Home Two new inflammatory markers related to the CURB-65 score for disease severity in patients with community-acquired pneumonia: The hypersensitive C-reactive protein to albumin ratio and fibrinogen to albumin ratio
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Two new inflammatory markers related to the CURB-65 score for disease severity in patients with community-acquired pneumonia: The hypersensitive C-reactive protein to albumin ratio and fibrinogen to albumin ratio

  • Bing Luo , Minjie Sun , Xingxing Huo and Yun Wang EMAIL logo
Published/Copyright: January 22, 2021
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Open Life Sciences
From the journal Open Life Sciences Volume 16 Issue 1

Abstract

Background

The objective of this study was to investigate the relationship among hypersensitive C-reactive protein to albumin ratio (CAR), fibrinogen to albumin ratio (FAR), and the CURB-65 score for community-acquired pneumonia (CAP) severity.

Methods

Clinical data and laboratory indicators of 82 patients with CAP and 40 healthy subjects were retrospectively analysed. The relationship among CAR, FAR, and the severity of CAP was then analysed.

Results

CAR and FAR in patients with low-risk CAP were significantly higher than those in the normal control group (P < 0.05). CAR and FAR in patients with medium–high-risk CAP were further increased compared with those in patients with low-risk CAP (P < 0.05). CAR and FAR were positively correlated with hypersensitive C-reactive protein, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and CURB-65 scores (P < 0.05). In the receiver operating characteristic curve for predicting severe CAP, the area under the curve of combining four biomarkers (CAR + FAR + NLR + PLR) was the largest. CAR was also an independent risk factor for severe CAP (OR = 8.789, 95% CI: 1.543–50.064, P = 0.014).

Conclusions

CAR and FAR may be used as the inflammatory markers for CAP severity evaluation.

Keywords: community-acquired pneumonia; hypersensitive C-reactive protein to albumin ratio; fibrinogen to albumin ratio; CURB-65

1 Introduction

Without timely and effective treatment, patients with community-acquired pneumonia (CAP) are at an increased risk for severe CAP, which may cause serious complications, significantly affecting patients' the quality of life and even put their lives in danger [1]. Therefore, the ability to evaluate the severity of CAP and provide reasonable treatment is clinically significant. Most commonly, the CAP severity index scoring system has been used to assess whether patients with CAP can be treated as outpatients or inpatients [2], but the CURB-65 scoring system is also an important tool used to predict the severity of CAP [3]. However, these scoring systems require substantial time and effort to collect multiple sets of patient data. Therefore, various biomarkers have been studied to assess the severity of CAP. Presently, the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), hypersensitive C-reactive protein (hs-CRP), and fibrinogen (FIB) are the primary inflammation markers that have been studied in patients with CAP; of those, the NLR has been shown to be an important marker of disease prognosis and risk stratification in patients with CAP [4,5], whereas NLR and PLR have also been shown to be related to the severity of CAP [6]. However, the area under the curve (AUC) of the receiver operating characteristic (ROC) curve of a single indicator that predicted severe CAP was relatively small, and thus the combined evaluation of multiple markers may provide more valuable diagnostic information.

C-reactive protein to albumin ratio (CAR) and fibrinogen to albumin ratio (FAR) as the new inflammatory markers have become useful indicators to predict the systemic inflammatory response status. Specifically, CAR has been widely used to evaluate the post operative survival rate of patients with pancreatic ductal adenocarcinoma, the prognosis of survival and recurrence in patients with oesophageal cancer, the activity of rheumatoid arthritis, and the severity of coronary heart disease [7,8,9,10]. Another new inflammatory marker, FAR, has shown utility in the evaluation of gastrointestinal stromal tumours, prognosis of resectable gastric cancer, and assessment of rheumatoid arthritis activity [9,11,12]. Moreover, both CAR and FAR have been shown to be correlated with the activity level of rheumatoid arthritis [9]. However, the application of CAR and FAR in the assessment of CAP severity has not been reported in the literature.

We assume that CAR and FAR might be two important markers that can be used to evaluate the severity of CAP. Therefore, this study intends to explore whether CAR and FAR are associated with CAP's severity and compare them with other known markers.

2 Materials and methods

2.1 Subjects

A total of 82 patients with CAP who presented at Anhui No. 2 Provincial People’s Hospital from January 2018 to April 2019 were classified as the CAP group and were enrolled in this retrospective study. All patients with CAP were diagnosed according to the American Thoracic Society/Infectious Disease Society of America's (2019) diagnostic standard [13]. The following patients were excluded from the study: patients who received other treatment for 3 months, patients with CAP complicated by malignant tumours, other chronic diseases, infection or inflammatory diseases, systemic autoimmune diseases, and cardiovascular and metabolic diseases. The normal control group was composed of 40 healthy subjects matched by age and sex in the physical examination centre.

  1. Informed consent: Informed consent has been obtained from all individuals included in this study.

  2. Ethical approval: The research related to human use has been complied with all the relevant national regulations, institutional policies, and in accordance with the tenets of the Helsinki Declaration and has been approved by the ethics committee of Anhui No. 2 Provincial People’s Hospital (No. 2017-05).

2.2 CAP severity index

The CURB-65 score, which is an important tool used to predict the severity of CAP, assigns different scores to patients according to disturbance in consciousness, blood urea nitrogen level, respiratory frequency, blood pressure, and patient age. The CURB-65 score was used for the classification of CAP severity. The total score ranges from 0 to 5: CURB-65 scores greater than or equal to 0 and less than or equal to 1 indicate low risk; scores equal to 2 indicate medium risk; scores greater than or equal to 3 and less than or equal to 5 indicate high risk [3]. The CURB-65 score was used to assess the severity of CAP at the time of admission, after which the patients were divided into two groups based on the CURB-65 score: the low-risk CAP group included 42 patients with CURB-65 scores greater than or equal to 0 and less than or equal to 1; the medium–high-risk CAP group included 40 patients with CURB-65 scores greater than or equal to 2 and less than or equal to 5.

