GUAN ; Er-Ya DENG ; Qiu-Yan LI ; Zheng-Biao JI ; Jiu-Ling QI ; Hui-Xiong XU ;
Ultrasonography 2024;43(1):68-77
Purpose:
This study evaluated the value of contrast-enhanced ultrasonography (CEUS) in the ultrasound-guided microwave ablation (MWA) treatment of symptomatic focal uterine adenomyosis.
Methods:
This retrospective study was conducted between March 2020 and January 2023, enrolling 52 patients with symptomatic focal uterine adenomyosis who had undergone MWA. All patients were examined with CEUS before and after MWA. The non-perfused volume (NPV) was compared between CEUS and dynamic contrast-enhanced magnetic resonance imaging (DCEMRI) following ablation. Therapeutic efficacy and safety were evaluated at 3-, 6-, and 12-month follow-ups. Additionally, this study explored the correlations between pre-treatment CEUS features and a volume reduction ratio indicating sufficient ablation, defined as 50% or more at the 3-month follow-up.
Results:
No significant differences in NPV were noted between CEUS and DCE-MRI immediately after MWA and during follow-up (all P>0.05). At the 3-month follow-up, the median VRRs for the uterus and adenomyosis were 33.2% and 63.9%, respectively. Sufficient ablation was achieved in 69.2% (36/52) of adenomyosis cases, while partial ablation was observed in the remaining 30.8% (16/52). The identification of non-enhancing areas on pre-treatment CEUS was associated with sufficient ablation (P=0.016). At the 12-month follow-up, significant decreases were observed in both the uterine and adenomyosis volumes (all P<0.001). Dysmenorrhea and menorrhagia were significantly alleviated at 12 months, and no major complications were encountered.
Conclusion
CEUS can be used to evaluate the ablation zone of focal adenomyosis that has been treated with MWA, similarly to DCE-MRI. The identification of non-enhancing areas on pretreatment CEUS indicates satisfactory treatment outcomes.
8.Value of contrast-enhanced ultrasonography in microwave ablation treatment of symptomatic focal uterine adenomyosis
Xiao-Long LI ; Jia-Xin LI ; Song-Yuan YU ; Pei-Li FAN ; Yun-Jie JIN ; Er-Jiao XU ; Sai-Nan GUAN ; Er-Ya DENG ; Qiu-Yan LI ; Zheng-Biao JI ; Jiu-Ling QI ; Hui-Xiong XU ;
Ultrasonography 2024;43(1):68-77
Purpose:
This study evaluated the value of contrast-enhanced ultrasonography (CEUS) in the ultrasound-guided microwave ablation (MWA) treatment of symptomatic focal uterine adenomyosis.
Methods:
This retrospective study was conducted between March 2020 and January 2023, enrolling 52 patients with symptomatic focal uterine adenomyosis who had undergone MWA. All patients were examined with CEUS before and after MWA. The non-perfused volume (NPV) was compared between CEUS and dynamic contrast-enhanced magnetic resonance imaging (DCEMRI) following ablation. Therapeutic efficacy and safety were evaluated at 3-, 6-, and 12-month follow-ups. Additionally, this study explored the correlations between pre-treatment CEUS features and a volume reduction ratio indicating sufficient ablation, defined as 50% or more at the 3-month follow-up.
Results:
No significant differences in NPV were noted between CEUS and DCE-MRI immediately after MWA and during follow-up (all P>0.05). At the 3-month follow-up, the median VRRs for the uterus and adenomyosis were 33.2% and 63.9%, respectively. Sufficient ablation was achieved in 69.2% (36/52) of adenomyosis cases, while partial ablation was observed in the remaining 30.8% (16/52). The identification of non-enhancing areas on pre-treatment CEUS was associated with sufficient ablation (P=0.016). At the 12-month follow-up, significant decreases were observed in both the uterine and adenomyosis volumes (all P<0.001). Dysmenorrhea and menorrhagia were significantly alleviated at 12 months, and no major complications were encountered.
Conclusion
CEUS can be used to evaluate the ablation zone of focal adenomyosis that has been treated with MWA, similarly to DCE-MRI. The identification of non-enhancing areas on pretreatment CEUS indicates satisfactory treatment outcomes.
