Startseite The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
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The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review

  • Jiecheng Huang , Yuxuan Fan , Yongshun Wang EMAIL logo und Jingjin Liu EMAIL logo
Veröffentlicht/Copyright: 9. Januar 2025
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Open Medicine
Aus der Zeitschrift Open Medicine Band 20 Heft 1

Abstract

Some of the millions of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have developed new sequelae after recovering from the initial disease, termed post-acute sequelae of coronavirus disease 2019 (PASC). One symptom is anxiety, which is likely due to three etiologies: brain structural changes, neuroendocrine disruption, and neurotransmitter alterations. This review provides an overview of the current literature on the pathophysiological pathways linking coronavirus disease 2019 to anxiety, as well as the possible mechanisms of action in which an increasingly scrutinized treatment method, enhanced external counter-pulsation (EECP), is able to alleviate anxiety. SARS-CoV-2 triggers increased inflammatory cytokine production, as well as oxidative stress; these processes contribute to the aforementioned three etiologies. The potential treatment approach of EECP, involving sequenced inflation and deflation of specifically-placed airbags, has become of increasing interest, as it has been found to alleviate PASC-associated anxiety by improving patient cardiovascular function. These functional improvements were achieved by EECP stimulating anti-inflammatory and pro-angiogenic processes, as well as improving endothelial cell function and coronary blood flow, partially via counteracting against the negative effects of SARS-CoV-2 infection on the renin–angiotensin–aldosterone system. Therefore, EECP could promote both psychosomatic and cardiac rehabilitation. Further research, though, is still needed to fully determine its benefits and mechanism of action.

Keywords: severe acute respiratory syndrome coronavirus 2; post-acute sequelae of coronavirus disease 2019; enhanced external counter-pulsation; anxiety; cardiovascular disease

1 Introduction

Since December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a huge impact globally. As of October 2023, >770 million infections and ∼7 million deaths have been reported worldwide (source: World Health Organization [WHO]). Some patients infected with SARS-CoV-2 develop new symptoms or sequelae after the disease, which can last for months or years; these manifestations are known as long covid, or post-acute sequelae of COVID-19 (PASC) [1], which has been defined by the WHO as a condition occurring in likely/confirmed SARS-CoV-2-infected individuals at least 3 months from COVID-19 onset, with symptoms lasting for ≥2 months, and unable to be explained with alternative diagnoses. The impact of PASC can be severe, affecting multiple organ systems, as demonstrated in a retrospective matched cohort study of 47,780 cases, which found that compared to the general population, those with acute COVID-19 had an increased risk for developing multiple organ dysfunction [2]. Furthermore, on top of damaging multiple organ systems, long COVID-19 could lead to negative alterations in psychological performance. Indeed, anxiety has been found to be one of the most common psychiatric symptoms among long COVID patients [3], as demonstrated in a meta-analysis of 132 studies, involving 9,320,687 patients, in which anxiety prevalence among PASC patients was 23% [4]. In line with this observation, a direct link between SARS-CoV-2 infection and anxiety has also been documented, further supporting the close relation between physical and psychological symptoms [5]. More specifically, stress, anxiety, and depression prevalence among the general population during the pandemic were, respectively, 29.6, 31.9, and 33.7% [6]; in particular, anxiety and depression prevalence in 2020 grew, correspondingly, by 27.6 and 25.6%, representing 76 and 53.2 million more cases [7]. PASC also has significant economic and social impacts, in that a prospective cohort study found that over a 3-month period, some patients had negative changes in their occupational status [8]. Considering that >65 million people suffer from PASC, the disease thus has a significant detrimental impact on employment and economic conditions.

In light of those findings, a number of potential strategies to alleviate the effects of PASC have been investigated, one of which is enhanced external counter-pulsation (EECP), a non-invasive assisted circulatory device developed in China. EECP was initially applied for treating various cardiovascular diseases (CVD), in which special airbags are used to arrange the calves, thighs, and buttocks of a patient in specified conformations. A computer then receives information regarding the diastolic and systolic phases of the heartbeat of the patient, based on their electrocardiogram R-wave, followed by inflation and deflation of the airbags in an orderly manner. More specifically, during diastole, the three groups of airbags are sequentially inflated, from the distal to the proximally located one, with a time difference of ∼50 ms between each inflation, leading to increases in diastolic pressure, as well as squeezing of the arterial and venous system of the lower half of the body. This results in more blood being supplied to the upper half of the body, in turn, improving perfusion of the heart, brain, and other important upper body organs. The sequential airbag inflation also simultaneously increases the venous return of the right heart, leading to improvements in heart volume per heartbeat and cardiac output. At the systolic phase, all airbags are synchronized to deflate, lowering the afterload and ejection resistance of the heart. This EECP procedure has also been found to have beneficial effects in treating COVID-19 sequelae in some studies [9,10,11], of which one of the most prominent sequelae is anxiety in PASC, which has increasingly become a topic of investigation. As anxiety has been demonstrated to be prevalent, and an important risk factor, among CVD patients [12], additional research regarding the underlying mechanisms behind anxiety and possible treatments to improve the quality of life among CVD patients would also be greatly beneficial for long COVID-19 patients. In fact, more and more research has been focused on how to decrease anxiety, rehabilitate sequelae, and help restore patient physical functions after PASC. In this review, we will describe the current literature on the pathophysiological pathways linking COVID-19 to anxiety, as well as the possible mechanisms of action in which EECP is able to alleviate anxiety and COVID-19 sequelae.

2 Mechanisms associated with PASC-associated anxiety

The main etiologies behind PASC-associated anxiety likely include brain structural changes, neuroendocrine disruption, and neurotransmitter alterations, all of which inflammation and oxidative stress (OS) play important roles. These three etiologies will be described below.

2.1 Brain structural changes

SARS-CoV-2 infection has been associated with neurologic manifestations, particularly in the form of brain structural changes; this has been documented in multiple case reports, but the underlying mechanisms have still not been fully elucidated. These mechanisms, though, may likely be related to SARS-CoV-2 neuro-invasiveness, -tropism, and -virulence [13,14], in which it has been found that compared to healthy controls, PASC patients with neuropsychiatric symptoms have significantly increased gray matter volume in various brain regions, including frontotemporal, cerebellum, hippocampus, amygdala, basal ganglia, and thalamus [15]. Additionally, a neuroimaging study has shown that patients with anxiety had structural and functional abnormalities in the prefrontal-limbic neural circuits, including prefrontal cortex, hippocampus, amygdala, insula, orbital frontal cortex, and cingulate gyrus, which may be closely related to anxiety onset [16]. In particular, the structures associated with the limbic system, comprising of different midbrain, diencephalon, and telencephalon components, are the most affected. This system is involved in numerous cognitive-associated processes, such as spatial memory, motivation, as well as emotional and social processing [17]. As a result, alterations in limbic system structure and function significantly correlate to psychiatric symptoms. This has been demonstrated in multiple studies, such as a meta-analysis of 320 studies, where patients with major depressive/anxiety disorders, and/or chronic pain had wide-ranging gray matter volume reductions in the insula and dorsomedial prefrontal/anterior cingulate cortices [18], as well as another meta-analysis of seven studies, where patients with anxiety disorders had significantly reduced spontaneous brain activity in regions such as the right putamen, right inferior orbitofrontal gyrus, and right temporal pole [19].

