Startseite Pemetrexed-based first-line chemotherapy had particularly prominent objective response rate for advanced NSCLC: A network meta-analysis
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Pemetrexed-based first-line chemotherapy had particularly prominent objective response rate for advanced NSCLC: A network meta-analysis

  • Yuankai Lv , Zhuo Cao , Jiongwei Pan , Enhui Gong , Hao Zheng und Xiaoping Cai EMAIL logo
Veröffentlicht/Copyright: 27. Januar 2021

Abstract

Objective

The aim of the present work was to investigate the clinical efficacy of first-line chemotherapy regimens in the treatment of advanced non-small cell lung cancer (NSCLC) through a comprehensive network meta-analysis (NMA).

Methods

The prospective randomized controlled clinical trials relevant to 10 first-line chemotherapy regimens in the treatment of advanced NSCLC were systematic electronic search in the databases of Pubmed, Embase, Cochrane Library and CNKI. The combined direct or indirect objective response rate (ORR) between each of the 10 first-line chemotherapy regimens was calculated.

Results

Seventeen prospective clinical trials of first-line chemotherapy regimens in treatment of advanced NSCLC were included in the NMA. The 10 treatment regimens including A = cisplatin + gemcitabine, B = carboplatin + gemcitabine, C = gemcitabine, D = carboplatin + paclitaxel, E = paclitaxel + gemcitabine, F = docetaxel + carboplatin, G = gemcitabine + vinorelbine, H = pemetrexed + carboplatin, I = cisplatin + pemetrexed and J = cisplatin + docetaxel were compared in the present NMA. Direct pooled results indicated that the ORR was not statistically different (P all > 0.05). However, NMA showed that the combined ORR for regimens A (OR = 1.47, 95% CI: 0.80–2.81), B (OR = 3.22, 95% CI: 1.45–6.923), D (OR = 3.30, 95% CI: 1.22–9.33), E (OR = 4.36, 95% CI: 1.64–12.82), G (OR = 3.72, 95% CI: 1.12–12.83) and I (OR = 5.80, 95% CI: 2.04–17.86) was superior to regimen C. Rank probability analysis indicated that regimen C = gemcitabine and regimen I = cisplatin + pemetrexed had the highest probability of inferior and superior treatment ORR among the 10 first-line chemotherapy regimens.

Conclusion

Cisplatin + pemetrexed may have particularly prominent ORR for advanced NSCLC as the first-line chemotherapy regimen.

1 Introduction

Lung cancer is known as the leading cause of cancer-relevant death worldwide and the most diagnosed carcinoma among male and the second most among female [1]. The morbidity of lung cancer in China is about 530/100,000 according to the recent tumor epidemiology data [2]. Lung cancer accounts for 18.74% of the newly diagnosed cancer cases annually [3], and 80% of the newly diagnosed lung cancer cases are at advanced stages with a poor 5-year survival rate of lower than 15% [4]. Lung cancer is generally divided into non-small cell lung cancer (NSCLC) and small cell lung cancer according to the pathology findings. NSCLC accounts for 80% of all the diagnosed lung cancer. However, most of the NSCLC are at advanced or locally advanced stages, would have lost the opportunity for surgery, with the poor overall survival. The standard treatment of the patients with newly diagnosed advanced NSCLC was platinum-based first-line chemotherapy regimens including cisplatin + gemcitabine, carboplatin + gemcitabine, carboplatin + docetaxel, carboplatin + pemetrexed, cisplatin + docetaxel, etc. Compared with the best supportive care, chemotherapy can improve the 1-year survival rate by 9% [5]. A number of clinical trials from Southwest Oncology Group (SWOG) and Eastern Cooperative Oncology Group (ECOG) showed that the response rate for DDP/CBP + PTX/VNR/DXI/GEM were not significantly different without considering the histological type for advanced NSCLC [6,7]. A meta-analysis found that compared with other platinum-based two-drug regimen, platinum + GEM can reduce the risk of death by 10% [8]. The response rate of first-line chemotherapy regimen for advanced NSCLC was not significantly different as shown by early clinical trials that did not further discriminate the pathological types of NSCLC. The response and adverse reactions of different platinum-based dual-drug regimens in patients with advanced NSCLC were similar.

Several meta-analyses have directly compared the response of platinum-based chemotherapy regimens, and most of them found negative results for advanced NSCLC [9,10]. However, not all the chemotherapy regimens were directly compared by prospective randomized controlled trials or meta-analysis. The response of these chemotherapy regimens without direct comparison was unclear. Therefore, we performed this network meta-analysis (NMA) in order to further evaluate the clinical efficacy of the first-line chemotherapy for advanced NSCLC.

2 Methods

2.1 Screening of electronic databases of Studies

Clinical trials about the first-line chemotherapy regimens in the treatment of advanced NSCLC involved systematic search of the databases of Pubmed, Embase, Cochrane Library and CNKI. The electronic search words were “non-small cell lung cancer,” “lung squamous cell carcinoma,” “squamous cell carcinoma of the lung,” “lung adenocarcinoma,” “adenocarcinoma of the lung,” “chemotherapy” and “first-line.” The clinical trials that were identified initially from the relevant databases were further independently screened by Yuankai Lv and Zhuo Cao and reviewed by Xiaoping Cai. The references of the included studies were also screened in order to identify the potential and suitable clinical trials.

