Startseite The perinatal factors that influence the excretion of fecal calprotectin in premature-born children
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The perinatal factors that influence the excretion of fecal calprotectin in premature-born children

  • Jelena R. Cekovic , Nikola S. Prodanovic EMAIL logo , Sara S. Mijailovic , Sanja M. Knezevic , Biljana P. Vuletic , Andjelka K. Stojkovic , Dragana M. Savic , Tijana V. Prodanovic , Marina M. Stanojevic und Aleksandra M. Simovic
Veröffentlicht/Copyright: 13. Juli 2022
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Open Medicine
Aus der Zeitschrift Open Medicine Band 17 Heft 1

Abstract

This study aimed to provide additional information on the influence of perinatal factors on fecal (f)-calprotectin values in preterm infants. Calprotectin was determined from the first spontaneous stool (analyzed on the Alegria device by using the enzyme-linked immunosorbent assay [ELISA] method) obtained from neonates at a mean age of 3.41 ± 2.44 days of life. We analyzed 114 subjects who had a body weight of 1847.67 ± 418.6 g and were born at a gestational age of 32.6 ± 2.43 weeks, without intestinal and other congenital anomalies or any diseases other than those related to premature birth. The values of f-calprotectin are in a positive correlation with female subjects, intrauterine growth restriction, significant ductus arteriosus, enteral feeding intolerance, postnatal prolonged use of broad-spectrum antibiotics, and values ​​of bicarbonates (analyzed in a sample of capillary arterial blood). Measurement of f-calprotectin in the first 7 days after birth can help to early detect the intestinal distress or early staging of necrotizing enterocolitis in premature infants.

Keywords: preterm newborn; calprotectin; necrotizing enterocolitis

1 Introduction

Calprotectin is the main component of soluble cytosolic proteins in human neutrophil granulocytes. The granulocytes excrete calprotectin actively into the lumen of the digestive tract [1,2,3,4,5]. Calprotectin concentration in the stool is about six times higher than in the plasma [6]. During the neonatal period, the levels of fecal (f)-calprotectin have been observed to be significantly higher, in both term and preterm infants, compared to the reference values ​​established for children and adults [1,2,3]. There is growing evidence of the potential role of calprotectin as a non-invasive diagnostic screening test of inflammation and the influence of stress factors on the digestive tract of the newborns, such as respiratory distress syndrome (RDS), perinatal asphyxia, significant ductus arteriosus, and the influence of some drugs (e.g., indomethacin or ibuprofen) [1,3]. It is of interest to determine the interdependence of f-calprotectin and the method of delivery, prenatal (gestational) or postnatal age, milk diet, volume of enteral feeding, enteral nutrition tolerance, and intestinal microflora [4,5,7,8,9]. All of the aforementioned factors, especially the quality of enteral colonization, are seen as possible modulating factors of the activity and differentiation of immune cells [7,8,10,11,12]. Some authors believe that bifidobacteria supplementation in the neonatal period may be associated with a significant reduction in f-calprotectin levels [7,8,10,11,12,13]. This study was aimed to provide more information regarding the factors that influence the excretion of f-calprotectin in premature-born children.

2 Materials and methods

The sample size was calculated “a priori” (G-power software), based on the following baseline parameters: study power (80%), clinically significant value of Pearson’s correlation coefficient (0.35) and first type error (α) (0.05). The required sample size in the study group is at least 61 subjects.

2.1 Ethics statement

This study was approved by the ethics committee of the University Clinical Center Kragujevac, Serbia 01.19.1973 13.05.2019 and Faculty of Medical Sciences, University of Kragujevac, Serbia. Data were prospectively collected over a period from January 2019 to September 2021.

The subjects included in our study were 114 premature infants (61 males and 53 females) hospitalized at the Neonatal Intensive Care Unit (NICU) of the Center for Neonatology, the University Clinical Center Kragujevac, Serbia. The inclusion criteria were as follows: gestational age of <37 weeks, postnatal age of <7 days, and the absence of any disease other than those related to premature birth (hyaline membrane disease, perinatal asphyxia, patent ductus arteriosus, anemia, etc.). Excluding criteria were death in the first 24 h of life, gestational age of <24 weeks, postnatal age of ≥7 days at the time of stool collection, gastrointestinal and other congenital anomalies, chromosomal aberrations, and congenital metabolic diseases.

After admission to the NICU, all the preterm infants were fed a reconstituted formula for preterm infants, as they were transported from 12 distant maternity hospitals. Calprotectin was determined from the first spontaneous thick, greenish-black and sticky stools after birth. Stools were collected once a day until 10 am from the infants at a mean age of 3.41 ± 2.44 days of life. Stool samples were not stored in the refrigerator. The duration of meconium passage was significantly prolonged in infants with very preterm (28–32 weeks), and especially, extremely preterm birth (less than 28 weeks). The values of f-calprotectin were analyzed immediately after taking the stool samples to the laboratory to be tested on the Alegria device, (24 Alegria® strips, range 0–1,000 µg/g) performing the enzyme-linked immunosorbent assay (ELISA) [14,15]. Blood was taken for laboratory processing at the same time as the stool was collected.

During the study period, all preterm infants underwent echocardiography on the third day of life. Significant ductus arteriosus was defined [16,17,18,19] as a ductal diameter >1.5 mm and the presence of at least 2 of the following criteria: left atrium/aorta ratio ≥1.6, pulsatile flow in the arterial duct, retrograde or absent diastolic flow in the anterior cerebral artery or descending aorta, or fractional shortening <40%.