2.3 Clinical evaluation and laboratory data

Clinical evaluation and laboratory data of all patients included age, sex, leukocyte count (WBC), neutrophil (N) count, lymphocyte (L) count, platelet (PLT) count, D–dimer (D–D), hypersensitive C-reactive protein (hs-CRP), albumin (ALB), and FIB. All patients fasted overnight for 8–10 h after admission. Whole blood was collected in the morning for testing according to the requirements of various test indicators. All operations were completed within 2 h in strict accordance with the standard operating procedures of the instrument and the requirements specified in the reagent manual (Sysmex automatic coagulation analyser CS-5100, Japan; Sysmex automatic blood cell analyser XN-1001, Japan; Hitachi automatic biochemical analyser 008AS, Japan). CAR, FAR, NLR, and PLR were calculated according to the results of individual items.

2.4 Statistical analysis

SPSS21.0 (Version 21.0, Chicago, IL, USA) and MedCalc15.2.2 were used for the statistical analysis, the measurement data were described by the mean (SD), and gender was shown as male (female). The Kolmogorov–Smirnov test was used to verify data normality, the chi-square test was used for counting data, independent sample t-test or one-way ANOVA was used for measurement data, and Pearson correlation analysis was used for linear correlation analysis. Spearman correlation was used for rank correlation analysis. The CURB-65 binary model (CURB-65 ≦ 1 and CURB-65 ≧ 2) was used to analyse the relationship between laboratory parameters and CAP severity by logistic regression. The statistical level was set at 0.05.

3 Results

3.1 Clinical data and laboratory results of study groups

The hospital records of 82 patients with CAP and 40 gender- and age-matched healthy control subjects were assessed. The clinical data and laboratory results of the two groups of subjects are presented in Table 1. Significant differences were observed in 14 parameters between the two groups but not gender (P = 0.585) and age (P = 0.239). Patients with CAP had elevated levels of WBC, N, NLR, PLR, D–D, hs-CRP, CAR, FIB, and FAR, whereas their levels of L, PLT, and ALB tended to be decreased (Table 1).

Table 1

Clinical data and laboratory results of study groups, mean (SD)

Parameters Control group (N = 40) CAP group (N = 82) t/χ 2 P-value
Gender: male (female) 25 (15) 47 (35) 0.299 0.585
Age: year, mean (SD) 75.93 (8.69) 78.00 (9.29) 1.183 0.239
WBC (109 L−1) 6.51 (1.69) 8.83 (4.69) 3.988 <0.001
N (109 L−1) 3.71 (1.32) 6.99 (4.67) 5.891 <0.001
L (109 L−1) 2.24 (0.73) 1.17 (0.64) −8.272 <0.001
NLR 1.77 (0.73) 8.64 (8.19) 7.539 <0.001
PLT (109 L−1) 247.00 (48.67) 189.02 (75.68) −5.103 <0.001
PLR 120.16 (43.49) 204.01 (129.36) 5.289 <0.001
D–D (mg L−1) 0.13 (0.11) 8.96 (15.47) 5.168 <0.001
ALB (g L−1) 47.36 (2.88) 34.68 (5.65) −16.404 <0.001
hs-CRP (mg L−1) 1.80 (3.93) 31.92 (21.37) 12.347 <0.001
CAR (mg g−1) 0.04 (0.09) 1.01 (0.75) 11.598 <0.001
FIB (mg L−1) 2892.75 (891.77) 4064.27 (1497.18) 5.391 <0.001
FAR (mg g−1) 61.47 (21.06) 123.89 (60.19) 8.397 <0.001

WBC: leukocytes; N: neutrophils; L: lymphocytes; NLR: neutrophil to lymphocyte ratio; PLT: platelets; PLR: platelet to lymphocyte ratio; D–D: D–dimer; ALB: albumin; hs-CRP: hypersensitive C-reactive protein; CAR: hypersensitive C-reactive protein to albumin ratio; FIB: fibrinogen; FAR: fibrinogen to albumin ratio.

3.2 Clinical data and laboratory results of three groups of subjects

The clinical data and laboratory results of 42 patients with low-risk CAP, 40 patients with medium–high-risk CAP, and 40 healthy subjects were evaluated, and the results are presented in Table 2. Significant differences were observed in the results of all parameters among the three groups except sex (P = 0.767) and age (P = 0.199). The NLR, PLR, D–D, hs-CRP, CAR, FIB, and FAR were all elevated in patients with low-risk CAP and medium–high-risk CAP, whereas PLT, L, and ALB were decreased, and WBC and N were significantly increased in patients with medium–high-risk CAP compared with the normal control group. In addition, the differences in WBC, N, L, NLR, PLR, D–D, hs-CRP, CAR, FAR, and ALB were statistically significant between the low-risk CAP group and medium–high-risk CAP group (P < 0.05) (Table 2).

