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Xuexian Z, Ruidong W, Yuhan D, Qingwei L, Feng X, Hong R, Jun Z, Wei L. Safety and efficacy of DEB-TACE in combination with lenvatinib and camrelizumab for the treatment of unresectable hepatocellular carcinoma (uHCC): a two-centre retrospective study. Front Immunol 2024; 15:1422784. [PMID: 39502690 PMCID: PMC11534867 DOI: 10.3389/fimmu.2024.1422784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Accepted: 10/03/2024] [Indexed: 11/08/2024] Open
Abstract
Objectives The purpose of this study was to compare the safety and efficacy of drug-eluting bead (DEB) transarterial chemoembolization combined with lenvatinib and camrelizumab (DEB-TACE-Len-C) and DEB-TACE-Len for the treatment of unresectable hepatocellular carcinoma (uHCC). Methods This retrospective study consecutively included uHCC patients who underwent DEB-TACE-Len-C or DEB-TACE-Len treatment at our hospital and Qujing Second People's Hospital from April 2020 to April 2022. In total, 85 patients were enrolled. There were 42 patients in the DEB-TACE-Len-C group and 43 patients in the DEB-TACE-Len group. The disease control rate (DCR), objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were compared between the two groups, and the factors influencing OS and PFS were analysed. Results The ORR, DCR, PFS and OS were significantly greater in the DEB-TACE-Len-C group than in the DEB-TACE-Len group (ORR: 76.2% vs. 46.5%, P = 0.005; DCR: 88.1% vs. 67.8%, P = 0.039; PFS: 10 months vs. 6 months, P <0.0001; OS: 24 months vs. 16 months, P = 0.0038). Multivariate Cox proportional hazard regression analysis revealed that portal tumour thrombus (PVTT) and therapeutic approach were independent factors affecting PFS and OS. There were no statistically significant differences in the incidence of AEs between the two groups (P > 0.05). Conclusion Compared with DEB-TACE-Len, DEB-TACE-Len-C is an effective treatment option that can improve the tumour therapeutic response and prolong the OS and PFS in uHCC patients.
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MESH Headings
- Humans
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/mortality
- Liver Neoplasms/drug therapy
- Liver Neoplasms/mortality
- Quinolines/therapeutic use
- Quinolines/adverse effects
- Quinolines/administration & dosage
- Male
- Female
- Retrospective Studies
- Middle Aged
- Phenylurea Compounds/adverse effects
- Phenylurea Compounds/therapeutic use
- Phenylurea Compounds/administration & dosage
- Aged
- Antibodies, Monoclonal, Humanized/therapeutic use
- Antibodies, Monoclonal, Humanized/adverse effects
- Antibodies, Monoclonal, Humanized/administration & dosage
- Chemoembolization, Therapeutic/adverse effects
- Chemoembolization, Therapeutic/methods
- Treatment Outcome
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Antineoplastic Combined Chemotherapy Protocols/adverse effects
- Adult
- Combined Modality Therapy
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Affiliation(s)
- Zhang Xuexian
- Department of Vascular Intervention, Jingmen People’s Hospital, Jingmen, Hubei, China
| | - Wang Ruidong
- Interventional Department, Qujing Second People’s Hospital, Qujing, Yunnan, China
| | - Ding Yuhan
- Department of Oncology, Jingmen Central Hospital, Jingmen Central Hospital Affiliated to Jingchu University of Technology, Jingmen, Hubei, China
| | - Li Qingwei
- Department of Vascular Intervention, Jingmen People’s Hospital, Jingmen, Hubei, China
| | - Xiong Feng
- Department of Vascular Intervention, Jingmen People’s Hospital, Jingmen, Hubei, China
| | - Ren Hong
- Interventional Department, Qujing Second People’s Hospital, Qujing, Yunnan, China
| | - Zhang Jun
- Department of Vascular Intervention, Jingmen People’s Hospital, Jingmen, Hubei, China
| | - Li Wei
- Department of Vascular Intervention, Jingmen People’s Hospital, Jingmen, Hubei, China
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Zhang JX, Cheng Y, Wei J, Fan WL, Liu J, Zhou CG, Liu S, Shi HB, Chu XY, Zheng WL, Zu QQ. Transarterial Chemoembolization Combined with Tyrosine Kinase Inhibitors Plus Immune Checkpoint Inhibitors Versus Tyrosine Kinase Inhibitors Plus Immune Checkpoint Inhibitors in Unresectable Hepatocellular Carcinoma with First- or Lower-Order Portal Vein Tumor Thrombosis. Cardiovasc Intervent Radiol 2024; 47:751-761. [PMID: 38671322 DOI: 10.1007/s00270-024-03724-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Accepted: 03/29/2024] [Indexed: 04/28/2024]
Abstract
