Home Pain in critically ill COVID-19 patients: An Italian retrospective study
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Pain in critically ill COVID-19 patients: An Italian retrospective study

  • Emiliano Petrucci , Vincenza Cofini , Barbara Pizzi , Marco Cascella , Gioele Marrocco , Gianmaria Ceccaroni , Stefano Necozione , Alessandro Vittori EMAIL logo and Franco Marinangeli
Published/Copyright: November 17, 2022
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Open Medicine
From the journal Open Medicine Volume 17 Issue 1

Abstract

We retrospectively analyzed the data from patients admitted to the intensive care unit (ICU) of the Hospital of L’Aquila during the first and second waves of pandemic to identify pain related to COVID-19. Pain was evaluated by using the Numerical Rating Scale, and the assessment for neuropathic disturbances of pain was performed with von Frey’s hair and Lindblom tests. Pain increased significantly during hospitalization (from 48% at hospital admission to 94.3% at ICU discharge). Female patients were affected by somatic pain in 32.8% of the cases and by somatic pain and pain with neuropathic features (NFs) in 23.5% of the cases, during the ICU stay. Somatic pain and pain with NFs affected more frequently patients with cardiological and respiratory comorbidities. Patients treated with continuous positive airway pressure via helmet had a higher frequency of somatic pain and pain with neuropathic disturbances (84 and 74%, respectively). The frequency of somatic pain and pain with neuropathic disturbances was lower in patients sedated with propofol combined with ketamine. Females have been associated with a higher risk of somatic pain and pain with NFs. Patients with cardiological and respiratory comorbidities undergoing noninvasive ventilation had higher levels of pain. As conclusion, ketamine may reduce the promotion or the worsening of pain in COVID-19 patients.

Keywords: pain; COVID-19; ARDS; post-intensive care syndrome; neuropathic pain

1 Introduction

Post-intensive care syndrome (PICS) is a complex multifactorial condition that comprehends cognitive, physical, and psychological dysfunction reported after intensive care unit (ICU) discharge. Persistent post-intensive care (PPIC) somatic pain with neuropathic features (NFs) is often part of this syndrome. There is a potential risk of post-COVID syndrome following ICU in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1,2,3,4,5]. Three months after ICU discharge, critical illness polyneuropathy and myopathy syndrome with somatic and neuropathic pain has been reported in approximately 25–45% of critically ill patients after intensive care stays treated with noninvasive or invasive mechanical ventilation (IMV) [6]. Commonly administered sedative agents (SAs) and neuromuscular blocking agents (NMBAs) used for patient comfort and lung-protective ventilation have been recognized as risk factors of these syndromes [7,8].

Actually, the question whether the clinical history and pharmacological treatments, including SAs and NMBAs, can influence the development or the increase in somatic pain with NFs in patients requiring respiratory support is poorly understood [9].

Considering the lack of studies assessing persistent symptoms, including pain following ICU discharge, this study aimed to investigate somatic pain associated with NFs in PICS of SARS-CoV-2 patients admitted in ICU for respiratory support.

To accomplish this, we retrospectively reported the clinical features and treatments and their possible influence on the development or the increase in pain in SARS-Cov-2 patients requiring ICU admission for respiratory support [10].

2 Methods

We retrospectively analyzed the data from SARS-Cov-2 patients admitted to the ICU of the COVID Hospital of L’Aquila (Italy) in accordance with the STROBE Statement.

2.1 Data sources

Data were collected from electronic medical records. The information was collected from emergency department records and discharge reports. COVID-19 infection was confirmed by nasopharyngeal swabs and by real-time polymerase chain reaction assay performed by the hospital-based clinical laboratory [11]. We included all patients with severe COVID-19 disease, who were admitted to ICU between April 30th, 2020 and May 20th, 2021. Patients with consciousness impairment and patients who died were excluded.

The objective was to investigate the clinical characteristics associated with pain development in ICU admitted respiratory support SARS-Cov-2 patients.

2.2 Variables

Baseline variables included the following: demographic data, presence of comorbidities, and treatments administered during the permanence in ICU.

Data collected included the following: sex, age, body mass index (BMI, kg m−2), time spent in ICU (days), development of acute respiratory distress syndrome (ARDS, yes/no), ventilation strategy (needing continuous positive airway pressure [CPAP, yes/no] with helmet, or noninvasive ventilation [NIV, yes/no] via full-face mask [FFM] or helmet, or IMV [yes/no] via oro-tracheal tube [OTT] followed or not by tracheostomy [Ts], pronosupination [yes/no]), SA and NMBA consumption, and history of somatic pain and NFs at the moment of hospital admission (yes/no) and at ICU discharge (yes/no).

