Case Report | Open Access
Vol.9 (2023) | Issue-3 | Page No: 138-149
Qiaoxin Lin1, Bin Liang1, Yangyang Li2, Ling Tian3*, Dianna Gu1*
Affiliations + Expand
1 Department of Medical Oncology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
2 Department of Clinical Pathology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
3 Department of Central Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
* Corresponding Author
Address for correspondence:
Ling Tian, Department of Central Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University, No. 241 Huaihai West Road, Xuhui District, Shanghai 200030, China. E-mail: TL09168@hotmail.com
Dianna Gu, Department of Medical Oncology, the First Affiliated Hospital of Wenzhou Medical University, Shangcai Village, Nanbaixiang Town, Ouhai District, Wenzhou 325000, Zhejiang, China. E-mail: yinuo801@126.com
Important Dates + Expand
Date of Submission: 28-Jul-2023
Date of Acceptance: 13-Sep-2023
Date of Publication: 09-Oct-2023
The impact of the COVID-19 global pandemic on human health goes far beyond the reported deaths. Individuals suffering from cancers are more susceptible to infection and have high rates of hospitalization and death. However, a fraction of cancer patients might benefit from the COVID-19 infection. Herein, we report a case of adrenocortical carcinoma treated with immune checkpoint blockade (ICB) recovered from COVID-19 infection and was found to have subsided liver and lung metastases. The patient who was previously resistant to ICB therapy and whose tumors continued to progress showed significant tumor regression after COVID-19 infection and recovery.
Keywords: COVID-19 infection; Immune checkpoint blockade; PD-1 inhibitor; Adrenocortical carcinoma; Tumor regression
Since its outbreak in 2019, the COVID-19 global pandemic has been profoundly affecting human health, causing far more deaths than ever reported. Individuals suffering from a variety of cancers are particularly vulnerable to COVID-19 infection and have higher rates of hospitalization and death than others due to coexisting chronic disease, poor overall health, and a systemic immunosuppression state resulting from cancer or anticancer treatment.[1] It has been reported that immune cells, such as Teffs (T effector cells), Tregs (T regulatory cells), NKs (natural killer cells), and APCs (antigen-presenting cells), exhibited uncontrolled functions in COVID-19.[2] However, the mechanisms that coordinate immune cell function and viral interaction remains unknown. As we know, severe COVID-19 is characterized by lymphopenia with a marked reduction in CD8+ T cells and upregulation of markers of exhaustion (e.g., PD-1). For anti-tumor agents, immunosuppressive cytotoxic chemotherapy is associated with worse outcomes. Nevertheless, it has been speculated that immune checkpoint blockades (ICBs) may have a beneficial association with COVID-19 outcomes.[3]
In the past decade, cancer immunotherapy has made unprecedented progress and the most widely used immunotherapy agents are antibodies that block immunosuppressive receptors, such as CTLA-4 (cytotoxic T-lymphocyte antigen 4), PD-1 (programmed cell death protein 1) and PD-L1 (programmed death-ligand 1). Despite the proven clinical benefits of PD-1 or PD-L1-targeted therapy for a wide range of cancers, some patients may not be sensitive to ICBs or develop drug resistance after a period of medication.[4]
Adrenocortical carcinoma (ACC) is an extremely rare and aggressive malignancy, yet treatment options are limited. Systemic therapy, based on etoposide combined with doxorubicin plus mitotane, is the most effective treatment but possesses an unfavorable prognosis for advanced ACC.[5] The evidence of the implementation of ICBs in advanced ACC is limited.[6] Herein, we report a case of a patient with advanced ACC who developed resistance to ICB treatment and showed regression of metastatic lesions after COVID-19 infection and recovery.