2.2 The contribution of inflammation and OS on neuroendocrine disruption

Inflammation and OS have been recognized as two major mechanisms contributing to COVID-19-caused anxiety (Table 1). In particular, an excessive inflammatory response has been observed to be triggered by the invasion of angiotensin-converting enzyme 2 (ACE2)-expressing immune cells with SARS-CoV-2. Indeed, ACE2 is widely expressed among human cells and has been identified as the host surface receptor for SARS-CoV-2 [20], whose spike (S) protein binds to it, facilitating viral entry. The excessive inflammatory response involves monocytes and macrophages producing copious amounts of inflammatory factors, such as interleukins (IL-1β, IL-6, IL-8, IL-18), tumor necrosis factor (TNF)-α, interferon (IFN)-γ, granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein-1 (MCP-1/CCL 2), macrophage inflammatory protein (MIP), and other chemokines. Elevated levels for those factors are characteristic of a “cytokine storm (CS)”, which has been documented to occur in some COVID-19 patients, such as in a meta-analysis of 28 studies involving 346 COVID-19 patients, in which 60% of COVID-19 patients had elevated IL-6 and 51% IL-8 in cerebrospinal fluid [21]. A 2024 meta-analysis, involving 103 studies and 5502 PASC patients, also found that those patients, versus control, had significantly higher levels of C-reactive protein (CRP) and 21 other cytokines; thus, PASC was associated with enhanced immune activation [22]. Additionally, PASC patients with neurological defects were found to have significantly higher IL-1β and IL-8 levels in a 2024 analysis of blood markers [23]. Furthermore, serum IL-6 and TNF-α have been particularly noted to be independent and significant predictors for disease severity and death [24], and PASC patients have been found to possess, mean IL-6 levels that were 29% higher in early recovery and 44% higher in late recovery stages, compared to controls [25]. This has been coupled with numerous other studies finding that COVID-19 patients had elevated IL-6 expression and decreased lymphocyte counts [26,27,28]. All of those observations were in line with Peluso et al. who found that persistent symptoms after COVID-19 may be associated with continued immune activation [25].

Table 1

The major mechanisms contributing to COVID-19-caused anxiety

Mechanism Explanation
Inflammation [13] Spike (S) protein of SARS-CoV-2 binds to ACE 2 expressed on the surface of host cells and mediates the entry of SARS-CoV-2 into the cells. As a result, SARS-CoV-2 could trigger CS
Oxidative stress [19,20,21] High ROS and RNS levels stem from SARS-CoV-2 interactions with ACE2. After binding to ACE2, both ACE2 and SARS-CoV-2 are endocytosed by the host cell, leading to ACE2 downregulation, increases in Ang II and AT1R expression. AT1R promotes vasoconstriction, inflammation, and oxidative stress

SARS-CoV-2 = Severe acute respiratory syndrome coronavirus 2; ACE2 = angiotensin-converting enzyme 2; CS = cytokine storm; Ang II = angiotensin II; AT1R = angiotensin receptor type 1; ROS = reactive oxygen species; RNS = reactive nitrogen species.

Another process that has been linked with COVID-19-caused anxiety is OS, a state of altered redox homeostasis caused by psychological, physiological, or environmental stresses, which involves abnormally high reactive oxygen species (ROS) and reactive nitrogen species (RNS) levels, along with impaired antioxidant capacity and malfunctioning redox control in vivo. ROS and RNS are redox-active molecules with unstable oxygen and nitrogen molecules, possessing ≥1 unpaired electrons. They play important roles under physiological conditions, such as cell signaling and regulating redox homeostasis, but they have also been found to play important roles in SARS-CoV-2 pathogenesis and progression. More specifically, high ROS and RNS levels stem from SARS-CoV-2 interactions with ACE2, which have been found to play an important role in SARS-CoV-2-induced injury through multiple mechanisms: direct myocardial injury upon SARS-CoV-2 interaction with ACE2, as well as ACE2 downregulation and subsequent overstimulation of the renin–angiotensin–aldosterone system (RAAS) [29]. Notably, after binding to ACE2, both ACE2 and SARS-CoV-2 are endocytosed by the host cell, leading to ACE2 downregulation [30]. Lowered ACE2 expression, in turn, yields increase in angiotensin (Ang) II [31], which stimulates angiotensin receptor type 1 (AT1R) expression. AT1R promotes vasoconstriction, inflammation, and OS, particularly via Ang II binding to that receptor, leading to nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and production of superoxide anions that result in mitochondrial damage and further ROS generation [32]. This ROS and RNS overproduction in SARS-CoV-2, owing to massive viral replication, leads to OS and damage to various host cell components, including proteins and mitochondria, yielding endothelial cell damage, disrupted lymphocyte and macrophage function, as well as exacerbated inflammation. Indeed, one study found that SARS-CoV-2-infected patients had higher OS biomarker levels compared to controls [33], demonstrating that OS is involved in tissue damage caused by SARS-CoV-2 infection. Moreover, another study conducted in 2023 found that compared to control, PASC patients were less able to resist oxidative damage, as indicated by lowered plasma total antioxidant capacity, glutathione peroxidase, and zinc levels [34]. Therefore, SARS-CoV-2 is associated not just with increased ROS and RNS production but also with lowered antioxidative defenses. As for PSAC-induced anxiety, it has been linked with elevated pro-inflammatory markers [35], such as in a cohort study showing that elevated CRP was observed in male patients with anxiety disorders [36]; another study found increased TNF-α in patients with anxiety disorders [37]. However, the specific mechanisms linking inflammatory factors to anxiety are still not fully elucidated and require further research.

The hypothalamic–pituitary–adrenal (HPA) axis, connecting the central nervous and endocrine systems, is an important structure in anxiety pathogenesis. It is involved in regulating hormones and the stress response. Upon stress and inflammation onset, the hypothalamus activates the HPA axis, via releasing corticotropin-releasing hormone, which subsequently stimulates adrenocorticotropic hormone (ACTH) release from the anterior pituitary gland; ACTH then acts on the adrenal cortex to induce cortisol synthesis and release. However, HPA regulatory mechanisms are altered under chronic stress, manifesting as sustained, elevated cortisol levels, and lowered sensitivity to cortisol feedback inhibition, resulting in decreased cortisol metabolism and higher plasma levels. Chronic cortisol dysregulation could lead to a variety of health problems, including anxiety [38]. Therefore, stress-induced neuroendocrine changes could serve as an important mechanism in the development of anxiety and other disorders [39]; the pathophysiological mechanisms are summarized in Figure 1.