Comorbidities included cardiovascular diseases, respiratory diseases, cancer, metabolic disorders, neurological disorders, and renal disorders.

This research analyzed data collected at the time of ICU admission, during the hospitalization, and at the moment of discharge.

Somatic pain was considered as the somatic nociceptive pain (superficial and deep) arising from the skin, soft and musculoskeletal tissue, due to actual or threatened damage to non-neural tissue with activation of nociceptors. Pain was defined according to the International Association for the Study of Pain (IASP) [12].

Pain levels were evaluated according to Numerical Rating Scale (NRS, an 11-point numeric rating scale from 0 [no pain] to 10 [worst imaginable pain]). Patients with an NRS score ≥4 were considered with somatic pain.

We considered as NFs of pain the combination of sensory loss and pain either with or without sensory hypersensitivity phenomena in the somatic painful area [13].

The assessment for NFs of pain was performed by testing the skin of arms, legs, abdomen, and back using von Frey’s hair test and the Lindblom test [14,15,16].

The positivity of the tests for one of the evaluated features (allodynia, dysesthesia, hypoesthesia, and hyperesthesia) was considered a sign of neuropathic disturbance, due to a somatosensory nervous system abnormal function [17].

At the time of this analysis, our institution experienced shortages of fentanyl, sufentanil, midazolam, and dexmedetomidine. The decision about the use of SAs was led by the drug’s availability during the emergency. For this reason, our strategy for patient sedation was the continuous intravenously (IV) adjunctive infusion of ketamine (PK) or remifentanil to propofol (PR). SAs were administered at the moment of ICU admission and during the hospitalization, based on the need of respiratory support.

Patients received 3–5 mg kg−1 h−1 of IV propofol combined with 0.05–0.10 μg kg−1 min−1 of IV remifentanil or combined with 0.12 mg kg−1 h−1 of IV ketamine [18,19].

A continuous IV infusion of 0.4 mg kg−1 h−1 of rocuronium bromide was administered to patients who required OTT or underwent resupination procedure, during IMV.

The sedation strategy was titrated to achieve a moderate to deep sedation (−3 to −4) using the Richmond Agitation and Sedation Scale [20].

The respiratory support consisted of NIV procedures (CPAP with helmet or NIV via FFM or helmet) or IMV procedures via OTT followed or not by Ts. The respiratory support in patients treated with CPAP consisted of positive-end respiratory pressure (PEEP) values of 8–10 cm H2O, while for the NIV strategy PEEP values were 8–10 cm H2O with pressure support (PS) of 8–12 cm H2O. Patients treated with IMV received a tidal volume of 4–6 mL kg−1, PEEP values from 13 to 24 cm H2O, and respiration rates were titrated in order to maintain pulse oximetry >90% and a pH >7.2 [21]. Arterial blood gas analysis (ABGA) and lung ultrasound score (LUSS) were performed three times a day [22].

Specific pharmacological treatment with antiviral therapy, including hydroxychloroquine, lopinavir/ritonavir, remdesivir, and plasma taken from convalescent donors of COVID-19, was administered [23,24] in all patients during ICU admission and during the hospitalization, in accordance with the Italian National Health Service recommendations [25].

2.3 Statistical analysis

We describe qualitative and ordinal variables as frequencies and percentages, respectively, and quantitative continuous variables as mean values and standard deviations (SD). The proportion within groups was compared using Cochran’s test. The Chi-square test or the Fisher exact test was used for categorical variables, while the Kruskal–Wallis test was used to compare continuous variables among independent groups.

The level of significance was set to 0.05. Statistical analysis was performed with Stata 14.

  1. Informed consent: Written informed consent was obtained from all subjects or their proxies or legal surrogates.

  2. Ethical approval: This study was approved by L’Aquila and Teramo Ethics Committee (approval number: 26100/21; date of registration: 24/02/2021).

3 Results

During the study period, 123 patients fulfilled the inclusion criteria. As reported in Table 1, survivor patients were mostly males (71%; 87/123) with a mean age of 64 (SD: 14.7); 72 patients had more than 3 pathologies; 33 patients were treated with IMV via OTT followed by Ts. The combination of PR was administered to 52 patients (42%), while 71 patients (58%) were treated with PK (Table 1).

