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Zalewska K, Skonieczna M, Nejc D, Pluta P. Is the Superparamagnetic Approach Equal to Radioisotopes in Sentinel Lymph Node Biopsy? The Over-Collecting Node Issue in Breast Cancer Patients. J Clin Med 2025; 14:3148. [PMID: 40364183 PMCID: PMC12072611 DOI: 10.3390/jcm14093148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 03/30/2025] [Accepted: 04/28/2025] [Indexed: 05/15/2025] Open
Abstract
Background: Sentinel lymph node biopsy (SLNB) is the primary procedure for nodal assessment in breast cancer patients. Radioisotopes (RIs) are considered the gold-standard tool. The ferromagnetic technique (superparamagnetic iron oxide-SPIO) is a non-isotope alternative SLNB method. This study compares the efficacy of SPIO and RI SLNB across two independent breast cancer centres. Methods: A total of 406 breast cancer patients, who underwent SLNB between January 2021 and December 2022, were analysed (SPIO-223 patients, RI-183 patients). Statistical tests, including Mann-Whitney U and chi-squared analyses, compared the SLN identification rates, the number of SLNs retrieved, and the positive node detection rates. Results: The identification rates were similar for SPIO and RI (two-tailed Fisher's exact test, p = 1.0). The SPIO method retrieved significantly more SLNs than RI (3.26 vs. 2.15; p < 0.001). A larger proportion of patients in the SPIO group had ≥ 5 SLNs removed (20.2% vs. 8.7%; p = 0.001). A statistically significant difference was observed in the proportion of metastatic SLNs to harvested SLNs between the techniques, with a larger proportion detected in the RI group (1/7.88) compared to the SPIO group (1/14.81) (chi-squared test, p < 0.03). Conclusions: In our study, the SPIO and RI methods effectively collected SLNs. The gold-standard RI method offers distinct advantages, including its precise and consistent dosing unaffected by patient-specific factors and a highly targeted approach to node identification. These features minimise the risk of over-dissection and ensure that only the most clinically relevant nodes are removed. We note that the SPIO technique in SLNB in breast cancer patients requires further standardisation.
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Affiliation(s)
- Karolina Zalewska
- Department of Surgical Oncology, Medical University of Lodz, 90-419 Lodz, Poland; (K.Z.); (D.N.)
| | - Maria Skonieczna
- Department of Surgical Oncology and Breast Diseases, Polish Mother’s Memorial Hospital—Research Institute in Lodz, 93-338 Lodz, Poland;
| | - Dariusz Nejc
- Department of Surgical Oncology, Medical University of Lodz, 90-419 Lodz, Poland; (K.Z.); (D.N.)
| | - Piotr Pluta
- Department of Surgical Oncology and Breast Diseases, Polish Mother’s Memorial Hospital—Research Institute in Lodz, 93-338 Lodz, Poland;
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Zhang QJ, Cao ZC, Zhu Q, Sun Y, Li RD, Tong JL, Zheng Q. Application value of indocyanine green fluorescence imaging in guiding sentinel lymph node biopsy diagnosis of gastric cancer: Meta-analysis. World J Gastrointest Surg 2024; 16:1883-1893. [PMID: 38983339 PMCID: PMC11230008 DOI: 10.4240/wjgs.v16.i6.1883] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 05/12/2024] [Accepted: 05/24/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND Gastric cancer is a common malignant tumor of the digestive system worldwide, and its early diagnosis is crucial to improve the survival rate of patients. Indocyanine green fluorescence imaging (ICG-FI), as a new imaging technology, has shown potential application prospects in oncology surgery. The meta-analysis to study the application value of ICG-FI in the diagnosis