On July 29, 2022, a 40-year-old female patient was admitted to our hospital due to gastric distention and pain. Besides, the patient also had other clinical manifestations such as a masculine voice, facial acne, hirsutism syndrome, and persistent menstrual irregularities. An abdominal computed tomography (CT) scan showed a large lesion in the liver [Figure 1A], and a chest CT scan revealed numerous scattered nodules, which were suspected to be metastatic lesions [Figure 1B]. And yet, no suspicious lesions were detected by CT scan in the adrenal cortex then. Subsequently, the patient underwent an ultrasound-guided liver aspiration biopsy. The pathological findings were reported as adrenocortical carcinoma with liver metastasis on August 15, 2022 [Figure 2]. To confirm the diagnosis, the patient also underwent a lung biopsy in Shanghai, and the biopsy specimen was sent for genomic RNA assay (Canhelp Genomics Co., Ltd) to detect the tumor origin, which was reported as an adrenal tumor [Supplementary Figure 1 & Supplementary Table 1]. The immunohistochemical analysis of PD-L1 expression in liver metastasis confirmed that tumor cell proportion score (TPS) and combined positive score (CPS) were both 0% [Supplementary Figure 2]. In addition, the next-generation sequencing (NGS) of the patient's liver metastatic samples revealed no detection of relevant genes affecting immune efficacy including ALK, EGFR, RET, KRAS, yet only one somatic mutation (AKAP8L-EWSR1(A1:E10) of EWSR1 gene) occurred, and the tumor mutational burden (TMB) was 0 [Supplementary Figure 3 & Supplementary Table 2, 3]. Thereupon, the patient was diagnosed with adrenocortical carcinoma stage IV with liver and lung metastases.
Then, in accordance with the patient’s preference, she was referred to the Shanghai Cancer Center of Fudan University and was advised mitotane treatment. However, after taking mitotane, the patient experienced severe malaise, vomiting, and other gastrointestinal reactions, hence the dosage was reduced. Later the patient returned to the First Affiliated Hospital of Wenzhou Medical University for further treatment. Based on some evidence of the potential benefit of immunotherapy in ACC7 and the poor performance status of the patient, the doctors in the First Affiliated Hospital of Wenzhou Medical University adjusted the treatment regimen to a modified dosage of mitotane plus pembrolizumab 200mg every 3 weeks using (q3w) in October 2022. However, she developed some more significant symptoms, including dyspnea and more pronounced abdominal discomfort. The CT evaluation showed her lung metastases continued to increase in both number and size. Furthermore, the patient's liver metastases initially showed transient shrinkage followed by enlargement [Figure 1C-1F], suggesting resistance to PD-1 blockade.
On December 23, 2022, the patient was infected with COVID-19. The patient underwent two positive rapid antigenic tests at home, instead of going to the hospital for COVID-19 nucleic acid test. During her infection, the patient developed a fever for one day and mild chest tightness for one week. The patient was administered non-steroidal anti-inflammatory drugs to relieve symptoms. One week later, she tested negative for COVID-19 antigen.
On January 17, 2023, the patient returned to the First Affiliated Hospital of Wenzhou Medical University for evaluation of tumor development. Surprisingly, we found a considerable regression in the extent and size of her pulmonary metastases [Figure 1H], and a regression in the diameter of the liver metastases [Figure 1G]. We then tested the patient's hormone levels and found that the adrenocorticotropic hormone (ACTH), prolactin, progesterone, and follicle-stimulating hormone (FSH) were elevated after COVID-19 infection [Figure 3A-3D], while testosterone, cortisol, luteinizing hormone (LH) and estradiol were decreased [Figure 3E-3H]. At follow-up, the patient began to experience recurrent hyponatremia, hyperkalemia, and other therapeutic drug response reactions that never occurred during the rapid progression of the disease. In terms of clinical presentation, her dyspnea and abdominal pain have improved. She will continue to use mitotane in combination with pembrolizumab as a treatment regimen.
It should be pointed out that, prior to diagnosis and medication, the patient had visited the First Affiliated Hospital in November 2021 for subxiphoid pain. At that time, abdominal CT showed a large occupancy in the right lobe of the liver, and then an ultrasound-guided liver puncture was performed in Shanghai. Due to the rarity of ACC and the lack of specific tumor biomarkers, the patient was once diagnosed with hepatocellular carcinoma (HCC) and underwent a series of HCC treatments. A timeline that summarizes these events is shown in Figure 3I.
