Startseite Downregulation of carbonic anhydrase IX expression in mouse xenograft nasopharyngeal carcinoma model via doxorubicin nanobubble combined with ultrasound
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Downregulation of carbonic anhydrase IX expression in mouse xenograft nasopharyngeal carcinoma model via doxorubicin nanobubble combined with ultrasound

  • Rong Li , Liugui Lu , Zhaoxi Huang und Yong Gao EMAIL logo
Veröffentlicht/Copyright: 13. Februar 2024
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Aus der Zeitschrift Open Medicine Band 19 Heft 1

Abstract

The purpose of this study was to investigate whether doxorubicin nanobubbles (DOX-NB) combined with diagnostic ultrasound (DUS) irradiation could downregulate the expression of carbonic anhydrase IX (CAIX) in mouse xenograft nasopharyngeal carcinoma (NPC) model. In this study, the prepared DOX-NB was round and well dispersed. The average diameter of DOX-NB was 250.9 ± 50.8 nm, with an average polydispersity of 0.321 ± 0.05. The cumulative release of DOX in the DOX-NB + DUS group was significantly higher compared with that of the DOX-NB group (p < 0.05). DOX-NB combined with DUS irradiation could significantly inhibit cell viability (p < 0.05). The expression of CAIX and microvessel density (MVD) in the xenografted tumors was the lowest in the DOX-NB + DUS group compared with that of other groups (p < 0.05). In conclusion, DOX-NB combined with DUS irradiation could improve DOX-NB drug release and synergistically inhibit NPC cell activity. DOX-NB combined with DUS irradiation can downregulate the expression of CAIX in mouse xenograft NPC model. This may be due to the synergistic effect of DUS combined with DOX-NB in reducing MVD in NPC.

Keywords: diagnostic ultrasound; nasopharyngeal carcinoma; carbonic anhydrase IX; doxorubicin nanobubbles; microvascular density

1 Introduction

Nasopharyngeal carcinoma (NPC) has a high prevalence in northern Africa and southeastern Asia, especially Southern China [1]. NPC tends to be more sensitive to ionizing radiation. Therefore, radiotherapy remains the most powerful treatment modality for NPC [2]. However, due to tumor resistance to radiotherapy, certain NPC patients present with local recurrences or distant metastases within 2 years after treatment [3,4]. Thus, tumor resistance to radiotherapy remains a serious obstacle to treatment success in some NPC cases.

Tumor hypoxia is known to be mainly responsible for tumor resistance to radiotherapy or chemotherapy, as well as for promoting tumor phenotypes that result in invasiveness, metastasis, and a poor prognosis [5]. Under the condition of tumor hypoxia, cancer cells become approximately two to three times more radioresistant than they are under normoxic conditions [6]. Hypoxia-induced resistance to radiation remains a serious obstacle in achieving optimal outcomes in patients with NPC [7].

Carbonic anhydrase IX (CAIX) is an important downstream factor of hypoxia inducible factor-1α (HIF-1α), which has a receptor that is mainly expressed in the cell membrane [8]. Some studies have shown that CAIX is associated with tumor radioresistance. High expression of CAIX may indicate poor prognosis [9]. A study of head and neck cancer found that CAIX upregulation correlates with tumor necrosis and microvessel density (MVD) [10]. Regulation of CAIX expression is a new therapeutic target for NPC [11]. However, the methods to block the function of CAIX or regulating its expression are still a challenge [12].

Studies have shown that ultrasound-targeted microbubble destruction (UTMD) technology can increase the permeability of tumor vasculature and effectively enhance the transport and uptake of therapeutic agents [13]. The latest research has shown that microbubbles combined with diagnostic ultrasound (DUS) irradiation could improve the blood perfusion of the tumor [14,15]. At present, no research has been conducted on reducing the expression of CAIX by nanobubbles (NBs) combined with DUS irradiation. In this study, we investigated whether doxorubicin (DOX)-NB combined with DUS irradiation could downregulate the expression of CAIX in NPC, and we preliminarily explored the relationship between its expression level and MVD.