Figure 1 SARS-CoV-2 S protein binds to ACE2 on host cell surfaces, facilitating viral infection and triggering an excessive inflammatory response, entailing a CS comprising of IL-1β, IL-6, IL-8, IL-18, IFN-γ, TNF-α, G-CSF, MCP-1, and MIP. Additionally, SARS-CoV-2 binding to ACE2 lowers ACE2 expression levels, leading to increased Ang II levels, which subsequently increases AT1R and NADPH oxidase stimulation. The resulting increase in ROS and RNS, along with CS, yields alterations of hypothalamic–pituitary–adrenal (HPA) axis function and IDO activation, leading to increased anxiety, via cortisol dysregulation and inhibition of 5-HT production, owing to IDO conversion of tryptophan (Tryp) to kynurenine. Furthermore, ROS, RNS, and CS increases BH4 degradation, thereby negatively affecting 5-HT, DA, and NE synthesis. CRH = corticotropin-releasing hormone; CORT = cortisol.
Figure 1

SARS-CoV-2 S protein binds to ACE2 on host cell surfaces, facilitating viral infection and triggering an excessive inflammatory response, entailing a CS comprising of IL-1β, IL-6, IL-8, IL-18, IFN-γ, TNF-α, G-CSF, MCP-1, and MIP. Additionally, SARS-CoV-2 binding to ACE2 lowers ACE2 expression levels, leading to increased Ang II levels, which subsequently increases AT1R and NADPH oxidase stimulation. The resulting increase in ROS and RNS, along with CS, yields alterations of hypothalamic–pituitary–adrenal (HPA) axis function and IDO activation, leading to increased anxiety, via cortisol dysregulation and inhibition of 5-HT production, owing to IDO conversion of tryptophan (Tryp) to kynurenine. Furthermore, ROS, RNS, and CS increases BH4 degradation, thereby negatively affecting 5-HT, DA, and NE synthesis. CRH = corticotropin-releasing hormone; CORT = cortisol.

2.3 Neurotransmitter disruption

Neurotransmitters have been documented to be important inflammatory mediators in the brain, in which peripheral inflammation could enter via three major pathways: humoral, neural, and cellular. The humoral pathway entails circulating cytokines entering the brain through “leaky” regions in the blood–brain barrier, followed by active transport into brain parenchyma via cytokine-specific saturable transport proteins, while the neural pathway involves cytokine signals being transmitted in the brain via afferent nerve fiber activation. The cellular pathway consists of activated microglia attracting peripheral inflammatory cells to the meninges and brain parenchyma. Therefore, cytokines and their associated signaling pathways play key roles in influencing anxiety-related neurotransmitter systems, as well as being involved in neurotransmitter synthesis, reuptake, and release; one prominent example is their activation of indoleamine 2,3 dioxygenase (IDO), which converts tryptophan, the primary amino acid for the neurotransmitter 5-hydroxytryptamine (5-HT), to kynurenine, thereby inhibiting 5-HT synthesis in the brain. Other mechanisms in which cytokines influence neurotransmitter activity are by facilitating the destruction of tetrahydrobiopterin (BH4) via increased ROS and RNS production, as it is extremely OS sensitive, resulting in its irreversible degradation to dihydroxyanthopterin. BH4 is an essential cofactor for tryptophan hydroxylase and tyrosine hydroxylase, both of which are rate-limiting enzymes for 5-HT, dopamine (DA), and norepinephrine (NE) synthesis; as a result, BH4 availability significantly impacts 5-HT, DA, and NE availability [40]. Furthermore, inflammatory cytokines increase the transporter protein expression and function for serotonin, DA, and NE, as well as upregulating neurotransmitter/precursor re-uptake and lowering their release. It should be noted that other neurotransmitter systems, such as gamma-aminobutyric acid and acetylcholine, may also play a role in anxiety development, though further investigation is needed to fully clarify the underlying mechanisms [41].

3 Mechanisms through which EECP treats COVID-19 sequelae

With respect to EECP, a number of recent studies, involving different patient populations, reported that it could aid in treating COVID-19 sequelae. One such study examined 51 patients with long COVID-19 and found that EECP treatment improved patient cognitive performances [9]. This was further reinforced by a retrospective analysis of 80 long-COVID-19 patients, of whom 38 had cognitive impairments and 42 did not; there, EECP substantially improved cognitive functioning in the impaired group [42]. Another COVID-19 sequela, which favorably responded to EECP, is fatigue, as observed in a systematic review of 20 studies, involving 5,629 PASC patients, where fatigue symptoms improved after receiving EECP [43]. This result was replicated for a single 38-year-old female with PASC symptoms after acute COVID-19, who had fatigue, headache, body aches, and shortness of breath during the acute infection phase. Even after most symptoms had been resolved, she still had periodic fatigue, headache, and “brain fog” for several months, which, however, improved with EECP treatment [10], thereby demonstrating the effectiveness of EECP in treating fatigue symptoms. Aside from psychological and mental improvements, EECP was also found to significantly improve cardiac function and exercise capacities, such as in one investigation where EECP, compared to baseline, yielded improvements in New York Heart Association functional classifications and left ventricular ejection fraction [11]. This finding was further supported by a study of 50 patients with refractory angina pectoris, where during the EECP treatment period, the average number of daily anginal episodes fell from 2.7 to 0.9, along with >70% of the patients having ≥1 grade reduction in their Canadian Cardiovascular Society classification, plus significant improvements in quality of life and exercise capacity, at 12 months post-EECP [44]. Cardiac functional and exercise capability improvements post-EECP administration were also found in a retrospective analysis of long-COVID-19 patients from seven different outpatient centers, where compared to baseline, they had improved scores on several functional tests after EECP, including the Seattle Angina Questionnaire and 6-min walk test [45]. Therefore, EECP has been noted to alleviate long covid symptoms and improve cardiac function, though it is still not fully clarified as to its mechanism of action in doing so. Nevertheless, some investigations have already been conducted regarding the mechanisms in which EECP exerts its beneficial effects, particularly in regard to hemodynamics and endothelial shear stresses [46]. These beneficial impacts, in turn, may serve as the basis behind EECP being able to alleviate PASC-associated anxiety (Table 2).