Table 2

Clinical data and laboratory results of three groups of subjects, mean (SD)

Parameters Control group (N = 40) Low-risk CAP group (N = 42) Medium–high-risk CAP group (N = 40) F/χ 2 P-value
Gender: male (female) 25 (15) 23 (19) 24 (16) 0.531 0.767
Age: year, mean (SD) 75.93 (8.69) 76.67 (7.97) 79.40 (10.42) 1.099 0.199
WBC (109 L−1) 6.51 (1.69) 7.35 (4.10) 10.38 (4.81) *# 11.657 <0.001
N (109 L−1) 3.71 (1.32) 5.25 (4.12) 8.81 (4.57) *# 20.658 <0.001
L (109 L−1) 2.24 (0.73) 1.35 (0.54) * 0.99 (0.68) *# 38.833 <0.001
NLR 1.77 (0.73) 5.25 (6.26) * 12.20 (8.52) *# 30.162 <0.001
PLT (109 L−1) 247.00 (48.67) 196.12 (67.99) * 181.58 (83.22) * 10.207 <0.001
PLR 120.16 (43.49) 168.56 (85.84) * 241.23 (155.69) *# 13.387 <0.001
D–D (mg L−1) 0.13 (0.11) 3.75 (5.70) * 14.43 (20.08) *# 15.462 <0.001
ALB (g L−1) 47.36 (2.88) 36.16 (4.70) * 33.13 (6.19) *# 98.535 <0.001
hs-CRP (mg L−1) 1.80 (3.93) 22.58 (20.72) * 41.74 (17.43) *# 63.182 <0.001
CAR (mg g−1) 0.04 (0.09) 0.68 (0.65) * 1.37 (0.69) *# 58.285 <0.001
FIB (mg L−1) 2892.75 (891.77) 3741.43 (1431.05) * 4403.25 (1507.48) * 13.405 <0.001
FAR (mg g−1) 61.47 (21.06) 107.23 (49.26) * 141.38 (66.02) *# 26.690 <0.001

Note: * P < 0.05, when compared with the normal control group; # P < 0.05, when compared with low-risk CAP group.

3.3 ROC curve of NLR, PLR, CAR, FAR, and combining four biomarkers (CAR + FAR + NLR + PLR) for predicting severity in patients with CAP

The prediction efficacy of NLR, PLR, CAR, FAR, and combining four biomarkers (CAR + FAR + NLR + PLR) for severity in patients with CAP was evaluated by comparing the AUC of the ROC curve, which is shown in Figure 1. The results of the AUC analysis are presented in Table 3. The AUC of combining four biomarkers (AUC = 0.813; 95% CI: 0.712–0.891; P < 0.001) was the largest, followed by NLR (AUC = 0.786; 95% CI: 0.686–0.887; P < 0.001), CAR (AUC = 0.773; 95% CI: 0.675–0.872; P < 0.001), FAR (AUC = 0.668; 95% CI: 0.551–0.785; P = 0.009), and PLR (AUC = 0.655; 95% CI: 0.535–0.776; P = 0.015).

Figure 1 ROC curve of NLR, PLR, CAR, and FAR for severity in patients with CAP.
Figure 1

ROC curve of NLR, PLR, CAR, and FAR for severity in patients with CAP.

Table 3

AUC analysis results of ROC curve of NLR, PLR, CAR, and FAR for predicting severe in patients with CAP

Laboratory indicators AUC Standard error P-value 95% CI
NLR 0.786 0.051 <0.001 0.686–0.887
PLR 0.655 0.062 0.015 0.535–0.776
CAR 0.773 0.050 <0.001 0.675–0.872
FAR 0.668 0.060 0.009 0.551–0.785
CAR + FAR + NLR + PLR 0.813 0.046 <0.001 0.712–0.891

3.4 Correlation analysis of NLR, PLR, CAR, FAR, and CURB-65 score in patients with CAP

In this study, a bivariate Spearman correlation analysis was performed for NLR, PLR, CAR, FAR, and the CURB-65 score of patients with CAP. As presented in Table 4, the NLR, PLR, CAR, and FAR were positively correlated with the CURB-65 score (r s = 0.528, P < 0.001; r s = 0.271, P = 0.014; r s = 0.499, P < 0.001; r s = 0.344, P = 0.002, for NLR, PLR, CAR, and FAR, respectively).

Table 4

Correlation analysis of NLR, PLR, CAR, FAR, and CURB-65 score in patients with CAP

NLR PLR CAR FAR
CURB-65 r s = 0.528 r s = 0.271 r s = 0.499 r s = 0.344
Score P < 0.001 P = 0.014 P < 0.001 P = 0.002

3.5 Correlation analysis of NLR, PLR, CAR, FAR, and other laboratory indicators

In this study, a linear correlation analysis of NLR, PLR, CAR, FAR, and other laboratory indicators was performed using a bivariate Pearson correlation analysis. The results are shown in Table 5 and Figures 2 and 3. CAR was positively correlated with NLR (r = 0.547, P < 0.001), PLR (r = 0.504, P < 0.001), and hs-CRP (r = 0.974, P < 0.001) (Figure 2), whereas FAR was positively correlated with NLR (r = 0.399, P < 0.001), PLR (r = 0.439, P < 0.001), and hs-CRP (r = 0.775, P < 0.001) (Figure 3). NLR was positively correlated with WBC (r = 0.676, P < 0.001), N (r = 0.798, P < 0.001), D–D (r = 0.311, P < 0.001), and FIB (r = 0.311, P < 0.001) but was negatively correlated with L (r = −0.617, P < 0.001), PLT (r = −0.237, P = 0.008), and ALB (r = −0.451, P < 0.001) (Table 5). PLR was positively correlated with N (r = 0.328, P < 0.001) and FIB (r = 0.343, P < 0.001) but was negatively correlated with L (r = −0.631, P < 0.001) and ALB (r = −0.455, P < 0.001) (Table 5).