2.2 Statistical analysis

Statistical analyses were performed using SPSS version 18.0 (SPSS, Chicago, IL, USA). The continuous variables were presented as the mean value and standard deviation (SD) or median and interquartile range (IQR). The categorical data were presented as the number and proportion (%). Comparisons of f-calprotectin according to clinical factors were performed by Mann–Whitney U test. Spearman’s rank correlation coefficient was used for correlating f-calprotectin and continuous variables. A value of p < 0.05 was considered statistically significant.

3 Results

The demographic characteristics of the patients included in the study are shown in Table 1 and other clinical and laboratory variables included in the investigation are shown in Tables 2 and 3. In our study, the median level of fecal calprotectin in the first 7 days of life was 76.12 ± 175.44 μg/g. Female subjects had significantly higher levels of f-calprotectin, while birth weight, gestational age, delivery mode, and a 5-minute Apgar score did not significantly affect its values (Table 1).

Table 1

Association of demographic characteristics of patients and calprotectin

Characteristic (n = 114) Mean value ± SD; median (IQR) p
Gender 0.003*
 Male (n = 61) 66.57 ± 184.15; 18.3 (31.7)
 Female (n = 53) 86.93 ± 166.10; 30.0 (63.0)
Birth weight (g) 1847.67 ± 418.60; 1830.0 (567.5) 0.351 **
Gestational age (weeks) 32.60 ± 2.43; 33.0 (4.0) 0.445 **
Apgar score 6.53 ± 1.65; 7.0 (2.0) 0.735 **
Delivery mode 0.571*
 Vaginal (n = 50) 70.28 ± 157.64; 23.7 (39.9)
 Caesarean section (n = 64) 80.75 ± 189.49; 23.4 (37.4)

SD = standard deviation; IQR = interquartile range; *Mann–Whitney U test; ** Spearman correlation.

Table 2

Correlations of laboratory values and calprotectin

Variables Mean value ± SD Median (IQR) Normative value* Spearman ρ/p value
Fecal calprotectin (µg/g) 76.12 ± 175.44 23.0 (36.60) —
CRP (mg/L) 14.97 ± 31.93 2.95 (7.43) 0.0–7.0 –0.020/0.831
Serum procalcitonin (ng/mL) 11.55 ± 18.96 4.19 (13.71) 0.5–2.0 0.008/0.935
Urea (mmol/L) 3.83 ± 2.53 3.2 (3.90) 1.1–9.1 0.019/0.846
Creatinine (µmol/L) 71.37 ± 19.28 69.5 (23.75) 49.0–106.0 0.015/0.878
pH value 7.29 ± 0.11 7.3 (0.15) 7.30 –7.45 0.020/0.830
pCO2 (kPa) 6.80 ± 2.23 6.30 (3.10) 3.5–4.5 0.052/0.583
pO2 (kPa) 6.10 ± 1.92 5.95 (2.20) 8.0–10.0 –0.037/0.695
Sodium (mmol/L) 133.57 ± 4.25 133.5 (5.0) 133.0–146.0 –0.084/0.378
Potassium (mmol/L) 5.70 ± 1.42 5.6 (1.90) 4.6–6.7 –0.040/0.678
Calcium (mmol/L) 1.18 ± 0.15 1.20 (0.19) 1.04–1.52 0.011/0.910
Glycaemia (mmol/L) 4.81 ± 4.04 3.80 (2.80) 1.5–5.5 0.076/0.424
Bicarbonates (mmol/L) 22.74 ± 4.18 22.60 (4.7) 22.0–28.0 0.215/0.022
Base excess (mmol/L) –2.72 ± 4.35 –3.00 (5.2) –1.0 to 1.0 0.039/0.685
Leukocytes (×109/L) 15.62 ± 8.73 13.71 (8.6) 5.0–21.0 0.060/0.526
Neutrophils (%) 48.75 ± 12.28 49.50 (17.7) 55.0–65.0 0.168/0.080
Erythrocyte (×1012/L) 4.73 ± 0.90 4.80 (1.31) 4.22–5.95 –0.029/0.759
Hemoglobin (g/L) 173.40 ± 32.74 176.25 (49.3) 179.0–209.0 –0.047/0.619
Hematocrit (L/L) 0.60 ± 0.87 0.52 (0.15) 0.59–0.71 –0.062/0.523
Thrombocytes (×109/L) 216.13 ± 114.68 191.45 (130.8) 150.0–350.0 –0.083/0.382

*Normal laboratory values for newborns <37 weeks of gestation, up to 7 days of age. https://www.bettersafercare.vic.gov.au/clinical-guidance/neonatal/normal-laboratory-values-for-neonates.