It is generally accepted that people with cancer are more likely to suffer from severe disease and have a higher mortality rate compared with non-cancer patients infected with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2).[1],[6] However, a retrospective cohort study revealed that there was no difference in mortality between cancer and noncancer patients, and the increased risk of mortality was associated with obesity and active smoking.[8] Some scholars even believe that a second SARS-CoV-2 infection seems to be beneficial in controlling tumor progression.[9] Furthermore, instances of spontaneous tumor regression have been documented in certain tumors in conjunction with COVID-19 infection.[10] However, a dysfunctional status of T cells and abnormal PD-1/PD-L1 immune checkpoint axis were observed in patients who recovered from COVID-19.[11] So far, the impact of SARS-CoV-2 infection on the efficacy of PD-1 inhibitor in patients with cancer is yet unknown.
This is the first report, to our knowledge, describing a patient with advanced ACC treated with mitotane in combination with immunotherapy. The patient recovered from COVID-19 and subsequently experienced a significant reduction of lung and liver metastases. Prior to COVID-19 infection, the patient with negative expression of PD-L1 in tumor tissue had presented resistance to mitotane in combination with anti-PD-1. Due to the cytotoxic effects of mitotane on mitochondria in adrenal cortical cells,[12] the efficacy of the treatment was substantially improved after COVID-19 infection, suggesting that COVID-19 infection could increase the sensitivity of anti-PD-1.
The upregulation of immune checkpoints, such as PD-1, PD-L1, PD-L2 (Programmed Death-Ligand 2), CTLA-4, TIM-3 (T-cell Immunoglobulin and Mucin Domain 3), TIGIT (T-cell Immunoreceptor with Ig and ITIM Domains), etc, on T cells in patients with COVID-19, is one of the most manifestations leading to T-cell exhaustion, contributing to worse clinical outcomes.[13] Blockade of PD-1 signaling in the exhausted T cells isolated from COVID-19 patients restored T cell functional response to COVID-19 and helped to control the infection.[11] Thus, the PD-1 blockade might alleviate the symptoms of this ACC patient infected with COVID-19, who just had a fever for one day and mild chest tightness for one week, contributing to the viral clearance.
Surprisingly, despite the fact that the lung and liver metastases were PD-1 inhibitor-resistant before SARS-CoV-2 infection, we noticed a considerable decline in metastases assessed by CT post-infection. Currently, we know that multiple factors, such as tumor immunogenicity, T cell function, PD-L1 expression, tumor microenvironment, and so on, have been found to be associated with the efficacy of PD-1/PD-L1 blockade therapy.[14] It was reported that, during the acute phase of viral infection, an increase in the number of functional (not exhausted) PD-1+CD8+ T cells was detected in patients with SARS-CoV-2 infection.[15] However, the PD-1 receptor expression on the surface of CD8+ T cells is transient during the acute phase, which is distinguished from the sustained PD-1 expression on CD8+ T cells in patients with chronic infection or in cancer, rendering T-cell exhaustion or dysfunction.[16] In this case, PD-1 inhibitor seems to exert the effect at the crossroad between SARS-CoV-2 induced infection and ACC progression. We speculate that the increased PD-1 or PD-L1 expression during acute SARS-CoV-2 infection can restore T-cell function mediated by immune checkpoint blockade, and potentially reverse resistance in cancer patients with initial PD-L1 negative expression, as in the case reported above.