Table 5

Correlation analysis of NLR, PLR, CAR, FAR, and other laboratory indicators

Laboratory indicators CAR FAR NLR PLR
r P-Value r P-Value r P-Value r P-Value
WBC (109 L−1) 0.445 <0.001 0.303 0.001 0.676 <0.001 0.174 0.055
N (109 L−1) 0.527 <0.001 0.361 <0.001 0.798 <0.001 0.328 <0.001
L (109 L−1) −0.502 <0.001 −0.378 <0.001 −0.617 <0.001 −0.631 <0.001
PLT (109 L−1) −0.090 0.324 0.019 0.837 −0.237 0.008 0.152 0.095
D–D (mg L−1) 0.284 <0.001 0.155 0.089 0.311 <0.001 0.112 0.219
ALB (g L−1) −0.829 <0.001 −0.749 <0.001 −0.451 <0.001 −0.455 <0.001
FIB (mg L−1) 0.685 <0.001 0.926 <0.001 0.311 <0.001 0.343 <0.001
Figure 2 Correlation analysis of CAR with NLR, PLR, and hs-CRP in patients with CAP, CAR, and NLR (a); CAR and PLR (b); and CAR and hs-CRP (c).
Figure 2

Correlation analysis of CAR with NLR, PLR, and hs-CRP in patients with CAP, CAR, and NLR (a); CAR and PLR (b); and CAR and hs-CRP (c).

Figure 3 Correlation analysis of FAR with NLR, PLR, and hs-CRP in patients with CAP, FAR, and NLR (a); FAR and PLR (b); and FAR and hs-CRP (c).
Figure 3

Correlation analysis of FAR with NLR, PLR, and hs-CRP in patients with CAP, FAR, and NLR (a); FAR and PLR (b); and FAR and hs-CRP (c).

3.6 Multivariate logistic regression analysis of risk factors for severe CAP

In this study, we used P < 0.05 as the critical value to select meaningful variables and eliminate age, sex, FIB, and PLT, and then to select the WBC, N, L, NLR, PLR, D–D, ALB, CAR, and FAR as independent variables to include in the multivariate logistic regression analysis according to the results presented in Table 2. There was a collinearity problem between hs-CRP and CAR with variance inflation factor equal to 12.511, and thus hs-CRP was excluded from the regression model. The updated results are presented in Table 6. Multivariate logistic regression analysis showed that high CAR was an independent risk factor for severe CAP (OR = 8.789, 95% CI: 1.543–50.064, P = 0.014).

Table 6

Multivariate logistic regression analysis of risk factors for severe CAP

Index B Wald χ 2 OR OR 95% CI P-value
WBC (109 L−1) −1.067 1.188 0.344 0.051–2.343 0.344
N (109 L−1) 1.067 1.056 2.906 0.380–22.233 0.304
L (109 L−1) 1.538 1.284 4.653 0.326–66.481 0.257
D–D (mg L−1) 0.092 3.712 1.096 0.998–1.203 0.054
ALB (g L−1) 0.094 0.958 1.098 0.910–1.324 0.328
NLR 0.087 0.778 1.091 0.899–1.324 0.378
PLR 0.000 0.004 1.000 0.993–1.007 0.949
CAR (mg g−1) 2.173 5.995 8.789 1.543–50.064 0.014
FAR (mg g−1) −0.004 0.199 0.996 0.979–1.013 0.655

4 Discussion

This study's results are as follows: CAR, FAR, NLR, and PLR in patients with CAP were significantly higher than the corresponding values in normal controls. NLR, PLR, D–D, hs-CRP, CAR, FIB, and FAR were higher in patients with low-risk and medium–high-risk CAP compared with those of the normal control group. PLT, L, and ALB were lower than the corresponding values in the normal control group, whereas the WBC and N in patients with medium–high-risk CAP were significantly increased compared with those of the normal control group. Compared with low-risk CAP patients, WBC, N, NLR, PLR, D–D, hs-CRP, CAR, and FAR levels in medium–high-risk CAP patients increased significantly, whereas the levels of ALB and L significantly decreased. In the ROC curve for predicting severe CAP, the AUC of NLR was the largest, followed by CAR, FAR, and PLR. Additionally, CAR and FAR were positively correlated with NLR, PLR, hs-CRP, and the CURB-65 score, but only CAR was an independent risk factor for severe CAP. Therefore, we considered CAR, FAR, NLR, and PLR as important potential predictors of severe CAP.

The severity of CAP depends on the degree of local inflammation, lung inflammation spread, and the extent of systemic inflammation. Studies have shown that neutrophils and platelets are involved in inflammation, which regulates the immune system [14,15], and lymphocytes in patients with CAP are consumed in the anti-infection immunity response [16]. Therefore, NLR and PLR are considered to be representative of the inflammatory status [17,18]. It has been reported that NLR and PLR may be alternative markers of CAP-related inflammation [19,20,21]. Moreover, NLR and PLR have been shown to be predictors of CAP severity [6]. As shown in this study, NLR and PLR are positively correlated with the CURB-65 score and can distinguish the severity of CAP, which is consistent with what is reported in the literature. Therefore, NLR and PLR may be potential predictors of the CAP's severity.

CAR is the ratio of hs-CRP to ALB, and both hs-CRP and ALB are associated with inflammation. hs-CRP belongs to the acute phase reaction protein response, which is increased in inflammatory conditions [22]. At the same time, inflammation can reduce plasma albumin synthesis, resulting in hypoalbuminaemia [9], and thus CAR is a more sensitive predictor of inflammatory status. CAR has been widely used in the evaluation of the post operative survival rate of pancreatic ductal adenocarcinoma patients, the prognosis of colorectal cancer patients after surgery, the activity of rheumatoid arthritis, and coronary heart disease severity [7,8,9,10]. However, thus far, nothing has been published on the relationship between CAR and the severity of CAP. To the best of our knowledge, this is the first clinical study that has shown that CAR levels are elevated in patients with CAP and that a significant increase in the levels of CAR is observed in patients with medium–high-risk CAP compared with patients with low-risk CAP. At the same time, CAR was positively correlated with NLR, PLR, hs-CRP, and the CURB-65 score, and CAR was an independent risk factor for severe CAP compared with the NLR and PLR. This study suggests that CAR may be an inflammatory parameter and a potential predictor of CAP severity.