Table 3

Association of laboratory values and calprotectin

N (%) Median (IQR) p
RDS
 Yes 82 (71.9) 23.4 (34.9)
 No 32 (28.1) 25.3 (44.4) 0.794*
Asphyxia
 Yes 58 (50.9) 20.3 (27.1)
 No 49 (49.1) 29.5 (50.5) 0.124*
Meal volume — 45.5 (25.5) 0.916**
Intrauterine growth retardation
 Yes 10 (8.8) 26.7 (39.5)
 No 104 (91.1) 15.5 (9.2) 0.039 *
Vomiting
 Yes 34 (29.8) 35.9 (70.3)
 No 80 (70.2) 20.2 (30.2) 0.038 *
Silverman score — 4.0 (3.0) 0.842**
Mechanical ventilation
 Yes 45 (39.5) 26.7 (42.9)
 No 69 (60.5) 23.4 (34.1) 0.993*
Dopamine
 Yes 9 (7.9) 17.3 (21.8)
 No 105 (92.1) 25.3 (38.8) 0.203*
Prenatal antibiotics
 Yes 8 (7.0) 18.4 (23.8)
 No 106 (93.0) 25.3 (38.3) 0.059*
Postnatal antibiotics
 Initial, empiric 75 (65.8) 19.0 (33.9)
 Broad-spectrum and prolonged 39 (34.2) 30.0 (45.6) 0.040 *
Positive blood culture
 Yes 8 (7.1) 21.8 (33.5)
 No 104 (92.9) 23.4 (38.4) 0.842*
PROM
 Yes 18 (15.8) 21.6 (28.5)
 No 96 (84.2) 23.4 (40.0) 0.361*
Prenatal progesterone
 Yes 19 (16.7) 29.6 (27.1)
 No 95 (83.3) 21.5 (38.8) 0.450*
Prenatal dexamethasone
 Yes 26 (23.6) 25.6 (20.9)
 No 84 (76.4) 20.2 (38.4) 0.725*
Methyldopa (mother)
 Yes 16 (14.5) 24.3 (40.1)
 No 94 (85.5) 22.2 (32.5) 0.794*
Anemia (mother)
 Yes 8 (7.2) 28.3 (42.5)
 No 103 (92.8) 21.5 (34.3) 0.468*
Thrombophilia (mother)
 Yes 13 (11.7) 23.4 (27.7)
 No 98 (88.3) 22.2 (38.8) 0.511*
Mortality
 Yes 4 (3.5) 35.7 (47.8)
 No 110 (96.5) 23.4 (36.6) 0.877*
NEC
 Yes 8 (7.0) 29.2 (60.1)
 No 106 (93.0) 22.2 (37.1) 0.463*
Significant ductus arteriosus
 Yes 12 (19.0) 60.8 (92.5)
 No 51 (81.0) 25.0 (34.4) 0.025 *

RDS-Respiratory distress syndrome; PROM-Premature rupture of fetal membranes; NEC-Necrotizing enterocolitis; *Mann–Whitney U test; ** Spearman correlation.

Results obtained have shown that the values of f-calprotectin are in a positive correlation with bicarbonates (Table 2), while pH, base excess, partial pressure of oxygen (pO2), and carbon dioxide (pCO2) analyzed in a sample of capillary arterial blood were not. Significantly higher fecal calprotectin were detected in female newborn (p = 0.003) significant ductus arteriosus (p = 0.025), postnatal prolonged use of broad-spectrum antibiotics (p = 0.040), and vomiting (p = 0.038) (Tables 1 and 3).

Significantly higher fecal calprotectin levels (median 35.9; IQR 70.3 μg/g) were detected in subject with feeding intolerance (performed due to vomiting) compared with the group without enteral feeding intolerance (median 20.2; IQR 30.2 μg/g; p = 0.038).

Maternal diseases, prenatal use of antibiotics, corticosteroids and other prenatal therapy did not significantly affect f-calprotectin values. Moreover, postnatal age and other clinical characteristics of subjects: RDS, use of conventional mechanical ventilation or inotropes, a complete blood count, C-reactive protein (CRP), serum procalcitonin, urea, creatinine, and positive blood culture did not significantly affect its values (Table 3).

4 Discussion

The gastrointestinal tract (GIT) of the newborns is considered sterile at birth. After birth, it becomes rapidly colonized by microorganisms from the birth canal or from the environment. According to the recent hypothesis, the GIT of the neonate is first inhabited by the microorganisms from the mother’s GIT and uterus, followed by the colonization of the bacteria present in mother’s milk. The mechanism is still unclear. Bacterial colonization of the GIT of the newborn can be considered a kind of the fetus’ immune response to adapt to life outside the uterus [20]. Today, it is known that the effect of interaction between intestinal bacteria and fetal development can have long-term consequences, including the development of gastrointestinal, allergic and metabolic diseases.

During the study period, significantly higher fecal calprotectin levels were recorded in female newborns with intrauterine growth restriction (IUGR) than in the group of males without IUGR. Certain studies [21,22,23] revealed a correlation between IUGR, female infants, and adverse perinatal outcomes that include perinatal asphyxia and polycythemia, which may favor the later development of intestinal distress or necrotizing enterocolitis, with a consequent increase in f-calprotectin. However, certain authors [24,25,26] suggest that high levels of f-calprotectin are associated with enteral feeding and do not always imply pathological GIT inflammation in very low body weight (VLBW) infants. New studies and further investigations are needed to determine the mechanisms underlying this.

In the era of personalized medicine, non-invasive biomarkers can play a key role in reducing neonatal mortality, first and foremost, by enabling more accurate assessment of the risk for the development of neonatal diseases, more appropriate therapeutic treatment, and earlier prediction of the clinical outcome. Previous research suggested that the determination of the calprotectin in the stool of preterm infants could be crucially important since it has already been validated in adults and children as a sensitive marker of inflammatory bowel disease (Crohn’s disease and ulcerative colitis [27]. F-calprotectin is still not sufficiently validated as a non-invasive marker of necrotizing enterocolitis, especially for the early stages according to Bell’s criteria. The influence of other factors on the excretion of f-calprotectin in newborns is still incompletely known and controversial [15,26]. The level of f-calprotectin in children born after a cesarean section did not differ significantly in relation to children born after vaginal delivery, and no significant difference was found in its values with respect to gestational age, postnatal age, and birth weight, which is similar to the findings of other authors [1,2].