2 Materials and methods

2.1 Preparation of DOX-NB

The lipids 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphate monosodium salt, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine, and mPEG2000-DSPE were dissolved in chloroform in a 4:1:1:1 mass ratio. The solvent was then removed by evaporation, and the lipids were hydrated at 60°C for 30 min in a solution containing 50 μL of glycerol and 1 mL of phosphate-buffered saline (PBS) containing 0.06% Pluronic 124, 0.5% Irgacure 2959, and 0.2% DOX. After hydration, N,N′,-diethylaniline and N,Nʹ-bis(acryloyl)cystamine were dissolved in the lipid solution. The air in the vial was replaced with octafluoropropane (C3F8) using a 10 mL syringe with a needle.

The vial was shaken on an HL-AH series amalgamator (Hangzhou ZhongRun Medical Instrument Co., Ltd) at a high speed for 60 s, then irradiated at 254 nm using an ultraviolet lamp for 30 min. Finally, the mixture was stored upside down at 4°C.

2.2 Characterization of DOX-NB

Fluorescence microscopy was used to observe DOX in nanocapsules. The size, zeta potential, and polydispersity index of DOX-NB were measured using a Zetasizer NanoZS instrument (Malvern Instruments, UK).

Bubble size was determined by diluting a sample with PBS at pH 7.4 to a dilution of 1:1,000. Measurements were performed at 25°C with a laser wavelength of 660 nm at an angle of 90°. DOX-NB concentrations were counted using blood cell counting plates. The contrast imaging of DOX-NB in vitro was performed in an acrylamide gel phantom with a clinical ultrasound imaging system (LogiQ E9, GE, USA). The DOX-NB samples were diluted with PBS to a dilution of 1:100. Imaging parameters were set to contrast imaging with a frequency of 5.5 MHz, mechanical index (MI) of 0.16, and gain of 5 dB.

2.3 Drug loading content (DLC) and encapsulation efficiency

DOX-NB was dialyzed with a dialysis bag (12,000 Da, 5 h) to remove free DOX. The suspension of DOX-NB was freeze-dried for 1 day with a freeze dryer (−55°C, <0.010 mbar). Lyophilized DOX-NB was then weighed and dissolved in PBS. The amount of encapsulated DOX was determined by measuring the absorbance at 483 nm. DOX content is expressed as DLC, which is the ratio of the weight of the loaded DOX to the total weight of the material. Encapsulation efficiency (%EE) is the percentage of encapsulated DOX to initial feeding DOX.

2.4 DOX release from DOX-NB in vitro

DOX-NB was enclosed in a dialysis bag (cutoff: 12,000 Da), placed in a container with 100 mL of PBS, and shaken at 100 rpm at a temperature of 37°C. The DOX-NB + DUS group was irradiated by DUS (LogiQ E9, GE, USA; probe frequency: 5.5 MHz, MI: 1.2, thermal index in soft tissue [TIS]: 0.3) for 3 min. DOX release was measured for up to 24 h, withdrawing 1 mL at each fixed time and replacing it with 1 mL of PBS. The concentration of DOX in the external buffer was measured using a Synergy H1 microplate reader at 483 nm. The experiments were performed in triplicate.

2.5 Cell culture

NPC cells (5-8F) were purchased from Shanghai Yaji Biotech Co., Ltd. The cells were cultured in 1640 complete medium (10% fetal bovine serum, 1% penicillin–streptomycin) and placed in a humidified atmosphere (37°C, 5% CO2). Cells in the logarithmic growth phase were harvested for the experiments.