However, we should admit that severe SARS-CoV2 can induce systemic hyperinflammation and immune dysregulation, by increasing pro-inflammatory cytokines and chemokines,[17] which may create a microenvironment favorable to tumorigenesis and metastatic relapse.[18] Regrettably, due to the COVID-19 pandemic in the community in China, this patient opted to take home medication for symptomatic treatment, which left us with a lack of cytokine testing during her infection. Currently, the interactions among COVID-19, tumor cells, and the immune system are unknown. The effect of COVID-19-induced inflammation on tumor cells and their microenvironment needs to be investigated in detail, which is crucial for the evaluation of the potential long-term risks of COVID-19 in cancer patients, as well as for the selection of safe and effective antitumor immunotherapeutic regimens.
In conclusion, there is not enough data about tumor reduction in patients under ICB therapy after infected with COVID-19, but we would like to share this case. Based on the currently available data, we cannot make recommendations regarding the contribution of SARS-CoV-2 infection on ICB therapy, and further studies are clearly needed. Therefore, we believe it is important to share our experiences.
FINANCIAL SUPPORT AND SPONSORSHIP
This study was partially supported by the funding of the National Natural Science Foundation of China awarded to Ling Tian and Dianna Gu (No.82073203 to Ling Tian and No.81802328 to Dianna Gu).
CONFLICTS OF INTEREST
The authors declare no conflicts of interest.
ETHICS APPROVAL AND CONSENT TO PARTICIPATE
Written informed consent has been obtained from the patient to publish this paper.
AUTHOR CONTRIBUTIONS
Qiaoxin Lin contributed to the data curation and original draft preparation of the manuscript. Bin Liang played a significant role in conceptualizing the study. Yangyang Li contributed to the methodology development and provided valuable resources. Ling Tian's contributions encompassed reviewing and providing supervision. Dianna Gu was involved in conceptualizing the study and reviewing it. All authors contributed to the Manuscript editing and approved the version.
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José M. Santos‑Pereira1, Sandra Muñoz‑Galván2
Manuel P. Jiménez‑García, Eva M. Verdugo‑Sivianes, Antonio Lucena‑Cacace
Marco Perez, Lola Navas, Amancio Carnero
Behnam Sayanjali1,2
Reecha A. Parikh, Toral P. Kobawala, Trupti I. Trivedi, Mahnaz M. Kazi, Nandita R. Ghosh
Nadia Hindi1,2, Javier Martin‑Broto1,2
Pengxing Zhang1, Hongwei Yang2, Xin Wang2, Liang Wang3, Yingduan Cheng4, Yongsheng Zhang5, Yanyang Tu1,2
Yi‑Zhou Jiang1, Demeng Chen2
Aaron Yun Chen, Glenn D. Braunstein, Megan S. Anselmo, Jair A. Jaboni, Fernando Troy Viloria, Julie A. Neidich, Xiang Li, Anja Kammesheidt
Binliang Liu, Yalan Yang, Zongbi Yi, Xiuwen Guan, Fei Ma
Pablo Reclusa1, Anna Valentino1, Rafael Sirera1,2, Martin Frederik Dietrich3, Luis Estuardo Raez3, Christian Rolfo1
Martin Frederik Dietrich1, Christian Rolfo2, Pablo Reclusa2, Marco Giallombardo2, Anna Valentino2, Luis E. Raez1
Ting Chen1,2, Rongzhang He1,3, Xinglin Hu1,3,4, Weihao Luo1, Zheng Hu1,3, Jia Li1, Lili Duan1, Yali Xie1,2, Wenna Luo1,2, Tan Tan1,2, Di‑Xian Luo1,2
Poonam Sonawane1, Young A. Choi1, Hetal Pandya2, Denise M. Herpai1, Izabela Fokt3,
Waldemar Priebe3, Waldemar Debinski1
Pei Liang, Michael Gao Jr.