of gastric cancer sentinel lymph node biopsy is helpful to comprehensively evaluate the clinical effect of this technology and provide more reliable guidance for clinical practice. AIM To assess the diagnostic efficacy of optical imaging in conjunction with indocyanine green (ICG)-guided sentinel lymph node (SLN) biopsy for gastric cancer. METHODS Electronic databases such as PubMed, Embase, Medline, Web of Science, and the Cochrane Library were searched for prospective diagnostic tests of optical imaging combined with ICG-guided SLN biopsy. Stata 12.0 software was used for analysis by combining the "bivariable mixed effect model" with the "midas" command. The true positive value, false positive value, false negative value, true negative value, and other information from the included literature were extracted. A literature quality assessment map was drawn to describe the overall quality of the included literature. A forest plot was used for heterogeneity analysis, and P < 0.01 was considered to indicate statistical significance. A funnel plot was used to assess publication bias, and P < 0.1 was considered to indicate statistical significance. The summary receiver operating characteristic (SROC) curve was used to calculate the area under the curve (AUC) to determine the diagnostic accuracy. If there was interstudy heterogeneity (I 2 > 50%), meta-regression analysis and subgroup analysis were performed. RESULTS Optical imaging involves two methods: Near-infrared (NIR) imaging and fluorescence imaging. A combination of optical imaging and ICG-guided SLN biopsy was useful for diagnosis. The positive likelihood ratio was 30.39 (95%CI: 0.92-1.00), the sensitivity was 0.95 (95%CI: 0.82-0.99), and the specificity was 1.00 (95%CI: 0.92-1.00). The negative likelihood ratio was 0.05 (95%CI: 0.01-0.20), the diagnostic odds ratio was 225.54 (95%CI: 88.81-572.77), and the SROC AUC was 1.00 (95%CI: The crucial values were sensitivity = 0.95 (95%CI: 0.82-0.99) and specificity = 1.00 (95%CI: 0.92-1.00). The Deeks method revealed that the "diagnostic odds ratio" funnel plot of SLN biopsy for gastric cancer was significantly asymmetrical (P = 0.01), suggesting significant publication bias. Further meta-subgroup analysis revealed that, compared with fluorescence imaging, NIR imaging had greater sensitivity (0.98 vs 0.73). Compared with optical imaging immediately after ICG injection, optical imaging after 20 minutes obtained greater sensitivity (0.98 vs 0.70). Compared with that of patients with an average SLN detection number < 4, the sensitivity of patients with a SLN detection number ≥ 4 was greater (0.96 vs 0.68). Compared with hematoxylin-eosin (HE) staining, immunohistochemical (+ HE) staining showed greater sensitivity (0.99 vs 0.84). Compared with subserous injection of ICG, submucosal injection achieved greater sensitivity (0.98 vs 0.40). Compared with 5 g/L ICG, 0.5 and 0.05 g/L ICG had greater sensitivity (0.98 vs 0.83), and cT1 stage had greater sensitivity (0.96 vs 0.72) than cT2 to cT3 clinical stage. Compared with that of patients ≤ 26, the sensitivity of patients > 26 was greater (0.96 vs 0.65). Compared with the literature published before 2010, the sensitivity of the literature published after 2010 was greater (0.97 vs 0.81), and the differences were statistically significant (all P < 0.05). CONCLUSION For the diagnosis of stomach cancer, optical imaging in conjunction with ICG-guided SLN biopsy is a therapeutically viable approach, especially for early gastric cancer. The concentration of ICG used in the SLN biopsy of gastric cancer may be too high. Moreover, NIR imaging is better than fluorescence imaging and may obtain higher sensitivity.