2.2 Inclusion of studies and data extraction

The studies were further screened to identify the suitable clinical trials for data pooling. The studies should fulfill the below items for inclusion. (1) The study type should be prospective randomized clinical trials. (2) The patients of the original studies should be pathology- or cytology-confirmed NSCLC in advanced stages. (3) The patients of the original studies should have received the first-line chemotherapy regimens. (4) The objective response ratio (ORR) requires to be extracted or calculated from the original study. (5) Studies published in either English or Chinese. The studies exclusion criteria include (1) retrospective study, case report or review; (2) small cell lung cancer patients or patients without pathology or cytology confirmation, (3) neoadjuvant chemotherapy for early stage NSCLC and (4) duplicated publications or data.

2.3 Quality assessment

The general methodical quality of the included clinical trials were independently assessed by two reviewers (Jiongwei Pan and Enhui Gong) and checked by Xiaoping Cai. The general quality of the included studies was evaluated by a six-item questionnaire including adequate sequence generation? Allocation concealment? Blinding? Incomplete outcome data address? Free of selective reporting? Free of other bias aspects according to the Cochrane Library handbook for systematic review.

2.4 Statistical analysis

Stata16.0 and R3.6.2 statistical software were applied for data analysis. Network of the chemotherapy regimen interaction was performed by stata16.0. The NMA was done based on the Bayesian approach. NMA was pooled by consistency or inconsistency model according to the inconsistency test. Two-tail p < 0.05 was deemed statistically different.

3 Results

3.1 Publication searching

Through searching the relevant electronic databases of Pubmed, Embase, Cochrane Library and CNKI, 3,684 studies relevant to the first-line chemotherapy regimens in treatment of advanced NSCLC were identified. After removal of unsuitable studies, 17 randomized controlled trials were included in the NMA (Figure 1). The main features of the included clinical trials are shown in Table 1.

Figure 1 
                  The clinical trials’ electronic search flowchart.
Figure 1

The clinical trials’ electronic search flowchart.

Table 1

General characteristics of the included studies

Study Year Region Treatment Sample size Response
T1 T2 n1 n2 R1 R2
Yang et al. [11] 2016 China H B 84 60 44 32
Wu et al. [12] 2014 China A I 116 121 24 30
Xing et al. [13] 2014 China I G 49 49 22 20
Minami et al. [14] 2013 Japan B D 25 25 4 9
Kusagaya et al. [15] 2012 Japan B C 31 30 7 3
Huang et al. [16] 2012 China I A 127 127 31 18
Biesma 2011 The Netherlands B D 74 68 20 13
Xie et al. [17] 2011 China J I 21 19 5 6
Socinski et al. [18] 2010 U.S. H F 74 72 16 20
Vergnenegre et al. [19] 2009 France A E 45 42 7 9
Kosmidis et al. [20] 2008 Greece B E 227 225 62 70
Scagliotti et al. [21] 2008 Italy I A 839 830 257 234
Langer et al. [22] 2007 America A D 100 100 23 14
Yi et al. [23] 2006 China J F 21 24 9 9
Sederholm et al. [24] 2005 Sweden B C 142 59 42 18
Lilenbaum et al. [25] 2005 America D G 83 82 14 12
Zatloukal et al. [26] 2003 Czech Republic A B 87 89 36 26

T = treatment; A = cisplatin + gemcitabine; B = carboplatin + gemcitabine; C = gemcitabine; D = carboplatin + paclitaxel; E = paclitaxel + gemcitabine; F = carboplatin + docetaxel; G = gemcitabine + vinorelbine; H = carboplatin + pemetrexed; I = cisplatin + pemetrexed; J = cisplatin + docetaxel.

3.2 Quality assessment

The methodical quality of the included 17 clinical trials is shown in Figure 2. Most of the studies had moderate risk of bias in the aspects of adequate sequence generation, allocation concealment, incomplete outcome data address and free of selective reporting.

Figure 2 
                  The general assessment of the included 17 clinical trials.
Figure 2

The general assessment of the included 17 clinical trials.

3.3 Meta-analysis of direct comparison between treatments

Ten treatment regimens included A = cisplatin + gemcitabine, B = carboplatin + gemcitabine, C = gemcitabine, D = carboplatin + paclitaxel, E = paclitaxel + gemcitabine, F = docetaxel + carboplatin, G = gemcitabine + vinorelbine, H = pemetrexed + carboplatin, I = cisplatin + pemetrexed and J = cisplatin + docetaxel. Direct pooled results indicated that the ORR was not statistically different (P all > 0.05; Figure 3).