Table 2

Mechanisms of EECP on PASC-associated anxiety

Mechanism Explanation
Hemodynamics [33,34,35] EECP improves left ventricular hemodynamics by modulating aortic pressure, thereby increasing diastolic and decreasing systolic pressures, and subsequently increasing coronary blood flow velocity and pressure
EECP reduces myocardial oxygen demand, in turn improving ventricular diastolic and systolic function, as well as increasing myocardial oxygen supply by promoting coronary artery collateral growth
ESS [38,39] EECP induces increases in systemic ESS, which contributes to endothelial functional improvement. Additionally, ESS, through triggering multiple endothelial gene expression and signaling pathways, is able to inhibit abnormal cell proliferation, inflammation, and atherosclerosis; all of these processes aid in alleviating anxiety

EECP = enhanced external counter-pulsation; ESS = Endothelial shear stress.

3.1 EECP positively impacts hemodynamics and endothelial shear stress

EECP has been found to improve left ventricular hemodynamics by modulating aortic pressure, thereby increasing diastolic and decreasing systolic pressures, and subsequently increasing coronary blood flow velocity and pressure [47]. Additionally, EECP reduces myocardial oxygen demand, in turn, improving ventricular diastolic and systolic function [48], as well as increasing myocardial oxygen supply by promoting coronary artery collateral growth [49]. Indeed, a study of 50 patients found significant improvement in cardiac function classification and anxiety scale scores after just 1 course of EECP [50], while another study highlighted significant psychological improvements post-EECP among refractory angina patients [51].

EECP also induces increases in systemic endothelial shear stress (ESS), an important physiological stimulus for maintaining proper vascular endothelial function [52]. ESS has been noted to be a phenomenon associated with regulating the release of vascular endothelial factors, which, along with inhibiting inflammation, contributes to endothelial functional improvements. Therefore, EECP can affect OS and inflammation levels by increasing ESS, as previously documented in the literature [53,54]. Additionally, ESS, through triggering multiple endothelial gene expression and signaling pathways, is able to inhibit abnormal cell proliferation, inflammation, and atherosclerosis [55]. This was observed by Casey et al., where 35 h of EECP treatment increased both overall and local ESS, which subsequently lowered the expression levels of pro-inflammatory TNF-α and MCP-1 by, respectively, 29 and 20% [56]. As a result, EECP promoted anti-inflammatory and anti-atherosclerotic effects by increasing ESS and promoting NO release from endothelial cells; ultimately, all of these processes aid in alleviating anxiety.

3.2 EECP promotes cardiac and psychosomatic rehabilitation processes

EECP could also aid in cardiac rehabilitation, particularly in terms of recovery from SARS-CoV-2-linked myocardial injury and improving patient quality of life. This recovery is likely facilitated by EECP regulation of RAAS, along with stimulating increases in coronary perfusion and lowering endothelial injury. With respect to RAAS, ACE catalyzes Ang I conversion to Ang II, while ACE2 degrades both Ang I and II to, respectively, Ang 1–9 and Ang 1–7 [57]. SARS-CoV-2, though, lowers ACE2 expression in RAAS, resulting in increased ACE-catalyzed conversion of Ang I to Ang II. As Ang II binds to AT1R, this ultimately yields vasoconstriction and increased expression of cellular injury pathways. By contrast, EECP has been found in animal experiments to inhibit ACE expression, thereby counteracting against cardiomyocyte damage associated with the negative impact of SARS-CoV-2 on RAAS. This postulation is further supported by findings confirming that EECP increases diastolic coronary perfusion pressure and blood supply, with a meta-analysis showing a 150% increase in coronary flow velocity and a 28% increase in coronary flow after EECP [58]. Therefore, EECP augments myocardial perfusion via increasing coronary vasodilation, as well as promoting the angiogenesis of neoplastic collateral vessels in the myocardium. In particular, EECP stimulates the release of vasoactive factors, such as α-actinin, von Willebrand, and vascular endothelial growth factors (VEGF); in a randomized controlled study of 240 coronary artery disease (CAD) patients, VEGF1 and VEGFR2 expression levels were significantly higher in EECP versus control group after the 1-year follow-up period, and EECP-treated patients also had significantly improved endothelial function [59]. Additionally, EECP was associated with significant improvements in flow-mediated dilatation (FMD) among patients with left ventricular dysfunction, demonstrating that the treatment could significantly improve endothelial function [60]. Indeed, a controlled clinical study of coronary slow flow patients found significantly increased FMD and lowered CRP in EECP-treated, compared to control, suggesting that EECP is able to improve vascular inflammation and endothelial function [61].

Psychosomatic factors have been closely linked to heart disease occurrence and development, such as mental stress serving as an important trigger for myocardial ischemia in coronary heart disease. In fact, multiple studies have identified higher stress levels being associated with increased CVD risk [62], and strong correlations between abnormal psychosomatic states and adverse cardiac events [63,64,65]. Based on those findings, EECP may be able to provide beneficial effects, to a greater extent than conventional approaches, on psychological health factors.

3.3 Comparison with other treatments

EECP also ranks favorably with other non-invasive treatments for post-COVID anxiety, yielding comparable improvements to them. One of those other treatments is physical exercise, as found in a systematic meta-analysis of 8 randomized clinical trials, where compared to control patients who did not exercise, the exercise group had greater improvements in anxiety levels [66]. Another approach is prescribing anti-depressants, such as oxytocin and lithium salts [67], or herbal remedies, including valerian root [68] and passionflower extract [69], as well as kava-kava rhizome [70]. In particular, Silexan, a proprietary essential oil from Lavandula angustifolia, has been found in a meta-analysis of 13 studies by Kasper et al. to be effective in treating post-COVID-19 patients, particularly with respect to anxiety, owing to the therapeutic profile of Silexan overlapping with the range of psychiatric symptoms in those patients [71]. Additionally, an alternative electrical stimulation approach, transcranial direct current stimulation, has been found to be effective in alleviating fatigue [72] and anxiety [67]. However, it is still unclear precisely how effective these treatments are; future studies will thus be required to determine whether they are more or less effective than EECP and/or whether any complementary effects between these therapies are present.

4 Conclusion

This review summarizes the possible mechanisms underlying PASC-associated anxiety and explores the possible role and underlying mechanisms of EECP in serving as a treatment approach. SARS-CoV-2 results in anxiety via multiple pathways, including brain structural changes, neuroendocrine disruption, and neurotransmitter alterations, all of which inflammation and OS play important roles. EECP is able to counteract against the negative effects of SARS-CoV-2, by lowering inflammation, in turn promoting cardiac functional recovery, and ultimately decreasing patient anxiety. Therefore, EECP could serve as a potential treatment approach, in which it plays a dual role in psychosomatic and cardiac rehabilitation. Further research, though, is still needed to fully determine the benefits and mechanism of action for EECP, as few clinical studies have been conducted on EECP in treating long COVID sequelae. Therefore, future studies, involving multiple centers, double-blinding, and larger patient cohorts, should be carried out to further confirm the effectiveness of EECP for treating PASC-associated anxiety. These studies should also further identify the precise mechanisms/mediators underlying the anti-inflammatory and anti-oxidative effects of EECP, which ultimately counteract against the adverse brain structural changes, neuroendocrine disruption, and neurotransmitter alterations responsible for PASC-associated anxiety. Furthermore, these studies should compare the effectiveness of other treatment strategies, such as Silexan, to that of EECP for anxiety treatment, and formulate the optimal protocol for treating this disease, possibly involving additive or synergistic effects from a combination of those different strategies.