Table 1

Characteristics of COVID-19 patients at hospital admission

N = 123
Characteristics N (%) or median (IQR)
Gender
 Female 36 (29)
 Male 87 (71)
Age (years) 67 (25)
BMI (kg m−2) 25 (3.2)
Diseases
 Cardiovascular (yes) 113 (92)
 Metabolic (yes) 47 (38)
 Respiratory (yes) 58 (47)
 Neurological (yes) 28 (23)
 Renal (yes) 29 (24)
 Cancer (yes) 22 (18)
 Other (yes) 42 (34)
ARDS (yes) 66 (54)
Time spent in ICU (days) 14 (6)
Ventilation strategy
 CPAP (yes) 26 (21)
 NIV followed IMV (yes) 28 (23)
 NIV (yes) 64 (52)
 IMV (yes) 5 (4)
SAs
 PR 52 (42)
 PK 71 (58)
NMBAs (yes) 42 (34)

Abbreviations: BMI: body mass index; ARDS: acute respiratory distress syndrome; ICU: intensive care unit; CPAP: continuous positive airway pressure; NIV: noninvasive mechanical ventilation; IMV: invasive mechanical ventilation; SAs: sedative agents; PR: combination of propofol + remifentanil; PK: combination of propofol + ketamine; NMBAs: neuromuscular blocking agents.

During admission, 59 out of 123 patients reported pain (48%; 95% CI: 39−57%), and they were classified as patients with somatic pain (36), pain with NFs (11), and patients with somatic pain and pain with NFs (12), as reported in Table 2.

Table 2

Patient’s classification by pain

n %
Somatic pain 36 29.27
Pain with NFs 11 8.94
Somatic pain and pain with NFs 12 9.76
No pain 64 52.03

NFs: neuropathic features.

At ICU discharge, 116 patients reported pain (94.3%; 95% CI: 88.4−97.3%), indicating a significant difference over time (Cochran’s chi2 = 51.57; p < 0.001). Figure 1 reports the distribution of the patients over time by pain classification: all comparisons resulted in statistically significant value (p < 0.05). This indicates a decrease in the proportion of patients with pain with NFs (9% vs 6%) during the permanence in ICU. Just 6% of the admitted patients were pain-free.

Figure 1 Neuropathic pain feature proportions by time.
Figure 1

Neuropathic pain feature proportions by time.

Table 3 reports the patient’s characteristics by type of pain. During the ICU hospitalization, male patients were affected by somatic pain at 67.2% of the cases (39 patients out of 58) and by somatic pain and pain with NFs at 76.5% of the cases (39 patients out of 51), while only 19 women (32.8%) had somatic pain. Somatic pain with NFs was recorded in 12 female patients (23.5%). Cardiological disorders and respiratory disorders were observed in 57 (93%) and in 33 (57%) patients with somatic pain, respectively. Patients with somatic pain with NFs were affected by cardiological disorders in 82% of the cases (42 patients out of 51). With respect to ventilation strategy, 84% of the patients (49) with somatic pain were treated by CPAP via helmet and 74% of the cases suffered from somatic pain and pain with NFs (38 patients out of 51). On the contrary, 9 patients treated with mechanical ventilation (invasive or noninvasive) had somatic pain (16%: 9/58) and 26% of the cases (13/51) reported somatic pain and somatic pain with NFs. All patients with pain with NFs received CPAP with a helmet, while no patients treated with mechanical ventilation had this symptom. The PK combination was administered on 42 patients (75%) who reported somatic pain, while 14 patients (25%) received the PR combination as a sedation strategy. Propofol was combined with remifentanil as SAs in 32 patients (63%) with somatic pain and pain with NFs, while 19 patients (37%) with these disturbances received the combination with ketamine. NMBAs were used in 18 patients (31%) who had somatic pain and in 17 patients (33%) suffering from somatic pain and pain with NFs.

Table 3

Frequency distribution of patients’ characteristics during ICU staying by perceived pain