Figure 3 
                  The forest plot of ORR for the first-line chemotherapy regimens in treatment of advanced NSCLC. A = cisplatin + gemcitabine, B = carboplatin + gemcitabine, C = gemcitabine, D = carboplatin + paclitaxel, E = paclitaxel + gemcitabine, F = carboplatin + docetaxel, G = gemcitabine + vinorelbine, H = carboplatin + pemetrexed, I = cisplatin + pemetrexed and J = cisplatin + docetaxel.
Figure 3

The forest plot of ORR for the first-line chemotherapy regimens in treatment of advanced NSCLC. A = cisplatin + gemcitabine, B = carboplatin + gemcitabine, C = gemcitabine, D = carboplatin + paclitaxel, E = paclitaxel + gemcitabine, F = carboplatin + docetaxel, G = gemcitabine + vinorelbine, H = carboplatin + pemetrexed, I = cisplatin + pemetrexed and J = cisplatin + docetaxel.

3.4 Network evidence of first-line chemotherapy regimens to treat advanced NSCLC

The chemotherapy regimens’ interaction network showed that the NSLCS patients mostly received regimens B = carboplatin + gemcitabine, A = cisplatin + gemcitabine and I = cisplatin + pemetrexed. Other chemotherapy regimens were rarely applied (Figure 4).

Figure 4 
                  The chemotherapy regimens’ interaction network of ORR for the 10 chemotherapy regimens (Every node represented one chemotherapy regimen; the node size represented the sample size of the corresponding chemotherapy regimen; the line thickness between two nodes represented the number of RCT of two chemotherapy regimens.). A = cisplatin + gemcitabine, B = carboplatin + gemcitabine, C = gemcitabine, D = carboplatin + paclitaxel, E = paclitaxel + gemcitabine, F = carboplatin + docetaxel, G = gemcitabine + vinorelbine, H = carboplatin + pemetrexed, I = cisplatin + pemetrexed and J = cisplatin + docetaxel.
Figure 4

The chemotherapy regimens’ interaction network of ORR for the 10 chemotherapy regimens (Every node represented one chemotherapy regimen; the node size represented the sample size of the corresponding chemotherapy regimen; the line thickness between two nodes represented the number of RCT of two chemotherapy regimens.). A = cisplatin + gemcitabine, B = carboplatin + gemcitabine, C = gemcitabine, D = carboplatin + paclitaxel, E = paclitaxel + gemcitabine, F = carboplatin + docetaxel, G = gemcitabine + vinorelbine, H = carboplatin + pemetrexed, I = cisplatin + pemetrexed and J = cisplatin + docetaxel.

3.5 Inconsistency test

Node-splitting method was applied in the aspect of inconsistency analysis for the ORR among the 10 first-line chemotherapy regimens. The results indicated that direct and indirect ORRs were consistent (P all > 0.05; Table 2). The NMA was conducted through consistency model.

Table 2

Inconsistency test of direct and indirect pairwise comparisons of six treatment modalities under six end point outcomes

Name Direct effect Indirect effect Overall P value
A, B −0.54 (−1.53, 0.47) −0.23 (−1.18, 0.68) −0.38 (−1.03, 0.22) 0.61
A, D −0.58 (−1.62, 0.39) −0.08 (−0.99, 0.88) −0.37 (−1.02, 0.33) 0.44
A, E 0.44 (−0.88, 1.79) −0.30 (−1.46, 0.76) −0.08 (−0.85, 0.75) 0.34
A, I 0.23 (−0.21, 0.83) −0.22 (−1.67, 1.27) 0.20 (−0.21, 0.73) 0.55
B, D 0.05 (−0.80, 0.99) −0.02 (−1.20, 1.25) 0.02 (−0.60, 0.74) 0.94
B, E 0.15 (−0.66, 1.01) 0.99 (−0.50, 2.51) 0.30 (−0.31, 1.08) 0.32
B, H −0.04 (−1.01, 0.90) −0.42 (−2.82, 2.08) −0.15 (−0.99, 0.81) 0.73
D, G −0.17 (−1.31, 0.90) 0.57 (−0.76, 1.96) 0.13 (−0.71, 0.95) 0.33
F, H −0.26 (−1.32, 0.62) 0.51 (−2.40, 2.44) −0.27 (−1.25, 0.67) 0.57
F, J 0.28 (−1.14, 1.56) 0.01 (−2.46, 2.18) 0.16 (−0.99, 1.37) 0.89
G, I 0.19 (−0.91, 1.25) 0.95 (−0.50, 2.32) 0.48 (−0.37, 1.30) 0.39
I, J −0.47 (−2.05, 1.19) −0.15 (−2.22, 2.10) −0.28 (−1.59, 0.95) 0.73

A = cisplatin + gemcitabine; B = carboplatin + gemcitabine; C = gemcitabine; D = carboplatin + paclitaxel; E = paclitaxel + gemcitabine; F = carboplatin + docetaxel; G = gemcitabine + vinorelbine; H = carboplatin + pemetrexed; I = cisplatin + pemetrexed; J = cisplatin + docetaxel.

3.6 NMA

NMA showed that the combined ORR for regimens A (OR = 1.47, 95% CI: 0.80–2.81), B (OR = 3.22, 95% CI: 1.45–6.923), D (OR = 3.30, 95% CI: 1.22–9.33), E (OR = 4.36, 95% CI: 1.64–12.82), G (OR = 3.72, 95% CI: 1.12–12.83) and I (OR = 5.80, 95% CI: 2.04–17.86) were superior to regimen C. Rank probability analysis indicated that regimen C = gemcitabine and regimen I = cisplatin + pemetrexed had the highest probability of inferior and superior treatment ORR among the 10 first-line chemotherapy regimens (Figure 5).