PURPOSE To compare the efficacy of transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) (TACE-TKI-ICI) versus TKIs plus ICIs (TKI-ICI) for unresectable hepatocellular carcinoma (HCC) with first- or lower-order portal vein tumor thrombosis (PVTT). MATERIALS AND METHODS A retrospective study was performed in HCC patients with first- or lower-order PVTT receiving TKIs (Lenvatinib or sorafenib) plus ICIs (camrelizumab, sintilimab, or atezolizumab) with or without TACE from four institutions between January 2019 and January 2022. Propensity score-based method was performed to minimize bias by confounding factors. Tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated and compared between the two groups. RESULTS After inverse probability of treatment weighting, two balanced pseudopopulations were created: 106 patients in the TACE-TKI-ICI group and 109 patients in the TKI-ICI group. The objective response rate was higher in the TACE-TKI-ICI group (50.9% vs. 28.4%, P < 0.001). The median PFS and OS were significantly longer in the TACE-TKI-ICI group than in the TKI-ICI group (PFS: 9.1 vs. 5.0 months, P = 0.005; OS: 19.1 vs. 12.7 months, P = 0.002). In Cox regression, TACE-TKI-ICI treatment was an independent predictor of favorable OS. Treatment-related grade 3/4 AEs were comparable between the two groups (22.6% vs. 17.9%, P = 0.437). CONCLUSION TACE-TKI-ICI therapy contributed to better tumor control, PFS and OS than TKI-ICI therapy in unresectable HCC patients with first- or lower-order PVTT.
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Affiliation(s)
- Jin-Xing Zhang
- Department of Interventional Radiology, The First Affiliated Hospital With Nanjing Medical University, No. 300, Guangzhou Rd, Nanjing, 210029, China
| | - Yuan Cheng
- Department of Medical Oncology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, China
| | - Juan Wei
- Department of Oncology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, China
| | - Wen-Long Fan
- Department of Radiology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310020, China
| | - Jin Liu
- Department of Clinical Medicine Research Institution, The First Affiliated Hospital With Nanjing Medical University, Nanjing, 210029, China
| | - Chun-Gao Zhou
- Department of Interventional Radiology, The First Affiliated Hospital With Nanjing Medical University, No. 300, Guangzhou Rd, Nanjing, 210029, China
| | - Sheng Liu
- Department of Interventional Radiology, The First Affiliated Hospital With Nanjing Medical University, No. 300, Guangzhou Rd, Nanjing, 210029, China
| | - Hai-Bin Shi
- Department of Interventional Radiology, The First Affiliated Hospital With Nanjing Medical University, No. 300, Guangzhou Rd, Nanjing, 210029, China
| | - Xiao-Yuan Chu
- Department of Medical Oncology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, China.
| | - Wei-Liang Zheng
- Department of Radiology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310020, China.
| | - Qing-Quan Zu
- Department of Interventional Radiology, The First Affiliated Hospital With Nanjing Medical University, No. 300, Guangzhou Rd, Nanjing, 210029, China.
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Ma KP, Fu JX, Duan F, Wang MQ. Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma. World J Gastrointest Oncol 2024; 16:1236-1247. [PMID: 38660650 PMCID: PMC11037041 DOI: 10.4251/wjgo.v16.i4.1236] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 12/29/2023] [Accepted: 02/18/2024] [Indexed: 04/10/2024] Open
Abstract
BACKGROUND The efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib plus programmed cell death protein-1 (PD-1) for unresectable hepatocellular carcinoma (HCC) have rarely been evaluated and it is unknown which factors are related to efficacy. AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC. METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022. Overall survival (OS) and progression-free survival (PFS) were determined. The objective response rate (ORR) and disease control rate (DCR) were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors. Additionally, the prognostic factors affecting the clinical outcome were assessed. RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months. The median OS was 26.43 months (95%CI: 17.00-35.87), and the median PFS was 10.07 months (95%CI: 8.50-11.65). The ORR and DCR were 61.76% and 81.37%, respectively. The patients with Barcelona Clinic Liver Cancer Classification (BCLC) B stage, early neutrophil-to-lymphocyte ratio (NLR) response (decrease), or early alpha-fetoprotein (AFP) response (decrease > 20%) had superior OS and PFS than their counterparts. CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC. The patients with BCLC B-stage disease with early NLR response (decrease) and early AFP response (decrease > 20%) may achieve better clinical outcomes with this triple therapy.