Similar to CAR and FAR (ratio of FIB to ALB), FIB is also involved in the acute phase reaction protein response, which is increased in inflammatory conditions [23], and inflammatory conditions will reduce the serum albumin levels [9]. In addition, FIB and ALB are associated with CAP [24,25], and these findings have aroused our interest in combining FIB and ALB as a new potential indicator and exploring its relationship with the severity of CAP. In this study, we found a significant increase in the FAR in patients with CAP, whereas the FAR in patients with medium–high-risk CAP was further increased compared with patients with low-risk CAP. However, no statistically significant difference was found in FIB between the low- and medium–high-risk CAP group. Therefore, FAR is superior to FIB in predicting the severity of CAP, and FAR was positively correlated with NLR, PLR, hs-CRP, and the CURB-65 score; therefore, FAR may be an important marker that can be used to assess the severity of CAP.

This study has several limitations that should be discussed. The study's first constraint is a limited retrospective case-control study with relatively small sample size and possible selection bias. The second limitation is that other inflammatory markers related to CAP, such as procalcitonin and interleukins, were not evaluated. The third limitation is that we did not evaluate the effect of treatment on the FAR, CAR, NLR, and PLR.

In conclusion, the development of novel biomarkers and the joint assessment of the severity of CAP are urgently needed and will provide more diagnostic information. To the best of our knowledge, this is the first clinical study to explore the relationship between CAR, FAR, and the severity of CAP. A significant increase in CAR and FAR was observed in patients with CAP, compared with low-risk CAP patients, and CAR and FAR in patients with medium–high-risk CAP were further increased. Additionally, CAR and FAR were positively correlated with the severity of the CAP CURB-65 score. As a result, the CAR and FAR might be two new biomarkers for the evaluation of CAP severity, and because their detection is fast and inexpensive, and they both are easy to analyze, they are worthy of clinical application.

  1. Funding: This study was funded by the National Natural Science Foundation of China (No. 81803938) and the Natural Science Key Project Foundation of Anhui Province Education Department (No. KJ2019A1099).

  2. Conflict of interest: The authors state no conflict of interest.

  3. 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: 2020-10-16
Revised: 2020-11-20
Accepted: 2020-11-26
Published Online: 2021-01-22

