Home Application of the integrated airway humidification device enhances the humidification effect of the rabbit tracheotomy model
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Application of the integrated airway humidification device enhances the humidification effect of the rabbit tracheotomy model

  • Honglan Sheng , Jie Ni EMAIL logo , Feng Zhao , Mi Tian , Yuhang Zhao , Longmei Dai , Ting Li , Yun Xue , Zongze Song and Qiong Yu EMAIL logo
Published/Copyright: February 8, 2024
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Open Life Sciences
From the journal Open Life Sciences Volume 19 Issue 1

Abstract

Long-term mechanical ventilation after tracheotomy is a common treatment in intensive care unit patients. This study investigated the differences among the effects of different wetting states on the airway, lung, and serum inflammatory factors. New Zealand rabbits (n = 36) were selected to construct tracheotomy models and then divided into four groups: Model, Mask, YTH, and Sham groups. Lung tissue dry/wet ratio was used to evaluate the humidification effect; cytokines, including tumor necrosis factor-α, interleukin (IL)-6, IL-8, and IL-10, were used to evaluate the inflammatory response; hematoxylin and eosin staining was used to evaluate the histopathology. Post hoc analysis based on the Dunnett t-test was applied. A self-developed integrated wetting device could increase the utilization of wetting solution, enhance the effect of wetting to protect tissue integrity, and suppress airway inflammation, reducing the expression of pro-inflammatory factors while promoting the expression of anti-inflammatory factor IL-10 to inhibit the inflammatory response, compared to other methods. The integrated humidification device provided a new method for clinical nursing practice, improving clinical efficiency and reducing nursing workload. Further clinical trials are required to test its effectiveness and safety in the clinic.

Graphical abstract

Keywords: tracheotomy; airway humidification; animal model; inflammatory response; histopathology

1 Introduction

Tracheotomy is a procedure during which a tracheal tube is placed in the trachea through an incision in the anterior tracheal wall to construct an artificial airway. Long-term mechanical ventilation based on tracheotomy has been an important treatment for critically ill patients. Also, early tracheotomy has been associated with reduced mortality and pneumonia rates in patients with long-term follow-up [1,2]. However, direct airway opening in medium- and long-term tracheotomy patients leads to airway water loss, resulting in airway dryness and sputum stickiness, and may even lead to sputum blockage, causing hypoxia and asphyxia. The incidence of tracheal tube occlusion after tracheotomy was reported to be 14–43% [3]. Moreover, tracheotomy patients can lose more than 800 ml of airway water daily. In addition, the inflammatory condition may appear in the airway post-tracheotomy [4]. Besides, prolonged tracheotomy increases the possibility of complications, including pneumothorax, bleeding, infection, intubation obstruction, and fistula formation [5,6]. The intact upper respiratory tract protects the inhaled air by adsorbing and removing foreign bodies and pathogens. Meanwhile, the airway epithelium warms and humidifies the inhaled air under physiological conditions. On the contrary, tracheotomy deprives patients of the warming and humidifying effect of the airway on inhaled oxygen. Therefore, direct inhalation of cold and dry oxygen in patients with assisted breathing may damage the airway, resulting in decreased body temperature, dyspnea, and airway obstruction [7,8]. In addition, ventilator-associated pneumonia is the leading cause of death in patients equipped with invasive mechanical ventilation, accounting for 25% of infections in intensive care unit wards [9,10].

Airway humidification can reduce mortality and pulmonary infections in patients with assisted ventilation [11]. There are several types of humidification devices in clinical use, including oxygen atomizers (OA), heat and moisture exchangers (HME), and heated humidifiers (HH) [12]. Fogging devices can be divided into Jet and ultrasonic nebulizers according to their principle. Jet nebulizers are based on the venturi principle, while ultrasonic nebulizers utilize the inverse piezoelectric effect to convert alternating current into high-frequency acoustic energy to atomize liquid water [13,14]. A clinical study compared the effects of OA, HH, and HME in patients with severe traumatic brain injury and suggested that HH and HME are superior to OA in reducing the incidence of infection; however, OA relieved the care-related burden [12]. In addition, other studies reported the difference in effectiveness between HH and HME wetting. A meta-analysis of HH on wetting in adults and children reported no significant difference between the effect of HH and HME on the incidence of airway obstruction, pneumonia, and death. However, some evidence indicated that hydrophobic HME prevents the incidence of pneumonia better than the other [10,15].

During mechanical ventilation, if bypassing the upper airway, manual humidification is necessary in case the cold and dry oxygen causes secondary damage by directly injuring the airway epithelium [16,17]. Airway humidification is also mandatory, especially for patients with nasopharyngeal and pulmonary diseases or postoperative and neurological disorders. Depending on the degree of airway humidification, patients can present with symptoms from inadequate humidification (such as hardly absorbable mucous sputum and crackling breath sounds) to appropriate humidification (such as moderate volume of thin sputum that is easily absorbed and clear airway) to excessive humidification (such as large volume of foamy sputum and dyspnea) [12]. However, existing studies rarely addressed the effect of the degree and duration of humidification on airway and lung inflammation.

This study investigated the degree of wetting by different devices for inhaled oxygen wetting in a well-studied rabbit tracheotomy model [18] to establish the differences among the effects of different wetting states on the airway and lung and serum inflammatory factors.

2 Materials and methods

2.1 Animal models

Thirty-six New Zealand rabbits weighing 2.5–3.0 kg were purchased from the Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences [license number: SCXK (Shanghai) 2022-0027] and housed in the animal house of Shanghai Academy of Agricultural Sciences at 25 ± 2°C, 50 ± 15% humidity, 12 h light–dark cycle, with free access to food and water. All animal studies were done in compliance with the regulations and guidelines of Shanghai Medical College of Fudan University institutional animal care and conducted according to the AAALAC and the IACUC guidelines (ethics number: 20200615S).

These 36 rabbits were randomly divided into four groups (n = 9/group): sham operation group (Sham), model group (Model), mask group (Mask), and integrated device group (YTH). Each group was then randomly divided into three subgroups depending on the time (6, 12, and 48 h; n = 9/group). Rabbits in the Model, Mask, and YTH subgroups received tracheotomy and airway humidification, while rabbits in the Sham group underwent sham surgical operation without airway wetting. After reaching the wetting time, each subgroup’s blood was collected via a vein at the ear margin. Then, euthanasia and rapid tracheal and lung tissue extraction were performed. The blood was undisturbed, kept at room temperature for 2 h, and then centrifuged at 3500g at 4°C for 20 min. The serum was frozen at −80°C. After removal, the trachea was quickly fixed in 4% paraformaldehyde to prepare hematoxylin and eosin (HE)-stained pathological sections. The wet and dry weight of the lung tissues were measured respectively, and ultimately, the wet-to-dry ratio was calculated.