Variable Somatic pain (n  =  58) Pain with NFs (n  =  7) Somatic pain and pain with NFs (n = 51) No pain (n = 7) p
Female sex 19 (32.8%) 3 (42.9%) 12 (23.5%) 2 (28.6%) 0.620
Age (years) 63 (SD: 15.3) 65 (SD: 15.5) 64 (SD: 14.5) 68 (SD: 12.2) 0.8299
BMI 22.5 (SD: 2.4) 24.4 (SD: 4.4) 23.5 (SD: 3.2) 24.1 (SD: 3.1)
Time stay (ICU) 12.3 (SD: 5.3) 17.3 (SD: 3.7) 14.0 (SD: 4.0) 13.8 (SD: 2.2) 0.0438
Cardiological disorders (yes) 57 (93%) 7 (100%) 42 (82%) 7 (100%) 0.014
Metabolic disorders (yes) 28 (48%) 4 (57%) 12 (23%) 3 (43%) 0.041
Respiratory disorders (yes) 33 (57%) 5 (71%) 17 (33%) 3 (43%) 0.050
Neurological disorders (yes) 12 (21%) 1 (14%) 11 (22%) 4 (57%) 0.159
Renal disorders (yes) 15 (26%) 0 (0%) 12 (23%) 2 (29%) —
Cancer (yes) 2 (3%) 2 (29%) 18 (35%) 0 (0%) —
Other disorders (yes) 20 (34%) 4 (57%) 17 (57%) 1 (33%) 0.409
Ventilation strategy
 Continuous positive airway pressure via helmet 49 (84%) 7 (100%) 38 (74%) 3 (43%) 0.029
 Mechanical ventilation (invasive or noninvasive) 9 (16%) 0 (0%) 13 (26%) 4 (57%)
SAs: sedative agents
 PR: a combination of propofol + remifentanil 14 (25%) 2 (29%) 32 (63%) 4 (57%)
 PK: a combination of propofol + ketamine 42 (75%) 5 (71%) 19 (37%) 3 (43%) 0.001
 NMBAs: neuromuscular blocking agents 18 (31%) 1 (14%) 17 (33%) 1 (33%) 0.584

4 Discussion

We found that the distribution of the patients with pain increased significantly over time (from 48% at hospital admission to 94.3% at the ICU discharge). A significant difference (p < 0.05) was noted between the somatic pain and somatic pain with NFs, indicating that during the permanence in ICU, there was an increase in the proportion of patients with these symptoms. At the moment of ICU discharge, only 6% of the patients were pain free, and we observed a decrease in the number of patients with NFs of pain (9% vs 6%). These data seem to be aligned with the extensive body of literature, which clearly suggests that during ICU treatment up to 40% to 70% of the patients experience pain [26]. In addition, these results can confirm the possible existence of a PICS in SARS-CoV-2 patients who survived the acute phase of the disease post-COVID syndrome after the ICU discharge, as postulated by Vittori et al. [1].

The evidence regarding sex differences in pain perception suggests that male and female patients requiring ICU admission differ in their responses to pain. An increased pain sensitivity and risk for clinical pain is commonly observed in women, demonstrating that pain is more frequently reported by women than men [27,28]. Pain is the most common symptom during an active COVID-19 infection. We found that female patients were affected by somatic pain in 32.8% of the cases and by somatic pain and pain with NFs in 23.5% of the cases, during the ICU hospitalization. These data may be explained by assuming that women appear to be twice as likely to experience pain as men but until around age 60 years, when the risk level becomes similar [29].

We also found that somatic pain and somatic pain with NFs were more common in patient with cardiological and respiratory disease comorbidities. A significantly higher prevalence of pain in adults (aged 65 and over) who are also affected with cardiological disease has been demonstrated, but it is still not possible to clearly qualify the strength of this association [30]. Recent retrospective studies reported a higher incidence of cardiovascular disease in COVID-19 patients, underlying that cardiovascular and respiratory comorbidities may be risk factors for poor prognosis during ICU admission for respiratory support and for development of a post-COVID syndrome with PPIC somatic pain with NFs as postulated by Vittori et al. [1,2,4,31].

Our data underline that ventilation strategy may influence pain development or attribute to an increasing level of pain in critically ill SARS-Cov-2 patients. Pain in ICU patients is a complex multifactorial condition. Intubated and mechanically ventilated patients cannot fit the IASP definition of pain, as they cannot self-report pain sensations or assess their intensity [32]. Respecting these premises, patients treated with CPAP via helmet had a higher frequency of somatic pain and pain with NFs (84 and 74%, respectively) than patients who received mechanical ventilation. Sedation treatments and NMBAs administered to improve patient’s comfort and to facilitate lung-protective ventilation may have impaired the evaluation of pain in these patients. This is one of the drawbacks of this research. With respect to sedation treatments, the frequency of somatic pain and pain with NFs is lower in patients treated with PK combination than in patients who received the combination of propofol and remifentanil. We explain our results by considering the pharmacological profile of each SA. Ketamine causes bronchodilation, increase in blood pressure and heart rate by releasing endogenous catecholamines and maintaining respiratory drive and airway reflexes, without opioid-induced side effects with some benefits in promoting weaning from respiratory support, probably due to the minimal impairment of the diaphragmatic and respiratory muscular function, in comparison with the combination of PR [7,33,34].