Wenxiu Zhao1, Yvonne Li2, Xun Zhang1
Andrew Fesler1, Hua Liu1, Ning Wu1,2, Fei Liu3, Peixue Ling3, Jingfang Ju1,3
Simona Gurzu1,2,3, Marius Alexandru Beleaua1, Laura Banias2, Ioan Jung1
Liyuan Zhou1,2, Yujun Li1,2, Changchen Hu3, Binquan Wang1,2
Jeremy A. Hengst1,2, Taryn E. Dick1,2, Arati Sharma1, Kenichiro Doi3, Shailaja Hegde4, Su‑Fern Tan5, Laura M. Geffert1,2, Todd E. Fox5, Arun K. Sharma1, Dhimant Desai1, Shantu Amin1, Mark Kester5, Thomas P. Loughran5, Robert F. Paulson4, David F. Claxton6, Hong‑Gang Wang3, Jong K. Yun1,2
Feng Yu1, Bangxing Hong1, Xiao‑Tong Song1,2,3
Yasar Ahmed1, Nemer Osman1, Rizwan Sheikh2, Sarah Picardo1, Geoffrey Watson1
Hatel Rana Moonat, Gangxiong Huang, Pooja Dhupkar, Keri Schadler, Nancy Gordon,
Eugenie Kleinerman
Tongwei Wu, Xiao Yang, Min An, Wenqin Luo, Danxian Cai, Xiaolong Qi
Xiao Liang1, Fang‑Fang Yin1,2, Yilin Liu1, Brian Czito2, Manisha Palta2, Mustafa Bashir3, Jing Cai1,2
Xiaofeng Zhu1, Yu Lei1, Dandan Zheng1, Sicong Li1, Vivek Verma1, Mutian Zhang1, Qinghui Zhang1, Xiaoli Tang2, Jun Lian2, Sha X. Chang2, Haijun Song3, Sumin Zhou1, Charles A. Enke1
Wang Qu, Ma Fei, Binghe Xu
Yanlan Li1,2*, Zheng Hu1*, Yufang Yin3, Rongzhang He1, Jian Hu1, Weihao Luo1, Jia Li1, Gebo Wen2, Li Xiao1, Kai Li1, Duanfang Liao4, Di-Xian Luo1,5
Xiaoshan Xu1, Hongwei Yang2, Xin Wang2, Yanyang Tu1
Lei Zhang1,2, Yawei Zhang2, You Zhang1,2,3, Wendy B. Harris1,2, Fang‑Fang Yin1,2,4, Jing Cai1,4,5, Lei Ren1,2
Yasuka Azuma1,2, Masako Mizuno‑Kamiya3, Eiji Takayama1, Harumi Kawaki1, Toshihiro Inagaki4, Eiichi Chihara2, Yasunori Muramatsu5, Nobuo Kondoh1
Yi‑Rong Xiang, Li Liu
Kazunori Hamamura1, Koichi Furukawa2
Qing‑Hao Zhu1*, Qing‑Chao Shang1*, Zhi‑Hao Hu1*, Yuan Liu2, Bo Li1, Bo Wang1, An‑Hui Wang1
Nadège Dubois1, Sharon Berendsen2, Aurélie Henry1,2, Minh Nguyen1, Vincent Bours1,
Pierre Alain Robe1,2
Toshihiro Inagaki1,2, Masako Mizuno‑Kamiya3, Eiji Takayama1, Harumi Kawaki1, Eiichi Chihara4, Yasunori Muramatsu5, Shinichiro Sumitomo5, Nobuo Kondoh1
Anjali Geethadevi1, Ansul Sharma2, Manish Kumar Sharma3, Deepak Parashar1
Ernest K. Amankwah
Xiaohui Xu1, Zilong Dang2, Taoli Sun3, Shengping Zhang1, Hongyan Zhang1
Javier de la Rosa*, Alejandro Urdiciain*, Juan Jesús Aznar‑Morales, Bárbara Meléndez1,
Juan A. Rey2, Miguel A. Idoate3, Javier S. Castresana