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Affiliation(s)
- Qi-Jia Zhang
- Department of Oncology, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing 210003, Jiangsu Province, China
| | - Zhi-Cheng Cao
- Department of Oncology, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing 210003, Jiangsu Province, China
| | - Qin Zhu
- Department of Oncology, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing 210003, Jiangsu Province, China
| | - Yu Sun
- Department of Oncology, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing 210003, Jiangsu Province, China
| | - Rong-Da Li
- Department of Gastrointestinal Surgery, Qilu Hospital of Shandong University, Jinan 250063, Shandong Province, China
| | - Jin-Long Tong
- Department of Oncology, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing 210003, Jiangsu Province, China
| | - Qin Zheng
- Department of Oncology, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing 210003, Jiangsu Province, China
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Bozhok AA, Zikiryakhodzhaev AD, Kvetenadze GE, Moshurova MV, Timoshkin VO, Shomova MV, Manelov AE. [Diagnostic value of fluorescence lymphography for sentinel lymph node biopsy in breast cancer. Summary experience of several specialized centers]. Khirurgiia (Mosk) 2024:49-61. [PMID: 39422006 DOI: 10.17116/hirurgia202410149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2024]
Abstract
OBJECTIVE To study the diagnostic value of fluorescent lymphography for sentinel lymph node biopsy in breast cancer. MATERIAL AND METHODS The cohort study, conducted at 4 specilized centers between June 2019 and March 2024, included 333 patients with cT1-4 N0-1M0 breast cancer. 50 patients received neoadjuvant systemic therapy, 14 of them had single metastases, confirmed by cytological or histological methods, which clinically completely regressed after systemic treatment. Immediately before the operation, 1 ml (5mg) of indocyanine green was injected subareolarly or subcutaneously into the tumor projection. Fluorescence imaging was performed using various devices for ICG navigation in the open surgical field - MARS, IC-Flow, Stryker SPY-PHI, IC-GOR. In 78 patients after sentinel lymph node biopsy standard axillary lymphadenectomy was performed. RESULTS Detection level was 99.1%. The average number of sentinel lymph nodes was 3.4. Metastatic lesions of sentinel lymph nodes were detected in 54 of 330 patients (16.4%). The average number of metastatic lymph nodes was 1.6; in 90.7% of cases metastases to 1-2 lymph nodes were registered. Intraoperative morphological examination revealed metastases only in 59% of cases. No systemic adverse events were recorded. The false-negative error rate in the group of patients who underwent axillary lymphadenectomy was 6.6%. The overall accuracy of fluorescent lymphography for sentinel lymph node biopsy in breast cancer was 94%. CONCLUSION The SLNB technique using fluorescence lymphography is safe and highly accurate as a stand-alone method.
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Affiliation(s)
- A A Bozhok
- Saint-Petersburg State Pediatric Medical University, St. Petersburg, Russia
- North-Western District Scientific and Clinical Center named after L.G. Sokolov of the Federal Medical and Biological Agency, St. Petersburg, Russia
| | - A D Zikiryakhodzhaev
- P. Hertsen Moscow Oncology Research Institute - Branch of the National Medical Radiology Research Centre of the Ministry of Health of the Russian Federation, Moscow, Russia
- People's Friendship University of Russia, Moscow, Russia (RUDN University), Moscow, Russia
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - G E Kvetenadze
- The Loginov Moscow Clinical Scientific Center Moscow Health Department, Moscow, Russia
| | - M V Moshurova
- P. Hertsen Moscow Oncology Research Institute - Branch of the National Medical Radiology Research Centre of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - V O Timoshkin
- P. Hertsen Moscow Oncology Research Institute - Branch of the National Medical Radiology Research Centre of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - M V Shomova
- Regional Clinical Oncological Dispensary, Ryazan, Russia
- Ryazan State Medical University, Ryazan, Russia
| | - A E Manelov
- North-Western State Medical University named after I.I. Mechnikov, St. Petersburg, Russia
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Johnston ME, Farooqui ZA, Nagarajan R, Pressey JG, Turpin B, Dasgupta R. Fluorescent-guided surgery and the use of indocyanine green sentinel lymph node mapping in the pediatric and young adult oncology population. Cancer 2023; 129:3962-3970. [PMID: 37740680 DOI: 10.1002/cncr.35023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Revised: 07/16/2023] [Accepted: 08/03/2023] [Indexed: 09/25/2023]
Abstract