Due to large inter- and intra-individual variations, the precise determination of the limit values ​​for f-calprotectin remains an unachievable target, and the proposed limit values, depending on the author, range from 200 to 2,000 μg/g [20,21,22]. During our study, the median calprotectin values were 76.12 ± 175.44 μg/g (from a minimum of 4.4 to a maximum of 1,000 μg/g).

Vomiting, compensatory elevated values of bicarbonates, hemodynamically significant ductus arteriosus, and prolonged postnatal treatment of broad-spectrum antibiotics were associated with higher values of fecal calprotectin, as a sign of intestinal distress or GIT inflammation [27,28]. It is known that, in addition to immaturity, inflammation stimulates cyclooxygenase 2 activation and prostaglandin synthesis, which favors the persistence of the ductus arteriosus. On the other hand, its persistence may worsen pre-existing intestinal ischemia [29].

Enteral feeding intolerance is very common in preterm infants [25,28] and can be a sign of reduced gastrointestinal motility due to the insufficiency of insufficient mature enzymatic system (lactase, lipase, enterokinase, etc.) or may be the initial manifestation of the necrotizing enterocolitis (NEC) [30,31,32,33,34,35,36]. In our study, initial empiric antimicrobial therapy (in which the aminoglycosides have been used in conjunction with beta-lactam antibiotics) was initiated promptly at a high risk of sepsis in symptomatic infants. However, the replacement of the empiric therapy, especially with broad-spectrum antibiotics treatment in the setting of negative cultures, correlated with an increase in the values ​​of f-calprotectin in preterm infants. The benefits of initial antibiotic therapy when indicated are clearly enormous, but the continued use of antibiotics without any microbiological justification is dangerous [37] and may lead to gut microbiota imbalance, antibiotic resistance, or the development of NEC with high mortality.

NEC almost exclusively occurs in preterm infants followed by the development of intestinal inflammation with a significant participation of neutrophils, because of the immature enterocyte response to bacterial stimulation and the onset of oral feeding. While some authors find that f-calprotectin levels increase significantly in VLBW premature infants with NEC [30], other authors believe that this parameter does not play a role in the diagnosis of NEC, especially in the early stages of this disease [26]. In our study, the increase in f-calprotectin did not precede the clinical symptoms and radiographic evidence of NEC IIa-IIb stages, according to Bell, in 8 VLBW premature infants (7%). In many published cases, increased f-calprotectin levels occurred later than acute NEC, so sequential measurement of calprotectin values ​​in stool is necessary when diagnosing NEC. This represents one of the limitations of this study. It may be that the limits in the diagnostic value of f-calprotectin come from variables that affect its levels (e.g., postnatal use of antibiotics and/or probiotics, age, etc.) [36]. Certain variables can be the cause of the unusually low values of calprotectin even in cases of fulminant NEC. Despite few reported cases, the correlation of f-calprotectin with acute NEC is important for neonatologists, since tracking the dynamics of its level changes could be useful for the prospective assessment of NEC and the prediction of outcome. NEC was indicated by the bland necrosis observed in respected specimens. The inflammation, if present, is at the junction of the ischemic bowel that maintains the circulation. Calprotectin may then only indicate the infant’s response to an injury that has already occurred. It has recently been reported that the concentration of f-calprotectin was higher in VLBW premature infants with gastrointestinal “injuries” or gut inflammation than in those with a lower degree of systemic inflammation or perinatal stress, similar to our results. This indicates that calprotectin decreases with healing [9,26]. Longitudinal studies in terms of the long-term follow-up of f-calprotectin during the neonatal period could be of crucial importance.

5 Conclusion

New findings on calprotectin as a potentially useful non-invasive parameter of the intestinal distress in preterm infants can be of great importance in the era of a personalized medical approach to the newborns. The diagnostic accuracy of f-calprotectin measurement in preterm infants can be confirmed and increased by including this parameter in the panel with other biomarkers, as well as with the better understanding of the factors that affect its excretion. Our results show that an increase in f-calprotectin, in a population of preterm infants, correlates with IUGR, the enteral feeding intolerance, significant patent ductus arteriosus, and prolonged antibiotic therapy. Measurement of f-calprotectin in the first 7 days after birth can help to detect early the intestinal distress or early staging of NEC in premature infants.

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Acknowledgments

None.

  1. Funding information: No funding was received for the preparation of this article.

  2. Author contributions: The authors are liable for its content and for having contributed to the conception, design and execution of the work, analysis, and data interpretation, and for having participated in writing and reviewing the text, as well as approving the final version to be submitted.

  3. Conflict of interest: None of the authors has any potential conflict of interest related to this manuscript. During the review, the corresponding author (Nikola S Prodanovic) became the editor of the Open Medicine, which did not affect the review process.

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

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Received: 2022-03-18
Revised: 2022-06-04
Accepted: 2022-06-12
Published Online: 2022-07-13

© 2022 Jelena R. Cekovic et al., published by De Gruyter

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

Artikel in diesem Heft

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  212. Erratum to “Effect of femoral head necrosis cystic area on femoral head collapse and stress distribution in femoral head: A clinical and finite element study”
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https://doi.org/10.1515/med-2022-0522
Schlagwörter für diesen Artikel
preterm newborn; calprotectin; necrotizing enterocolitis
Creative Commons
BY 4.0