# These authors contributed equally to this work.

Acknowledgment

All authors contributed to the study and agreed to be listed as authors. We thank Alina Yao for her assistance in manuscript preparation and editing. We thank Gangcheng Shen for his assistance with technical support from EECP.

  1. Funding information: This work was supported by the National Natural Science Foundation (Project # 82200315), the Guangdong Basic and Applied Basic Research Foundation (2021A1515111145), Sanming Project of Medicine in Shenzhen (No. SZSM201412012), and Major Scientific Research Project of Shenzhen People’s Hospital (SYWGSJCYJ202301).

  2. Author contributions: Jiecheng Huang and Jingjin Liu are responsible for writing the manuscript; Jiecheng Huang and Yongshun Wang are responsible for collecting literature; Jiecheng Huang is responsible for creating images; Jingjin Liu is responsible for guiding the content of the article; Yuxuan Fan is responsible for editing the manuscript before final submission.

  3. Conflict of interest: The authors declare that they have no conflicts of interest.

  4. Data availability statement: The data could be obtained by contacting the corresponding author.

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Received: 2024-05-17
Revised: 2024-09-19
Accepted: 2024-09-27
Published Online: 2025-01-09

© 2025 the author(s), published by De Gruyter

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

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  121. Development of a nomogram for predicting cancer-specific survival in patients with renal pelvic cancer following surgery
  122. Inhibition of ATG7 promotes orthodontic tooth movement by regulating the RANKL/OPG ratio under compression force
  123. A machine learning-based prognostic model integrating mRNA stemness index, hypoxia, and glycolysis‑related biomarkers for colorectal cancer
  124. Glutathione attenuates sepsis-associated encephalopathy via dual modulation of NF-κB and PKA/CREB pathways
  125. FAHD1 prevents neuronal ferroptosis by modulating R-loop and the cGAS–STING pathway
  126. Association of placenta weight and morphology with term low birth weight: A case–control study
  127. Investigation of the pathogenic variants induced Sjogren’s syndrome in Turkish population
  128. Nucleotide metabolic abnormalities in post-COVID-19 condition and type 2 diabetes mellitus patients and their association with endocrine dysfunction
  129. TGF-β–Smad2/3 signaling in high-altitude pulmonary hypertension in rats: Role and mechanisms via macrophage M2 polarization
  130. Ultrasound-guided unilateral versus bilateral erector spinae plane block for postoperative analgesia of patients undergoing laparoscopic cholecystectomy
  131. Profiling gut microbiome dynamics in subacute thyroiditis: Implications for pathogenesis, diagnosis, and treatment
  132. Delta neutrophil index, CRP/albumin ratio, procalcitonin, immature granulocytes, and HALP score in acute appendicitis: Best performing biomarker?
  133. Anticancer activity mechanism of novelly synthesized and characterized benzofuran ring-linked 3-nitrophenyl chalcone derivative on colon cancer cells
  134. H2valdien3 arrests the cell cycle and induces apoptosis of gastric cancer
  135. Prognostic relevance of PRSS2 and its immune correlates in papillary thyroid carcinoma
  136. Association of SGLT2 inhibition with psychiatric disorders: A Mendelian randomization study
  137. Motivational interviewing for alcohol use reduction in Thai patients
  138. Luteolin alleviates oxygen-glucose deprivation/reoxygenation-induced neuron injury by regulating NLRP3/IL-1β signaling
  139. Polyphyllin II inhibits thyroid cancer cell growth by simultaneously inhibiting glycolysis and oxidative phosphorylation
  140. Relationship between the expression of copper death promoting factor SLC31A1 in papillary thyroid carcinoma and clinicopathological indicators and prognosis
  141. CSF2 polarized neutrophils and invaded renal cancer cells in vitro influence
  142. Proton pump inhibitors-induced thrombocytopenia: A systematic literature analysis of case reports
  143. The current status and influence factors of research ability among community nurses: A sequential qualitative–quantitative study
  144. OKAIN: A comprehensive oncology knowledge base for the interpretation of clinically actionable alterations
  145. The relationship between serum CA50, CA242, and SAA levels and clinical pathological characteristics and prognosis in patients with pancreatic cancer
  146. Identification and external validation of a prognostic signature based on hypoxia–glycolysis-related genes for kidney renal clear cell carcinoma
  147. Engineered RBC-derived nanovesicles functionalized with tumor-targeting ligands: A comparative study on breast cancer targeting efficiency and biocompatibility
  148. Relationship of resting echocardiography combined with serum micronutrients to the severity of low-gradient severe aortic stenosis
  149. Effect of vibration on pain during subcutaneous heparin injection: A randomized, single-blind, placebo-controlled trial
  150. The diagnostic performance of machine learning-based FFRCT for coronary artery disease: A meta-analysis
  151. Comparing biofeedback device vs diaphragmatic breathing for bloating relief: A randomized controlled trial
  152. Serum uric acid to albumin ratio and C-reactive protein as predictive biomarkers for chronic total occlusion and coronary collateral circulation quality
  153. Multiple organ scoring systems for predicting in-hospital mortality of sepsis patients in the intensive care unit
  154. Single-cell RNA sequencing data analysis of the inner ear in gentamicin-treated mice via intraperitoneal injection
  155. Suppression of cathepsin B attenuates myocardial injury via limiting cardiomyocyte apoptosis
  156. Review Articles
  157. The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
  158. Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
  159. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  160. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  161. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  162. The safety and efficacy of BCG combined with mitomycin C compared with BCG monotherapy in patients with non-muscle-invasive bladder cancer: A systematic review and meta-analysis
  163. The application of augmented reality in robotic general surgery: A mini-review
  164. The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
  165. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  166. Plant polyphenols, terpenes, and terpenoids in oral health
  167. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  168. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  169. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  170. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  171. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  172. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  173. Giant borderline ovarian tumours – review of the literature
  174. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
  175. Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
  176. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  177. Supplement strategies for infertility in overweight women: Evidence and legal insights
  178. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  179. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  180. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  181. Strategies for hyperkalemia management in dialysis patients: A systematic review
  182. C-reactive protein-to-albumin ratio in peripheral artery disease
  183. Case Reports
  184. Delayed graft function after renal transplantation
  185. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
  186. Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
  187. Giant right atrial hemangioma presenting with ascites: A case report
  188. Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
  189. EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
  190. Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
  191. Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
  192. Rapid Communication
  193. Biological properties of valve materials using RGD and EC
  194. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  195. Letter to the Editor
  196. Role of enhanced external counterpulsation in long COVID
  197. Expression of Concern
  198. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  199. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  200. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  201. Corrigendum
  202. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  203. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  204. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  205. Retraction
  206. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  207. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  208. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  209. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  210. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  211. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  212. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  213. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
  214. Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
  215. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
  216. Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
  217. Special Issue The evolving saga of RNAs from bench to bedside - Part III
  218. Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
  219. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
  220. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
  221. Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
  222. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
  223. Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
  224. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  225. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  226. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  227. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  228. A review of brain research on T2DM-related cognitive dysfunction
  229. Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
  230. Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
  231. CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
https://doi.org/10.1515/med-2024-1067
Schlagwörter für diesen Artikel
severe acute respiratory syndrome coronavirus 2; post-acute sequelae of coronavirus disease 2019; enhanced external counter-pulsation; anxiety; cardiovascular disease
Creative Commons
BY 4.0