2.6 Effects of DOX-NB on 5-8F cells in vitro

The viability of the 5-8F cells was measured using a Cell Counting Kit-8 (CCK-8). The cells were cultured in 1640 complete medium (10% fetal bovine serum, 1% penicillin–streptomycin) and placed in a humidified atmosphere (37°C, 5% CO2). Cells were passaged until they were 90% confluent and then detached with 0.25% trypsin-EDTA. The 5-8F cells (at 8 × 103 cells per plate) were seeded into 96-well plates. After 24 h of culture, the surface medium was aspirated and the cells were randomly divided into five groups: Control, DOX, DOX + DUS, DOX-NB, and DOX-NB + DUS. The DUS parameters were set as follows: frequency, 5.5 MHz; MI, 1.2; TIS, 0.3; and irradiation time, 3 min. After 3 h of incubation at 37°C, the treatment solution was removed. The cells were washed with PBS three times. Then, 10 μL of CCK-8 solution was added to each well, and the cells were cultured for 1.5 h. A microplate reader (Synergy H1, BioTek Instruments, USA) was used to determine the absorbance at 450 nm.

2.7 Apoptosis experiment

Annexin V-FITC and propyridine iodide (PI) apoptosis kit (MultiSciences Biotech Co., Ltd) were used to detect apoptotic cells. The 5-8F cells (at 6 × 105 cells per plate) were seeded into 35 mm cell culture dishes. After 24 h of culture, the cells were randomly divided into five groups: Control, DOX, DOX + DUS, DOX-NB, and DOX-NB + DUS. The DUS parameters were set as follows: frequency, 5.5 MHz; MI, 1.2; TIS, 0.3; and irradiation time, 3 min. After 3 h of incubation at 37°C, the treatment solution was removed. The cells were washed with PBS. Then, complete medium was added to each dish and the cells were cultured in a humidified atmosphere (37°C, 5% CO2). After 24 h of culture, 5-8F cells were collected and washed with PBS two times. The cells were resuspended in 500 µL 1× binding buffer, stained with 5 µL Annexin V-FITC and 10 µL PI for 5 min at room temperature in the dark. Apoptosis was analyzed with a BD FACS flow cytometer (BD Bioscience, USA).

2.8 Animal preparation and subcutaneous implantation models

The animals were handled according to the Institutional Animal Care and Use Committee. The study was approved by the Ethics Committee of Guangxi Medical University (Approval number 202109016). BALB/c-nu nude mice (4–6 weeks old) were purchased from Guangxi Medical University Lab Animal Research Center. The 5-8F cells and 200 µL of Matrigel mixture (1 × 106 cells/mL) were injected subcutaneously into the hind flanks of the mice. When the tumor diameter reached 8–10 mm, the mice were randomly divided into five groups (five mice/group): Control, DOX, DOX + DUS, DOX-NB, and DOX-NB + DUS. The mice were then anesthetized with 3% pentobarbital sodium (0.1 mL/10 g). Each mouse was injected once with 200 μL sample solution via tail vein injection. The DOX intake of all treatment groups was 184 nmol (5 mg/kg). One minute after the injection of the sample solution via the tail vein, the mice in the DOX + DUS group or DOX-NB + DUS group received ultrasound irradiation on the tumor surface, using DUS instruments (frequency: 5.5 MHz, MI: 1.2, TIS: 0.3, and irradiation time: 3 min). After 3 h, the mice were sacrificed by euthanasia and by CO2 asphyxiation. Tumors were collected for analysis.

2.9 Detection of CAIX expression in tumor tissues by immunohistochemistry

The tumors extracted from each group were fixed with 4% paraformaldehyde for 24 h (4°C) and then embedded in paraffin. The tissues were sectioned after dewaxing (thickness 4 µm), and then immunohistochemical CAIX detection was performed. The presence of brown granules on the cytomembrane was considered to be the positive expression of CAIX. Five high-magnification fields (×400) were randomly selected from each section under a light microscope. The representative figures were captured and semiquantitatively analyzed using ImageJ. The integrated optical density (IOD) was measured as the expression of CAIX in the target area, and the average IOD of five fields was calculated for the final analysis.

