Home Medicine The role of auto-HSCT in extranodal natural killer/T cell lymphoma
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The role of auto-HSCT in extranodal natural killer/T cell lymphoma

  • Yin-yin Peng EMAIL logo , Xin Wang and Lin Liu
Published/Copyright: October 3, 2024
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Open Medicine
From the journal Open Medicine Volume 19 Issue 1

Abstract

Objectives

Autologous hematopoietic stem cell transplantation (auto-HSCT) is considered optional consolidation therapy especially for relapsed/refractory extranodal NK/T-cell lymphoma (ENKL), but its applications to newly diagnosed advanced-stage ENKL is currently limited.

Methods

We collected 51 cases of newly diagnosed advanced-stage ENKL patients, including 26 with auto-HSCT and 25 with chemotherapy rather than HSCT, from our hospital between 2014/01 and 2023/12. We summarized the patients’ characteristics, conducted survival analysis of the 51 cases, and analyzed the potential benefits of auto-HSCT to ENKL patients.

Results

It shows that after a median follow-up time of 39 months, the estimated 5-year overall survival (OS) of the 51 newly diagnosed advanced-stage ENKL patients is 73.4%, and their estimated 5-year progression-free survival (PFS) is 73.4%. For patients receiving auto-HSCT, the 5-year OS (91.7%) and PFS (91.0%) are significantly different from those of patients receiving chemotherapy without HSCT (OS 53.3%, PFS 54.5%) (p < 0.05). Univariate and multivariate analysis results suggest that only the l-asparaginase usage in chemotherapy showed significant impact on the OS, and none of concerned factors showed significant impact on the PFS.

Conclusions

Auto-HSCT is indeed an option to newly diagnosed advanced-stage ENKL, but further studies are still required for more strict disease management.

Keywords: extranodal NK/T-cell lymphoma; chemotherapy; autologous; hematopoietic stem cell transplantation

1 Introduction

Extranodal NK/T-cell lymphoma (ENKL) is rarely diagnosed in Western countries but relatively more common in East Asian countries. It is closely associated with Epstein-Barr virus (EBV). Among newly diagnosed advanced and limited stage of ENKLs, the limited-stage ENKL responds relatively much better to radiotherapy or concurrent radiation and chemotherapy. Regimes containing l-asparaginase are effective to limited-stage ENKL, but are not that satisfactory to advanced-stage ENKL [1]. Studies show that the complete remission (CR) rate of advanced-stage patients with l-asparaginase, etoposide, and dexamethasone (AspaMetDex) regimen was 30%, and the 5-year survival rate of those patients with the l-asparaginase, vincristine, and dexamethasone regimen was only 25% [2,3]. As advanced-stage ENKLs are highly progressive and sometimes multi-drug resistant, there is so far no standard management for advanced-stage ENKLs.

In most clinical management guidelines and expert consensuses, autologous hematopoietic stem cell transplantation (auto-HSCT) is considered as an optional consolidation therapy for newly diagnosed advanced-stage ENKL. However in clinic, the rules for choice of auto-HSCT to high-risk ENKL patients are still unclear. Previous papers about auto-HSCT mostly talked not specifically about ENKL, but generally about peripheral T-cell lymphoma, including many other subtypes like anaplastic large-cell lymphoma, angioimmunoblastic T-cell lymphoma, hepatosplenic T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, enteropathy-associated T-cell lymphoma, cutaneous T-cell lymphoma, and aggressive NK-cell leukemia [4–8].

In this study, in order to provide more insights into the rules for choice of auto-HSCT, we summarized and analyzed the clinical cases of newly diagnosed advanced-stage ENKLs from our hospital (the First Affiliated Hospital of Chongqing Medical University) between 2014/01 and 2023/12. From our hospital, 51 newly diagnosed advanced-stage ENKL patients were included in this analysis, of which 26 underwent auto-HSCT, the other 25 received chemotherapy without HSCT. We summarized the characteristics of all 51 newly diagnosed advanced-stage ENKL patients and evaluated potential benefits of these characteristics to ENKL patients. We hope to provide insights into the clinical practice of auto-HSCT to ENKL patients.

2 Materials and methods

2.1 Patients

From the department of hematology at our hospital, between 2014/01 and 2023/12, we retrospectively analyzed the clinical data of newly diagnosed patients with advanced-stage ENKL, and compared the data of patients with auto-HSCT to that of patients without auto-HSCT. As auto-HSCT is usually performed in patients with age below 60 years, patients older than 60 years were excluded during data collection.

Totally 51 newly diagnosed advanced-stage ENKL patients were collected retrospectively, of which 26 received auto-HSCT, while the other 25 received chemotherapy without HSCT. The choice of auto-HSCT was first recommended to but finally determined by the patients themselves. For young (age <60 years) patients, we would like to recommend auto-HSCT, but still the final decision is up to the patients themselves. All patients were diagnosed by lymph node biopsy and were confirmed by pathology, according to the criteria of the World Health Organization for the classification of lymphoid tissue tumors in 2016. Following the guidelines of American National Comprehensive Cancer Network [9], the prognostic indicators of natural killer cell lymphoma containing Epstein-Barr virus DNA (PINK-E) were selected for prognostic evaluation and risk stratification. Disease stages of the patients were classified according to a modification of the Ann Arbor system.

2.2 Transplantation

About 24/26 patients received chemotherapy without radiotherapeutic initial treatment before transplant. Two of them had external radiotherapy for nasopharynx lymphomas. They all received either l-asparaginase-containing chemotherapy or l-asparaginase-absent chemotherapy. After that, they received peripheral blood hematopoietic stem cells (PBSC) transplantation. Granulocyte colony stimulating factor 10 mg/kg per day was applied to patients for the mobilization of PBSC. Their conditioning regimens were myeloablative, including lomustine, etoposide, cytarabine, and cyclophosphamide (CEAC) for eight auto-HSCT patients; carmustine, etoposide, cytarabine, and melphalan (BEAM) for 16 auto-HSCT patient; idarubicin, etoposide, cytarabine, and cyclophosphamide (IEAC) for two auto-HSCT patients (details in Table 1). All other 25 patients received chemotherapy containing l-asparaginase without HSCT (details in Table 2).