Artikel in diesem Heft

  1. Research Articles
  2. Network pharmacological analysis and in vitro testing of the rutin effects on triple-negative breast cancer
  3. Impact of diabetes on long-term survival in elderly liver cancer patients: A retrospective study
  4. Knockdown of CCNB1 alleviates high glucose-triggered trophoblast dysfunction during gestational diabetes via Wnt/β-catenin signaling pathway
  5. Risk factors for severe adverse drug reactions in hospitalized patients
  6. Analysis of the effect of ALA-PDT on macrophages in footpad model of mice infected with Fonsecaea monophora based on single-cell sequencing
  7. Development and validation of headspace gas chromatography with a flame ionization detector method for the determination of ethanol in the vitreous humor
  8. CMSP exerts anti-tumor effects on small cell lung cancer cells by inducing mitochondrial dysfunction and ferroptosis
  9. Predictive value of plasma sB7-H3 and YKL-40 in pediatric refractory Mycoplasma pneumoniae pneumonia
  10. Antiangiogenic potential of Elaeagnus umbellata extracts and molecular docking study by targeting VEGFR-2 pathway
  11. Comparison of the effectiveness of nurse-led preoperative counseling and postoperative follow-up care vs standard care for patients with gastric cancer
  12. Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis
  13. Adhered macrophages as an additional marker of cardiomyocyte injury in biopsies of patients with dilated cardiomyopathy
  14. Association between statin administration and outcome in patients with sepsis: A retrospective study
  15. Exploration of the association between estimated glucose disposal rate and osteoarthritis in middle-aged and older adults: An analysis of NHANES data from 2011 to 2018
  16. A comparative analysis of the binary and multiclass classified chest X-ray images of pneumonia and COVID-19 with ML and DL models
  17. Lysophosphatidic acid 2 alleviates deep vein thrombosis via protective endothelial barrier function
  18. Transcription factor A, mitochondrial promotes lymph node metastasis and lymphangiogenesis in epithelial ovarian carcinoma
  19. Serum PM20D1 levels are associated with nutritional status and inflammatory factors in gastric cancer patients undergoing early enteral nutrition
  20. Hydromorphone reduced the incidence of emergence agitation after adenotonsillectomy in children with obstructive sleep apnea: A randomized, double-blind study
  21. Vitamin D replacement therapy may regulate sleep habits in patients with restless leg syndrome
  22. The first-line antihypertensive nitrendipine potentiated the therapeutic effect of oxaliplatin by downregulating CACNA1D in colorectal cancer
  23. Health literacy and health-related quality of life: The mediating role of irrational happiness
  24. Modulatory effects of Lycium barbarum polysaccharide on bone cell dynamics in osteoporosis
  25. Mechanism research on inhibition of gastric cancer in vitro by the extract of Pinellia ternata based on network pharmacology and cellular metabolomics
  26. Examination of the causal role of immune cells in non-alcoholic fatty liver disease by a bidirectional Mendelian randomization study
  27. Clinical analysis of ten cases of HIV infection combined with acute leukemia
  28. Investigating the cardioprotective potential of quercetin against tacrolimus-induced cardiotoxicity in Wistar rats: A mechanistic insights
  29. Clinical observation of probiotics combined with mesalazine and Yiyi Baitouweng Decoction retention enema in treating mild-to-moderate ulcerative colitis
  30. Diagnostic value of ratio of blood inflammation to coagulation markers in periprosthetic joint infection
  31. Sex-specific associations of sex hormone binding globulin and risk of bladder cancer
  32. Core muscle strength and stability-oriented breathing training reduces inter-recti distance in postpartum women
  33. The ERAS nursing care strategy for patients undergoing transsphenoidal endoscopic pituitary tumor resection: A randomized blinded controlled trial
  34. The serum IL-17A levels in patients with traumatic bowel rupture post-surgery and its predictive value for patient prognosis
  35. Impact of Kolb’s experiential learning theory-based nursing on caregiver burden and psychological state of caregivers of dementia patients
  36. Analysis of serum NLR combined with intraoperative margin condition to predict the prognosis of cervical HSIL patients undergoing LEEP surgery
  37. Commiphora gileadensis ameliorate infertility and erectile dysfunction in diabetic male mice
  38. The correlation between epithelial–mesenchymal transition classification and MMP2 expression of circulating tumor cells and prognosis of advanced or metastatic nasopharyngeal carcinoma
  39. Tetrahydropalmatine improves mitochondrial function in vascular smooth muscle cells of atherosclerosis in vitro by inhibiting Ras homolog gene family A/Rho-associated protein kinase-1 signaling pathway
  40. A cross-sectional study: Relationship between serum oxidative stress levels and arteriovenous fistula maturation in maintenance dialysis patients
  41. A comparative analysis of the impact of repeated administration of flavan 3-ol on brown, subcutaneous, and visceral adipose tissue
  42. Identifying early screening factors for depression in middle-aged and older adults: A cohort study
  43. Perform tumor-specific survival analysis for Merkel cell carcinoma patients undergoing surgical resection based on the SEER database by constructing a nomogram chart
  44. Unveiling the role of CXCL10 in pancreatic cancer progression: A novel prognostic indicator
  45. High-dose preoperative intraperitoneal erythropoietin and intravenous methylprednisolone in acute traumatic spinal cord injuries following decompression surgeries
  46. RAB39B: A novel biomarker for acute myeloid leukemia identified via multi-omics and functional validation
  47. Impact of peripheral conditioning on reperfusion injury following primary percutaneous coronary intervention in diabetic and non-diabetic STEMI patients
  48. Clinical efficacy of azacitidine in the treatment of middle- and high-risk myelodysplastic syndrome in middle-aged and elderly patients: A retrospective study
  49. The effect of ambulatory blood pressure load on mitral regurgitation in continuous ambulatory peritoneal dialysis patients
  50. Expression and clinical significance of ITGA3 in breast cancer
  51. Single-nucleus RNA sequencing reveals ARHGAP28 expression of podocytes as a biomarker in human diabetic nephropathy
  52. rSIG combined with NLR in the prognostic assessment of patients with multiple injuries
  53. Toxic metals and metalloids in collagen supplements of fish and jellyfish origin: Risk assessment for daily intake
  54. Exploring causal relationship between 41 inflammatory cytokines and marginal zone lymphoma: A bidirectional Mendelian randomization study
  55. Gender beliefs and legitimization of dating violence in adolescents
  56. Effect of serum IL-6, CRP, and MMP-9 levels on the efficacy of modified preperitoneal Kugel repair in patients with inguinal hernia
  57. Effect of smoking and smoking cessation on hematological parameters in polycythemic patients
  58. Pathogen surveillance and risk factors for pulmonary infection in patients with lung cancer: A retrospective single-center study
  59. Necroptosis of hippocampal neurons in paclitaxel chemotherapy-induced cognitive impairment mediates microglial activation via TLR4/MyD88 signaling pathway
  60. Celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the NLRP3 pathway
  61. Cord-lamina angle and foraminal diameter as key predictors of C5 palsy after anterior cervical decompression and fusion surgery