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Affiliation(s)
- Kun-Peng Ma
- Department of Interventional Radiology, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing 100853, China
- Chinese People's Liberation Army Medical School, Beijing 100853, China
| | - Jin-Xin Fu
- Department of Interventional Radiology, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Feng Duan
- Department of Interventional Radiology, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Mao-Qiang Wang
- Department of Interventional Radiology, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing 100853, China
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Yu W, Liu W, Zhang K, Chen S, Wang X. Transarterial interventional therapy combined with tyrosine kinase inhibitors with or without anti-PD-1 antibodies as initial treatment for hepatocellular carcinoma with major portal vein tumor thrombosis: a single-center retrospective study. Cancer Immunol Immunother 2023; 72:3609-3619. [PMID: 37566127 PMCID: PMC10991362 DOI: 10.1007/s00262-023-03511-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Accepted: 07/28/2023] [Indexed: 08/12/2023]
Abstract
Transarterial interventional therapy combined with tyrosine kinase inhibitors (TKIs) and anti-Pd-1 antibodies (triplet regimen) has shown promising results in advanced HCC. However, the clinical utility of the triplet regimen in patients with HCC and major portal vein tumor thrombosis (PVTT) remains unclear. This study compared the efficacy and safety of the triplet regimen versus transarterial interventional therapy combined with TKIs (double regimen) for such patients. Thirty-nine patients treated with the triplet regimen were retrospectively compared with 37 patients treated with the double regimen. The objective response rate (ORR), the response rate of PVTT treatment, and safety were observed; progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan‒Meier method and log-rank test. Predictors of survival were identified using multivariate analysis. Median OS and median PFS were significantly improved in the Triplet Group compared with the Double Group (482 vs. 310 days; 208 vs. 85 days). The ORR and the response rate of PVTT were significantly higher in the Triplet Group than in the Double Group (59% vs. 35%; 62% vs. 35%). There was no significant difference in the incidence of grade 3/4 adverse events between the two groups (33% vs. 21%). The most frequent grade 3/4 adverse events were thrombocytopenia (10%) in the Triplet Group and hand-foot syndrome (14%) in the Double Group. Multivariable analysis showed that treatment method and PVTT treatment response were significant predictors of OS. The triplet regimen showed superiority over the doublet regimen in improving OS and PFS and had acceptable safety in patients with HCC and major PVTT.
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Affiliation(s)
- Wenchang Yu
- Department of Interventional Oncology, Fujian Provincial Key Laboratory of Tumor Biotherapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China.
| | - Weifu Liu
- Department of Interventional Oncology, Fujian Provincial Key Laboratory of Tumor Biotherapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China
| | - Kongzhi Zhang
- Department of Interventional Oncology, Fujian Provincial Key Laboratory of Tumor Biotherapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China
| | - Shiguang Chen
- Department of Interventional Oncology, Fujian Provincial Key Laboratory of Tumor Biotherapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China
| | - Xiaolong Wang
- Department of Interventional Oncology, Fujian Provincial Key Laboratory of Tumor Biotherapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China
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5
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Tian JC, Liu H, Yan LJ, Ding ZN, Han CL, Tian BW, Tan SY, Dong ZR, Wang DX, Xue JS, Mao XC, Yan YC, Li T. Adverse events of immune checkpoint inhibitors in hepatocellular carcinoma: a systemic review and meta-analysis. Clin Exp Med 2023; 23:2115-2129. [PMID: 36385419 DOI: 10.1007/s10238-022-00938-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Accepted: 10/27/2022] [Indexed: 11/17/2022]
Abstract
The introduction of immune checkpoint inhibitors (ICIs) has reshaped the therapy of hepatocellular carcinoma (HCC). ICIs are a novel therapy with frequent adverse events (AEs), including treatment-related adverse events (trAEs) and immune-related adverse events (irAEs). However, no comprehensive overview of the toxicity spectrum of ICIs in HCC patients has been provided. Electronic databases were searched to identify eligible studies. A meta-analysis of the incidence rate of AEs in HCC patients treated with ICIs was performed. Lastly, the prognostic value of irAEs in HCC patients treated with ICIs was verified. Forty-seven studies with 6472 participations met the inclusion criteria. The pooled all-grade trAEs incidence rate was 83.4% (95% confidence interval [95% CI] 77.0-89.1%), ≥ grade 3 trAEs incidence rate was 33.0% (95% CI 26.9-39.5%), all-grade irAEs incidence rate was 34% (95% CI 22-47%), and ≥ grade 3 irAEs incidence rate was 9% (95% CI 5-14%). Aspartate aminotransferase (AST) increase (38%, 95% CI 35-40%) is the most common trAEs. Fatigue (14%, 95% CI 7-23%) is the most common irAEs. The pooled results also showed that 18.8% (95% CI 13.2-25.2%) of patients required systemic steroid therapy due to AEs, while 6.6% (95% CI 4.6-9.0%) of patients withdrew from treatment due to AEs. Additionally, patients experiencing irAEs may have a better progression-free survival (PFS) (multivariate analysis: hazard ratio [HR] = 0.41, 95% CI 0.27-0.61, I2 = 36.3%) but not overall survival (OS) (multivariate analysis: HR = 0.54, 95% CI 0.22-1.36, I2 = 83.2%) than those with no irAEs. Our study presents a systemic assessment of the AEs profile in HCC patients receiving ICIs, providing important reference for clinicians on toxicity profile. Besides, patients with irAEs may have a better PFS. More large-scale and prospective studies are needed to confirm our conclusions.