2.10 Quantification of MVD in xenograft tumors by immunohistochemistry

Paraffin-embedded blocks were retrieved and cut into 4 µm sections. All sections underwent dewaxing, rehydration, and heat-mediated antigen retrieval with Tris-EDTA buffer (pH 9.0, epitope retrieval solution) for 20 min. They were then subjected to endogenous peroxidase blocking. After cooling at room temperature, they were rinsed in PBS and incubated overnight at 4°C with rabbit anti-CD31 monoclonal antibody. Next, the slides were incubated with a goat anti-rabbit antibody for 45 min at 37°C. Five high-magnification fields (200×) were selected randomly from each section under a light microscope to count the number of microvessels and determine the MVD with Image J software.

2.11 Statistical analysis

All experiments were performed in triplicate, and the data were presented as mean ± standard deviation. Statistical analyses were performed using SPSS version 25.0. Differences between the two groups were analyzed using the two-way repeated measure analysis of variance (ANOVA). Differences among multiple groups were evaluated using one-way ANOVA). A p-value <0.05 was considered to be statistically significant.

3 Results

3.1 DOX-NB characterization

The average diameter of DOX-NB was 250.9 ± 50.8 nm, with an average polydispersity of 0.321 ± 0.05 (Figure 1). The zeta potential was −23.6 ± 2.21 mV measured by the particle size and zeta potential analyzer. The DOX-NBs were round and well dispersed, with a density of 9.28 × 108/mL under an optical microscope (Figure 2a). A fluorescence microscope was used to clearly show the red fluorescence signals of DOX on the shell of DOX-NB (Figure 2b). Figure 3a shows the contrast-enhanced ultrasound image of PBS buffer as an anechoic dark area, while Figure 3b shows DOX-NB as a strong and uniform high enhancement area.

Figure 1 Size distribution of the DOX-NB obtained by Zetasizer NanoZS.
Figure 1

Size distribution of the DOX-NB obtained by Zetasizer NanoZS.

Figure 2 (a) DOX-NB under an optical microscope (×400). (b) Fluorescence microscope image of DOX-NB (×400) (scale bar = 500 μm).
Figure 2

(a) DOX-NB under an optical microscope (×400). (b) Fluorescence microscope image of DOX-NB (×400) (scale bar = 500 μm).

Figure 3 (a) Contrast-enhanced ultrasound image of PBS buffer shows an anechoic dark area. (b) DOX-NB contrast-enhanced ultrasound image shows a dense and uniform high enhanced area.
Figure 3

(a) Contrast-enhanced ultrasound image of PBS buffer shows an anechoic dark area. (b) DOX-NB contrast-enhanced ultrasound image shows a dense and uniform high enhanced area.

3.2 Loading and DOX release from DOX-NB in vitro

Encapsulated DOX content in particles was determined using the dialysis technique. The DLC of DOX-NB was 10.17 ± 4.79 μg/mg. The encapsulation efficiency was 23.4 ± 0.08%. Figure 4 shows the release curve of DOX from DOX-NB with and without DUS irradiation in vitro. The cumulative of DOX released from DOX-NB was significantly different between the DOX-NB + DUS group and the DOX-NB group (p < 0.05) (Table A1). The DOX-NB group released 52.2% of the DOX after 24 h. However, 84.1% of the DOX was released in the DOX-NB + DUS group.

Figure 4 DOX release curve of DOX-NB + DUS group compared with DOX-NB group within 24 h in vitro (n = 3/group).
Figure 4

DOX release curve of DOX-NB + DUS group compared with DOX-NB group within 24 h in vitro (n = 3/group).