  1. Ethical approval: The research related to animal use has been complied with all the relevant national regulations and institutional policies for the care and use of animals, and has been approved by the Ethics Committee of Shanghai Medical College of Fudan University (ethics number: 20200615S).

2.2 Tracheotomy and humidification

The rabbit was fasted for 12 h before surgery and then anesthetized using dexmedetomidine at a dose of 60 µg/kg (Yangtze River Pharmaceutical Group Co., Ltd., lot no. 22011731). After the pain reaction and corneal reflexes disappeared, the rabbit was fixed in a supine position. The skin was prepared, a cavity towel was laid, and the area was disinfected three times. A longitudinal incision of approximately 1 cm was then made along the anterior midline and 2 cm above the superior sternal recess, and the trachea was exposed after bluntly separating the muscular layer by layer. An inverted T-shaped incision was then performed under the thyroid cartilage, where a homemade rabbit tracheal cannula was inserted. The cannula was fixed with surgical thread, and the muscle layers and skin were successively sewn. Next, erythromycin ointment was applied to the wound to prevent the infection. In the sham-operated group, the skin was incised, the trachea was exposed after anesthesia, and the muscle layers and skin were sutured afterward. Postoperatively, wound bleeding and breathing were closely observed to avoid asphyxia due to body position.

Oxygen-driven continuous airway wetting (0.45% NaCl solution, oxygen flow rate 4 L/min) was selectively performed in different groups after the operation. Model and Sham groups received no airway wetting, while oxygen mask wetting was used in the Mask group and oxygen-supplied wetting with an integrated device in the YTH group. Sputum was aspirated from all rabbits in the Model, Mask, and YTH groups after each humidification session. Sputum consistency criteria were as follows [19]: Degree I (thin sputum): sputum was abundant and thin, coughs were frequent, wheeze rale could be heard in the airway, and no sputum was detected on the inner wall of the aspiration tube after aspiration; Degree II (moderate mucous sputum): the appearance of sputum was thicker than Degree I, no dry rales were heard when pulmonary auscultation, and a small amount of sputum was detected on the inner wall of the aspiration tube after aspiration which could be easily flushed out by water; Degree III (severe mucous sputum): the appearance of sputum was sticky, yellow, and accompanied by blood crust, and it was not easy to be aspirated or coughed out.

2.3 Pulmonary dryness and humidity

The pulmonary wet-to-dry ratio was one of the indicators used to evaluate the effect of wetting quantitatively. Fresh lung tissue was removed quickly from rabbits after euthanasia. After using filter paper to aspirate surface water, direct weight was defined as the wet lung weight. The lung tissue was subsequently baked in an oven at 80°C for 1 week to dry the tissue moisture, and then the dry lung weight was weighed. The lung dry-to-wet ratio was calculated using the following formula: lung dry weight/lung wet weight × 100%.

2.4 Enzyme-linked immunosorbent assay (ELISA)

Tissue specimens were taken from both ends and the central part of the main trachea (from 2 cm below the tracheal intubation and two portions of the hilar area). Five specimens were placed in a 10% formaldehyde solution for pathological examination. After 48 h, 2 ml of venous blood was drawn from the marginal ear vein and centrifuged at 3000 rpm for 20 min. The supernatant was divided into EP tubes and stored at −80°C in a refrigerator. Kits of tumor necrosis factor-α (TNF-α) (Cloud-Clone SEA133Rb, L210507091), interleukin (IL)-6 (Cloud-Clone SEA079Rb, L210506259), IL-8 (Cloud-Clone SEA080Rb, L210507080), and IL-10 (Cloud-Clone SEA056Rb, L210507084) were used to detect inflammatory factors in rabbit serum and evaluate the inflammation index. The standard curves were performed according to the instructions of the kits. Ultimately, the absolute levels of TNF-α, IL-6, IL-8, and IL-10 in each group were calculated according to the absorbance of the samples.

2.5 Histopathology

Tracheal tissues (3 cm in diameter) were selected from New Zealand rabbits, 1 cm below the tracheal ligation line. The tissues were then fixed with 4% paraformaldehyde for 48 h, paraffin-embedded to prepare wax blocks, sectioned, dewaxed, stained, dehydrated, and sealed to construct stained tissue slices. The slices were observed and photographed under a microscope (Nikon). The tracheal histopathology scoring criteria [20] are shown in Table 1. Tracheal histopathology score = 3 A + B + C + D.

Table 1

Tracheal histopathology scoring criteria

Score Pseudostratified ciliated columnar epithelium (PCCE) Microglandular hyperplasia (MH) Intracavitary secretion (IS) Inflammatory cell infiltration (ICI)
0 Orderly, neat, without missing None Little Not infiltrated
1 Slightly disordered, cilia vary in length A little Increased A little infiltration in the lumen or submucosa
2 Significantly disordered, intermittent Much Much with a formed element Multiple infiltrations of inflammatory cells
3 Necrosis and detachment, submucosal tissue exposed Much with secreta Significantly increased

2.6 Statistical analysis

Statistical analysis was performed using GraphPad Prism 7.0. The rank sum test was used to compare dryness and pathology scores among groups. Inflammatory factors were compared by analysis of variance (ANOVA). Multiple comparisons with the model group as a control were performed using post hoc analysis based on the Dunnett t-test. P-values <0.05 were considered statistically significant.

3 Results

3.1 Animal model construction

The mean preoperative weight of the experimental rabbits was 2.48 ± 0.14 kg. A total of 27 New Zealand rabbits received tracheotomy and intubation, while 9 received sham surgery. No intraoperative anesthetic death or hemorrhage occurred, and there was no significant dyspnea or poor sputum evacuation after anesthesia and aspiration.