Figure 5 
                  Network meta-analysis results in comparing the 10 first-line chemotherapy regimens. A = cisplatin + gemcitabine, B = carboplatin + gemcitabine, C = gemcitabine, D = carboplatin + paclitaxel, E = paclitaxel + gemcitabine, F = carboplatin + docetaxel, G = gemcitabine + vinorelbine, H = carboplatin + pemetrexed, I = cisplatin + pemetrexed and J = cisplatin + docetaxel.
Figure 5

Network meta-analysis results in comparing the 10 first-line chemotherapy regimens. A = cisplatin + gemcitabine, B = carboplatin + gemcitabine, C = gemcitabine, D = carboplatin + paclitaxel, E = paclitaxel + gemcitabine, F = carboplatin + docetaxel, G = gemcitabine + vinorelbine, H = carboplatin + pemetrexed, I = cisplatin + pemetrexed and J = cisplatin + docetaxel.

3.7 Rank probability

Rank probability analysis indicated that regimen C = gemcitabine and regimen I = cisplatin + pemetrexed had the highest probability of inferior and superior treatment ORR among the 10 first-line chemotherapy regimens (Figure 6).

Figure 6 
                  Bar plot of the rank probability of the 10 first-line chemotherapy regimens for advance NSCLC. A = cisplatin + gemcitabine, B = carboplatin + gemcitabine, C = gemcitabine, D = carboplatin + paclitaxel, E = paclitaxel + gemcitabine, F = carboplatin + docetaxel, G = gemcitabine + vinorelbine, H = carboplatin + pemetrexed, I = cisplatin + pemetrexed and J = cisplatin + docetaxel.
Figure 6

Bar plot of the rank probability of the 10 first-line chemotherapy regimens for advance NSCLC. A = cisplatin + gemcitabine, B = carboplatin + gemcitabine, C = gemcitabine, D = carboplatin + paclitaxel, E = paclitaxel + gemcitabine, F = carboplatin + docetaxel, G = gemcitabine + vinorelbine, H = carboplatin + pemetrexed, I = cisplatin + pemetrexed and J = cisplatin + docetaxel.

4 Discussion

Although new chemotherapy drugs have been developed and used in clinic, the prognosis of lung cancer is still poor for advanced stage cases. For patients with advanced NSCLC of relative well-performance status, standardized chemoradiation treatment should be applied as early as possible, which can prolong the overall survival and improve the patients’ life quality [27]. Three generation chemotherapy drugs (gemcitabine, paclitaxel, docetaxel, irinotecan and vinorelbine) are the standard first-line treatment of advanced NSCLC [28]. Studies have shown that gemcitabine-based chemotherapy had a higher disease control rate, while paclitaxel-based chemotherapy has a higher risk of progression [29].

Several meta-analysis [9,10] have directly compared the response of platinum-based chemotherapy regimens and most of them found negative results for advanced NSCLC. The response and long-term prognosis of the above regimens are similar. The main differences among the schemes are toxicity, drug pretreatment and treatment costs.

However, not all the chemotherapy regimens were directly compared by prospective randomized controlled trials or meta-analysis. The response of these chemotherapy regimens without direct comparison was unclear. Therefore, we performed this NMA in order to further evaluate the clinical efficacy of the first-line chemotherapy for advanced NSCLC. In our NMA, we compared the objective response of 10 chemotherapy regimen (A = cisplatin + gemcitabine, B = carboplatin + gemcitabine, C = gemcitabine, D = carboplatin + paclitaxel, E = paclitaxel + gemcitabine, F = carboplatin + docetaxel, G = gemcitabine + vinorelbine, H = carboplatin + pemetrexed, I = cisplatin + pemetrexed and J = cisplatin + docetaxel) by directly or indirectly pooling the open published data. The combined results indicated that the direct pooled ORR was not statistically different (P all > 0.05) for all the abovementioned chemotherapy regimens. However, NMA showed that the combined ORR for regimens A (cisplatin + gemcitabine), B (carboplatin + gemcitabine), D (carboplatin + paclitaxel), E (paclitaxel + gemcitabine), G (gemcitabine + vinorelbine) and I (cisplatin + docetaxel) were superior to regimen C = gemcitabine. Rank probability analysis indicated that regimen C = gemcitabine and regimen I = cisplatin + pemetrexed had the highest probability of inferior and superior treatment ORR among the 10 first-line chemotherapy regimens. The results indicated that cisplatin + pemetrexed may have particularly prominent ORR for advanced NSCLC as the first-line chemotherapy regimen.

Pemetrexed is a multitarget antimetabolic chemotherapeutic drug [30]. Scagliotti et al. [21] first reported the efficacy of cisplatin + pemetrexed compared with cisplatin + gemcitabine regimen in the first-line treatment of advanced NSCLC. The results showed that cisplatin + pemetrexed regimen was more effective than cisplatin + gemcitabine in the aspect of overall survival for non-squamous cell carcinoma. However, for squamous cell carcinoma, no statistical difference was observed for the two chemotherapy regimens. Therefore, based on Scagliotti’s prospective clinical trial and our NMA, cisplatin + pemetrexed was recommend for NSCLC especially in patients with non-squamous cell carcinoma.