© 2021 Bing Luo et al., published by De Gruyter

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

Articles in the same Issue

  1. Biomedical Sciences
  2. Research progress on the mechanism of orexin in pain regulation in different brain regions
  3. Adriamycin-resistant cells are significantly less fit than adriamycin-sensitive cells in cervical cancer
  4. Exogenous spermidine affects polyamine metabolism in the mouse hypothalamus
  5. Iris metastasis of diffuse large B-cell lymphoma misdiagnosed as primary angle-closure glaucoma: A case report and review of the literature
  6. LncRNA PVT1 promotes cervical cancer progression by sponging miR-503 to upregulate ARL2 expression
  7. Two new inflammatory markers related to the CURB-65 score for disease severity in patients with community-acquired pneumonia: The hypersensitive C-reactive protein to albumin ratio and fibrinogen to albumin ratio
  8. Circ_0091579 enhances the malignancy of hepatocellular carcinoma via miR-1287/PDK2 axis
  9. Silencing XIST mitigated lipopolysaccharide (LPS)-induced inflammatory injury in human lung fibroblast WI-38 cells through modulating miR-30b-5p/CCL16 axis and TLR4/NF-κB signaling pathway
  10. Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats
  11. ABCB1 polymorphism in clopidogrel-treated Montenegrin patients
  12. Metabolic profiling of fatty acids in Tripterygium wilfordii multiglucoside- and triptolide-induced liver-injured rats
  13. miR-338-3p inhibits cell growth, invasion, and EMT process in neuroblastoma through targeting MMP-2
  14. Verification of neuroprotective effects of alpha-lipoic acid on chronic neuropathic pain in a chronic constriction injury rat model
  15. Circ_WWC3 overexpression decelerates the progression of osteosarcoma by regulating miR-421/PDE7B axis
  16. Knockdown of TUG1 rescues cardiomyocyte hypertrophy through targeting the miR-497/MEF2C axis
  17. MiR-146b-3p protects against AR42J cell injury in cerulein-induced acute pancreatitis model through targeting Anxa2
  18. miR-299-3p suppresses cell progression and induces apoptosis by downregulating PAX3 in gastric cancer
  19. Diabetes and COVID-19
  20. Discovery of novel potential KIT inhibitors for the treatment of gastrointestinal stromal tumor
  21. TEAD4 is a novel independent predictor of prognosis in LGG patients with IDH mutation
  22. circTLK1 facilitates the proliferation and metastasis of renal cell carcinoma by regulating miR-495-3p/CBL axis
  23. microRNA-9-5p protects liver sinusoidal endothelial cell against oxygen glucose deprivation/reperfusion injury
  24. Long noncoding RNA TUG1 regulates degradation of chondrocyte extracellular matrix via miR-320c/MMP-13 axis in osteoarthritis
  25. Duodenal adenocarcinoma with skin metastasis as initial manifestation: A case report
  26. Effects of Loofah cylindrica extract on learning and memory ability, brain tissue morphology, and immune function of aging mice
  27. Recombinant Bacteroides fragilis enterotoxin-1 (rBFT-1) promotes proliferation of colorectal cancer via CCL3-related molecular pathways
  28. Blocking circ_UBR4 suppressed proliferation, migration, and cell cycle progression of human vascular smooth muscle cells in atherosclerosis
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  30. Downregulation of circ_0037655 impedes glioma formation and metastasis via the regulation of miR-1229-3p/ITGB8 axis
  31. Vitamin D deficiency and cardiovascular risk in type 2 diabetes population
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  34. lncRNA myocardial infarction-associated transcript (MIAT) knockdown alleviates LPS-induced chondrocytes inflammatory injury via regulating miR-488-3p/sex determining region Y-related HMG-box 11 (SOX11) axis
  35. Identification of circRNA circ-CSPP1 as a potent driver of colorectal cancer by directly targeting the miR-431/LASP1 axis
  36. Hyperhomocysteinemia exacerbates ischemia-reperfusion injury-induced acute kidney injury by mediating oxidative stress, DNA damage, JNK pathway, and apoptosis
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  38. Gamma irradiation-mediated inactivation of enveloped viruses with conservation of genome integrity: Potential application for SARS-CoV-2 inactivated vaccine development
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  43. T cell epitopes of SARS-CoV-2 spike protein and conserved surface protein of Plasmodium malariae share sequence homology
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  46. Glucocorticoids protect HEI-OC1 cells from tunicamycin-induced cell damage via inhibiting endoplasmic reticulum stress
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  49. Silencing of LINC00707 suppresses cell proliferation, migration, and invasion of osteosarcoma cells by modulating miR-338-3p/AHSA1 axis
  50. Successful extracorporeal membrane oxygenation resuscitation of patient with cardiogenic shock induced by phaeochromocytoma crisis mimicking hyperthyroidism: A case report
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  58. Inhibition of ADAM10 ameliorates doxorubicin-induced cardiac remodeling by suppressing N-cadherin cleavage
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  62. WDR74 promotes proliferation and metastasis in colorectal cancer cells through regulating the Wnt/β-catenin signaling pathway
  63. Down-regulation of IGHG1 enhances Protoporphyrin IX accumulation and inhibits hemin biosynthesis in colorectal cancer by suppressing the MEK-FECH axis
  64. Curcumin suppresses the progression of gastric cancer by regulating circ_0056618/miR-194-5p axis
  65. Scutellarin-induced A549 cell apoptosis depends on activation of the transforming growth factor-β1/smad2/ROS/caspase-3 pathway
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  69. Changes of immune cells in patients with hepatocellular carcinoma treated by radiofrequency ablation and hepatectomy, a pilot study
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  71. Aberrant expression of PI3K/AKT signaling is involved in apoptosis resistance of hepatocellular carcinoma
  72. Clinical significance of activated Wnt/β-catenin signaling in apoptosis inhibition of oral cancer
  73. circ_CHFR regulates ox-LDL-mediated cell proliferation, apoptosis, and EndoMT by miR-15a-5p/EGFR axis in human brain microvessel endothelial cells
  74. Resveratrol pretreatment mitigates LPS-induced acute lung injury by regulating conventional dendritic cells’ maturation and function
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  76. Carriage of HLA-DRB1*11 and 1*12 alleles and risk factors in patients with breast cancer in Burkina Faso
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  80. Downregulation of STOX1 is a novel prognostic biomarker for glioma patients
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  84. The influence of MTHFR genetic polymorphisms on methotrexate therapy in pediatric acute lymphoblastic leukemia
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  93. Downregulation of PITX2 inhibits the proliferation and migration of liver cancer cells and induces cell apoptosis
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  96. Investigation of molecular regulation mechanism under the pathophysiology of subarachnoid hemorrhage
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https://doi.org/10.1515/biol-2021-0011
Keywords for this article
community-acquired pneumonia; hypersensitive C-reactive protein to albumin ratio; fibrinogen to albumin ratio; CURB-65
Creative Commons
BY 4.0