3.2 Effect of airway wetting with different devices on sputum viscosity and pulmonary dryness and humidity

Consistent with clinical practice, we performed aspiration on the Model and Mask groups after airway wetting treatment to ensure that post-wetting sputum and softened sputum crusts would not block the airway and interfere with normal breathing. Overall, the sputum in the YTH and Mask groups was clear and thin, easily aspirated, occasionally with yellow sputum and crusts, and it hardly affected breathing. In contrast, in the Model group, the sputum was sticky with sputum and blood crusts; the sputum was not easy to aspirate. Also, respiratory distress with phlegm sound was detected in some rabbits in the Model group. Moreover, the tracheal dissection after the euthanasia of rabbits in each group revealed that the trachea of groups treated with wetting was cleaner, with fewer secretions blocking the airway. Also, the effect of the YTH device-wetting group was superior to that of the Mask wetting group. As for the Model group, the viscosity of sputum and crust formation in the airway gradually increased with time. In 48-h subgroups, beanbag-like sputum accumulation with blood oozing was observed in the main trachea, seriously affecting airway patency. These data indicate that airway humidification is an important nursing regimen for sustained airway patency and sputum removal after tracheotomy and that adequate humidification is more likely to maintain airway ventilation, which improves prognosis.

By weighing the whole lung tissues of rabbits with dry and wet weights, the wet-to-dry ratio of the lungs was calculated to evaluate the degree of pulmonary tissue dehydration and the wetting effect of different devices. The lung wet-to-dry ratio of rabbits in the Sham group remained high from 6 to 48 h, while it decreased in the Model group, suggesting a lack of water in the pulmonary tissues (Figure 1). The mask and the integrated device had a wetting effect and increased the lung wet-to-dry ratio. The Mask group gradually increased the lung wet-to-dry ratio from 6 to 48 h and reached the normal level at 48 h, while the YTH group achieved a better wetting effect at 12 h, basically reaching the normal level. As depicted in Figure 1, the YTH group had a higher lung wet-to-dry ratio than the Mask group at 6 and 12 h, indicating that the integrated device has a better wetting effect at an early stage and could reach normal levels more quickly. However, the data analysis was not statistically significant, which may be due to the small sample size at each time point and the strict rank sum test method. At 48 h, the lung wet-to-dry ratio was maintained at an approximately normal level in all three groups except the Model group, indicating the improvement of pulmonary dehydration.

Figure 1 Lung wet-to-dry ratio in rabbits exposed to different wetting methods. The wet-to-dry ratio of whole lungs in different groups at different time points. The relative water content of lung tissue was used to represent the wetting effect. The results of each group are expressed as x ± s (n = 3). A rank sum test was used to compare the difference between the Model group and other groups. *P < 0.05.
Figure 1

Lung wet-to-dry ratio in rabbits exposed to different wetting methods. The wet-to-dry ratio of whole lungs in different groups at different time points. The relative water content of lung tissue was used to represent the wetting effect. The results of each group are expressed as x ± s (n = 3). A rank sum test was used to compare the difference between the Model group and other groups. *P < 0.05.

3.3 Effect of different wetting devices on serum inflammatory factors

We obtained the expression of serum inflammatory factors at different times in rabbits by ELISA. In the Model group, serum TNF-α levels significantly increased at 6 h compared with the Sham group (Figure 2a, P < 0.01) and decreased to normal levels after 12 h. In the Sham group, serum TNF-α levels were significantly decreased at 48 h (Figure 2a, P < 0.01) compared with the Model group. In addition, the TNF-α level was significantly lower in the Mask group compared with the Model group at 48 h (Figure 2a, P < 0.05) but remained unchanged from 6 to 12 h. The YTH group showed a significant decrease in serum TNF-α levels at 6 h (Figure 2a, P < 0.05) and a decreasing trend at 48 h.

Figure 2 Effect of different wetting methods on serum inflammatory factors. The effect of different wetting methods on serum validation factors was detected by ELISA. a, b, c, and d show changes in serum TNF-α, IL-6, IL-8, and IL-10 levels in each group, respectively. The results were expressed as x ± s (n = 3). ANOVA was used to compare the differences. *P < 0.05, **P < 0.01, and ***P < 0.001.
Figure 2

Effect of different wetting methods on serum inflammatory factors. The effect of different wetting methods on serum validation factors was detected by ELISA. a, b, c, and d show changes in serum TNF-α, IL-6, IL-8, and IL-10 levels in each group, respectively. The results were expressed as x ± s (n = 3). ANOVA was used to compare the differences. *P < 0.05, **P < 0.01, and ***P < 0.001.

The pro-inflammatory factors IL-6 and IL-8 in the Model group increased from 12 to 48 h (Figure 2a, all P < 0.01). In the Mask and YTH groups, IL-6 and IL-8 decreased at 12 h (Figure 2b and c, Mask IL-6 P < 0.01, YTH IL-6 P < 0.01, Mask IL-8 P < 0.05, YTH IL-8 P < 0.01) and 48 h (Figure 2b and c, Mask IL-6 P < 0.001, YTH IL-6 P < 0.001, Mask IL-8 P < 0.001, YTH IL-8 P < 0.001). In addition, Figure 2a and b suggests that the integrated device had an enhanced inhibitory effect on IL-6 and IL-8 expression than the Mask group. Figure 2d shows that tracheotomy decreased the expression of anti-inflammatory cytokines, and the difference between the Model and Sham groups reached its maximum at 12 h (P < 0.05). IL-10 expression was higher in the YTH and Mask groups than in the Model group but with no statistical significance (P > 0.05). These results suggest that inadequate post-tracheotomy wetting might increase the expression of pro-inflammatory factors, while an integrated device suppresses airway inflammation.

3.4 Histopathological effects of different airway wetting devices

We then collected tracheal tissues from each experimental group and performed HE staining to evaluate the effects of tracheal intubation and airway wetting on the trachea’s general morphology and changes in pathological scores. There were no significant pathological changes in the general trachea morphology in the Sham group. As seen in Figure 2, the Sham group had intact and clear pseudocomplex ciliated columnar epithelium without secretion in the tracheal lumen 6–48 h postoperatively; yet, a little infiltration of inflammatory cells was seen at 6 h, probably due to local irritation from the sham surgery. In contrast, the Model group had a disorganized tracheal tissue structure with exfoliated airway epithelial tissue, more secretions in the lumen, and a large infiltration of inflammatory cells in the subepithelial tissue (Figure 3), and had the highest pathological score among groups (Figure 4).

Figure 3 Pathological changes of rabbit trachea under different wetting methods. Morphological changes (HE-stained sections) of rabbit trachea in different groups at different time points. The YTH group maintained the structural integrity of the airway epithelium at 48 h (marked by ellipses). The Mask group showed structural disruption of the airway epithelium at 6 h (marked by arrows). Scale bar: 100 μm.
Figure 3

Pathological changes of rabbit trachea under different wetting methods. Morphological changes (HE-stained sections) of rabbit trachea in different groups at different time points. The YTH group maintained the structural integrity of the airway epithelium at 48 h (marked by ellipses). The Mask group showed structural disruption of the airway epithelium at 6 h (marked by arrows). Scale bar: 100 μm.