Artikel in diesem Heft

  1. Research Articles
  2. AMBRA1 attenuates the proliferation of uveal melanoma cells
  3. A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma
  4. Differences in complications between hepatitis B-related cirrhosis and alcohol-related cirrhosis
  5. Effect of gestational diabetes mellitus on lipid profile: A systematic review and meta-analysis
  6. Long noncoding RNA NR2F1-AS1 stimulates the tumorigenic behavior of non-small cell lung cancer cells by sponging miR-363-3p to increase SOX4
  7. Promising novel biomarkers and candidate small-molecule drugs for lung adenocarcinoma: Evidence from bioinformatics analysis of high-throughput data
  8. Plasmapheresis: Is it a potential alternative treatment for chronic urticaria?
  9. The biomarkers of key miRNAs and gene targets associated with extranodal NK/T-cell lymphoma
  10. Gene signature to predict prognostic survival of hepatocellular carcinoma
  11. Effects of miRNA-199a-5p on cell proliferation and apoptosis of uterine leiomyoma by targeting MED12
  12. Does diabetes affect paraneoplastic thrombocytosis in colorectal cancer?
  13. Is there any effect on imprinted genes H19, PEG3, and SNRPN during AOA?
  14. Leptin and PCSK9 concentrations are associated with vascular endothelial cytokines in patients with stable coronary heart disease
  15. Pericentric inversion of chromosome 6 and male fertility problems
  16. Staple line reinforcement with nebulized cyanoacrylate glue in laparoscopic sleeve gastrectomy: A propensity score-matched study
  17. Retrospective analysis of crescent score in clinical prognosis of IgA nephropathy
  18. Expression of DNM3 is associated with good outcome in colorectal cancer
  19. Activation of SphK2 contributes to adipocyte-induced EOC cell proliferation
  20. CRRT influences PICCO measurements in febrile critically ill patients
  21. SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis
  22. lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells
  23. circ_AKT3 knockdown suppresses cisplatin resistance in gastric cancer
  24. Prognostic value of nicotinamide N-methyltransferase in human cancers: Evidence from a meta-analysis and database validation
  25. GPC2 deficiency inhibits cell growth and metastasis in colon adenocarcinoma
  26. A pan-cancer analysis of the oncogenic role of Holliday junction recognition protein in human tumors
  27. Radiation increases COL1A1, COL3A1, and COL1A2 expression in breast cancer
  28. Association between preventable risk factors and metabolic syndrome
  29. miR-29c-5p knockdown reduces inflammation and blood–brain barrier disruption by upregulating LRP6
  30. Cardiac contractility modulation ameliorates myocardial metabolic remodeling in a rabbit model of chronic heart failure through activation of AMPK and PPAR-α pathway
  31. Quercitrin protects human bronchial epithelial cells from oxidative damage
  32. Smurf2 suppresses the metastasis of hepatocellular carcinoma via ubiquitin degradation of Smad2
  33. circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury
  34. Sonoclot’s usefulness in prediction of cardiopulmonary arrest prognosis: A proof of concept study
  35. Four drug metabolism-related subgroups of pancreatic adenocarcinoma in prognosis, immune infiltration, and gene mutation
  36. Decreased expression of miR-195 mediated by hypermethylation promotes osteosarcoma
  37. LMO3 promotes proliferation and metastasis of papillary thyroid carcinoma cells by regulating LIMK1-mediated cofilin and the β-catenin pathway
  38. Cx43 upregulation in HUVECs under stretch via TGF-β1 and cytoskeletal network
  39. Evaluation of menstrual irregularities after COVID-19 vaccination: Results of the MECOVAC survey
  40. Histopathologic findings on removed stomach after sleeve gastrectomy. Do they influence the outcome?
  41. Analysis of the expression and prognostic value of MT1-MMP, β1-integrin and YAP1 in glioma
  42. Optimal diagnosis of the skin cancer using a hybrid deep neural network and grasshopper optimization algorithm
  43. miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells
  44. Clinical value of SIRT1 as a prognostic biomarker in esophageal squamous cell carcinoma, a systematic meta-analysis
  45. circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8
  46. miR-22-5p regulates the self-renewal of spermatogonial stem cells by targeting EZH2
  47. hsa-miR-340-5p inhibits epithelial–mesenchymal transition in endometriosis by targeting MAP3K2 and inactivating MAPK/ERK signaling
  48. circ_0085296 inhibits the biological functions of trophoblast cells to promote the progression of preeclampsia via the miR-942-5p/THBS2 network
  49. TCD hemodynamics findings in the subacute phase of anterior circulation stroke patients treated with mechanical thrombectomy
  50. Development of a risk-stratification scoring system for predicting risk of breast cancer based on non-alcoholic fatty liver disease, non-alcoholic fatty pancreas disease, and uric acid
  51. Tollip promotes hepatocellular carcinoma progression via PI3K/AKT pathway
  52. circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis
  53. Human amniotic fluid as a source of stem cells
  54. lncRNA NONRATT013819.2 promotes transforming growth factor-β1-induced myofibroblastic transition of hepatic stellate cells by miR24-3p/lox
  55. NORAD modulates miR-30c-5p-LDHA to protect lung endothelial cells damage
  56. Idiopathic pulmonary fibrosis telemedicine management during COVID-19 outbreak
  57. Risk factors for adverse drug reactions associated with clopidogrel therapy
  58. Serum zinc associated with immunity and inflammatory markers in Covid-19
  59. The relationship between night shift work and breast cancer incidence: A systematic review and meta-analysis of observational studies