3.3 DOX cytotoxicity in vitro

To investigate the anticancer effects in vitro, the viability of 5-8F cells was measured using a CCK-8 assay. The cell viability results were 27.7 ± 8.08% in the DOX-NB + DUS group, 67.6 ± 15.99% in the DOX-NB group, 71.1 ± 17.50% in the DOX + DUS group, 77.8 ± 5.85% in the DOX group, and 100% in the Control group (Figure 5, Table A2). The viability of 5-8F cells in the DOX-NB + DUS group was lower than that in the other groups (p < 0.05), suggesting that DOX-NB combined with ultrasound irradiation had a better inhibitory effect on the viability of 5-8F cells.

Figure 5 Cell viability of 5-8F cells (n = 3/group) with different treatments (*p < 0.05).
Figure 5

Cell viability of 5-8F cells (n = 3/group) with different treatments (*p < 0.05).

To further investigate the anticancer effects in vitro, we used flow cytometry to assess the apoptosis of 5-8F cells. Annexin V-FITC/PI apoptosis kit was used to detect the induction of apoptosis. The apoptosis rate of cells was 9.8 ± 0.52% in the DOX-NB + DUS group, 6.7 ± 0.52% in the DOX-NB group, 6.7 ± 0.21% in the DOX + DUS group, 5.5 ± 0.24% in the DOX group, and 4.4 ± 1.18% in the Control group (Figure 6, Table A3). The apoptosis rate of 5-8F cells in the DOX-NB + DUS group was higher than that in the other groups (p < 0.05), further verifying that DOX-NB combined with ultrasound irradiation inhibited the viability of 5-8F cells well.

Figure 6 Apoptosis rate of 5-8F cells (n = 3/group) with different treatments (*p < 0.05).
Figure 6

Apoptosis rate of 5-8F cells (n = 3/group) with different treatments (*p < 0.05).

3.4 Expression of CAIX antigen by immunohistochemistry in vivo

Figure 7 exhibits immunohistochemical images of the CAIX-stained in xenografted tumor. The expression of CAIX in the xenografted tumors was downregulated in the DOX-NB + DUS group compared with that in the other groups (p < 0.05) (Table A4).

Figure 7 Different expressions of CAIX by immunohistochemical staining in xenografted tumors in different treatment groups (n = 5/group). (a–e) Representative immunohistochemical staining of CAIX: (a) Control group, (b) DOX group, (c) DOX + DUS group, (d) DOX-NB group, (e) DOX-NB + DUS group (×400) (scale bar = 200 μm). (f) Quantification of CAIX as presented in (a)–(e) (*p < 0.05).
Figure 7

Different expressions of CAIX by immunohistochemical staining in xenografted tumors in different treatment groups (n = 5/group). (a–e) Representative immunohistochemical staining of CAIX: (a) Control group, (b) DOX group, (c) DOX + DUS group, (d) DOX-NB group, (e) DOX-NB + DUS group (×400) (scale bar = 200 μm). (f) Quantification of CAIX as presented in (a)–(e) (*p < 0.05).

3.5 Expression of MVD in tumor tissues by immunohistochemistry

To determine the effects of treatment on tumor angiogenesis, immunohistochemical staining of CD31 was performed to quantify MVD in xenograft tumors (Figure 8). The MVDs of the DOX-NB + DUS, DOX-NB, DOX + DUS, DOX, and Control groups were calculated as 20.90 ± 3.18, 39.70 ± 2.98, 42.00 ± 2.16, 46.60 ± 2.37, and 46.80 ± 2.70, respectively. The difference between the Control group and DOX groups was not significant (p = 0.869). Compared with the DOX + DUS group, the MVD of the DOX-NB group was decreased, but the difference was not statistically significant (p = 0.064). The DOX-NB + DUS group had the lowest MVD compared with the other groups (p < 0.05) (Table A5).