Akiko Sasaki1, Yuko Tsunoda2, Kanji Furuya3, Hideto Oyamada1, Mayumi Tsuji1, Yuko Udaka1, Masahiro Hosonuma1, Haruna Shirako1, Nana Ichimura1, Yuji Kiuchi1
Hui Liu1, Hongwei Yang2, Xin Wang3, Yanyang Tu1
Xiaoshan Xu, Zhen Wang, Nan Liu, Pengxing Zhang, Hui Liu, Jing Qi, Yanyang Tu
Lei Zhang1,2, Fang‑Fang Yin1,2,3, Brittany Moore1,2, Silu Han1,2, Jing Cai1,2,4
Sulin Zeng1,2, Wen H. Shen2, Li Liu1
Yanhua Mou1, Quan Wang1, Bin Li1,2
Raquel Luque Caro, Carmen Sánchez Toro, Lucia Ochoa Vallejo
Shazima Sheereen1, Flora D. Lobo1, Waseemoddin Patel2, Shamama Sheereen3,
Abhishek Singh Nayyar4, Mubeen Khan5
Feiyifan Wang1, Christopher J. Pirozzi2, Xuejun Li1
Jian‑Hong Zhong1,2, Kang Chen1, Bhavesh K. Ahir3, Qi Huang4, Ye Wu4, Cheng‑Cheng Liao1, Rong‑Rong Jia1, Bang‑De Xiang1,2, Le‑Qun Li1,2
Antonio Lucena‑Cacace1,2,3, Amancio Carnero1,2
Michael Zhang, Kelvin Zheng, Muhammad Choudhury, John Phillips, Sensuke Konno
Ajay Sasidharan, Rahul Krishnatry
Leping Liu1, Xuejun Li1,2
Gerard Cathal Millen1, Karen A. Manias1,2, Andrew C. Peet1,2, Jenny K. Adamski1
Ge Ren1,2,3, Yawei Zhang1,2, Lei Ren1,2
Qing Du1, Xiaoying Ji2, Guangjing Yin3, Dengxian Wei3, Pengcheng Lin1, Yongchang Lu1,
Yugui Li3, Qiaohong Yang4, Shizhu Liu5, Jinliang Ku5, Wenbin Guan6, Yuanzhi Lu7
Lei Zhang1, Guoyu Qiu2, Xiaohui Xu2, Yufeng Zhou3, Ruiming Chang4
Aanchal Tandon, Bharadwaj Bordoloi, Safia Siddiqui, Rohit Jaiswal
Dongni Ren1, Xin Wang2, Yanyang Tu1,2
Xipeng Wang1,2, Mitsuteru Yokoyama2, Ping Liu3
Xiaohui Xu1, Guoyu Qiu1, Lupeng Ji2, Ruiping Ma3, Zilong Dang4, Ruling Jia1, Bo Zhao1
Mansoor C. Abdulla
Guru Prasad Sharma1, Anjali Geethadevi2, Jyotsna Mishra3, G. Anupa4, Kapilesh Jadhav5,
K. S. Vikramdeo6, Deepak Parashar2
Ge Zengzheng1, Huang-Sheng Ling2, Ming-Feng Li2, Xu Xiaoyan1, Yao Kai1, Xu Tongzhen3,
Ge Zengyu4, Li Zhou5
Guoyu Qiu1, Xiaohui Xu1, Lupeng Ji2, Ruiping Ma3, Zilong Dang4, Huan Yang5
Steven Lehrer1, Peter H. Rheinstein2
Umair Ali Khan Saddozai1, Qiang Wang1, Xiaoxiao Sun1, Yifang Dang1, JiaJia Lv1,2, Junfang Xin1, Wan Zhu3, Yongqiang Li1, Xinying Ji1, Xiangqian Guo1
Elias Adikwu, Nelson Clemente Ebinyo, Beauty Tokoni Amgbare
Zengzheng Ge1, Xiaoyan Xu1, Zengyu Ge2, Shaopeng Zhou3, Xiulin Li1, Kai Yao1, Lan Deng4
Crystal R. Montgomery‑Goecker1, Andrew A. Martin2, Charles F. Timmons3, Dinesh Rakheja3, Veena Rajaram3, Hung S. Luu3