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Affiliation(s)
- Jin-Cheng Tian
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Hui Liu
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Lun-Jie Yan
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Zi-Niu Ding
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Cheng-Long Han
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Bao-Wen Tian
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Si-Yu Tan
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Zhao-Ru Dong
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Dong-Xu Wang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Jun-Shuai Xue
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Xin-Cheng Mao
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Yu-Chuan Yan
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Tao Li
- Department of Hepatobiliary Surgery, The Second Hospital of Shandong University, No. 247 Beiyuan Street, Jinan, 250033, China.
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Xie S, Wang M, Zeng C, Ou Y, Zhao L, Wang D, Chen L, Kong F, Yi D. Research progress of targeted therapy combined with immunotherapy for hepatocellular carcinoma. Front Oncol 2023; 13:1197698. [PMID: 37305582 PMCID: PMC10248438 DOI: 10.3389/fonc.2023.1197698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Accepted: 05/16/2023] [Indexed: 06/13/2023] Open
Abstract
Hepatocellular carcinoma is a common gastrointestinal malignancy with a high mortality rate and limited treatment options. Molecularly targeted drugs combined with immune checkpoint inhibitors have shown unique advantages over single-agent applications, significantly prolonging patient survival. This paper reviews the research progress of molecular-targeted drugs combined with immune checkpoint inhibitors in the treatment of hepatocellular carcinoma and discusses the effectiveness and safety of the combination of the two drugs to provide a reference for the further application of molecular-targeted drugs combined with immune checkpoint inhibitors in clinical practice.
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Affiliation(s)
| | | | | | | | | | | | - Liwei Chen
- Department of Oncology, The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
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Gao F, Li J, Liao H, Fan P, Wang M, Liu Y, Ding L, Du G. Case report: Apatinib combined with neoadjuvant therapy for primary squamous cell carcinoma of the breast: a case report. Front Pharmacol 2023; 14:1115422. [PMID: 37251309 PMCID: PMC10213914 DOI: 10.3389/fphar.2023.1115422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Accepted: 05/02/2023] [Indexed: 05/31/2023] Open
Abstract
Primary squamous cell carcinoma of the breast is a rare subtype of carcinoma of chemosis for which there is no effective chemotherapy regimen. Breast squamous cell carcinoma is usually "triple negative", with poor chemotherapy effects and poor prognosis. Here, we report a successful case of primary breast squamous cell carcinoma treated with apatinib. The patient was treated with 2 cycles of apatinib. The efficacy was evaluated as partial remission, and a sublesion of approximately 4 cm fell off.
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Affiliation(s)
- Fangfang Gao
- Department of Breast Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Jingtai Li
- Department of Breast Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Haoran Liao
- Department of Breast Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Pingming Fan
- Department of Breast Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, China
- Guangxi Medical University Cancer Hospital, Nanning, China
| | - Minjian Wang
- Department of Pathology, The First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Yu Liu
- Department of Breast Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Linwei Ding
- Key Laboratory of Molecular Biology, Hainan Medical University, Haikou, China
| | - Guankui Du
- Department of Breast Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, China
- Key Laboratory of Molecular Biology, Hainan Medical University, Haikou, China
- Department of Biochemistry and Molecular Biology, Hainan Medical University, Haikou, China
- Biotechnology and Biochemistry Laboratory, Hainan Medical University, Haikou, China
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