Figure 8 Different expressions of CD31 by immunohistochemical staining in xenografted tumors in different treatment groups (n = 5/group). (a–e) Representative immunohistochemical staining of CD31: (a) Control group, (b) DOX group, (c) DOX + DUS group, (d) DOX-NB group, (e) DOX-NB + DUS group (×200) (scale bar = 100 μm). (f) Quantification of CD31 as presented in (a)–(e) (*p < 0.05).
Figure 8

Different expressions of CD31 by immunohistochemical staining in xenografted tumors in different treatment groups (n = 5/group). (a–e) Representative immunohistochemical staining of CD31: (a) Control group, (b) DOX group, (c) DOX + DUS group, (d) DOX-NB group, (e) DOX-NB + DUS group (×200) (scale bar = 100 μm). (f) Quantification of CD31 as presented in (a)–(e) (*p < 0.05).

4 Discussion

Tumor hypoxia has been demonstrated in 100% of primary NPC and closely related to tumor radiotherapy resistance [16]. Therefore, hypoxia is increasingly being recognized as an important therapeutic target to improve tumor radiosensitivity. CAIX expression has been demonstrated to correlate with tumor hypoxia [17]. Jiang et al. showed that downregulation of CAIX expression could promote radiosensitivity in CNE-2 cells [18].

In this study, the expression of CAIX in xenografted tumors of NPC was significantly downregulated when treated with DOX-NB + DUS group compared with DOX + DUS group or DOX-NB group, as determined using immunohistochemical staining. A previous study found that the expression of CAIX in head and neck cancer cells is positively correlated with MVD [19]. Reijnen et al. found that the poor outcome in hypoxic endometrial carcinoma may be related to vascular density and the expression of CAIX [20]. Rubio-Briones et al. found that the expressions of MVD and the CAIX were related to histological subtypes. The expression of CAIX can be used as a surrogate indicator of microvascular density [21]. To prove this relationship, the present study further detected the expression of MVD labeled by CD31 in subcutaneous transplanted tumors of NPC with different treatment groups. The results indicated that MVD was significantly lower when treated with DOX-NB + DUS compared with other treatment groups. Therefore, DOX-NB combined with DUS irradiation can downregulate the expression of CAIX in xenograft tumor, which is possibly related to the decrease in MVD within the tumor.

The reason for the decrease in MVD may be related to the cavitation effect induced by UTMD. Studies have shown that with appropriate ultrasound pressure, this cavitation effect can produce microfluidics, which can cause endothelial cell damage and microvascular rupture, thereby achieving the effect of destroying tumor microvessels [22]. Another reason for the decrease in MVD may be related to the increasing DOX concentration within the tumor. In vitro, we found that DOX-NB could effectively release DOX after exposure to DUS irradiation. In cell viability experiments, the viability of 5-8F cells in the DOX-NB + DUS group was significantly reduced compared with the other treatment groups (Control, DOX, DOX + DUS, and DOX-NB). The apoptosis rate of 5-8F cells in the DOX-NB + DUS group was significantly higher compared with the other treatment groups (Control, DOX, DOX + DUS, and DOX-NB). It was indicated that DOX-NB combined with DUS irradiation could improve the intracellular uptake of DOX in vitro. On the one hand, UTMD could produce instantaneous pores on the cell membrane and increase its permeability, which could lead to more DOX entering the tumor cells [13]. On the other hand, UTMD could promote the release of DOX encapsulated in drug-loaded nanovesicles and increase the concentration of DOX in tumor cells. It can effectively enhance the transport and uptake of DOX [23,24]. Studies have shown that chemotherapy not only kills tumor cells but also destroys the blood supply of tumor tissue by killing or inhibiting activated endothelial cells on blood vessels.