9.Biomechanical Evaluation of 2 Endoscopic Spine Surgery Methods for Treating Lumbar Disc Herniation: A Finite Element Study
Yang ZOU ; Shuo JI ; Hui Wen YANG ; Tao MA ; Yue Kun FANG ; Zhi Cheng WANG ; Miao Miao LIU ; Ping Hui ZHOU ; Zheng Qi BAO ; Chang Chun ZHANG ; Yu Chen YE
Neurospine 2024;21(1):273-285
Objective:
This study aimed to evaluate the effects of 2 endoscopic spine surgeries on the biomechanical properties of normal and osteoporotic spines.
Methods:
Based on computed tomography images of a healthy adult volunteer, 6 finite element models were created. After validating the normal intact model, a concentrated force of 400 N and a moment of 7.5 Nm were exerted on the upper surface of L3 to simulate 6 physiological activities of the spine. Five types of indices were used to assess the biomechanical properties of the 6 models, range of motion (ROM), maximum displacement value, intervertebral disc stress, maximum stress value, and articular protrusion stress, and by combining them with finite element stress cloud.
Results:
In normal and osteoporotic spines, there was no meaningful change in ROM or disc stress in the 2 surgical models for the 6 motion states. Model N1 (osteoporotic percutaneous transforaminal endoscopic discectomy model) showed a decrease in maximum displacement value of 20.28% in right lateral bending. Model M2 (unilateral biportal endoscopic model) increased maximum displacement values of 16.88% and 17.82% during left and right lateral bending, respectively. The maximum stress value of L4–5 increased by 11.72% for model M2 during left rotation. In addition, using the same surgical approach, ROM, maximum displacement values, disc stress, and maximum stress values were more significant in the osteoporotic model than in the normal model.
Conclusion
In both normal and osteoporotic spines, both surgical approaches were less disruptive to the physiologic structure of the spine. Furthermore, using the same endoscopic spine surgery, normal spine biomechanical properties are superior to osteoporotic spines.
10.Value of contrast-enhanced ultrasonography in microwave ablation treatment of symptomatic focal uterine adenomyosis
Xiao-Long LI ; Jia-Xin LI ; Song-Yuan YU ; Pei-Li FAN ; Yun-Jie JIN ; Er-Jiao XU ; Sai-Nan GUAN ; Er-Ya DENG ; Qiu-Yan LI ; Zheng-Biao JI ; Jiu-Ling QI ; Hui-Xiong XU ;
Ultrasonography 2024;43(1):68-77
Purpose:
This study evaluated the value of contrast-enhanced ultrasonography (CEUS) in the ultrasound-guided microwave ablation (MWA) treatment of symptomatic focal uterine adenomyosis.
Methods:
This retrospective study was conducted between March 2020 and January 2023, enrolling 52 patients with symptomatic focal uterine adenomyosis who had undergone MWA. All patients were examined with CEUS before and after MWA. The non-perfused volume (NPV) was compared between CEUS and dynamic contrast-enhanced magnetic resonance imaging (DCEMRI) following ablation. Therapeutic efficacy and safety were evaluated at 3-, 6-, and 12-month follow-ups. Additionally, this study explored the correlations between pre-treatment CEUS features and a volume reduction ratio indicating sufficient ablation, defined as 50% or more at the 3-month follow-up.
Results:
No significant differences in NPV were noted between CEUS and DCE-MRI immediately after MWA and during follow-up (all P>0.05). At the 3-month follow-up, the median VRRs for the uterus and adenomyosis were 33.2% and 63.9%, respectively. Sufficient ablation was achieved in 69.2% (36/52) of adenomyosis cases, while partial ablation was observed in the remaining 30.8% (16/52). The identification of non-enhancing areas on pre-treatment CEUS was associated with sufficient ablation (P=0.016). At the 12-month follow-up, significant decreases were observed in both the uterine and adenomyosis volumes (all P<0.001). Dysmenorrhea and menorrhagia were significantly alleviated at 12 months, and no major complications were encountered.
Conclusion
CEUS can be used to evaluate the ablation zone of focal adenomyosis that has been treated with MWA, similarly to DCE-MRI. The identification of non-enhancing areas on pretreatment CEUS indicates satisfactory treatment outcomes.

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