Figure 4 Tracheal pathology scores under different wetting methods. Changes in tracheal pathology scores in different groups at different time points. (a) The total pathology scores of each group at each time point. (b–d) The percentage of each part of the scores at each time point. Results are expressed as x ± s (n = 3). A rank sum test was used to compare the differences. *P < 0.05, **P < 0.01, ***P < 0.001.
Figure 4

Tracheal pathology scores under different wetting methods. Changes in tracheal pathology scores in different groups at different time points. (a) The total pathology scores of each group at each time point. (b–d) The percentage of each part of the scores at each time point. Results are expressed as x ± s (n = 3). A rank sum test was used to compare the differences. *P < 0.05, **P < 0.01, ***P < 0.001.

Mask and YTH device wetting reduced pathological scores, and the effect of YTH device wetting was more effective (Figure 4a). Mask and YTH wetting could protect the structural integrity of airway tissue and suppress the airway inflammatory response to varying degrees (Figure 3). For airway epithelium, the YTH device ensured the structural integrity of airway epithelial cells at 48 h. Mask wetting slowed airway epithelial cell exfoliation, although the airway epithelium in this group was damaged due to inadequate wetting at 48 h (Figures 3 and 4d). Also, the YTH device performed better at suppressing inflammatory cell aggregation and inflammatory response in the airway subepithelial tissue at 48 h and accounted for less weight in the pathologic score (Figure 4b–d). It was noteworthy that neither sham surgical manipulation nor two wetting methods resulted in glandular hyperplasia in the airway.

Representative HE staining images of lung tissue at 48 h are shown in Figure 5. The lung tissue of rabbits in the Sham group showed normal morphology and structure. The lung tissue of rabbits in the Model group had blurred morphology and alveolar structure with inflammatory cell infiltration (shown by black arrows, Figure 5). The alveolar structure of rabbits in the Mask group was preserved after 48 h humidification; however, many erythrocytes were observed (shown by blue arrows, Figure 5). The lung tissue of rabbits in the YTH group maintained normal morphology with less infiltration of inflammatory cells.

Figure 5 Representative HE staining images of lung tissue at 48 h. Representative image of lung tissue. Black arrows: infiltration of inflammatory cells; blue arrows: infiltration of erythrocytes.
Figure 5

Representative HE staining images of lung tissue at 48 h. Representative image of lung tissue. Black arrows: infiltration of inflammatory cells; blue arrows: infiltration of erythrocytes.

4 Discussion

Long-term tracheotomy leads to loss of airway water due to the airway opening, resulting in patients’ dry airways, sticky sputum, and even sputum blockage, causing hypoxia and asphyxia, which poses a challenging issue in critical clinical care [21,22]. The airway mucosa exerts the protective function, requiring inhalation of moisture-saturated air. The degree of airway mucosal damage is directly proportional to the duration of ventilation without humidified gas [23]. The newly developed integrated device for continuous airway humidity and oxygen supply converts the wetting water in the collection cup into small atomized molecules through oxygen drive, reducing airway irritation. In this way, the device ensures oxygen supply and provides continuous airway humidity, avoiding respiratory water loss and airway blockade by sputum crust, conforming to the airway environment, increasing the utilization of the wetting solution, protecting tissue integrity, and inhibiting airway inflammation. The device is more stable, safe, and effective compared to other methods.

Foreign countries usually use active humidification equipment (MR850), HH, and artificial nose for humidification. However, the high cost of the MR850 humidifier and the airway-blocking effect of the artificial nose for patients with viscous sputum limit their clinical application. The common care method in China is the continuous airway drip method, which is more convenient and inexpensive. However, the wetting solution is easily deposited in the thicker trachea, leaving the bronchioles undetected. Besides, the connection of the wetting solution falls off easily. The external fixation tape, which is exposed to contamination and requires frequent replacement, increases the occurrence of cross-infection. In addition, the external mouth of the air vent may be partially closed by the tape, resulting in ventilation disorders. On the other hand, these procedures increase the workload of medical and nursing care [24]. To solve the practical clinical difficulties and reduce complications caused by inadequate and improper nursing operations, we developed an integrated airway wetting device as demonstrated in Figure S1 (Patent No. ZL201821869778.6). The device was more stable, calling for simple operations, eliminating the need for frequent care, and reducing staff workload. This study’s result suggests that the integrated device could provide better wetting efficiency under the same wetting conditions and provide stable wetting conditions in a shorter time. Compared to mask wetting, the integrated device could return to normal levels from pulmonary water loss within 12 h, preserving the integrity of airway epithelial tissue and reducing tissue damage in the early stage of tracheotomy. The underlying reason for the effect might be the higher utilization of the wetting solution of the integrated device at the same ventilation volume (4 L/min, SaO2 around 95% in each group). In this study, no mucus glands and cupped cell hyperplasia were observed in the trachea of the tracheotomy rabbit model within 48 h, which contradicted clinical observations [15]; this might be due to the relatively short observation time of 48 h compared to the clinical prolonged dry gas inhalation stimulation. We inferred that there could be more significant manifestations of glandular hyperplasia if the observation time was extended.

Inadequate humidification in tracheotomized patients results in poor sputum clearance and an increased possibility of infection. A humidifier, nebulizer, or passive humidifier can prevent sputum crust formation and reduce postoperative complications such as infection [25,26]. Respiratory cell injury due to dry gas triggers an inflammatory response, notably the release of inflammatory mediators, which is a systemic effect that can damage other tissues and organs [27]. As one of the inflammatory cytokines mainly produced by mononuclear macrophages, TNF-α is involved in various cellular immune responses, inducing elevated expression of pulmonary capillary adhesion molecules and the release of the inflammatory factor IL-8, which function as an important chemokine of neutrophils [28]. TNF-α also promotes mononuclear macrophages to produce IL-6 through Toll-like receptor-mediated signaling that activates the cis-regulatory element of IL-6 [29]. IL-8 and IL-6 promote inflammatory responses, and their elevated expression reflects the severity of inflammation [30]. In this study, water vapor loss due to an open airway caused desiccation damage to airway epithelial cells, resulting in local epithelial tissue necrosis, subcutaneous inflammatory cell infiltration, and elevated expression of circulating inflammatory factors. Rapid and adequate airway humidification suppressed the expression of pro-inflammatory factors in the serum after tracheotomy in the early stage, reducing the inflammatory response and local accumulation of inflammatory cells, thus protecting the normal function of the airway. Similar findings have been previously reported suggesting that adequate airway wetting inhibits TNF-α in the BALF [18] and serum TNF-α and IL-6 expression in the mechanically ventilated model [27]. IL-10 is an inflammatory suppressor produced by various immune cells, including macrophages, neutrophils, NK cells, and T cells. It inhibits the release of immune mediators, antigen expression, and phagocytosis [31,32]. IL-10 mainly activates the downstream JAK/STAT signaling pathway and regulates the expression of IL-10 effector genes [33]. In this study, we observed a partial increase in circulating IL-10 expression at 12 h of airway wetting, suggesting that airway wetting might participate in suppressing the inflammatory response by promoting IL-10 expression.