BACKGROUND Technetium-99 (99m Tc) lymphoscintigraphy with blue dye injection is an accepted method for sentinel lymph node (SLN) mapping, but blue dye has known adverse effects, and injection of 99m Tc may increase time under anesthesia for pediatric patients. Indocyanine green (ICG) may serve as an adjunct to assist with visibility and identification of SLNs. We hypothesized that sensitivity of ICG was similar to blue dye in SLN biopsies. METHODS Thirty patients (36 procedures with 96 total specimens) underwent preoperative intradermal injection of 99m Tc, followed by intradermal injection of isosulfan blue and ICG. Test characteristics of blue dye, ICG, and 99m Tc included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS ICG had a sensitivity of 87% and PPV of 83% for detection of 99m Tc-hot lymph nodes; blue dye had a sensitivity of 44% and PPV of 97%. For detection of pathologically confirmed lymph nodes, ICG had a sensitivity of 84% and a positive predictive value (PPV) of 91%. 99m Tc had a sensitivity of 82% and a PPV of 94%. ICG had no significant difference in odds of being positive in pathology-confirmed lymph nodes compared to 99m Tc (odds ratio [OR], 0.818; 95% confidence interval [CI], 0.3-2.172; p = .823) and had higher odds than isosulfan blue (OR, 0.025, 95% CI, 0.001-0.148; p < .001). CONCLUSION This study established the efficacy of ICG as an adjunct to SLNB in the pediatric and young adult population. ICG was safe, more efficacious than blue dye, and may obviate the need for lymphoscintigraphy in selected patients resulting in reduced time under anesthesia.
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Affiliation(s)
- Michael E Johnston
- Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA
- Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Zishaan A Farooqui
- Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA
- Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Rajaram Nagarajan
- Cancer and Blood Disease Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Joseph G Pressey
- Cancer and Blood Disease Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Brian Turpin
- Cancer and Blood Disease Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Roshni Dasgupta
- Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA
- Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
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Akrida I, Michalopoulos NV, Lagadinou M, Papadoliopoulou M, Maroulis I, Mulita F. An Updated Review on the Emerging Role of Indocyanine Green (ICG) as a Sentinel Lymph Node Tracer in Breast Cancer. Cancers (Basel) 2023; 15:5755. [PMID: 38136301 PMCID: PMC10742210 DOI: 10.3390/cancers15245755] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 12/04/2023] [Accepted: 12/06/2023] [Indexed: 12/24/2023] Open
Abstract
Sentinel lymph node biopsy (SLNB) has become the standard of care for clinically node-negative breast cancer and has recently been shown by clinical trials to be also feasible for clinically node-positive patients treated with primary systemic therapy. The dual technique using both radioisotope (RI) and blue dye (BD) as tracers for the identification of sentinel lymph nodes is considered the gold standard. However, allergic reactions to blue dye as well as logistics issues related to the use of radioactive agents, have led to research on new sentinel lymph node (SLN) tracers and to the development and introduction of novel techniques in the clinical practice. Indocyanine green (ICG) is a water-soluble dye with fluorescent properties in the near-infrared (NIR) spectrum. ICG has been shown to be safe and effective as a tracer during SLNB for breast cancer and accumulating evidence suggests that ICG is superior to BD and at least comparable to RI alone and to RI combined with BD. Thus, ICG was recently proposed as a reliable SLN tracer in some breast cancer clinical practice guidelines. Nevertheless, there is lack of consensus regarding the optimal role of ICG for SLN mapping. Specifically, it is yet to be determined whether ICG should be used in addition to BD and/or RI, or if ICG could potentially replace these long-established traditional SLN tracers. This article is an updated overview of somerecent studies that compared ICG with BD and/or RI regarding their accuracy and effectiveness during SLNB for breast cancer.
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Affiliation(s)
- Ioanna Akrida
- Department of Surgery, General University Hospital of Patras, 26504 Rio, Greece; (I.A.); (I.M.)
| | - Nikolaos V. Michalopoulos
- 4th Department of Surgery, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 1 Rimini Street, Chaidari, 12462 Athens, Greece; (N.V.M.); (M.P.)
| | - Maria Lagadinou
- Department of Internal Medicine, General University Hospital of Patras, 26504 Rio, Greece;
| | - Maria Papadoliopoulou
- 4th Department of Surgery, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 1 Rimini Street, Chaidari, 12462 Athens, Greece; (N.V.M.); (M.P.)
| | - Ioannis Maroulis
- Department of Surgery, General University Hospital of Patras, 26504 Rio, Greece; (I.A.); (I.M.)
| | - Francesk Mulita
- Department of Surgery, General University Hospital of Patras, 26504 Rio, Greece; (I.A.); (I.M.)