Elias Adikwu, Nelson Clemente Ebinyo, Loritta Wasini Harris
Ling Wang1,2, Run Wan1,2, Cong Chen1,2, Ruiliang Su1,2, Yumin Li1,2
Priyanka Priyaarshini1, Tapan Kumar Sahoo2
Debasish Mishra1, Gopal Krushna Ray1, Smita Mahapatra2, Pankaj Parida2
Yang Li1, Zhenfan Huang2, Haiping Jiang3
Srigopal Mohanty1, Yumkhaibam Sobita Devi2, Nithin Raj Daniel3, Dulasi Raman Ponna4,
Ph. Madhubala Devi5, Laishram Jaichand Singh2
Xiaohui Xu1, Zilong Dang2, Lei Zhang3, Lingxue Zhuang4, Wutang Jing5, Lupeng Ji6, Guoyu Qiu1
Debasish Mishra1, Dibyajyoti Sahoo1, Smita Mahapatra2, Ashutosh Panigrahi3
Nadeema Rafiq1, Tauseef Nabi2, Sajad Ahmad Dar3, Shahnawaz Rasool4
Palash Kumar Mandal1, Anindya Adhikari2, Subir Biswas3, Amita Giri4, Arnab Gupta5,
Arindam Bhattacharya6
Seyyed Majid Bagheri1,2, Davood Javidmehr3, Mohammad Ghaffari1, Ehsan Ghoderti‑Shatori4
Mun Kyoung Kim1, Aidin Iravani2, Matthew K. Topham2,3
Yan Liu1,2,3,4#, Chen Cui1,2,3,4#, Jidong Liu1,2,3,4, Peng Lin1,2,3,4,Kai Liang1,2,3,4, Peng Su5, Xinguo Hou1,2,3,4, Chuan Wang1,2,3,4, Jinbo Liu1,2,3,4, Bo Chen6, Hong Lai1,2,3,4, Yujing Sun1,2,3,4* and Li Chen 1,2,3,4*
Zhiyu Xia1,2, Haotian Tian1, Lei Shu1,2, Guozhang Tang3, Zhenyu Han4, Yangchun Hu1*, Xingliang Dai1*
Jianfeng Xu1,2, Hanwen Zhang1,2, Xiaohui Song1,2, Yangong Zheng3, Qingning Li1,2,4*
Bowen Hu1#, Lingyu Du2#, Hongya Xie1, Jun Ma1, Yong Yang1*, Jie Tan2*
Umair Ali Khan Saddozai, Zhendong Lu, Fengling Wang, Muhammad Usman Akbar, Saadullah Khattak, Muhammad Badar, Nazeer Hussain Khan, Longxiang Xie, Yongqiang Li, Xinying Ji, Xiangqian Guo
Suxia Hu, Abdusemer Reyimu, Wubi Zhou, Xiang Wang, Ying Zheng, Xia Chen, Weiqiang Li, Jingjing Dai
Yuting Chen, Yuzhen Rao, Zhiyu Zeng, Jiajie Luo, Chengkuan Zhao, Shuyao Zhang
Jun Li, Ziyong Wang, Qilin Wang
Jinghua Qi1,2, Hangping Chen3，Huaqing Lin2,4，Hongyuan Chen1,2,5* and Wen Rui2,3,5,6*
Xingli Qi1,2, Huaqing Lin2,3, Wen Rui2,3,4,5 and Hongyuan Chen1,2,3
Yulou Luo1, Lan Chen2, Ximing Qu3, Na Yi3, Jihua Ran4, Yan Chen3,5*
Xiumin Zhang1,2#, Xinyue Lin1,3#, Siman Su1,3#, Wei He3, Yuying Huang4, Chengkuan Zhao3, Xiaoshan Chen3, Jialin Zhong3, Chong Liu3, Wang Chen3, Chengcheng Xu3, Ping Yang5, Man Zhang5, Yanli Lei5*, Shuyao Zhang1,3*
Min Jiang1#, Rui Zheng1#, Ling Shao1, Ning Yao2, Zhengmao Lu1*
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