The present meta-analysis also had limitations. The statistical heterogeneity was significant; therefore, the random effect model was applied. Ten chemotherapy regimens were included in the meta-analysis, and some of the regimens only have limited original studies. The statistical power of combining this work was limited. Only studies published in English and Chinese had been searched and included in the present work. This language restriction inevitably leads to missing out on potential suitable studies.

  1. Conflict of interest: Authors state no conflict of interest.

  2. Data availability statement: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Received: 2020-09-21
Revised: 2020-10-24
Accepted: 2020-11-04
Published Online: 2021-01-27

© 2021 Yuankai Lv et al., published by De Gruyter

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

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  1. Research Articles
  2. Identification of ZG16B as a prognostic biomarker in breast cancer
  3. Behçet’s disease with latent Mycobacterium tuberculosis infection
  4. Erratum
  5. Erratum to “Suffering from Cerebral Small Vessel Disease with and without Metabolic Syndrome”
  6. Research Articles
  7. GPR37 promotes the malignancy of lung adenocarcinoma via TGF-β/Smad pathway
  8. Expression and role of ABIN1 in sepsis: In vitro and in vivo studies
  9. Additional baricitinib loading dose improves clinical outcome in COVID-19
  10. The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats
  11. SLC12A8 plays a key role in bladder cancer progression and EMT
  12. LncRNA ATXN8OS enhances tamoxifen resistance in breast cancer
  13. Case Report
  14. Serratia marcescens as a cause of unfavorable outcome in the twin pregnancy
  15. Spleno-adrenal fusion mimicking an adrenal metastasis of a renal cell carcinoma: A case report and embryological background
  16. Research Articles
  17. TRIM25 contributes to the malignancy of acute myeloid leukemia and is negatively regulated by microRNA-137
  18. CircRNA circ_0004370 promotes cell proliferation, migration, and invasion and inhibits cell apoptosis of esophageal cancer via miR-1301-3p/COL1A1 axis
  19. LncRNA XIST regulates atherosclerosis progression in ox-LDL-induced HUVECs
  20. Potential role of IFN-γ and IL-5 in sepsis prediction of preterm neonates
  21. Rapid Communication
  22. COVID-19 vaccine: Call for employees in international transportation industries and international travelers as the first priority in global distribution
  23. Case Report
  24. Rare squamous cell carcinoma of the kidney with concurrent xanthogranulomatous pyelonephritis: A case report and review of the literature
  25. An infertile female delivered a baby after removal of primary renal carcinoid tumor
  26. Research Articles
  27. Hypertension, BMI, and cardiovascular and cerebrovascular diseases
  28. Case Report
  29. Coexistence of bilateral macular edema and pale optic disc in the patient with Cohen syndrome
  30. Research Articles
  31. Correlation between kinematic sagittal parameters of the cervical lordosis or head posture and disc degeneration in patients with posterior neck pain
  32. Review Articles
  33. Hepatoid adenocarcinoma of the lung: An analysis of the Surveillance, Epidemiology, and End Results (SEER) database
  34. Research Articles
  35. Thermography in the diagnosis of carpal tunnel syndrome
  36. Pemetrexed-based first-line chemotherapy had particularly prominent objective response rate for advanced NSCLC: A network meta-analysis
  37. Comparison of single and double autologous stem cell transplantation in multiple myeloma patients
  38. The influence of smoking in minimally invasive spinal fusion surgery
  39. Impact of body mass index on left atrial dimension in HOCM patients
  40. Expression and clinical significance of CMTM1 in hepatocellular carcinoma
  41. miR-142-5p promotes cervical cancer progression by targeting LMX1A through Wnt/β-catenin pathway
  42. Comparison of multiple flatfoot indicators in 5–8-year-old children
  43. Early MRI imaging and follow-up study in cerebral amyloid angiopathy
  44. Intestinal fatty acid-binding protein as a biomarker for the diagnosis of strangulated intestinal obstruction: A meta-analysis
  45. miR-128-3p inhibits apoptosis and inflammation in LPS-induced sepsis by targeting TGFBR2
  46. Dynamic perfusion CT – A promising tool to diagnose pancreatic ductal adenocarcinoma
  47. Biomechanical evaluation of self-cinching stitch techniques in rotator cuff repair: The single-loop and double-loop knot stitches
  48. Review Articles
  49. The ambiguous role of mannose-binding lectin (MBL) in human immunity
  50. Case Report
  51. Membranous nephropathy with pulmonary cryptococcosis with improved 1-year follow-up results: A case report
  52. Fertility problems in males carrying an inversion of chromosome 10
  53. Acute myeloid leukemia with leukemic pleural effusion and high levels of pleural adenosine deaminase: A case report and review of literature
  54. Metastatic renal Ewing’s sarcoma in adult woman: Case report and review of the literature
  55. Burkitt-like lymphoma with 11q aberration in a patient with AIDS and a patient without AIDS: Two cases reports and literature review
  56. Skull hemophilia pseudotumor: A case report