5 Conclusions

Our self-developed integrated wetting device can increase the utilization of wetting solutions, enhance the effect of wetting to protect tissue integrity, suppress airway inflammation, simplify nursing operation steps, and reduce labor waste and airway complications such as infection caused by human operation. It may be potentially used as a new method for clinical nursing practice.

Rapid and adequate humidification is important to ensure the structural integrity of the airway tissue and suppress the inflammatory response after tracheotomy. Recently, we have designed an anti-sputum spattering sputum collector (Patent No. 2018208423205). During the pandemic of COVID-19, the workload of nursing and the danger from aerosols were closely connected. In the future, we will extend the role of this airway humidity device function and further explore methods to avoid injury to healthcare workers by aerosol spraying during the airway care of tracheotomized non-mechanically ventilated patients, simplify nursing procedures, relieve clinical workload, and induce incidence of infection and hospitalization expense.

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  1. Funding information: This work was supported by the Start-up fund of Huashan Hospital affiliated to Fudan University and the National Natural Science Foundation of China (No. 82171188).

  2. Author contributions: Honglan Sheng and Jie Ni carried out the studies, participated in collecting data, and drafted the manuscript. Feng Zhao, Mi Tian, and Yuhang Zhao performed the statistical analysis and participated in its design. Longmei Dai, Ting Li, Yun Xue, and Zongze Song participated in the acquisition, analysis, and interpretation of data and drafted the manuscript. Qiong Yu made great contributions to the later development of the project and the subsequent revision of the paper. All authors read and approved the final article.

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

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

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Received: 2023-08-21
Revised: 2023-10-26
Accepted: 2023-12-18
Published Online: 2024-02-08

© 2024 the author(s), published by De Gruyter

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

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https://doi.org/10.1515/biol-2022-0825
Keywords for this article
tracheotomy; airway humidification; animal model; inflammatory response; histopathology
Creative Commons
BY 4.0