Table 1

Clinical data of 26 newly diagnosed advanced-stage ENKL patients treated with auto-HSCT in our hospital

Patient no. Gender Age Stage Bone marrow infiltration LDH PINK-E score Chemotherapy before auto-HSCT l-asparaginase-containing chemotherapy before auto-HSCT Disease status at auto-HSCT Radiotherapy Conditioning regimens OS (month) PFS (month) Alive
1 Male 36 III No N 3 3 Yes PR No CEAC 73 73 Yes
2* Female 25 IV No E 3 5 No PR No CEAC 15 10 No
3 Male 42 IV No E 3 5 Yes CR No CEAC 83 83 Yes
4** Male 46 IV No N 3 6 No PR No CEAC 17 17 No
5# Female 42 IV No E 4 2 Yes CR No CEAC 83 23 Yes
6 Male 26 III No N 3 4 Yes CR No CEAC 115 115 Yes
7 Male 19 IV No N 4 4 Yes CR No CEAC 85 85 Yes
8 Male 21 III No N 3 4 Yes CR No BEAM 58 58 Yes
9 Female 41 III No N 3 4 Yes CR No IEAC 65 65 Yes
10 Female 24 IV No N 3 5 Yes CR No CEAC 60 60 Yes
11 Female 54 IV Yes N 3 5 Yes CR No IEAC 59 59 Yes
12 Female 25 IV No E 3 6 Yes CR No BEAM 56 56 Yes
13 Female 52 IV No N 3 3 Yes CR No BEAM 55 55 Yes
14 Female 33 IV Yes E 3 5 Yes CR No BEAM 57 57 Yes
15 Female 34 IV No N 3 5 Yes CR No BEAM 45 45 Yes
16 Female 35 IV Yes E 3 6 Yes CR No BEAM 27 27 Yes
17 Male 31 IV No N 3 4 Yes PR No BEAM 25 25 Yes
18 Female 36 IV No N 3 5 Yes CR No BEAM 23 23 Yes
19 Female 56 IV No N 4 3 Yes CR No BEAM 22 22 Yes
20 Male 35 IV No E 3 5 Yes CR No BEAM 27 27 Yes
21 Male 42 IV No N 3 6 Yes CR No BEAM 30 30 Yes
22 Male 38 IV No N 3 6 Yes PR No BEAM 32 32 Yes
23 Male 37 IV No E 3 4 Yes CR No BEAM 56 56 yes
24 Male 30 III No E 3 5 Yes CR Yes BEAM 9 9 Yes
25 Male 59 IV No E 3 5 Yes CR No BEAM 8 8 Yes
26 Male 34 IV No N 3 5 Yes CR Yes BEAM 27 12 Yes

Abbreviations: ENKL, extranodal NK/T-cell lymphoma; LDH, lactate dehydrogenase; PINK-E, prognostic indicators of natural killer cell lymphoma containing Epstein-Barr virus DNA; auto-HSCT, autologous hematopoietic stem cell transplantation; allo-HSCT, allogeneic hematopoietic stem cell transplantation; OS, overall survival; PFS, progression-free survival; E, elevated; N, normal; CR, complete remission; PR, partial remission; CEAC, lomustine, etoposide, cytarabine, and cyclophosphamide; BEAM, carmustine, etoposide, cytarabine, and melphalan; IEAC, idarubicin, etoposide, cytarabine, and cyclophosphamide.

*The patient replased in 10 months after being diagnosed, then received chemotherapy of GLIDE (gemcitabine, pegaspargase, ifosfamide, dexamethasone, and etoposide)+chidamide, but died 15 months after being diagnosed because of disease progression.

**The patient remained CR, but died of severe pneumonia 17 month after being diagnosed.

#The patient replased in 23 months after auto-HSCT, then received four cycles of chemotherapy of P-GEMOX, maintained with chidamide without any disease progression for 76 month after being diagnosed.

Table 2

Clinical data of 25 newly diagnosed advanced-stage ENKL patients treated with chemotherapy without HSCT in our hospital

Patient no. Gender Age Stage Bone marrow infiltration LDH PINK-E score l-asparaginase-containing chemotherapy Chemotherapy cycle Radiotherapy OS (month) PFS (month) Alive
1 Male 53 III No N 2 Yes 8 No 46 40 No
2 Male 47 III No E 3 Yes 8 No 54 54 Yes
3 Male 14 IV Yes E 3 Yes 8 No 54 54 Yes
4 Male 51 IV No E 3 Yes 9 No 15 12 No
5 Male 45 IV No E 3 Yes 6 No 10 7 No
6 Male 53 III No E 3 Yes 8 Yes 109 109 Yes
7 Male 45 III No N 2 Yes 6 Yes 122 122 Yes
8 Female 39 IV No N 4 Yes 4 No 4 4 No
9 Male 52 IV No N 3 Yes 8 Yes 64 64 Yes
10 Female 49 IV Yes E 4 Yes 1 No 1 1 No
11 Male 55 IV Yes E 4 Yes 8 No 61 61 Yes
12 Male 42 IV No N 3 Yes 6 No 8 8 No
13 Male 51 III Yes E 3 Yes 3 No 3 3 No
14 Female 27 IV No E 3 Yes 3 No 36 36 Yes
15 Female 47 IV No E 3 Yes 6 No 5 5 No
16 Male 55 IV Yes N 3 Yes 8 No 33 33 Yes
17 Female 58 IV Yes N 3 Yes 1 No 1 1 No
18 Male 22 IV Yes E 3 Yes 5 No 34 34 Yes
19 Female 58 IV Yes E 4 Yes 4 No 21 21 Yes
20 Female 34 IV Yes N 3 Yes 5 No 12 12 Yes
21 Male 40 IV No E 3 Yes 6 No 9 9 Yes
22 Male 57 IV No E 3 Yes 6 No 16 16 Yes
23 Male 22 IV No E 3 Yes 3 No 14 11 No
24 Female 16 III No N 2 Yes 4 No 13 13 Yes
25 Male 59 IV No N 3 Yes 6 Yes 18 18 Yes

Abbreviations: ENKL, extranodal NK/T-cell lymphoma; LDH, lactate dehydrogenase; PINK-E, prognostic indicators of natural killer cell lymphoma containing Epstein-Barr virus DNA; OS, overall survival; PFS, progression-free survival; E, elevated; N, normal.