  62. GATA1: A key biomarker for predicting the prognosis of patients with diffuse large B-cell lymphoma
  63. Influencing factors of false lumen thrombosis in type B aortic dissection: A single-center retrospective study
  64. MZB1 regulates the immune microenvironment and inhibits ovarian cancer cell migration
  65. Integrating experimental and network pharmacology to explore the pharmacological mechanisms of Dioscin against glioblastoma
  66. Trends in research on preterm birth in twin pregnancy based on bibliometrics
  67. Four-week IgE/baseline IgE ratio combined with tryptase predicts clinical outcome in omalizumab-treated children with moderate-to-severe asthma
  68. Single-cell transcriptomic analysis identifies a stress response Schwann cell subtype
  69. Acute pancreatitis risk in the diagnosis and management of inflammatory bowel disease: A critical focus
  70. Effect of subclinical esketamine on NLRP3 and cognitive dysfunction in elderly ischemic stroke patients
  71. Interleukin-37 mediates the anti-oral tumor activity in oral cancer through STAT3
  72. CA199 and CEA expression levels, and minimally invasive postoperative prognosis analysis in esophageal squamous carcinoma patients
  73. Efficacy of a novel drainage catheter in the treatment of CSF leak after posterior spine surgery: A retrospective cohort study
  74. Comprehensive biomedicine assessment of Apteranthes tuberculata extracts: Phytochemical analysis and multifaceted pharmacological evaluation in animal models
  75. Relation of time in range to severity of coronary artery disease in patients with type 2 diabetes: A cross-sectional study
  76. Dopamine attenuates ethanol-induced neuronal apoptosis by stimulating electrical activity in the developing rat retina
  77. Correlation between albumin levels during the third trimester and the risk of postpartum levator ani muscle rupture
  78. Factors associated with maternal attention and distraction during breastfeeding and childcare: A cross-sectional study in the west of Iran
  79. Mechanisms of hesperetin in treating metabolic dysfunction-associated steatosis liver disease via network pharmacology and in vitro experiments
  80. The law on oncological oblivion in the Italian and European context: How to best uphold the cancer patients’ rights to privacy and self-determination?
  81. The prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and prognostic nutritional index for survival in patients with colorectal cancer
  82. Factors affecting the measurements of peripheral oxygen saturation values in healthy young adults
  83. Comparison and correlations between findings of hysteroscopy and vaginal color Doppler ultrasonography for detection of uterine abnormalities in patients with recurrent implantation failure
  84. The effects of different types of RAGT on balance function in stroke patients with low levels of independent walking in a convalescent rehabilitation hospital
  85. Causal relationship between asthma and ankylosing spondylitis: A bidirectional two-sample univariable and multivariable Mendelian randomization study
  86. Correlations of health literacy with individuals’ understanding and use of medications in Southern Taiwan
  87. Correlation of serum calprotectin with outcome of acute cerebral infarction
  88. Comparison of computed tomography and guided bronchoscopy in the diagnosis of pulmonary nodules: A systematic review and meta-analysis
  89. Curdione protects vascular endothelial cells and atherosclerosis via the regulation of DNMT1-mediated ERBB4 promoter methylation
  90. The identification of novel missense variant in ChAT gene in a patient with gestational diabetes denotes plausible genetic association
  91. Molecular genotyping of multi-system rare blood types in foreign blood donors based on DNA sequencing and its clinical significance
  92. Exploring the role of succinyl carnitine in the association between CD39⁺ CD4⁺ T cell and ulcerative colitis: A Mendelian randomization study
  93. Dexmedetomidine suppresses microglial activation in postoperative cognitive dysfunction via the mmu-miRNA-125/TRAF6 signaling axis
  94. Analysis of serum metabolomics in patients with different types of chronic heart failure
  95. Diagnostic value of hematological parameters in the early diagnosis of acute cholecystitis
  96. Pachymaran alleviates fat accumulation, hepatocyte degeneration, and injury in mice with nonalcoholic fatty liver disease
  97. Decrease in CD4 and CD8 lymphocytes are predictors of severe clinical picture and unfavorable outcome of the disease in patients with COVID-19
  98. METTL3 blocked the progression of diabetic retinopathy through m6A-modified SOX2
  99. The predictive significance of anti-RO-52 antibody in patients with interstitial pneumonia after treatment of malignant tumors
  100. Exploring cerebrospinal fluid metabolites, cognitive function, and brain atrophy: Insights from Mendelian randomization
  101. Development and validation of potential molecular subtypes and signatures of ocular sarcoidosis based on autophagy-related gene analysis
  102. Widespread venous thrombosis: Unveiling a complex case of Behçet’s disease with a literature perspective
  103. Uterine fibroid embolization: An analysis of clinical outcomes and impact on patients’ quality of life
  104. Discovery of lipid metabolism-related diagnostic biomarkers and construction of diagnostic model in steroid-induced osteonecrosis of femoral head
  105. Serum-derived exomiR-188-3p is a promising novel biomarker for early-stage ovarian cancer
  106. Enhancing chronic back pain management: A comparative study of ultrasound–MRI fusion guidance for paravertebral nerve block
  107. Peptide CCAT1-70aa promotes hepatocellular carcinoma proliferation and invasion via the MAPK/ERK pathway
  108. Electroacupuncture-induced reduction of myocardial ischemia–reperfusion injury via FTO-dependent m6A methylation modulation
  109. Hemorrhoids and cardiovascular disease: A bidirectional Mendelian randomization study
  110. Cell-free adipose extract inhibits hypertrophic scar formation through collagen remodeling and antiangiogenesis
  111. HALP score in Demodex blepharitis: A case–control study
  112. Assessment of SOX2 performance as a marker for circulating cancer stem-like cells (CCSCs) identification in advanced breast cancer patients using CytoTrack system
  113. Risk and prognosis for brain metastasis in primary metastatic cervical cancer patients: A population-based study
  114. Comparison of the two intestinal anastomosis methods in pediatric patients
  115. Factors influencing hematological toxicity and adverse effects of perioperative hyperthermic intraperitoneal vs intraperitoneal chemotherapy in gastrointestinal cancer
  116. Endotoxin tolerance inhibits NLRP3 inflammasome activation in macrophages of septic mice by restoring autophagic flux through TRIM26
  117. Lateral transperitoneal laparoscopic adrenalectomy: A single-centre experience of 21 procedures
  118. Petunidin attenuates lipopolysaccharide-induced retinal microglia inflammatory response in diabetic retinopathy by targeting OGT/NF-κB/LCN2 axis
  119. Procalcitonin and C-reactive protein as biomarkers for diagnosing and assessing the severity of acute cholecystitis
  120. Factors determining the number of sessions in successful extracorporeal shock wave lithotripsy patients
  121. Development of a nomogram for predicting cancer-specific survival in patients with renal pelvic cancer following surgery
  122. Inhibition of ATG7 promotes orthodontic tooth movement by regulating the RANKL/OPG ratio under compression force