Articles in the same Issue

  1. Biomedical Sciences
  2. Research progress on the mechanism of orexin in pain regulation in different brain regions
  3. Adriamycin-resistant cells are significantly less fit than adriamycin-sensitive cells in cervical cancer
  4. Exogenous spermidine affects polyamine metabolism in the mouse hypothalamus
  5. Iris metastasis of diffuse large B-cell lymphoma misdiagnosed as primary angle-closure glaucoma: A case report and review of the literature
  6. LncRNA PVT1 promotes cervical cancer progression by sponging miR-503 to upregulate ARL2 expression
  7. Two new inflammatory markers related to the CURB-65 score for disease severity in patients with community-acquired pneumonia: The hypersensitive C-reactive protein to albumin ratio and fibrinogen to albumin ratio
  8. Circ_0091579 enhances the malignancy of hepatocellular carcinoma via miR-1287/PDK2 axis
  9. Silencing XIST mitigated lipopolysaccharide (LPS)-induced inflammatory injury in human lung fibroblast WI-38 cells through modulating miR-30b-5p/CCL16 axis and TLR4/NF-κB signaling pathway
  10. Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats
  11. ABCB1 polymorphism in clopidogrel-treated Montenegrin patients
  12. Metabolic profiling of fatty acids in Tripterygium wilfordii multiglucoside- and triptolide-induced liver-injured rats
  13. miR-338-3p inhibits cell growth, invasion, and EMT process in neuroblastoma through targeting MMP-2
  14. Verification of neuroprotective effects of alpha-lipoic acid on chronic neuropathic pain in a chronic constriction injury rat model
  15. Circ_WWC3 overexpression decelerates the progression of osteosarcoma by regulating miR-421/PDE7B axis
  16. Knockdown of TUG1 rescues cardiomyocyte hypertrophy through targeting the miR-497/MEF2C axis
  17. MiR-146b-3p protects against AR42J cell injury in cerulein-induced acute pancreatitis model through targeting Anxa2
  18. miR-299-3p suppresses cell progression and induces apoptosis by downregulating PAX3 in gastric cancer
  19. Diabetes and COVID-19
  20. Discovery of novel potential KIT inhibitors for the treatment of gastrointestinal stromal tumor
  21. TEAD4 is a novel independent predictor of prognosis in LGG patients with IDH mutation
  22. circTLK1 facilitates the proliferation and metastasis of renal cell carcinoma by regulating miR-495-3p/CBL axis
  23. microRNA-9-5p protects liver sinusoidal endothelial cell against oxygen glucose deprivation/reperfusion injury
  24. Long noncoding RNA TUG1 regulates degradation of chondrocyte extracellular matrix via miR-320c/MMP-13 axis in osteoarthritis
  25. Duodenal adenocarcinoma with skin metastasis as initial manifestation: A case report
  26. Effects of Loofah cylindrica extract on learning and memory ability, brain tissue morphology, and immune function of aging mice
  27. Recombinant Bacteroides fragilis enterotoxin-1 (rBFT-1) promotes proliferation of colorectal cancer via CCL3-related molecular pathways
  28. Blocking circ_UBR4 suppressed proliferation, migration, and cell cycle progression of human vascular smooth muscle cells in atherosclerosis
  29. Gene therapy in PIDs, hemoglobin, ocular, neurodegenerative, and hemophilia B disorders
  30. Downregulation of circ_0037655 impedes glioma formation and metastasis via the regulation of miR-1229-3p/ITGB8 axis
  31. Vitamin D deficiency and cardiovascular risk in type 2 diabetes population
  32. Circ_0013359 facilitates the tumorigenicity of melanoma by regulating miR-136-5p/RAB9A axis
  33. Mechanisms of circular RNA circ_0066147 on pancreatic cancer progression
  34. lncRNA myocardial infarction-associated transcript (MIAT) knockdown alleviates LPS-induced chondrocytes inflammatory injury via regulating miR-488-3p/sex determining region Y-related HMG-box 11 (SOX11) axis
  35. Identification of circRNA circ-CSPP1 as a potent driver of colorectal cancer by directly targeting the miR-431/LASP1 axis
  36. Hyperhomocysteinemia exacerbates ischemia-reperfusion injury-induced acute kidney injury by mediating oxidative stress, DNA damage, JNK pathway, and apoptosis
  37. Potential prognostic markers and significant lncRNA–mRNA co-expression pairs in laryngeal squamous cell carcinoma
  38. Gamma irradiation-mediated inactivation of enveloped viruses with conservation of genome integrity: Potential application for SARS-CoV-2 inactivated vaccine development
  39. ADHFE1 is a correlative factor of patient survival in cancer
  40. The association of transcription factor Prox1 with the proliferation, migration, and invasion of lung cancer
  41. Is there a relationship between the prevalence of autoimmune thyroid disease and diabetic kidney disease?
  42. Immunoregulatory function of Dictyophora echinovolvata spore polysaccharides in immunocompromised mice induced by cyclophosphamide
  43. T cell epitopes of SARS-CoV-2 spike protein and conserved surface protein of Plasmodium malariae share sequence homology
  44. Anti-obesity effect and mechanism of mesenchymal stem cells influence on obese mice
  45. Long noncoding RNA HULC contributes to paclitaxel resistance in ovarian cancer via miR-137/ITGB8 axis
  46. Glucocorticoids protect HEI-OC1 cells from tunicamycin-induced cell damage via inhibiting endoplasmic reticulum stress
  47. Prognostic value of the neutrophil-to-lymphocyte ratio in acute organophosphorus pesticide poisoning
  48. Gastroprotective effects of diosgenin against HCl/ethanol-induced gastric mucosal injury through suppression of NF-κβ and myeloperoxidase activities
  49. Silencing of LINC00707 suppresses cell proliferation, migration, and invasion of osteosarcoma cells by modulating miR-338-3p/AHSA1 axis
  50. Successful extracorporeal membrane oxygenation resuscitation of patient with cardiogenic shock induced by phaeochromocytoma crisis mimicking hyperthyroidism: A case report
  51. Effects of miR-185-5p on replication of hepatitis C virus
  52. Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis
  53. Primary localized cutaneous nodular amyloidosis presenting as lymphatic malformation: A case report
  54. Multimodal magnetic resonance imaging analysis in the characteristics of Wilson’s disease: A case report and literature review
  55. Therapeutic potential of anticoagulant therapy in association with cytokine storm inhibition in severe cases of COVID-19: A case report
  56. Neoadjuvant immunotherapy combined with chemotherapy for locally advanced squamous cell lung carcinoma: A case report and literature review