2.3 Statistical methods

Overall evaluation of the patients was performed based on the following information: medical record review, physical examination, blood chemistry, computed tomography (CT) imaging (total body positron emission tomography/CT or CT of the head, neck, chest, and abdomen), ultrasound imaging of systemic superficial lymph nodes, and bone marrow aspiration.

We not only summarized the characteristics of the patients during the treatment in our hospital, but also performed survival analysis to those cases. The overall survival (OS) is the time from diagnosis to death, or to the last follow-up time which was set on 2024/04/30 in this study. The progression-free survival (PFS) is the time from diagnosis to relapse, disease progression, death, or to the last follow-up time. The OS and PFS were estimated using Kaplan–Meier method in IBM SPSS v23.0, survival comparisons were made using the log-rank test. The impacts of factors to the OS and PFS were evaluated using Kaplan–Meier regression for univariate analysis and using Cox regression for multivariate analysis. The status variables for OS and PFS were survival and progression, respectively. And a p value (two-tailed) <0.05 was considered statistically significant.

  1. Ethical approval: The study was approved by the ethics committee of the First Affiliated Hospital of Chongqing Medical University (number: 2021-504).

  2. Informed consent: This study was a retrospective study, HSCT treatment was not administered for the purpose of research, consent to participate for the purpose of study was not required; however, it is a routine procedure of our hospital that patients must sign informed consent before any treatment. Obtaining consent is also definitely required before transplantation. Consent to publish was obtained after the study when we were preparing the manuscript, following the suggestion of the director of our department according to the regulations of our department.

3 Results

3.1 Patient characteristics

Of the 51 newly diagnosed advanced-stage ENKL patients, 26 received auto-HSCT. They included 14 males and 12 females with median age 37 years (range 19–59) (Table 1). They were all in good physical conditions with the Eastern Cooperative Oncology Group score 0–1. At diagnosis, their serum EBV-DNAs value was high, their tumor proliferation indices (Ki-67) were ≥40%, and their PINK-E indicated high-risk lymphomas. As the first-line chemotherapy, l-asparaginase-containing regimens were applied to 24 of them (92.3%) for 2–6 cycles, and l-asparaginase-absent regimens were applied to the other two (7.7%) for 5–6 cycles, with the overall median cycle 5. Before auto-HSCT, 80.8% (21/26) of them got CR, while 19.2% (5/26) were in partial remission (PR) condition. After auto-HSCT, their conditioning regimens included BEAM (applied to 16 patients), CEAC (to 8), and IEAC (to 2).

The other 25 newly diagnosed advanced-stage ENKL patients received chemotherapy without HSCT. All of them received chemotherapy containing l-asparaginase for 1–9 cycles (median cycle 6). They were 17 males and 8 females with median age 44 years (range 14–59) (Table 2).

3.2 Outcomes

The PBSCs of all 26 patients showed complete engraftment within 3 weeks without any engraftment failure. Of the 26 patients with auto-HSCT, their median follow-up time is 47 months (range: 8–115 months). After auto-HSCT, two patients died of disease progression and severe pneumonia in 15 and 17 months, respectively, other 24 achieved CR condition without disease progression and survived for at least 8 months after auto-HSCT. The other of the 24 (No. 5 patient) auto-HSCT patients relapsed 23 months later after transplantation. He then received four cycles of chemotherapy of gemcitabine, oxaliplatin, and pegaspargase (P-GEMOX), and was maintained with chidamide without any disease progression for at least 83 months after auto-HSCT (details in Table 1).

3.3 Survival analysis

After the median follow-up time (39 months), the estimated 5-year OS of the total 51 newly diagnosed advanced-stage ENKL patients is 73.4%, and their estimated 5-year PFS is 73.4%. For the patients with auto-HSCT, after the median follow-up time (47 months), the estimated 5-year OS is 91.7% (Figure 1) and the estimated 5-year PFS is 91.0% (Figure 2). After auto-HSCT, two patients relapsed but only one died of disease progression while the other got CR again after salvage chemotherapy. However, the 5-year OS in patients who received chemotherapy without HSCT is 53.3% (Figure 1), and the 5-year PFS is 54.5% (Figure 2), showing significant difference from those of auto-HSCT patients (p = 0.003 for OS, p = 0.004 for PFS).

Figure 1 Kaplan-Meier curves of OS for newly diagnosed advanced-stage ENKL patients, patients received auto-HSCT vs chemotherapy in our hospital.
Figure 1

Kaplan-Meier curves of OS for newly diagnosed advanced-stage ENKL patients, patients received auto-HSCT vs chemotherapy in our hospital.

Figure 2 Kaplan-Meier curves of PFS for newly diagnosed advanced-stage ENKL patients, patients received auto-HSCT vs chemotherapy in our hospital.
Figure 2

Kaplan-Meier curves of PFS for newly diagnosed advanced-stage ENKL patients, patients received auto-HSCT vs chemotherapy in our hospital.

We then conducted further regression analysis on potential impact factors to the OS and PFS for the total 51 patients. The focused impact factors we selected included sex, age (grouped into “>50 years” and “<50 years”), stage (“III” or “IV”), bone marrow infiltration (“presence” or “absence”), LDH (“elevated” or “normal”), PINK-E score, l-asparaginase regimens used in chemotherapy (“yes” or “not”), radiotherapy (“received” or “not received”). Results show that only the l-asparaginase usage in chemotherapy showed significance in both the univariate analysis (p = 0.024) and the multivariate analysis (p = 0.027), and none of these factors showed significant impact on the PFS.

4 Discussion

ENKL is a relatively rare non-Hodgkin lymphoma with poor prognosis. Many previous studies have reported poor survival outcome in patients with ENKL. For ENKL treatment, auto-HSCT is typically used either for consolidation of first complete remission in advanced-stage ENKL with high PINK-E, or for the achievement of CR after relapse [10]. However, the roles of auto-HSCT in newly diagnosed advanced-stage ENKLs still remain unclear [10].

Thus, we conducted this analysis of outcomes of patients with newly diagnosed advanced-stage ENKL. In the department of hematology of the First Affiliated Hospital of Chongqing Medical University, between 2014/01 and 2023/12, we had treated over 100 ENKL patients, but most of them were early stage, only 51 of them were newly diagnosed with advanced-stage and high risk ENKL.