  57. Judicious use of low-dosage corticosteroids for non-severe COVID-19: A case report
  58. Adult-onset citrullinaemia type II with liver cirrhosis: A rare cause of hyperammonaemia
  59. Clinicopathologic features of Good’s syndrome: Two cases and literature review
  60. Fatal immune-related hepatitis with intrahepatic cholestasis and pneumonia associated with camrelizumab: A case report and literature review
  61. Research Articles
  62. Effects of hydroxyethyl starch and gelatin on the risk of acute kidney injury following orthotopic liver transplantation: A multicenter retrospective comparative clinical study
  63. Significance of nucleic acid positive anal swab in COVID-19 patients
  64. circAPLP2 promotes colorectal cancer progression by upregulating HELLS by targeting miR-335-5p
  65. Ratios between circulating myeloid cells and lymphocytes are associated with mortality in severe COVID-19 patients
  66. Risk factors of left atrial appendage thrombus in patients with non-valvular atrial fibrillation
  67. Clinical features of hypertensive patients with COVID-19 compared with a normotensive group: Single-center experience in China
  68. Surgical myocardial revascularization outcomes in Kawasaki disease: systematic review and meta-analysis
  69. Decreased chromobox homologue 7 expression is associated with epithelial–mesenchymal transition and poor prognosis in cervical cancer
  70. FGF16 regulated by miR-520b enhances the cell proliferation of lung cancer
  71. Platelet-rich fibrin: Basics of biological actions and protocol modifications
  72. Accurate diagnosis of prostate cancer using logistic regression
  73. miR-377 inhibition enhances the survival of trophoblast cells via upregulation of FNDC5 in gestational diabetes mellitus
  74. Prognostic significance of TRIM28 expression in patients with breast carcinoma
  75. Integrative bioinformatics analysis of KPNA2 in six major human cancers
  76. Exosomal-mediated transfer of OIP5-AS1 enhanced cell chemoresistance to trastuzumab in breast cancer via up-regulating HMGB3 by sponging miR-381-3p
  77. A four-lncRNA signature for predicting prognosis of recurrence patients with gastric cancer
  78. Knockdown of circ_0003204 alleviates oxidative low-density lipoprotein-induced human umbilical vein endothelial cells injury: Circulating RNAs could explain atherosclerosis disease progression
  79. Propofol postpones colorectal cancer development through circ_0026344/miR-645/Akt/mTOR signal pathway
  80. Knockdown of lncRNA TapSAKI alleviates LPS-induced injury in HK-2 cells through the miR-205/IRF3 pathway
  81. COVID-19 severity in relation to sociodemographics and vitamin D use
  82. Clinical analysis of 11 cases of nocardiosis
  83. Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
  84. Four long noncoding RNAs act as biomarkers in lung adenocarcinoma
  85. Real-world evidence of cytomegalovirus reactivation in non-Hodgkin lymphomas treated with bendamustine-containing regimens
  86. Relation between IL-8 level and obstructive sleep apnea syndrome
  87. circAGFG1 sponges miR-28-5p to promote non-small-cell lung cancer progression through modulating HIF-1α level
  88. Nomogram prediction model for renal anaemia in IgA nephropathy patients
  89. Effect of antibiotic use on the efficacy of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer: A meta-analysis
  90. NDRG2 inhibition facilitates angiogenesis of hepatocellular carcinoma
  91. A nomogram for predicting metabolic steatohepatitis: The combination of NAMPT, RALGDS, GADD45B, FOSL2, RTP3, and RASD1
  92. Clinical and prognostic features of MMP-2 and VEGF in AEG patients
  93. The value of miR-510 in the prognosis and development of colon cancer
  94. Functional implications of PABPC1 in the development of ovarian cancer
  95. Prognostic value of preoperative inflammation-based predictors in patients with bladder carcinoma after radical cystectomy
  96. Sublingual immunotherapy increases Treg/Th17 ratio in allergic rhinitis
  97. Prediction of improvement after anterior cruciate ligament reconstruction
  98. Effluent Osteopontin levels reflect the peritoneal solute transport rate
  99. circ_0038467 promotes PM2.5-induced bronchial epithelial cell dysfunction
  100. Significance of miR-141 and miR-340 in cervical squamous cell carcinoma
  101. Association between hair cortisol concentration and metabolic syndrome
  102. Microvessel density as a prognostic indicator of prostate cancer: A systematic review and meta-analysis
  103. Characteristics of BCR–ABL gene variants in patients of chronic myeloid leukemia
  104. Knee alterations in rheumatoid arthritis: Comparison of US and MRI
  105. Long non-coding RNA TUG1 aggravates cerebral ischemia and reperfusion injury by sponging miR-493-3p/miR-410-3p
  106. lncRNA MALAT1 regulated ATAD2 to facilitate retinoblastoma progression via miR-655-3p
  107. Development and validation of a nomogram for predicting severity in patients with hemorrhagic fever with renal syndrome: A retrospective study
  108. Analysis of COVID-19 outbreak origin in China in 2019 using differentiation method for unusual epidemiological events
  109. Laparoscopic versus open major liver resection for hepatocellular carcinoma: A case-matched analysis of short- and long-term outcomes
  110. Travelers’ vaccines and their adverse events in Nara, Japan