Articles in the same Issue

  1. Biomedical Sciences
  2. Constitutive and evoked release of ATP in adult mouse olfactory epithelium
  3. LARP1 knockdown inhibits cultured gastric carcinoma cell cycle progression and metastatic behavior
  4. PEGylated porcine–human recombinant uricase: A novel fusion protein with improved efficacy and safety for the treatment of hyperuricemia and renal complications
  5. Research progress on ocular complications caused by type 2 diabetes mellitus and the function of tears and blepharons
  6. The role and mechanism of esketamine in preventing and treating remifentanil-induced hyperalgesia based on the NMDA receptor–CaMKII pathway
  7. Brucella infection combined with Nocardia infection: A case report and literature review
  8. Detection of serum interleukin-18 level and neutrophil/lymphocyte ratio in patients with antineutrophil cytoplasmic antibody-associated vasculitis and its clinical significance
  9. Ang-1, Ang-2, and Tie2 are diagnostic biomarkers for Henoch-Schönlein purpura and pediatric-onset systemic lupus erythematous
  10. PTTG1 induces pancreatic cancer cell proliferation and promotes aerobic glycolysis by regulating c-myc
  11. Role of serum B-cell-activating factor and interleukin-17 as biomarkers in the classification of interstitial pneumonia with autoimmune features
  12. Effectiveness and safety of a mumps containing vaccine in preventing laboratory-confirmed mumps cases from 2002 to 2017: A meta-analysis
  13. Low levels of sex hormone-binding globulin predict an increased breast cancer risk and its underlying molecular mechanisms
  14. A case of Trousseau syndrome: Screening, detection and complication
  15. Application of the integrated airway humidification device enhances the humidification effect of the rabbit tracheotomy model
  16. Preparation of Cu2+/TA/HAP composite coating with anti-bacterial and osteogenic potential on 3D-printed porous Ti alloy scaffolds for orthopedic applications
  17. Aquaporin-8 promotes human dermal fibroblasts to counteract hydrogen peroxide-induced oxidative damage: A novel target for management of skin aging
  18. Current research and evidence gaps on placental development in iron deficiency anemia
  19. Single-nucleotide polymorphism rs2910829 in PDE4D is related to stroke susceptibility in Chinese populations: The results of a meta-analysis
  20. Pheochromocytoma-induced myocardial infarction: A case report
  21. Kaempferol regulates apoptosis and migration of neural stem cells to attenuate cerebral infarction by O‐GlcNAcylation of β-catenin
  22. Sirtuin 5 regulates acute myeloid leukemia cell viability and apoptosis by succinylation modification of glycine decarboxylase
  23. Apigenin 7-glucoside impedes hypoxia-induced malignant phenotypes of cervical cancer cells in a p16-dependent manner
  24. KAT2A changes the function of endometrial stromal cells via regulating the succinylation of ENO1
  25. Current state of research on copper complexes in the treatment of breast cancer
  26. Exploring antioxidant strategies in the pathogenesis of ALS
  27. Helicobacter pylori causes gastric dysbacteriosis in chronic gastritis patients
  28. IL-33/soluble ST2 axis is associated with radiation-induced cardiac injury
  29. The predictive value of serum NLR, SII, and OPNI for lymph node metastasis in breast cancer patients with internal mammary lymph nodes after thoracoscopic surgery
  30. Carrying SNP rs17506395 (T > G) in TP63 gene and CCR5Δ32 mutation associated with the occurrence of breast cancer in Burkina Faso
  31. P2X7 receptor: A receptor closely linked with sepsis-associated encephalopathy
  32. Probiotics for inflammatory bowel disease: Is there sufficient evidence?
  33. Identification of KDM4C as a gene conferring drug resistance in multiple myeloma
  34. Microbial perspective on the skin–gut axis and atopic dermatitis
  35. Thymosin α1 combined with XELOX improves immune function and reduces serum tumor markers in colorectal cancer patients after radical surgery
  36. Highly specific vaginal microbiome signature for gynecological cancers
  37. Sample size estimation for AQP4-IgG seropositive optic neuritis: Retinal damage detection by optical coherence tomography
  38. The effects of SDF-1 combined application with VEGF on femoral distraction osteogenesis in rats
  39. Fabrication and characterization of gold nanoparticles using alginate: In vitro and in vivo assessment of its administration effects with swimming exercise on diabetic rats
  40. Mitigating digestive disorders: Action mechanisms of Mediterranean herbal active compounds
  41. Distribution of CYP2D6 and CYP2C19 gene polymorphisms in Han and Uygur populations with breast cancer in Xinjiang, China
  42. VSP-2 attenuates secretion of inflammatory cytokines induced by LPS in BV2 cells by mediating the PPARγ/NF-κB signaling pathway
  43. Factors influencing spontaneous hypothermia after emergency trauma and the construction of a predictive model
  44. Long-term administration of morphine specifically alters the level of protein expression in different brain regions and affects the redox state
  45. Application of metagenomic next-generation sequencing technology in the etiological diagnosis of peritoneal dialysis-associated peritonitis
  46. Clinical diagnosis, prevention, and treatment of neurodyspepsia syndrome using intelligent medicine
  47. Case report: Successful bronchoscopic interventional treatment of endobronchial leiomyomas
  48. Preliminary investigation into the genetic etiology of short stature in children through whole exon sequencing of the core family
  49. Cystic adenomyoma of the uterus: Case report and literature review
  50. Mesoporous silica nanoparticles as a drug delivery mechanism
  51. Dynamic changes in autophagy activity in different degrees of pulmonary fibrosis in mice
  52. Vitamin D deficiency and inflammatory markers in type 2 diabetes: Big data insights
  53. Lactate-induced IGF1R protein lactylation promotes proliferation and metabolic reprogramming of lung cancer cells
  54. Meta-analysis on the efficacy of allogeneic hematopoietic stem cell transplantation to treat malignant lymphoma
  55. Mitochondrial DNA drives neuroinflammation through the cGAS-IFN signaling pathway in the spinal cord of neuropathic pain mice
  56. Application value of artificial intelligence algorithm-based magnetic resonance multi-sequence imaging in staging diagnosis of cervical cancer
  57. Embedded monitoring system and teaching of artificial intelligence online drug component recognition
  58. Investigation into the association of FNDC1 and ADAMTS12 gene expression with plumage coloration in Muscovy ducks
  59. Yak meat content in feed and its impact on the growth of rats
  60. A rare case of Richter transformation with breast involvement: A case report and literature review
  61. First report of Nocardia wallacei infection in an immunocompetent patient in Zhejiang province
  62. Rhodococcus equi and Brucella pulmonary mass in immunocompetent: A case report and literature review
  63. Downregulation of RIP3 ameliorates the left ventricular mechanics and function after myocardial infarction via modulating NF-κB/NLRP3 pathway
  64. Evaluation of the role of some non-enzymatic antioxidants among Iraqi patients with non-alcoholic fatty liver disease
  65. The role of Phafin proteins in cell signaling pathways and diseases
  66. Ten-year anemia as initial manifestation of Castleman disease in the abdominal cavity: A case report
  67. Coexistence of hereditary spherocytosis with SPTB P.Trp1150 gene variant and Gilbert syndrome: A case report and literature review
  68. Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells
  69. Exploratory evaluation supported by experimental and modeling approaches of Inula viscosa root extract as a potent corrosion inhibitor for mild steel in a 1 M HCl solution
  70. Imaging manifestations of ductal adenoma of the breast: A case report
  71. Gut microbiota and sleep: Interaction mechanisms and therapeutic prospects