The estimated 5-year OS of the total 51 newly diagnosed advanced-stage ENKL patients is 73.4% and median survival of these patients is 39 months. Compared with previous studies, our result of 5-year OS is higher but still close to that reported in literature which ranges from 20 to –72% [11–16], and our result of median survival is consistent with that reported previously ranging from 13 to –67 months [11–16]. In this study, the estimated 5-year PFS is 73.4% which is higher than that in literature ranging from 22.6 to 46.8% [17–22]. The reason for the differences in the 5-year OS and PFS might be not only due to the limit of the case number and follow-up time of the cases we collected, but also more importantly, due to the high 5-year OS and PFS of the 26 auto-HSCT patients, which largely contribute to the overall 5-year OS and PFS of the total 51 patients.

Among them, 26 received auto-HSCT, while the other 25 received chemotherapy without HSCT. According to the analysis of cases from our hospital, the estimated 5-year OS and PFS for the 26 patients with auto-HSCT is 91.7 and 91.0%, respectively, which are much higher than those reported in literature. Our data showed that HSCT can significantly improve the OS and PFS compared to those patients who received chemotherapy without HSCT (p < 0.05). This finding is accordant to previous studies showing that patients with high-dose chemotherapy and auto-HSCT tend to have longer survival time than non-HSCT patients [23–26]. So auto-HSCT is indeed an option for advanced-stage ENKL, and is indeed beneficial for survival.

Some studies have reported that, for ENKL patients who received HSCT, the CR condition before transplantation might significantly improve the OS and PFS [6,10,23,27–29]. Moreover, chemotherapy of l-asparaginase prior to HSCT significantly improved the OS and PFS too [6]. As for the cases from our hospital, since the patients were young and newly diagnosed with ENKL, they were not relapsed/refractory, and most of them (24/26) received l-asparaginase containing chemotherapy and attained CR/PR without any stable disease or progressive disease, besides the follow-up time is short; therefore, the OS and PFS for those patients who received auto-HSCT from our hospital were high.

It was also reported that, pretreatment PINK-E scores and chemotherapy regimen were strongly associated with OS and PFS [30,31]. But we find that only the l-asparaginase usage showed significant impact on only the OS rather than PFS. More cases need be included for further study in the future.

We searched in PubMed, Medline, and Embase for publications about auto-HSCT in ENKL patients. Most of the papers only reported very limited number of cases often even without randomized controlled trials. At present, the largest number of cases reported of HSCT for ENKL patients is a multicenter retrospective study on consecutively collected patient data from the Japanese nation-wide transplant registry database [32]. In that study, patients with all subtypes of lymphoma who received first auto-HSCT from 1980/01 to 2018/12 were analyzed, including 195 ENKL patients with auto-HSCT. However, the paper reported that the 5-year OS from event-free survival (EFS) was 89.9 and 93.8% for 24 and 60 months, respectively, in auto-HSCT ENKL patients, which implies that the relapse and death rate may decrease in the later period of HSCT, and the EFS status at 24 or 60 months could be an early end point after HSCT.

ENKL patients especially at advanced-stage usually have poor prognosis that nearly half of newly diagnosed patients experience continuous disease progression. It implies that the HSCT, as a front-line consolidation treatment, decreases the relapse rate, and helps improve outcomes in advanced-stage ENKL patients [33]. However, HSCT tends to sacrifice the treatment-related mortality (TRM) for long-term remission [33]. According to published literature, for patients after auto-HSCT, the TRM is mostly close to 0 [6,27,34], but it was once also reported in a study that the TRM was 14.3% [28]. So auto-HSCT is likely to be promising, but requires more medical experience and more strict disease management.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential curative treatment to high-risk lymphomas, owing to its associated graft-versus-lymphoma effect [1]. Asian experts propose that upfront allo-HSCT is beneficial when used in high-risk ENKL patients [35,36]. As those papers and guidelines may be subjected to personal subjective experiences and judgments, further studies are still needed to contribute to this topic.

5 Conclusion and limitation

In this study, we reported 51 advanced-stage of newly diagnosed ENKL patients collected from our hospital in recent 10 years, of which 26 received auto-HSCT, while the other 25 received chemotherapy without HSCT. Due to the rarity of ENKL and the difficulty in conducting randomized controlled trials, the optimal treatment regimen of ENKL is still undetermined. But at least we can confirm that auto-HSCT is able to benefit the OS and PFS for the advanced-stage of newly diagnosed ENKL patients, although at present the choice of auto-HSCT is mainly based upon subjective expertise, bringing heavy selection bias. Although the exact role of auto-HSCT is still unclear, they are indeed potential options to advanced stage ENKL. Novel treatments such as allo-HSCT [22], anti-CD30 antibody [37], programmed death protein ligand 1 [38], and histone deacetylase (HDAC) inhibitors [39] have been reported as feasible choices for advanced stage ENKLs.

Abbreviations

allo-HSCT

allogeneic hematopoietic stem cell transplantation

auto-HSCT

autologous hematopoietic stem cell transplantation

BEAM

carmustine, etoposide, cytarabine, melphalan

CEAC

lomustine, etoposide, cytarabine, cyclophosphamide

CR

complete remission

EBV

Epstein-Barr virus

ECOG

Eastern Cooperative Oncology Group

IEAC

idarubicin, etoposide, cytarabine, cyclophosphamide

EFS

event-free survival

ENKL

extranodal NK/T-cell lymphoma

G-CSF

granulocyte colony stimulating factor

HDAC

histone deacetylase

NCCN

National Comprehensive Cancer Network

NHL

non-Hodgkin lymphoma

OS

overall survival

PBSC

peripheral blood hematopoietic stem cell

PD

progressive disease

PD-L1

programmed death protein ligand 1

PET/CT

positron emission tomography/computed tomography

PFS

progression-free survival

P-GEMOX

gemcitabine, oxaliplatin, pegaspargase

PINK-E

prognostic indicators of natural killer cell lymphoma containing Epstein-Barr virus DNA

PR

partial remission

SD

stable disease

TRM

treatment-related mortality

WHO

World Health Organization

tel: +86-15123312126

  1. Funding information: No financial funding was available for this study.

  2. Author contributions: Yin-yin Peng, Xin Wang: study conception and design, literature search, manuscript preparation, and edition. Xin Wang, Lin Liu: manuscript review and edition. Yin-yin Peng, Xin Wang, Lin Liu: quality control.