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Zhou L, Gan Y, Wu Y, Xue D, Hu J, Zhang Y, Liu Y, Ma S, Zhou J, Luo G, Peng D, Qian W. Indocyanine Green Fluorescence Imaging in the Surgical Management of Skin Squamous Cell Carcinoma. Clin Cosmet Investig Dermatol 2023; 16:3309-3320. [PMID: 38021421 PMCID: PMC10657744 DOI: 10.2147/ccid.s413266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 10/28/2023] [Indexed: 12/01/2023]
Abstract
Introduction Indocyanine green (ICG) fluorescence imaging has been used in the resection surgery and sentinel lymph node biopsy of many tumors. The aim of the present study is to verify the feasibility and effectiveness of ICG fluorescence imaging used for guiding the biopsy and resection of skin squamous cell carcinoma (SSCC). Methods Sixty patients were enrolled, including 18 patients of suspected SSCC and 42 patients of diagnosed SSCC on admission. The ICG fluorescence imaging-guided skin biopsy was performed preoperatively in the 18 cases of suspected SSCC. Fifty-three patients underwent ICG fluorescence imaging-guided radical excision. Results The results showed that 138 skin tissue samples in 60 patients with preoperative or intraoperative ICG fluorescence imaging-guide biopsy were collected. For a total number of 138 biopsies, 122 specimens were squamous cell carcinoma, and the accuracy rate was 88.4%, which was significantly higher than that of the group without preoperative ICG fluorescence imaging (41/62, 66.1%, P < 0.05). Fifty-three patients underwent surgery guided with ICG fluorescence imaging. Residual fluorescent signals in 24 patients were intraoperatively found and the excision was then expanded until the signals disappeared. Follow-up to November 2022, 12 patients died, of which 5 cases died from the tumor recurrence, and the others died due to advanced ages or other reasons. The recurrence rate was 9.4%, which was not significantly different from that of the group received routine radical resection (4/35, 11.4%, P > 0.05). Moreover, sentinel lymph nodes were successfully detected under ICG fluorescence imaging in the 4 patients with suspected lymph node metastases, and the location of lymph nodes can be precisely identified. Conclusion ICG fluorescence imaging technique can guide the pathology biopsy to improve the accuracy of pathological examination, and help to identify the boundaries of tumor tissues and sentinel lymph nodes to resect tumor radically during operation.
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Affiliation(s)
- Ling Zhou
- Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University (Third Military Medical University), Chongqing, 400038, People’s Republic of China
| | - Yu Gan
- Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University (Third Military Medical University), Chongqing, 400038, People’s Republic of China
| | - Yanjun Wu
- Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University (Third Military Medical University), Chongqing, 400038, People’s Republic of China
| | - Dongdong Xue
- Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University (Third Military Medical University), Chongqing, 400038, People’s Republic of China
| | - Jianhong Hu
- Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University (Third Military Medical University), Chongqing, 400038, People’s Republic of China
| | - Yilan Zhang
- Department of Oral and Maxillofacial Head and Neck Surgery, Army Medical Center of PLA/Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, 400042, People’s Republic of China
| | - Yang Liu
- Department of Urology, Urology Institute of PLA, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, People’s Republic of China
| | - Siyuan Ma
- Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University (Third Military Medical University), Chongqing, 400038, People’s Republic of China
| | - Junyi Zhou
- Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University (Third Military Medical University), Chongqing, 400038, People’s Republic of China
| | - Gaoxing Luo
- Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University (Third Military Medical University), Chongqing, 400038, People’s Republic of China
| | - Daizhi Peng
- Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University (Third Military Medical University), Chongqing, 400038, People’s Republic of China
| | - Wei Qian
- Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University (Third Military Medical University), Chongqing, 400038, People’s Republic of China
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