  72. Isomangiferin promotes the migration and osteogenic differentiation of rat bone marrow mesenchymal stem cells
  73. Prognostic value and microenvironmental crosstalk of exosome-related signatures in human epidermal growth factor receptor 2 positive breast cancer
  74. Circular RNAs as potential biomarkers for male severe sepsis
  75. Knockdown of Stanniocalcin-1 inhibits growth and glycolysis in oral squamous cell carcinoma cells
  76. The expression and biological role of complement C1s in esophageal squamous cell carcinoma
  77. A novel GNAS mutation in pseudohypoparathyroidism type 1a with articular flexion deformity: A case report
  78. Predictive value of serum magnesium levels for prognosis in patients with non-small cell lung cancer undergoing EGFR-TKI therapy
  79. HSPB1 alleviates acute-on-chronic liver failure via the P53/Bax pathway
  80. IgG4-related disease complicated by PLA2R-associated membranous nephropathy: A case report
  81. Baculovirus-mediated endostatin and angiostatin activation of autophagy through the AMPK/AKT/mTOR pathway inhibits angiogenesis in hepatocellular carcinoma
  82. Metformin mitigates osteoarthritis progression by modulating the PI3K/AKT/mTOR signaling pathway and enhancing chondrocyte autophagy
  83. Evaluation of the activity of antimicrobial peptides against bacterial vaginosis
  84. Atypical presentation of γ/δ mycosis fungoides with an unusual phenotype and SOCS1 mutation
  85. Analysis of the microecological mechanism of diabetic kidney disease based on the theory of “gut–kidney axis”: A systematic review
  86. Omega-3 fatty acids prevent gestational diabetes mellitus via modulation of lipid metabolism
  87. Refractory hypertension complicated with Turner syndrome: A case report
  88. Interaction of ncRNAs and the PI3K/AKT/mTOR pathway: Implications for osteosarcoma
  89. Association of low attenuation area scores with pulmonary function and clinical prognosis in patients with chronic obstructive pulmonary disease
  90. Long non-coding RNAs in bone formation: Key regulators and therapeutic prospects
  91. The deubiquitinating enzyme USP35 regulates the stability of NRF2 protein
  92. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as potential diagnostic markers for rebleeding in patients with esophagogastric variceal bleeding
  93. G protein-coupled receptor 1 participating in the mechanism of mediating gestational diabetes mellitus by phosphorylating the AKT pathway
  94. LL37-mtDNA regulates viability, apoptosis, inflammation, and autophagy in lipopolysaccharide-treated RLE-6TN cells by targeting Hsp90aa1
  95. The analgesic effect of paeoniflorin: A focused review
  96. Chemical composition’s effect on Solanum nigrum Linn.’s antioxidant capacity and erythrocyte protection: Bioactive components and molecular docking analysis
  97. Knockdown of HCK promotes HREC cell viability and inner blood–retinal barrier integrity by regulating the AMPK signaling pathway
  98. The role of rapamycin in the PINK1/Parkin signaling pathway in mitophagy in podocytes
  99. Laryngeal non-Hodgkin lymphoma: Report of four cases and review of the literature
  100. Clinical value of macrogenome next-generation sequencing on infections
  101. Overview of dendritic cells and related pathways in autoimmune uveitis
  102. TAK-242 alleviates diabetic cardiomyopathy via inhibiting pyroptosis and TLR4/CaMKII/NLRP3 pathway
  103. Hypomethylation in promoters of PGC-1α involved in exercise-driven skeletal muscular alterations in old age
  104. Profile and antimicrobial susceptibility patterns of bacteria isolated from effluents of Kolladiba and Debark hospitals
  105. The expression and clinical significance of syncytin-1 in serum exosomes of hepatocellular carcinoma patients
  106. A histomorphometric study to evaluate the therapeutic effects of biosynthesized silver nanoparticles on the kidneys infected with Plasmodium chabaudi
  107. PGRMC1 and PAQR4 are promising molecular targets for a rare subtype of ovarian cancer
  108. Analysis of MDA, SOD, TAOC, MNCV, SNCV, and TSS scores in patients with diabetes peripheral neuropathy
  109. SLIT3 deficiency promotes non-small cell lung cancer progression by modulating UBE2C/WNT signaling
  110. The relationship between TMCO1 and CALR in the pathological characteristics of prostate cancer and its effect on the metastasis of prostate cancer cells
  111. Heterogeneous nuclear ribonucleoprotein K is a potential target for enhancing the chemosensitivity of nasopharyngeal carcinoma
  112. PHB2 alleviates retinal pigment epithelium cell fibrosis by suppressing the AGE–RAGE pathway
  113. Anti-γ-aminobutyric acid-B receptor autoimmune encephalitis with syncope as the initial symptom: Case report and literature review
  114. Comparative analysis of chloroplast genome of Lonicera japonica cv. Damaohua
  115. Human umbilical cord mesenchymal stem cells regulate glutathione metabolism depending on the ERK–Nrf2–HO-1 signal pathway to repair phosphoramide mustard-induced ovarian cancer cells
  116. Electroacupuncture on GB acupoints improves osteoporosis via the estradiol–PI3K–Akt signaling pathway
  117. Renalase protects against podocyte injury by inhibiting oxidative stress and apoptosis in diabetic nephropathy
  118. Review: Dicranostigma leptopodum: A peculiar plant of Papaveraceae
  119. Combination effect of flavonoids attenuates lung cancer cell proliferation by inhibiting the STAT3 and FAK signaling pathway
  120. Renal microangiopathy and immune complex glomerulonephritis induced by anti-tumour agents: A case report
  121. Correlation analysis of AVPR1a and AVPR2 with abnormal water and sodium and potassium metabolism in rats
  122. Gastrointestinal health anti-diarrheal mixture relieves spleen deficiency-induced diarrhea through regulating gut microbiota
  123. Myriad factors and pathways influencing tumor radiotherapy resistance
  124. Exploring the effects of culture conditions on Yapsin (YPS) gene expression in Nakaseomyces glabratus
  125. Screening of prognostic core genes based on cell–cell interaction in the peripheral blood of patients with sepsis
  126. Coagulation factor II thrombin receptor as a promising biomarker in breast cancer management
  127. Ileocecal mucinous carcinoma misdiagnosed as incarcerated hernia: A case report
  128. Methyltransferase like 13 promotes malignant behaviors of bladder cancer cells through targeting PI3K/ATK signaling pathway
  129. The debate between electricity and heat, efficacy and safety of irreversible electroporation and radiofrequency ablation in the treatment of liver cancer: A meta-analysis
  130. ZAG promotes colorectal cancer cell proliferation and epithelial–mesenchymal transition by promoting lipid synthesis
  131. Baicalein inhibits NLRP3 inflammasome activation and mitigates placental inflammation and oxidative stress in gestational diabetes mellitus
  132. Impact of SWCNT-conjugated senna leaf extract on breast cancer cells: A potential apoptotic therapeutic strategy
  133. MFAP5 inhibits the malignant progression of endometrial cancer cells in vitro
  134. Major ozonated autohemotherapy promoted functional recovery following spinal cord injury in adult rats via the inhibition of oxidative stress and inflammation
  135. Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neurons
  136. Differential expression of phosphoinositide 3-kinase/protein kinase B and Toll-like receptor/nuclear factor kappa B signaling pathways in experimental obesity Wistar rat model
  137. The therapeutic potential of targeting Oncostatin M and the interleukin-6 family in retinal diseases: A comprehensive review
  138. BA inhibits LPS-stimulated inflammatory response and apoptosis in human middle ear epithelial cells by regulating the Nf-Kb/Iκbα axis
  139. Role of circRMRP and circRPL27 in chronic obstructive pulmonary disease
  140. Investigating the role of hyperexpressed HCN1 in inducing myocardial infarction through activation of the NF-κB signaling pathway