  3. Conflict of interest: All authors have no conflict of interest to declare.

  4. Data availability statement: All data are included in this published article. Further inquiries can be directed to the corresponding author.

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Received: 2023-12-24
Revised: 2024-06-02
Accepted: 2024-08-05
Published Online: 2024-10-03

© 2024 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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https://doi.org/10.1515/med-2024-1024
Keywords for this article
extranodal NK/T-cell lymphoma; chemotherapy; autologous; hematopoietic stem cell transplantation
Creative Commons
BY 4.0

Articles in the same Issue

  1. Research Articles
  2. EDNRB inhibits the growth and migration of prostate cancer cells by activating the cGMP-PKG pathway
  3. STK11 (LKB1) mutation suppresses ferroptosis in lung adenocarcinoma by facilitating monounsaturated fatty acid synthesis
  4. Association of SOX6 gene polymorphisms with Kashin-Beck disease risk in the Chinese Han population
  5. The pyroptosis-related signature predicts prognosis and influences the tumor immune microenvironment in dedifferentiated liposarcoma
  6. METTL3 attenuates ferroptosis sensitivity in lung cancer via modulating TFRC
  7. Identification and validation of molecular subtypes and prognostic signature for stage I and stage II gastric cancer based on neutrophil extracellular traps
  8. Novel lumbar plexus block versus femoral nerve block for analgesia and motor recovery after total knee arthroplasty
  9. Correlation between ABCB1 and OLIG2 polymorphisms and the severity and prognosis of patients with cerebral infarction
  10. Study on the radiotherapy effect and serum neutral granulocyte lymphocyte ratio and inflammatory factor expression of nasopharyngeal carcinoma
  11. Transcriptome analysis of effects of Tecrl deficiency on cardiometabolic and calcium regulation in cardiac tissue
  12. Aflatoxin B1 induces infertility, fetal deformities, and potential therapies
  13. Serum levels of HMW adiponectin and its receptors are associated with cytokine levels and clinical characteristics in chronic obstructive pulmonary disease
  14. METTL3-mediated methylation of CYP2C19 mRNA may aggravate clopidogrel resistance in ischemic stroke patients
  15. Understand how machine learning impact lung cancer research from 2010 to 2021: A bibliometric analysis
  16. Pressure ulcers in German hospitals: Analysis of reimbursement and length of stay
  17. Metformin plus L-carnitine enhances brown/beige adipose tissue activity via Nrf2/HO-1 signaling to reduce lipid accumulation and inflammation in murine obesity
  18. Downregulation of carbonic anhydrase IX expression in mouse xenograft nasopharyngeal carcinoma model via doxorubicin nanobubble combined with ultrasound
  19. Feasibility of 3-dimensional printed models in simulated training and teaching of transcatheter aortic valve replacement
  20. miR-335-3p improves type II diabetes mellitus by IGF-1 regulating macrophage polarization
  21. The analyses of human MCPH1 DNA repair machinery and genetic variations
  22. Activation of Piezo1 increases the sensitivity of breast cancer to hyperthermia therapy
  23. Comprehensive analysis based on the disulfidptosis-related genes identifies hub genes and immune infiltration for pancreatic adenocarcinoma
  24. Changes of serum CA125 and PGE2 before and after high-intensity focused ultrasound combined with GnRH-a in treatment of patients with adenomyosis
  25. The clinical value of the hepatic venous pressure gradient in patients undergoing hepatic resection for hepatocellular carcinoma with or without liver cirrhosis
  26. Development and validation of a novel model to predict pulmonary embolism in cardiology suspected patients: A 10-year retrospective analysis
  27. Downregulation of lncRNA XLOC_032768 in diabetic patients predicts the occurrence of diabetic nephropathy
  28. Circ_0051428 targeting miR-885-3p/MMP2 axis enhances the malignancy of cervical cancer
  29. Effectiveness of ginkgo diterpene lactone meglumine on cognitive function in patients with acute ischemic stroke
  30. The construction of a novel prognostic prediction model for glioma based on GWAS-identified prognostic-related risk loci
  31. Evaluating the impact of childhood BMI on the risk of coronavirus disease 2019: A Mendelian randomization study
  32. Lactate dehydrogenase to albumin ratio is associated with in-hospital mortality in patients with acute heart failure: Data from the MIMIC-III database
  33. CD36-mediated podocyte lipotoxicity promotes foot process effacement
  34. Efficacy of etonogestrel subcutaneous implants versus the levonorgestrel-releasing intrauterine system in the conservative treatment of adenomyosis
  35. FLRT2 mediates chondrogenesis of nasal septal cartilage and mandibular condyle cartilage
  36. Challenges in treating primary immune thrombocytopenia patients undergoing COVID-19 vaccination: A retrospective study
  37. Let-7 family regulates HaCaT cell proliferation and apoptosis via the ΔNp63/PI3K/AKT pathway
  38. Phospholipid transfer protein ameliorates sepsis-induced cardiac dysfunction through NLRP3 inflammasome inhibition
  39. Postoperative cognitive dysfunction in elderly patients with colorectal cancer: A randomized controlled study comparing goal-directed and conventional fluid therapy
  40. Long-pulsed ultrasound-mediated microbubble thrombolysis in a rat model of microvascular obstruction
  41. High SEC61A1 expression predicts poor outcome of acute myeloid leukemia
  42. Comparison of polymerase chain reaction and next-generation sequencing with conventional urine culture for the diagnosis of urinary tract infections: A meta-analysis
  43. Secreted frizzled-related protein 5 protects against renal fibrosis by inhibiting Wnt/β-catenin pathway
  44. Pan-cancer and single-cell analysis of actin cytoskeleton genes related to disulfidptosis
  45. Overexpression of miR-532-5p restrains oxidative stress response of chondrocytes in nontraumatic osteonecrosis of the femoral head by inhibiting ABL1
  46. Autologous liver transplantation for unresectable hepatobiliary malignancies in enhanced recovery after surgery model
  47. Clinical analysis of incomplete rupture of the uterus secondary to previous cesarean section
  48. Abnormal sleep duration is associated with sarcopenia in older Chinese people: A large retrospective cross-sectional study
  49. No genetic causality between obesity and benign paroxysmal vertigo: A two-sample Mendelian randomization study
  50. Identification and validation of autophagy-related genes in SSc
  51. Long non-coding RNA SRA1 suppresses radiotherapy resistance in esophageal squamous cell carcinoma by modulating glycolytic reprogramming