  111. Association between Tfh and PGA in children with Henoch–Schönlein purpura
  112. Can exchange transfusion be replaced by double-LED phototherapy?
  113. circ_0005962 functions as an oncogene to aggravate NSCLC progression
  114. Circular RNA VANGL1 knockdown suppressed viability, promoted apoptosis, and increased doxorubicin sensitivity through targeting miR-145-5p to regulate SOX4 in bladder cancer cells
  115. Serum intact fibroblast growth factor 23 in healthy paediatric population
  116. Algorithm of rational approach to reconstruction in Fournier’s disease
  117. A meta-analysis of exosome in the treatment of spinal cord injury
  118. Src-1 and SP2 promote the proliferation and epithelial–mesenchymal transition of nasopharyngeal carcinoma
  119. Dexmedetomidine may decrease the bupivacaine toxicity to heart
  120. Hypoxia stimulates the migration and invasion of osteosarcoma via up-regulating the NUSAP1 expression
  121. Long noncoding RNA XIST knockdown relieves the injury of microglia cells after spinal cord injury by sponging miR-219-5p
  122. External fixation via the anterior inferior iliac spine for proximal femoral fractures in young patients
  123. miR-128-3p reduced acute lung injury induced by sepsis via targeting PEL12
  124. HAGLR promotes neuron differentiation through the miR-130a-3p-MeCP2 axis
  125. Phosphoglycerate mutase 2 is elevated in serum of patients with heart failure and correlates with the disease severity and patient’s prognosis
  126. Cell population data in identifying active tuberculosis and community-acquired pneumonia
  127. Prognostic value of microRNA-4521 in non-small cell lung cancer and its regulatory effect on tumor progression
  128. Mean platelet volume and red blood cell distribution width is associated with prognosis in premature neonates with sepsis
  129. 3D-printed porous scaffold promotes osteogenic differentiation of hADMSCs
  130. Association of gene polymorphisms with women urinary incontinence
  131. Influence of COVID-19 pandemic on stress levels of urologic patients
  132. miR-496 inhibits proliferation via LYN and AKT pathway in gastric cancer
  133. miR-519d downregulates LEP expression to inhibit preeclampsia development
  134. Comparison of single- and triple-port VATS for lung cancer: A meta-analysis
  135. Fluorescent light energy modulates healing in skin grafted mouse model
  136. Silencing CDK6-AS1 inhibits LPS-induced inflammatory damage in HK-2 cells
  137. Predictive effect of DCE-MRI and DWI in brain metastases from NSCLC
  138. Severe postoperative hyperbilirubinemia in congenital heart disease
  139. Baicalin improves podocyte injury in rats with diabetic nephropathy by inhibiting PI3K/Akt/mTOR signaling pathway
  140. Clinical factors predicting ureteral stent failure in patients with external ureteral compression
  141. Novel H2S donor proglumide-ADT-OH protects HUVECs from ox-LDL-induced injury through NF-κB and JAK/SATA pathway
  142. Triple-Endobutton and clavicular hook: A propensity score matching analysis
  143. Long noncoding RNA MIAT inhibits the progression of diabetic nephropathy and the activation of NF-κB pathway in high glucose-treated renal tubular epithelial cells by the miR-182-5p/GPRC5A axis
  144. Serum exosomal miR-122-5p, GAS, and PGR in the non-invasive diagnosis of CAG
  145. miR-513b-5p inhibits the proliferation and promotes apoptosis of retinoblastoma cells by targeting TRIB1
  146. Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p
  147. The diagnostic and prognostic value of miR-92a in gastric cancer: A systematic review and meta-analysis
  148. Prognostic value of α2δ1 in hypopharyngeal carcinoma: A retrospective study
  149. No significant benefit of moderate-dose vitamin C on severe COVID-19 cases
  150. circ_0000467 promotes the proliferation, metastasis, and angiogenesis in colorectal cancer cells through regulating KLF12 expression by sponging miR-4766-5p
  151. Downregulation of RAB7 and Caveolin-1 increases MMP-2 activity in renal tubular epithelial cells under hypoxic conditions
  152. Educational program for orthopedic surgeons’ influences for osteoporosis
  153. Expression and function analysis of CRABP2 and FABP5, and their ratio in esophageal squamous cell carcinoma
  154. GJA1 promotes hepatocellular carcinoma progression by mediating TGF-β-induced activation and the epithelial–mesenchymal transition of hepatic stellate cells
  155. lncRNA-ZFAS1 promotes the progression of endometrial carcinoma by targeting miR-34b to regulate VEGFA expression
  156. Anticoagulation is the answer in treating noncritical COVID-19 patients
  157. Effect of late-onset hemorrhagic cystitis on PFS after haplo-PBSCT
  158. Comparison of Dako HercepTest and Ventana PATHWAY anti-HER2 (4B5) tests and their correlation with silver in situ hybridization in lung adenocarcinoma
  159. VSTM1 regulates monocyte/macrophage function via the NF-κB signaling pathway
  160. Comparison of vaginal birth outcomes in midwifery-led versus physician-led setting: A propensity score-matched analysis
  161. Treatment of osteoporosis with teriparatide: The Slovenian experience
  162. New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB
  163. Superenhancer–transcription factor regulatory network in malignant tumors
  164. β-Cell function is associated with osteosarcopenia in middle-aged and older nonobese patients with type 2 diabetes: A cross-sectional study