  60. LncRNA expression in idiopathic achalasia: New insight and preliminary exploration into pathogenesis
  61. Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway
  62. Moscatilin suppresses the inflammation from macrophages and T cells
  63. Zoledronate promotes ECM degradation and apoptosis via Wnt/β-catenin
  64. Epithelial-mesenchymal transition-related genes in coronary artery disease
  65. The effect evaluation of traditional vaginal surgery and transvaginal mesh surgery for severe pelvic organ prolapse: 5 years follow-up
  66. Repeated partial splenic artery embolization for hypersplenism improves platelet count
  67. Low expression of miR-27b in serum exosomes of non-small cell lung cancer facilitates its progression by affecting EGFR
  68. Exosomal hsa_circ_0000519 modulates the NSCLC cell growth and metastasis via miR-1258/RHOV axis
  69. miR-455-5p enhances 5-fluorouracil sensitivity in colorectal cancer cells by targeting PIK3R1 and DEPDC1
  70. The effect of tranexamic acid on the reduction of intraoperative and postoperative blood loss and thromboembolic risk in patients with hip fracture
  71. Isocitrate dehydrogenase 1 mutation in cholangiocarcinoma impairs tumor progression by sensitizing cells to ferroptosis
  72. Artemisinin protects against cerebral ischemia and reperfusion injury via inhibiting the NF-κB pathway
  73. A 16-gene signature associated with homologous recombination deficiency for prognosis prediction in patients with triple-negative breast cancer
  74. Lidocaine ameliorates chronic constriction injury-induced neuropathic pain through regulating M1/M2 microglia polarization
  75. MicroRNA 322-5p reduced neuronal inflammation via the TLR4/TRAF6/NF-κB axis in a rat epilepsy model
  76. miR-1273h-5p suppresses CXCL12 expression and inhibits gastric cancer cell invasion and metastasis
  77. Clinical characteristics of pneumonia patients of long course of illness infected with SARS-CoV-2
  78. circRNF20 aggravates the malignancy of retinoblastoma depending on the regulation of miR-132-3p/PAX6 axis
  79. Linezolid for resistant Gram-positive bacterial infections in children under 12 years: A meta-analysis
  80. Rack1 regulates pro-inflammatory cytokines by NF-κB in diabetic nephropathy
  81. Comprehensive analysis of molecular mechanism and a novel prognostic signature based on small nuclear RNA biomarkers in gastric cancer patients
  82. Smog and risk of maternal and fetal birth outcomes: A retrospective study in Baoding, China
  83. Let-7i-3p inhibits the cell cycle, proliferation, invasion, and migration of colorectal cancer cells via downregulating CCND1
  84. β2-Adrenergic receptor expression in subchondral bone of patients with varus knee osteoarthritis
  85. Possible impact of COVID-19 pandemic and lockdown on suicide behavior among patients in Southeast Serbia
  86. In vitro antimicrobial activity of ozonated oil in liposome eyedrop against multidrug-resistant bacteria
  87. Potential biomarkers for inflammatory response in acute lung injury
  88. A low serum uric acid concentration predicts a poor prognosis in adult patients with candidemia
  89. Antitumor activity of recombinant oncolytic vaccinia virus with human IL2
  90. ALKBH5 inhibits TNF-α-induced apoptosis of HUVECs through Bcl-2 pathway
  91. Risk prediction of cardiovascular disease using machine learning classifiers
  92. Value of ultrasonography parameters in diagnosing polycystic ovary syndrome
  93. Bioinformatics analysis reveals three key genes and four survival genes associated with youth-onset NSCLC
  94. Identification of autophagy-related biomarkers in patients with pulmonary arterial hypertension based on bioinformatics analysis
  95. Protective effects of glaucocalyxin A on the airway of asthmatic mice
  96. Overexpression of miR-100-5p inhibits papillary thyroid cancer progression via targeting FZD8
  97. Bioinformatics-based analysis of SUMOylation-related genes in hepatocellular carcinoma reveals a role of upregulated SAE1 in promoting cell proliferation
  98. Effectiveness and clinical benefits of new anti-diabetic drugs: A real life experience
  99. Identification of osteoporosis based on gene biomarkers using support vector machine
  100. Tanshinone IIA reverses oxaliplatin resistance in colorectal cancer through microRNA-30b-5p/AVEN axis
  101. miR-212-5p inhibits nasopharyngeal carcinoma progression by targeting METTL3
  102. Association of ST-T changes with all-cause mortality among patients with peripheral T-cell lymphomas
  103. LINC00665/miRNAs axis-mediated collagen type XI alpha 1 correlates with immune infiltration and malignant phenotypes in lung adenocarcinoma
  104. The perinatal factors that influence the excretion of fecal calprotectin in premature-born children
  105. Effect of femoral head necrosis cystic area on femoral head collapse and stress distribution in femoral head: A clinical and finite element study
  106. Does the use of 3D-printed cones give a chance to postpone the use of megaprostheses in patients with large bone defects in the knee joint?
  107. lncRNA HAGLR modulates myocardial ischemia–reperfusion injury in mice through regulating miR-133a-3p/MAPK1 axis
  108. Protective effect of ghrelin on intestinal I/R injury in rats
  109. In vivo knee kinematics of an innovative prosthesis design
  110. Relationship between the height of fibular head and the incidence and severity of knee osteoarthritis
  111. lncRNA WT1-AS attenuates hypoxia/ischemia-induced neuronal injury during cerebral ischemic stroke via miR-186-5p/XIAP axis
  112. Correlation of cardiac troponin T and APACHE III score with all-cause in-hospital mortality in critically ill patients with acute pulmonary embolism
  113. LncRNA LINC01857 reduces metastasis and angiogenesis in breast cancer cells via regulating miR-2052/CENPQ axis