  52. Evaluation of quality of life in patients with schizophrenia: An inpatient social welfare institution-based cross-sectional study
  53. The possible role of oxidative stress marker glutathione in the assessment of cognitive impairment in multiple sclerosis
  54. Compilation of a self-management assessment scale for postoperative patients with aortic dissection
  55. Left atrial appendage closure in conjunction with radiofrequency ablation: Effects on left atrial functioning in patients with paroxysmal atrial fibrillation
  56. Effect of anterior femoral cortical notch grade on postoperative function and complications during TKA surgery: A multicenter, retrospective study
  57. Clinical characteristics and assessment of risk factors in patients with influenza A-induced severe pneumonia after the prevalence of SARS-CoV-2
  58. Analgesia nociception index is an indicator of laparoscopic trocar insertion-induced transient nociceptive stimuli
  59. High STAT4 expression correlates with poor prognosis in acute myeloid leukemia and facilitates disease progression by upregulating VEGFA expression
  60. Factors influencing cardiovascular system-related post-COVID-19 sequelae: A single-center cohort study
  61. HOXD10 regulates intestinal permeability and inhibits inflammation of dextran sulfate sodium-induced ulcerative colitis through the inactivation of the Rho/ROCK/MMPs axis
  62. Mesenchymal stem cell-derived exosomal miR-26a induces ferroptosis, suppresses hepatic stellate cell activation, and ameliorates liver fibrosis by modulating SLC7A11
  63. Endovascular thrombectomy versus intravenous thrombolysis for primary distal, medium vessel occlusion in acute ischemic stroke
  64. ANO6 (TMEM16F) inhibits gastrointestinal stromal tumor growth and induces ferroptosis
  65. Prognostic value of EIF5A2 in solid tumors: A meta-analysis and bioinformatics analysis
  66. The role of enhanced expression of Cx43 in patients with ulcerative colitis
  67. Choosing a COVID-19 vaccination site might be driven by anxiety and body vigilance
  68. Role of ICAM-1 in triple-negative breast cancer
  69. Cost-effectiveness of ambroxol in the treatment of Gaucher disease type 2
  70. HLA-DRB5 promotes immune thrombocytopenia via activating CD8+ T cells
  71. Efficacy and factors of myofascial release therapy combined with electrical and magnetic stimulation in the treatment of chronic pelvic pain syndrome
  72. Efficacy of tacrolimus monotherapy in primary membranous nephropathy
  73. Mechanisms of Tripterygium wilfordii Hook F on treating rheumatoid arthritis explored by network pharmacology analysis and molecular docking
  74. FBXO45 levels regulated ferroptosis renal tubular epithelial cells in a model of diabetic nephropathy by PLK1
  75. Optimizing anesthesia strategies to NSCLC patients in VATS procedures: Insights from drug requirements and patient recovery patterns
  76. Alpha-lipoic acid upregulates the PPARγ/NRF2/GPX4 signal pathway to inhibit ferroptosis in the pathogenesis of unexplained recurrent pregnancy loss
  77. Correlation between fat-soluble vitamin levels and inflammatory factors in paediatric community-acquired pneumonia: A prospective study
  78. CD1d affects the proliferation, migration, and apoptosis of human papillary thyroid carcinoma TPC-1 cells via regulating MAPK/NF-κB signaling pathway
  79. miR-let-7a inhibits sympathetic nerve remodeling after myocardial infarction by downregulating the expression of nerve growth factor
  80. Immune response analysis of solid organ transplantation recipients inoculated with inactivated COVID-19 vaccine: A retrospective analysis
  81. The H2Valdien derivatives regulate the epithelial–mesenchymal transition of hepatoma carcinoma cells through the Hedgehog signaling pathway
  82. Clinical efficacy of dexamethasone combined with isoniazid in the treatment of tuberculous meningitis and its effect on peripheral blood T cell subsets
  83. Comparison of short-segment and long-segment fixation in treatment of degenerative scoliosis and analysis of factors associated with adjacent spondylolisthesis
  84. Lycopene inhibits pyroptosis of endothelial progenitor cells induced by ox-LDL through the AMPK/mTOR/NLRP3 pathway
  85. Methylation regulation for FUNDC1 stability in childhood leukemia was up-regulated and facilitates metastasis and reduces ferroptosis of leukemia through mitochondrial damage by FBXL2
  86. Correlation of single-fiber electromyography studies and functional status in patients with amyotrophic lateral sclerosis
  87. Risk factors of postoperative airway obstruction complications in children with oral floor mass
  88. Expression levels and clinical significance of serum miR-19a/CCL20 in patients with acute cerebral infarction
  89. Physical activity and mental health trends in Korean adolescents: Analyzing the impact of the COVID-19 pandemic from 2018 to 2022
  90. Evaluating anemia in HIV-infected patients using chest CT
  91. Ponticulus posticus and skeletal malocclusion: A pilot study in a Southern Italian pre-orthodontic court
  92. Causal association of circulating immune cells and lymphoma: A Mendelian randomization study
  93. Assessment of the renal function and fibrosis indexes of conventional western medicine with Chinese medicine for dredging collaterals on treating renal fibrosis: A systematic review and meta-analysis
  94. Comprehensive landscape of integrator complex subunits and their association with prognosis and tumor microenvironment in gastric cancer
  95. New target-HMGCR inhibitors for the treatment of primary sclerosing cholangitis: A drug Mendelian randomization study
  96. Population pharmacokinetics of meropenem in critically ill patients
  97. Comparison of the ability of newly inflammatory markers to predict complicated appendicitis
  98. Comparative morphology of the cruciate ligaments: A radiological study
  99. Immune landscape of hepatocellular carcinoma: The central role of TP53-inducible glycolysis and apoptosis regulator
  100. Serum SIRT3 levels in epilepsy patients and its association with clinical outcomes and severity: A prospective observational study
  101. SHP-1 mediates cigarette smoke extract-induced epithelial–mesenchymal transformation and inflammation in 16HBE cells
  102. Acute hyper-hypoxia accelerates the development of depression in mice via the IL-6/PGC1α/MFN2 signaling pathway
  103. The GJB3 correlates with the prognosis, immune cell infiltration, and therapeutic responses in lung adenocarcinoma
  104. Physical fitness and blood parameters outcomes of breast cancer survivor in a low-intensity circuit resistance exercise program