  165. Clinical features of atypical tuberculosis mimicking bacterial pneumonia
  166. Proteoglycan-depleted regions of annular injury promote nerve ingrowth in a rabbit disc degeneration model
  167. Effect of electromagnetic field on abortion: A systematic review and meta-analysis
  168. miR-150-5p affects AS plaque with ASMC proliferation and migration by STAT1
  169. MALAT1 promotes malignant pleural mesothelioma by sponging miR-141-3p
  170. Effects of remifentanil and propofol on distant organ lung injury in an ischemia–reperfusion model
  171. miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway
  172. Identification of LIG1 and LIG3 as prognostic biomarkers in breast cancer
  173. MitoQ inhibits hepatic stellate cell activation and liver fibrosis by enhancing PINK1/parkin-mediated mitophagy
  174. Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
  175. circATP2A2 promotes osteosarcoma progression by upregulating MYH9
  176. Prognostic role of oxytocin receptor in colon adenocarcinoma
  177. Review Articles
  178. The function of non-coding RNAs in idiopathic pulmonary fibrosis
  179. Efficacy and safety of therapeutic plasma exchange in stiff person syndrome
  180. Role of cesarean section in the development of neonatal gut microbiota: A systematic review
  181. Small cell lung cancer transformation during antitumor therapies: A systematic review
  182. Research progress of gut microbiota and frailty syndrome
  183. Recommendations for outpatient activity in COVID-19 pandemic
  184. Rapid Communication
  185. Disparity in clinical characteristics between 2019 novel coronavirus pneumonia and leptospirosis
  186. Use of microspheres in embolization for unruptured renal angiomyolipomas
  187. COVID-19 cases with delayed absorption of lung lesion
  188. A triple combination of treatments on moderate COVID-19
  189. Social networks and eating disorders during the Covid-19 pandemic
  190. Letter
  191. COVID-19, WHO guidelines, pedagogy, and respite
  192. Inflammatory factors in alveolar lavage fluid from severe COVID-19 pneumonia: PCT and IL-6 in epithelial lining fluid
  193. COVID-19: Lessons from Norway tragedy must be considered in vaccine rollout planning in least developed/developing countries
  194. What is the role of plasma cell in the lamina propria of terminal ileum in Good’s syndrome patient?
  195. Case Report
  196. Rivaroxaban triggered multifocal intratumoral hemorrhage of the cabozantinib-treated diffuse brain metastases: A case report and review of literature
  197. CTU findings of duplex kidney in kidney: A rare duplicated renal malformation
  198. Synchronous primary malignancy of colon cancer and mantle cell lymphoma: A case report
  199. Sonazoid-enhanced ultrasonography and pathologic characters of CD68 positive cell in primary hepatic perivascular epithelioid cell tumors: A case report and literature review
  200. Persistent SARS-CoV-2-positive over 4 months in a COVID-19 patient with CHB
  201. Pulmonary parenchymal involvement caused by Tropheryma whipplei
  202. Mediastinal mixed germ cell tumor: A case report and literature review
  203. Ovarian female adnexal tumor of probable Wolffian origin – Case report
  204. Rare paratesticular aggressive angiomyxoma mimicking an epididymal tumor in an 82-year-old man: Case report
  205. Perimenopausal giant hydatidiform mole complicated with preeclampsia and hyperthyroidism: A case report and literature review
  206. Primary orbital ganglioneuroblastoma: A case report
  207. Primary aortic intimal sarcoma masquerading as intramural hematoma
  208. Sustained false-positive results for hepatitis A virus immunoglobulin M: A case report and literature review
  209. Peritoneal loose body presenting as a hepatic mass: A case report and review of the literature
  210. Chondroblastoma of mandibular condyle: Case report and literature review
  211. Trauma-induced complete pacemaker lead fracture 8 months prior to hospitalization: A case report
  212. Primary intradural extramedullary extraosseous Ewing’s sarcoma/peripheral primitive neuroectodermal tumor (PIEES/PNET) of the thoracolumbar spine: A case report and literature review
  213. Computer-assisted preoperative planning of reduction of and osteosynthesis of scapular fracture: A case report
  214. High quality of 58-month life in lung cancer patient with brain metastases sequentially treated with gefitinib and osimertinib
  215. Rapid response of locally advanced oral squamous cell carcinoma to apatinib: A case report
  216. Retrieval of intrarenal coiled and ruptured guidewire by retrograde intrarenal surgery: A case report and literature review
  217. Usage of intermingled skin allografts and autografts in a senior patient with major burn injury
  218. Retraction
  219. Retraction on “Dihydromyricetin attenuates inflammation through TLR4/NF-kappa B pathway”
  220. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part I
  221. An artificial immune system with bootstrap sampling for the diagnosis of recurrent endometrial cancers
  222. Breast cancer recurrence prediction with ensemble methods and cost-sensitive learning
Heruntergeladen am 21.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/med-2021-0202/html
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