  57. Rufinamide (RUF) suppresses inflammation and maintains the integrity of the blood–brain barrier during kainic acid-induced brain damage
  58. Inhibition of ADAM10 ameliorates doxorubicin-induced cardiac remodeling by suppressing N-cadherin cleavage
  59. Invasive ductal carcinoma and small lymphocytic lymphoma/chronic lymphocytic leukemia manifesting as a collision breast tumor: A case report and literature review
  60. Clonal diversity of the B cell receptor repertoire in patients with coronary in-stent restenosis and type 2 diabetes
  61. CTLA-4 promotes lymphoma progression through tumor stem cell enrichment and immunosuppression
  62. WDR74 promotes proliferation and metastasis in colorectal cancer cells through regulating the Wnt/β-catenin signaling pathway
  63. Down-regulation of IGHG1 enhances Protoporphyrin IX accumulation and inhibits hemin biosynthesis in colorectal cancer by suppressing the MEK-FECH axis
  64. Curcumin suppresses the progression of gastric cancer by regulating circ_0056618/miR-194-5p axis
  65. Scutellarin-induced A549 cell apoptosis depends on activation of the transforming growth factor-β1/smad2/ROS/caspase-3 pathway
  66. lncRNA NEAT1 regulates CYP1A2 and influences steroid-induced necrosis
  67. A two-microRNA signature predicts the progression of male thyroid cancer
  68. Isolation of microglia from retinas of chronic ocular hypertensive rats
  69. Changes of immune cells in patients with hepatocellular carcinoma treated by radiofrequency ablation and hepatectomy, a pilot study
  70. Calcineurin Aβ gene knockdown inhibits transient outward potassium current ion channel remodeling in hypertrophic ventricular myocyte
  71. Aberrant expression of PI3K/AKT signaling is involved in apoptosis resistance of hepatocellular carcinoma
  72. Clinical significance of activated Wnt/β-catenin signaling in apoptosis inhibition of oral cancer
  73. circ_CHFR regulates ox-LDL-mediated cell proliferation, apoptosis, and EndoMT by miR-15a-5p/EGFR axis in human brain microvessel endothelial cells
  74. Resveratrol pretreatment mitigates LPS-induced acute lung injury by regulating conventional dendritic cells’ maturation and function
  75. Ubiquitin-conjugating enzyme E2T promotes tumor stem cell characteristics and migration of cervical cancer cells by regulating the GRP78/FAK pathway
  76. Carriage of HLA-DRB1*11 and 1*12 alleles and risk factors in patients with breast cancer in Burkina Faso
  77. Protective effect of Lactobacillus-containing probiotics on intestinal mucosa of rats experiencing traumatic hemorrhagic shock
  78. Glucocorticoids induce osteonecrosis of the femoral head through the Hippo signaling pathway
  79. Endothelial cell-derived SSAO can increase MLC20 phosphorylation in VSMCs
  80. Downregulation of STOX1 is a novel prognostic biomarker for glioma patients
  81. miR-378a-3p regulates glioma cell chemosensitivity to cisplatin through IGF1R
  82. The molecular mechanisms underlying arecoline-induced cardiac fibrosis in rats
  83. TGF-β1-overexpressing mesenchymal stem cells reciprocally regulate Th17/Treg cells by regulating the expression of IFN-γ
  84. The influence of MTHFR genetic polymorphisms on methotrexate therapy in pediatric acute lymphoblastic leukemia
  85. Red blood cell distribution width-standard deviation but not red blood cell distribution width-coefficient of variation as a potential index for the diagnosis of iron-deficiency anemia in mid-pregnancy women
  86. Small cell neuroendocrine carcinoma expressing alpha fetoprotein in the endometrium
  87. Superoxide dismutase and the sigma1 receptor as key elements of the antioxidant system in human gastrointestinal tract cancers
  88. Molecular characterization and phylogenetic studies of Echinococcus granulosus and Taenia multiceps coenurus cysts in slaughtered sheep in Saudi Arabia
  89. ITGB5 mutation discovered in a Chinese family with blepharophimosis-ptosis-epicanthus inversus syndrome
  90. ACTB and GAPDH appear at multiple SDS-PAGE positions, thus not suitable as reference genes for determining protein loading in techniques like Western blotting
  91. Facilitation of mouse skin-derived precursor growth and yield by optimizing plating density
  92. 3,4-Dihydroxyphenylethanol ameliorates lipopolysaccharide-induced septic cardiac injury in a murine model
  93. Downregulation of PITX2 inhibits the proliferation and migration of liver cancer cells and induces cell apoptosis
  94. Expression of CDK9 in endometrial cancer tissues and its effect on the proliferation of HEC-1B
  95. Novel predictor of the occurrence of DKA in T1DM patients without infection: A combination of neutrophil/lymphocyte ratio and white blood cells
  96. Investigation of molecular regulation mechanism under the pathophysiology of subarachnoid hemorrhage
  97. miR-25-3p protects renal tubular epithelial cells from apoptosis induced by renal IRI by targeting DKK3
  98. Bioengineering and Biotechnology
  99. Green fabrication of Co and Co3O4 nanoparticles and their biomedical applications: A review
  100. Agriculture
  101. Effects of inorganic and organic selenium sources on the growth performance of broilers in China: A meta-analysis
  102. Crop-livestock integration practices, knowledge, and attitudes among smallholder farmers: Hedging against climate change-induced shocks in semi-arid Zimbabwe
  103. Food Science and Nutrition
  104. Effect of food processing on the antioxidant activity of flavones from Polygonatum odoratum (Mill.) Druce
  105. Vitamin D and iodine status was associated with the risk and complication of type 2 diabetes mellitus in China
  106. Diversity of microbiota in Slovak summer ewes’ cheese “Bryndza”
  107. Comparison between voltammetric detection methods for abalone-flavoring liquid
  108. Composition of low-molecular-weight glutenin subunits in common wheat (Triticum aestivum L.) and their effects on the rheological properties of dough
  109. Application of culture, PCR, and PacBio sequencing for determination of microbial composition of milk from subclinical mastitis dairy cows of smallholder farms
  110. Investigating microplastics and potentially toxic elements contamination in canned Tuna, Salmon, and Sardine fishes from Taif markets, KSA
  111. From bench to bar side: Evaluating the red wine storage lesion
  112. Establishment of an iodine model for prevention of iodine-excess-induced thyroid dysfunction in pregnant women
  113. Plant Sciences
  114. Characterization of GMPP from Dendrobium huoshanense yielding GDP-D-mannose
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