  105. Exploring anesthetic-induced gene expression changes and immune cell dynamics in atrial tissue post-coronary artery bypass graft surgery
  106. Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism
  107. Analysis of the risk factors of the radiation-induced encephalopathy in nasopharyngeal carcinoma: A retrospective cohort study
  108. Reproductive outcomes in women with BRCA 1/2 germline mutations: A retrospective observational study and literature review
  109. Evaluation of upper airway ultrasonographic measurements in predicting difficult intubation: A cross-section of the Turkish population
  110. Prognostic and diagnostic value of circulating IGFBP2 in pancreatic cancer
  111. Postural stability after operative reconstruction of the AFTL in chronic ankle instability comparing three different surgical techniques
  112. Research trends related to emergence agitation in the post-anaesthesia care unit from 2001 to 2023: A bibliometric analysis
  113. Frequency and clinicopathological correlation of gastrointestinal polyps: A six-year single center experience
  114. ACSL4 mediates inflammatory bowel disease and contributes to LPS-induced intestinal epithelial cell dysfunction by activating ferroptosis and inflammation
  115. Affibody-based molecular probe 99mTc-(HE)3ZHER2:V2 for non-invasive HER2 detection in ovarian and breast cancer xenografts
  116. Effectiveness of nutritional support for clinical outcomes in gastric cancer patients: A meta-analysis of randomized controlled trials
  117. The relationship between IFN-γ, IL-10, IL-6 cytokines, and severity of the condition with serum zinc and Fe in children infected with Mycoplasma pneumoniae
  118. Paraquat disrupts the blood–brain barrier by increasing IL-6 expression and oxidative stress through the activation of PI3K/AKT signaling pathway
  119. Sleep quality associate with the increased prevalence of cognitive impairment in coronary artery disease patients: A retrospective case–control study
  120. Dioscin protects against chronic prostatitis through the TLR4/NF-κB pathway
  121. Association of polymorphisms in FBN1, MYH11, and TGF-β signaling-related genes with susceptibility of sporadic thoracic aortic aneurysm and dissection in the Zhejiang Han population
  122. Application value of multi-parameter magnetic resonance image-transrectal ultrasound cognitive fusion in prostate biopsy
  123. Laboratory variables‐based artificial neural network models for predicting fatty liver disease: A retrospective study
  124. Decreased BIRC5-206 promotes epithelial–mesenchymal transition in nasopharyngeal carcinoma through sponging miR-145-5p
  125. Sepsis induces the cardiomyocyte apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway
  126. Assessment of iron metabolism and iron deficiency in incident patients on incident continuous ambulatory peritoneal dialysis
  127. Tibial periosteum flap combined with autologous bone grafting in the treatment of Gustilo-IIIB/IIIC open tibial fractures
  128. The application of intravenous general anesthesia under nasopharyngeal airway assisted ventilation undergoing ureteroscopic holmium laser lithotripsy: A prospective, single-center, controlled trial
  129. Long intergenic noncoding RNA for IGF2BP2 stability suppresses gastric cancer cell apoptosis by inhibiting the maturation of microRNA-34a
  130. Role of FOXM1 and AURKB in regulating keratinocyte function in psoriasis
  131. Parental control attitudes over their pre-school children’s diet
  132. The role of auto-HSCT in extranodal natural killer/T cell lymphoma
  133. Significance of negative cervical cytology and positive HPV in the diagnosis of cervical lesions by colposcopy
  134. Echinacoside inhibits PASMCs calcium overload to prevent hypoxic pulmonary artery remodeling by regulating TRPC1/4/6 and calmodulin
  135. ADAR1 plays a protective role in proximal tubular cells under high glucose conditions by attenuating the PI3K/AKT/mTOR signaling pathway
  136. The risk of cancer among insulin glargine users in Lithuania: A retrospective population-based study
  137. The unusual location of primary hydatid cyst: A case series study
  138. Intraoperative changes in electrophysiological monitoring can be used to predict clinical outcomes in patients with spinal cavernous malformation
  139. Obesity and risk of placenta accreta spectrum: A meta-analysis
  140. Shikonin alleviates asthma phenotypes in mice via an airway epithelial STAT3-dependent mechanism
  141. NSUN6 and HTR7 disturbed the stability of carotid atherosclerotic plaques by regulating the immune responses of macrophages
  142. The effect of COVID-19 lockdown on admission rates in Maternity Hospital
  143. Temporal muscle thickness is not a prognostic predictor in patients with high-grade glioma, an experience at two centers in China
  144. Luteolin alleviates cerebral ischemia/reperfusion injury by regulating cell pyroptosis
  145. Therapeutic role of respiratory exercise in patients with tuberculous pleurisy
  146. Effects of CFTR-ENaC on spinal cord edema after spinal cord injury
  147. Irisin-regulated lncRNAs and their potential regulatory functions in chondrogenic differentiation of human mesenchymal stem cells
  148. DMD mutations in pediatric patients with phenotypes of Duchenne/Becker muscular dystrophy
  149. Combination of C-reactive protein and fibrinogen-to-albumin ratio as a novel predictor of all-cause mortality in heart failure patients
  150. Significant role and the underly mechanism of cullin-1 in chronic obstructive pulmonary disease
  151. Ferroptosis-related prognostic model of mantle cell lymphoma
  152. Observation of choking reaction and other related indexes in elderly painless fiberoptic bronchoscopy with transnasal high-flow humidification oxygen therapy
  153. A bibliometric analysis of Prader-Willi syndrome from 2002 to 2022
  154. The causal effects of childhood sunburn occasions on melanoma: A univariable and multivariable Mendelian randomization study
  155. Oxidative stress regulates glycogen synthase kinase-3 in lymphocytes of diabetes mellitus patients complicated with cerebral infarction
  156. Role of COX6C and NDUFB3 in septic shock and stroke
  157. Trends in disease burden of type 2 diabetes, stroke, and hypertensive heart disease attributable to high BMI in China: 1990–2019
  158. Purinergic P2X7 receptor mediates hyperoxia-induced injury in pulmonary microvascular endothelial cells via NLRP3-mediated pyroptotic pathway
  159. Investigating the role of oviductal mucosa–endometrial co-culture in modulating factors relevant to embryo implantation
  160. Analgesic effect of external oblique intercostal block in laparoscopic cholecystectomy: A retrospective study