  114. Endothelial cell-specific molecule 1 (ESM1) promoted by transcription factor SPI1 acts as an oncogene to modulate the malignant phenotype of endometrial cancer
  115. SELENBP1 inhibits progression of colorectal cancer by suppressing epithelial–mesenchymal transition
  116. Visfatin is negatively associated with coronary artery lesions in subjects with impaired fasting glucose
  117. Treatment and outcomes of mechanical complications of acute myocardial infarction during the Covid-19 era: A comparison with the pre-Covid-19 period. A systematic review and meta-analysis
  118. Neonatal stroke surveillance study protocol in the United Kingdom and Republic of Ireland
  119. Oncogenic role of TWF2 in human tumors: A pan-cancer analysis
  120. Mean corpuscular hemoglobin predicts the length of hospital stay independent of severity classification in patients with acute pancreatitis
  121. Association of gallstone and polymorphisms of UGT1A1*27 and UGT1A1*28 in patients with hepatitis B virus-related liver failure
  122. TGF-β1 upregulates Sar1a expression and induces procollagen-I secretion in hypertrophic scarring fibroblasts
  123. Antisense lncRNA PCNA-AS1 promotes esophageal squamous cell carcinoma progression through the miR-2467-3p/PCNA axis
  124. NK-cell dysfunction of acute myeloid leukemia in relation to the renin–angiotensin system and neurotransmitter genes
  125. The effect of dilution with glucose and prolonged injection time on dexamethasone-induced perineal irritation – A randomized controlled trial
  126. miR-146-5p restrains calcification of vascular smooth muscle cells by suppressing TRAF6
  127. Role of lncRNA MIAT/miR-361-3p/CCAR2 in prostate cancer cells
  128. lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2
  129. Noninvasive diagnosis of AIH/PBC overlap syndrome based on prediction models
  130. lncRNA FAM230B is highly expressed in colorectal cancer and suppresses the maturation of miR-1182 to increase cell proliferation
  131. circ-LIMK1 regulates cisplatin resistance in lung adenocarcinoma by targeting miR-512-5p/HMGA1 axis
  132. LncRNA SNHG3 promoted cell proliferation, migration, and metastasis of esophageal squamous cell carcinoma via regulating miR-151a-3p/PFN2 axis
  133. Risk perception and affective state on work exhaustion in obstetrics during the COVID-19 pandemic
  134. lncRNA-AC130710/miR-129-5p/mGluR1 axis promote migration and invasion by activating PKCα-MAPK signal pathway in melanoma
  135. SNRPB promotes cell cycle progression in thyroid carcinoma via inhibiting p53
  136. Xylooligosaccharides and aerobic training regulate metabolism and behavior in rats with streptozotocin-induced type 1 diabetes
  137. Serpin family A member 1 is an oncogene in glioma and its translation is enhanced by NAD(P)H quinone dehydrogenase 1 through RNA-binding activity
  138. Silencing of CPSF7 inhibits the proliferation, migration, and invasion of lung adenocarcinoma cells by blocking the AKT/mTOR signaling pathway
  139. Ultrasound-guided lumbar plexus block versus transversus abdominis plane block for analgesia in children with hip dislocation: A double-blind, randomized trial
  140. Relationship of plasma MBP and 8-oxo-dG with brain damage in preterm
  141. Identification of a novel necroptosis-associated miRNA signature for predicting the prognosis in head and neck squamous cell carcinoma
  142. Delayed femoral vein ligation reduces operative time and blood loss during hip disarticulation in patients with extremity tumors
  143. The expression of ASAP3 and NOTCH3 and the clinicopathological characteristics of adult glioma patients
  144. Longitudinal analysis of factors related to Helicobacter pylori infection in Chinese adults
  145. HOXA10 enhances cell proliferation and suppresses apoptosis in esophageal cancer via activating p38/ERK signaling pathway
  146. Meta-analysis of early-life antibiotic use and allergic rhinitis
  147. Marital status and its correlation with age, race, and gender in prognosis of tonsil squamous cell carcinomas
  148. HPV16 E6E7 up-regulates KIF2A expression by activating JNK/c-Jun signal, is beneficial to migration and invasion of cervical cancer cells
  149. Amino acid profiles in the tissue and serum of patients with liver cancer
  150. Pain in critically ill COVID-19 patients: An Italian retrospective study
  151. Immunohistochemical distribution of Bcl-2 and p53 apoptotic markers in acetamiprid-induced nephrotoxicity
  152. Estradiol pretreatment in GnRH antagonist protocol for IVF/ICSI treatment
  153. Long non-coding RNAs LINC00689 inhibits the apoptosis of human nucleus pulposus cells via miR-3127-5p/ATG7 axis-mediated autophagy
  154. The relationship between oxygen therapy, drug therapy, and COVID-19 mortality
  155. Monitoring hypertensive disorders in pregnancy to prevent preeclampsia in pregnant women of advanced maternal age: Trial mimicking with retrospective data
  156. SETD1A promotes the proliferation and glycolysis of nasopharyngeal carcinoma cells by activating the PI3K/Akt pathway
  157. The role of Shunaoxin pills in the treatment of chronic cerebral hypoperfusion and its main pharmacodynamic components
  158. TET3 governs malignant behaviors and unfavorable prognosis of esophageal squamous cell carcinoma by activating the PI3K/AKT/GSK3β/β-catenin pathway
  159. Associations between morphokinetic parameters of temporary-arrest embryos and the clinical prognosis in FET cycles
  160. Long noncoding RNA WT1-AS regulates trophoblast proliferation, migration, and invasion via the microRNA-186-5p/CADM2 axis
  161. The incidence of bronchiectasis in chronic obstructive pulmonary disease
  162. Integrated bioinformatics analysis shows integrin alpha 3 is a prognostic biomarker for pancreatic cancer
  163. Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway
  164. Comparison of hospitalized patients with severe pneumonia caused by COVID-19 and influenza A (H7N9 and H1N1): A retrospective study from a designated hospital
  165. lncRNA ZFAS1 promotes intervertebral disc degeneration by upregulating AAK1
  166. Pathological characteristics of liver injury induced by N,N-dimethylformamide: From humans to animal models
  167. lncRNA ELFN1-AS1 enhances the progression of colon cancer by targeting miR-4270 to upregulate AURKB
  168. DARS-AS1 modulates cell proliferation and migration of gastric cancer cells by regulating miR-330-3p/NAT10 axis
  169. Dezocine inhibits cell proliferation, migration, and invasion by targeting CRABP2 in ovarian cancer
  170. MGST1 alleviates the oxidative stress of trophoblast cells induced by hypoxia/reoxygenation and promotes cell proliferation, migration, and invasion by activating the PI3K/AKT/mTOR pathway
  171. Bifidobacterium lactis Probio-M8 ameliorated the symptoms of type 2 diabetes mellitus mice by changing ileum FXR-CYP7A1
  172. circRNA DENND1B inhibits tumorigenicity of clear cell renal cell carcinoma via miR-122-5p/TIMP2 axis
  173. EphA3 targeted by miR-3666 contributes to melanoma malignancy via activating ERK1/2 and p38 MAPK pathways
  174. Pacemakers and methylprednisolone pulse therapy in immune-related myocarditis concomitant with complete heart block
  175. miRNA-130a-3p targets sphingosine-1-phosphate receptor 1 to activate the microglial and astrocytes and to promote neural injury under the high glucose condition
  176. Review Articles
  177. Current management of cancer pain in Italy: Expert opinion paper
  178. Hearing loss and brain disorders: A review of multiple pathologies
  179. The rationale for using low-molecular weight heparin in the therapy of symptomatic COVID-19 patients
  180. Amyotrophic lateral sclerosis and delayed onset muscle soreness in light of the impaired blink and stretch reflexes – watch out for Piezo2
  181. Interleukin-35 in autoimmune dermatoses: Current concepts
  182. Recent discoveries in microbiota dysbiosis, cholangiocytic factors, and models for studying the pathogenesis of primary sclerosing cholangitis
  183. Advantages of ketamine in pediatric anesthesia
  184. Congenital adrenal hyperplasia. Role of dentist in early diagnosis
  185. Migraine management: Non-pharmacological points for patients and health care professionals
  186. Atherogenic index of plasma and coronary artery disease: A systematic review
  187. Physiological and modulatory role of thioredoxins in the cellular function
  188. Case Reports
  189. Intrauterine Bakri balloon tamponade plus cervical cerclage for the prevention and treatment of postpartum haemorrhage in late pregnancy complicated with acute aortic dissection: Case series
  190. A case of successful pembrolizumab monotherapy in a patient with advanced lung adenocarcinoma: Use of multiple biomarkers in combination for clinical practice
  191. Unusual neurological manifestations of bilateral medial medullary infarction: A case report
  192. Atypical symptoms of malignant hyperthermia: A rare causative mutation in the RYR1 gene
  193. A case report of dermatomyositis with the missed diagnosis of non-small cell lung cancer and concurrence of pulmonary tuberculosis
  194. A rare case of endometrial polyp complicated with uterine inversion: A case report and clinical management
  195. Spontaneous rupturing of splenic artery aneurysm: Another reason for fatal syncope and shock (Case report and literature review)
  196. Fungal infection mimicking COVID-19 infection – A case report
  197. Concurrent aspergillosis and cystic pulmonary metastases in a patient with tongue squamous cell carcinoma
  198. Paraganglioma-induced inverted takotsubo-like cardiomyopathy leading to cardiogenic shock successfully treated with extracorporeal membrane oxygenation
  199. Lineage switch from lymphoma to myeloid neoplasms: First case series from a single institution
  200. Trismus during tracheal extubation as a complication of general anaesthesia – A case report
  201. Simultaneous treatment of a pubovesical fistula and lymph node metastasis secondary to multimodal treatment for prostate cancer: Case report and review of the literature
  202. Two case reports of skin vasculitis following the COVID-19 immunization
  203. Ureteroiliac fistula after oncological surgery: Case report and review of the literature
  204. Synchronous triple primary malignant tumours in the bladder, prostate, and lung harbouring TP53 and MEK1 mutations accompanied with severe cardiovascular diseases: A case report
  205. Huge mucinous cystic neoplasms with adhesion to the left colon: A case report and literature review
  206. Commentary
  207. Commentary on “Clinicopathological features of programmed cell death-ligand 1 expression in patients with oral squamous cell carcinoma”
  208. Rapid Communication
  209. COVID-19 fear, post-traumatic stress, growth, and the role of resilience
  210. Erratum
  211. Erratum to “Tollip promotes hepatocellular carcinoma progression via PI3K/AKT pathway”
  212. Erratum to “Effect of femoral head necrosis cystic area on femoral head collapse and stress distribution in femoral head: A clinical and finite element study”
  213. Erratum to “lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2”
  214. Retraction
  215. Expression and role of ABIN1 in sepsis: In vitro and in vivo studies
  216. Retraction to “miR-519d downregulates LEP expression to inhibit preeclampsia development”
  217. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part II
  218. Usefulness of close surveillance for rectal cancer patients after neoadjuvant chemoradiotherapy
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Heruntergeladen am 3.12.2025 von https://www.degruyterbrill.com/document/doi/10.1515/med-2022-0522/html
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