  141. Characterization of phenolic compounds and evaluation of anti-diabetic potential in Cannabis sativa L. seeds: In vivo, in vitro, and in silico studies
  142. Quantitative immunohistochemistry analysis of breast Ki67 based on artificial intelligence
  143. Ecology and Environmental Science
  144. Screening of different growth conditions of Bacillus subtilis isolated from membrane-less microbial fuel cell toward antimicrobial activity profiling
  145. Degradation of a mixture of 13 polycyclic aromatic hydrocarbons by commercial effective microorganisms
  146. Evaluation of the impact of two citrus plants on the variation of Panonychus citri (Acari: Tetranychidae) and beneficial phytoseiid mites
  147. Prediction of present and future distribution areas of Juniperus drupacea Labill and determination of ethnobotany properties in Antalya Province, Türkiye
  148. Population genetics of Todarodes pacificus (Cephalopoda: Ommastrephidae) in the northwest Pacific Ocean via GBS sequencing
  149. A comparative analysis of dendrometric, macromorphological, and micromorphological characteristics of Pistacia atlantica subsp. atlantica and Pistacia terebinthus in the middle Atlas region of Morocco
  150. Macrofungal sporocarp community in the lichen Scots pine forests
  151. Assessing the proximate compositions of indigenous forage species in Yemen’s pastoral rangelands
  152. Food Science
  153. Gut microbiota changes associated with low-carbohydrate diet intervention for obesity
  154. Reexamination of Aspergillus cristatus phylogeny in dark tea: Characteristics of the mitochondrial genome
  155. Differences in the flavonoid composition of the leaves, fruits, and branches of mulberry are distinguished based on a plant metabolomics approach
  156. Investigating the impact of wet rendering (solventless method) on PUFA-rich oil from catfish (Clarias magur) viscera
  157. Non-linear associations between cardiovascular metabolic indices and metabolic-associated fatty liver disease: A cross-sectional study in the US population (2017–2020)
  158. Knockdown of USP7 alleviates atherosclerosis in ApoE-deficient mice by regulating EZH2 expression
  159. Utility of dairy microbiome as a tool for authentication and traceability
  160. Agriculture
  161. Enhancing faba bean (Vicia faba L.) productivity through establishing the area-specific fertilizer rate recommendation in southwest Ethiopia
  162. Impact of novel herbicide based on synthetic auxins and ALS inhibitor on weed control
  163. Perspectives of pteridophytes microbiome for bioremediation in agricultural applications
  164. Fertilizer application parameters for drip-irrigated peanut based on the fertilizer effect function established from a “3414” field trial
  165. Improving the productivity and profitability of maize (Zea mays L.) using optimum blended inorganic fertilization
  166. Application of leaf multispectral analyzer in comparison to hyperspectral device to assess the diversity of spectral reflectance indices in wheat genotypes
  167. Animal Sciences
  168. Knockdown of ANP32E inhibits colorectal cancer cell growth and glycolysis by regulating the AKT/mTOR pathway
  169. Development of a detection chip for major pathogenic drug-resistant genes and drug targets in bovine respiratory system diseases
  170. Exploration of the genetic influence of MYOT and MB genes on the plumage coloration of Muscovy ducks
  171. Transcriptome analysis of adipose tissue in grazing cattle: Identifying key regulators of fat metabolism
  172. Comparison of nutritional value of the wild and cultivated spiny loaches at three growth stages
  173. Transcriptomic analysis of liver immune response in Chinese spiny frog (Quasipaa spinosa) infected with Proteus mirabilis
  174. Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis
  175. Plant Sciences
  176. Effect of long-term in-row branch covering on soil microorganisms in pear orchards
  177. Photosynthetic physiological characteristics, growth performance, and element concentrations reveal the calcicole–calcifuge behaviors of three Camellia species
  178. Transcriptome analysis reveals the mechanism of NaHCO3 promoting tobacco leaf maturation
  179. Bioinformatics, expression analysis, and functional verification of allene oxide synthase gene HvnAOS1 and HvnAOS2 in qingke
  180. Water, nitrogen, and phosphorus coupling improves gray jujube fruit quality and yield
  181. Improving grape fruit quality through soil conditioner: Insights from RNA-seq analysis of Cabernet Sauvignon roots
  182. Role of Embinin in the reabsorption of nucleus pulposus in lumbar disc herniation: Promotion of nucleus pulposus neovascularization and apoptosis of nucleus pulposus cells
  183. Revealing the effects of amino acid, organic acid, and phytohormones on the germination of tomato seeds under salinity stress
  184. Combined effects of nitrogen fertilizer and biochar on the growth, yield, and quality of pepper
  185. Comprehensive phytochemical and toxicological analysis of Chenopodium ambrosioides (L.) fractions
  186. Impact of “3414” fertilization on the yield and quality of greenhouse tomatoes
  187. Exploring the coupling mode of water and fertilizer for improving growth, fruit quality, and yield of the pear in the arid region
  188. Metagenomic analysis of endophytic bacteria in seed potato (Solanum tuberosum)
  189. Antibacterial, antifungal, and phytochemical properties of Salsola kali ethanolic extract
  190. Exploring the hepatoprotective properties of citronellol: In vitro and in silico studies on ethanol-induced damage in HepG2 cells
  191. Enhanced osmotic dehydration of watermelon rind using honey–sucrose solutions: A study on pre-treatment efficacy and mass transfer kinetics
  192. Effects of exogenous 2,4-epibrassinolide on photosynthetic traits of 53 cowpea varieties under NaCl stress
  193. Comparative transcriptome analysis of maize (Zea mays L.) seedlings in response to copper stress
  194. An optimization method for measuring the stomata in cassava (Manihot esculenta Crantz) under multiple abiotic stresses
  195. Fosinopril inhibits Ang II-induced VSMC proliferation, phenotype transformation, migration, and oxidative stress through the TGF-β1/Smad signaling pathway
  196. Antioxidant and antimicrobial activities of Salsola imbricata methanolic extract and its phytochemical characterization
  197. Bioengineering and Biotechnology
  198. Absorbable calcium and phosphorus bioactive membranes promote bone marrow mesenchymal stem cells osteogenic differentiation for bone regeneration
  199. New advances in protein engineering for industrial applications: Key takeaways
  200. An overview of the production and use of Bacillus thuringiensis toxin
  201. Research progress of nanoparticles in diagnosis and treatment of hepatocellular carcinoma
  202. Bioelectrochemical biosensors for water quality assessment and wastewater monitoring
  203. PEI/MMNs@LNA-542 nanoparticles alleviate ICU-acquired weakness through targeted autophagy inhibition and mitochondrial protection
  204. Unleashing of cytotoxic effects of thymoquinone-bovine serum albumin nanoparticles on A549 lung cancer cells
  205. Erratum
  206. Erratum to “Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM”
  207. Erratum to “Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation”
  208. Retraction
  209. Retraction to “MiR-223-3p regulates cell viability, migration, invasion, and apoptosis of non-small cell lung cancer cells by targeting RHOB”
  210. Retraction to “A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis”
  211. Special Issue on Advances in Neurodegenerative Disease Research and Treatment
  212. Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson’s disease
  213. Special Issue on Multi-omics
  214. Inflammasome complex genes with clinical relevance suggest potential as therapeutic targets for anti-tumor drugs in clear cell renal cell carcinoma
  215. Gastroesophageal varices in primary biliary cholangitis with anti-centromere antibody positivity: Early onset?
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