Ketamine also has anti-inflammatory properties. Significant decrease in plasma levels of interleukin-6 (IL-6) and C-reactive protein was observed after administration of ketamine in general surgical and cardiac surgical patients, as reported by Dale et al., compared with an opioid-based sedation [35]. After ketamine IV injection tumor-necrosis factor-α (TNF-α) and TNF-α receptor 1 also remained stable, as well as leukocyte counts [19].

On the contrary, remifentanil is an ultra-short-acting µ-opioid receptor agonist, which often generates and strengthens postoperative pain sensitization, known as remifentanil-induced postoperative hyperalgesia. Evidence suggests that the transient receptor potential vanilloid 1 (TRPV1) is involved in the development of neuropathic pain and hyperalgesia [23]. Continuous IV infusion of remifentanil induced thermal hyperalgesia and mechanical allodynia, which were accompanied by upregulation of TRPV1 and protein kinase C in dorsal root ganglion. Remifentanil also increases the TNF-α, IL-1β, and IL-6 levels and activates the NMDA receptors via the activation of calcium/calmodulin-dependent protein kinase II signaling pathways in DRG neurons [28]. The NMDA receptor activation plays a central role for the development of central and peripheral sensitization, which may contribute to develop or increase somatic pain with NFs [36].

Differently from remifentanil, the immune modulation effect and the NMDA receptor signaling pathway inhibition provide prolonged continuous IV infusion of ketamine (>10 days), which may attenuate the COVID-19-induced or increased neuropathic pain, avoiding central sensitization and pain hypersensitivity [36]. Furthermore, Park et al. noted that 1 month after discharge, 10–50% of COVID-19 population reported PICS after abrupt awakening from sedation with disorientation and severe stress. This may contribute to the development or increase the somatic pain with NFs [37,38]. On the contrary, the wearing off of the pharmacological effects of ketamine is slow, due to its long-acting metabolites.

Several limitations affect this research. First, this was a retrospective observational study with all related limitations of this design. An important drawback was that the correlation between weaning time from respiratory support and SAs results from ABGA and LUSS test, NMBA consumption and specific pharmacological treatment with antiviral therapy were not studied. Furthermore, we were not able to investigate other determinant conditions (e.g., cognitive, physical, and psychological dysfunctions), which may in turn promote the development of PPIC somatic pain with NF after the ICU discharge. In addition, we were not able to evaluate the time spent in prone position by each patient and the rehabilitation time. There was also a lack of data regarding specific pharmacological pain treatments among survivors.

In conclusion, our findings confirm the presence of somatic pain with NFs as a part of PICS in SARS-CoV-2 patients admitted in ICU for respiratory support. Sex, comorbidities, ventilatory strategy, and SAs might influence the development or the increase in somatic pain and neuropathies, presumably mitigating the long-term nociceptive hypersensitivity COVID19- and opioid-related effects. We believe that findings add significant evidence to the growing literature on pain prevention and treatment as a part of PICS, after acute phase of COVID 19 infection in critically ill patients. Further studies will be needed to confirm our findings.

Acknowledgments

We acknowledge all of staff of COVID Hospital of L’Aquila for the resilience, during the first and the second waves of pandemic and all staff of “Luca Tonini” Simulation Center.

  1. Funding information: Authors state no funding involved.

  2. Author contributions: Conceptualization, E.P., V.C., B.P., F.M., and A.V.; methodology, E.P., M.C., G.M., G.C., and N.S.; writing – original draft preparation, E.P., V.C., B.P., and A.V.; writing – review and editing, E.P., V.C., B.P., G.M., G.C., S.N., M.C., F.M., and A.V.; supervision, E.P., V.C., M.C., F.M, and A.V.; project administration, E.P. and A.V. The authors applied the “first-last-author-emphasis” norm for the sequence of authors. All authors read and approved the final manuscript.

  3. Conflict of interest: Dr Alessandro Vittori serves as Editor for Open Medicine, but it did not affect the peer-review process.

  4. Data availability statement: Emiliano Petrucci had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Received: 2022-06-24
Revised: 2022-10-12
Accepted: 2022-10-13
Published Online: 2022-11-17

© 2022 the author(s), published by De Gruyter

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

Articles in the same Issue

  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
https://doi.org/10.1515/med-2022-0600
Keywords for this article
pain; COVID-19; ARDS; post-intensive care syndrome; neuropathic pain
Creative Commons
BY 4.0

Articles in the same Issue

  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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