  123. A machine learning-based prognostic model integrating mRNA stemness index, hypoxia, and glycolysis‑related biomarkers for colorectal cancer
  124. Glutathione attenuates sepsis-associated encephalopathy via dual modulation of NF-κB and PKA/CREB pathways
  125. FAHD1 prevents neuronal ferroptosis by modulating R-loop and the cGAS–STING pathway
  126. Association of placenta weight and morphology with term low birth weight: A case–control study
  127. Investigation of the pathogenic variants induced Sjogren’s syndrome in Turkish population
  128. Nucleotide metabolic abnormalities in post-COVID-19 condition and type 2 diabetes mellitus patients and their association with endocrine dysfunction
  129. TGF-β–Smad2/3 signaling in high-altitude pulmonary hypertension in rats: Role and mechanisms via macrophage M2 polarization
  130. Ultrasound-guided unilateral versus bilateral erector spinae plane block for postoperative analgesia of patients undergoing laparoscopic cholecystectomy
  131. Profiling gut microbiome dynamics in subacute thyroiditis: Implications for pathogenesis, diagnosis, and treatment
  132. Delta neutrophil index, CRP/albumin ratio, procalcitonin, immature granulocytes, and HALP score in acute appendicitis: Best performing biomarker?
  133. Anticancer activity mechanism of novelly synthesized and characterized benzofuran ring-linked 3-nitrophenyl chalcone derivative on colon cancer cells
  134. H2valdien3 arrests the cell cycle and induces apoptosis of gastric cancer
  135. Prognostic relevance of PRSS2 and its immune correlates in papillary thyroid carcinoma
  136. Association of SGLT2 inhibition with psychiatric disorders: A Mendelian randomization study
  137. Motivational interviewing for alcohol use reduction in Thai patients
  138. Luteolin alleviates oxygen-glucose deprivation/reoxygenation-induced neuron injury by regulating NLRP3/IL-1β signaling
  139. Polyphyllin II inhibits thyroid cancer cell growth by simultaneously inhibiting glycolysis and oxidative phosphorylation
  140. Relationship between the expression of copper death promoting factor SLC31A1 in papillary thyroid carcinoma and clinicopathological indicators and prognosis
  141. CSF2 polarized neutrophils and invaded renal cancer cells in vitro influence
  142. Proton pump inhibitors-induced thrombocytopenia: A systematic literature analysis of case reports
  143. The current status and influence factors of research ability among community nurses: A sequential qualitative–quantitative study
  144. OKAIN: A comprehensive oncology knowledge base for the interpretation of clinically actionable alterations
  145. The relationship between serum CA50, CA242, and SAA levels and clinical pathological characteristics and prognosis in patients with pancreatic cancer
  146. Identification and external validation of a prognostic signature based on hypoxia–glycolysis-related genes for kidney renal clear cell carcinoma
  147. Engineered RBC-derived nanovesicles functionalized with tumor-targeting ligands: A comparative study on breast cancer targeting efficiency and biocompatibility
  148. Relationship of resting echocardiography combined with serum micronutrients to the severity of low-gradient severe aortic stenosis
  149. Effect of vibration on pain during subcutaneous heparin injection: A randomized, single-blind, placebo-controlled trial
  150. The diagnostic performance of machine learning-based FFRCT for coronary artery disease: A meta-analysis
  151. Comparing biofeedback device vs diaphragmatic breathing for bloating relief: A randomized controlled trial
  152. Serum uric acid to albumin ratio and C-reactive protein as predictive biomarkers for chronic total occlusion and coronary collateral circulation quality
  153. Multiple organ scoring systems for predicting in-hospital mortality of sepsis patients in the intensive care unit
  154. Single-cell RNA sequencing data analysis of the inner ear in gentamicin-treated mice via intraperitoneal injection
  155. Suppression of cathepsin B attenuates myocardial injury via limiting cardiomyocyte apoptosis
  156. Review Articles
  157. The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
  158. Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
  159. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  160. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  161. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  162. The safety and efficacy of BCG combined with mitomycin C compared with BCG monotherapy in patients with non-muscle-invasive bladder cancer: A systematic review and meta-analysis
  163. The application of augmented reality in robotic general surgery: A mini-review
  164. The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
  165. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  166. Plant polyphenols, terpenes, and terpenoids in oral health
  167. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  168. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  169. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  170. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  171. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  172. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  173. Giant borderline ovarian tumours – review of the literature
  174. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
  175. Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
  176. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  177. Supplement strategies for infertility in overweight women: Evidence and legal insights
  178. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  179. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  180. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  181. Strategies for hyperkalemia management in dialysis patients: A systematic review
  182. C-reactive protein-to-albumin ratio in peripheral artery disease
  183. Case Reports
  184. Delayed graft function after renal transplantation
  185. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
  186. Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
  187. Giant right atrial hemangioma presenting with ascites: A case report
  188. Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
  189. EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
  190. Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
  191. Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
  192. Rapid Communication
  193. Biological properties of valve materials using RGD and EC
  194. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  195. Letter to the Editor
  196. Role of enhanced external counterpulsation in long COVID
  197. Expression of Concern
  198. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  199. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  200. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  201. Corrigendum
  202. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  203. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  204. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  205. Retraction
  206. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  207. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  208. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  209. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  210. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  211. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  212. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  213. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
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Heruntergeladen am 27.11.2025 von https://www.degruyterbrill.com/document/doi/10.1515/med-2024-1067/html
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