  161. Elevated serum miR-142-5p correlates with ischemic lesions and both NSE and S100β in ischemic stroke patients
  162. Correlation between the mechanism of arteriopathy in IgA nephropathy and blood stasis syndrome: A cohort study
  163. Risk factors for progressive kyphosis after percutaneous kyphoplasty in osteoporotic vertebral compression fracture
  164. Predictive role of neuron-specific enolase and S100-β in early neurological deterioration and unfavorable prognosis in patients with ischemic stroke
  165. The potential risk factors of postoperative cognitive dysfunction for endovascular therapy in acute ischemic stroke with general anesthesia
  166. Fluoxetine inhibited RANKL-induced osteoclastic differentiation in vitro
  167. Detection of serum FOXM1 and IGF2 in patients with ARDS and their correlation with disease and prognosis
  168. Rhein promotes skin wound healing by activating the PI3K/AKT signaling pathway
  169. Differences in mortality risk by levels of physical activity among persons with disabilities in South Korea
  170. Review Articles
  171. Cutaneous signs of selected cardiovascular disorders: A narrative review
  172. XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis
  173. A narrative review on adverse drug reactions of COVID-19 treatments on the kidney
  174. Emerging role and function of SPDL1 in human health and diseases
  175. Adverse reactions of piperacillin: A literature review of case reports
  176. Molecular mechanism and intervention measures of microvascular complications in diabetes
  177. Regulation of mesenchymal stem cell differentiation by autophagy
  178. Molecular landscape of borderline ovarian tumours: A systematic review
  179. Advances in synthetic lethality modalities for glioblastoma multiforme
  180. Investigating hormesis, aging, and neurodegeneration: From bench to clinics
  181. Frankincense: A neuronutrient to approach Parkinson’s disease treatment
  182. Sox9: A potential regulator of cancer stem cells in osteosarcoma
  183. Early detection of cardiovascular risk markers through non-invasive ultrasound methodologies in periodontitis patients
  184. Advanced neuroimaging and criminal interrogation in lie detection
  185. Maternal factors for neural tube defects in offspring: An umbrella review
  186. The chemoprotective hormetic effects of rosmarinic acid
  187. CBD’s potential impact on Parkinson’s disease: An updated overview
  188. Progress in cytokine research for ARDS: A comprehensive review
  189. Utilizing reactive oxygen species-scavenging nanoparticles for targeting oxidative stress in the treatment of ischemic stroke: A review
  190. NRXN1-related disorders, attempt to better define clinical assessment
  191. Lidocaine infusion for the treatment of complex regional pain syndrome: Case series and literature review
  192. Trends and future directions of autophagy in osteosarcoma: A bibliometric analysis
  193. Iron in ventricular remodeling and aneurysms post-myocardial infarction
  194. Case Reports
  195. Sirolimus potentiated angioedema: A case report and review of the literature
  196. Identification of mixed anaerobic infections after inguinal hernia repair based on metagenomic next-generation sequencing: A case report
  197. Successful treatment with bortezomib in combination with dexamethasone in a middle-aged male with idiopathic multicentric Castleman’s disease: A case report
  198. Complete heart block associated with hepatitis A infection in a female child with fatal outcome
  199. Elevation of D-dimer in eosinophilic gastrointestinal diseases in the absence of venous thrombosis: A case series and literature review
  200. Four years of natural progressive course: A rare case report of juvenile Xp11.2 translocations renal cell carcinoma with TFE3 gene fusion
  201. Advancing prenatal diagnosis: Echocardiographic detection of Scimitar syndrome in China – A case series
  202. Outcomes and complications of hemodialysis in patients with renal cancer following bilateral nephrectomy
  203. Anti-HMGCR myopathy mimicking facioscapulohumeral muscular dystrophy
  204. Recurrent opportunistic infections in a HIV-negative patient with combined C6 and NFKB1 mutations: A case report, pedigree analysis, and literature review
  205. Letter to the Editor
  206. Letter to the Editor: Total parenteral nutrition-induced Wernicke’s encephalopathy after oncologic gastrointestinal surgery
  207. Erratum
  208. Erratum to “Bladder-embedded ectopic intrauterine device with calculus”
  209. Retraction
  210. Retraction of “XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis”
  211. Corrigendum
  212. Corrigendum to “Investigating hormesis, aging, and neurodegeneration: From bench to clinics”
  213. Corrigendum to “Frankincense: A neuronutrient to approach Parkinson’s disease treatment”
  214. Special Issue The evolving saga of RNAs from bench to bedside - Part II
  215. Machine-learning-based prediction of a diagnostic model using autophagy-related genes based on RNA sequencing for patients with papillary thyroid carcinoma
  216. Unlocking the future of hepatocellular carcinoma treatment: A comprehensive analysis of disulfidptosis-related lncRNAs for prognosis and drug screening
  217. Elevated mRNA level indicates FSIP1 promotes EMT and gastric cancer progression by regulating fibroblasts in tumor microenvironment
  218. Special Issue Advancements in oncology: bridging clinical and experimental research - Part I
  219. Ultrasound-guided transperineal vs transrectal prostate biopsy: A meta-analysis of diagnostic accuracy and complication rates
  220. Assessment of diagnostic value of unilateral systematic biopsy combined with targeted biopsy in detecting clinically significant prostate cancer
  221. SENP7 inhibits glioblastoma metastasis and invasion by dissociating SUMO2/3 binding to specific target proteins
  222. MARK1 suppress malignant progression of hepatocellular carcinoma and improves sorafenib resistance through negatively regulating POTEE
  223. Analysis of postoperative complications in bladder cancer patients
  224. Carboplatin combined with arsenic trioxide versus carboplatin combined with docetaxel treatment for LACC: A randomized, open-label, phase II clinical study
  225. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part I
  226. Comprehensive pan-cancer investigation of carnosine dipeptidase 1 and its prospective prognostic significance in hepatocellular carcinoma
  227. Identification of signatures associated with microsatellite instability and immune characteristics to predict the prognostic risk of colon cancer
  228. Single-cell analysis identified key macrophage subpopulations associated with atherosclerosis
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