Research has illustrated that vascular endothelial cells are 10–10,000 times more sensitive to cytotoxic drugs than tumor cells are. Most tumor chemotherapy drugs have the effect of blocking angiogenesis and destroying existing blood vessels, including DOX [25]. Interestingly, this study showed that there was no statistically significant difference in MVD between the free DOX group and the Control group. Such a difference was also lacking between the DOX + DUS group and the DOX-NB group. This indicated that without the synergistic effect of UTMD, the low dose of DOX could not effectively exert its anti-tumor angiogenesis effect under the lower DOX concentration used in this study. The increasing concentration of DOX in the tumor could not only enhance the anti-tumor effect but also increase the ability to inhibit angiogenesis.

This study had a few limitations. First, in cell experiments, the mechanism of UTMD on cells has not been thoroughly studied, such as using flow cytometry to detect the effect of UTMD on cell cycle and using electron microscopy to observe the effect of cavitation on cell structure. Second, we have not constructed a cell hypoxia model to evaluate the changes of CAIX in cells after treatment. Third, we have not performed survival experiments to observe the inhibitory effect of treatment on tumor size.

5 Conclusion

DOX-NB combined with DUS irradiation could improve DOX-NB drug release and synergistically inhibit NPC cell activity. Meanwhile, DOX-NB combined with DUS irradiation could downregulate the expression of CAIX and decrease the MVD in mouse xenograft NPC model. This may be due to the synergistic effect of DUS combined with DOX-NB in reducing MVD in the context of NPC. Therefore, DOX-NB combined with DUS irradiation may be a promising therapeutic method for NPC.

# These authors are co-first authors.

tel: +86 15977486866

  1. Funding information: This research was funded by Guangxi Natural Science Foundation General Project (Grant number: 2018GXNSFAA281171) and National Natural Science Foundation of China Youth Science Fund Project (Grant number: 82001827).

  2. Conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

  3. Data availability statement: All data generated or used during the study are available from the corresponding author by request.

Appendix

Table A1

The DOX release rate of DOX-NB + DUS group compared with DOX-NB group within 24 h in vitro(n = 3/group)

Time (h) Comulative release rate of DOX (%) P-value
DOX-NB + DUS DOX-NB
1 19.5 ± 4.19 8.6 ± 1.70 0.014*
2 29.9 ± 2.84 15.5 ± 1.61 0.002*
3 36.6 ± 1.35 22.5 ± 5.02 0.009*
4 47.3 ± 4.16 27.8 ± 7.15 0.015*
5 52.6 ± 3.54 33.9 ± 8.917 0.028*
8 57.9 ± 3.81 41.2 ± 9.35 0.046*
11 69.3 ± 1.72 45.5 ± 11.85 0.026*
24 84.1 ± 1.78 52.2 ± 10.42 0.006*

*p < 0.05.

Table A2

The Cell viability of 5–8 F cells with different treatments (n = 3/group)

Group Group P-value
Control DOX < 0.001*
DOX + DUS 0.026*
DOX-NB 0.009*
DOX-NB + DUS < 0.001*
DOX DOX + DUS 0.969
DOX-NB 0.704
DOX-NB + DUS < 0.001*
DOX + DUS DOX-NB 1.000
DOX-NB + DUS 0.002*
DOX-NB DOX-NB + DUS 0.001*

*p < 0.05.

Table A3

The apoptosis rate of 5–8 F cells with different treatments (n = 3/group)

Group Group P-value
Control DOX 1.26
DOX + DUS 0.005*
DOX-NB 0.005*
DOX-NB + DUS < 0.001*
DOX DOX + DUS 0.079
DOX-NB 0.089
DOX-NB + DUS < 0.001*
DOX + DUS DOX-NB 0.943
DOX-NB + DUS 0.001*
DOX-NB DOX-NB + DUS 0.001*

*p < 0.05.

Table A4

The expression of CAIX by Immunohistochemistry in differrence treatment group(n = 5/group)

Group Group P-value
Control DOX 0.001*
DOX + DUS < 0.001*
DOX-NB < 0.001*
DOX-NB + DUS < 0.001*
DOX DOX + DUS 0.277
DOX-NB 0.102
DOX-NB + DUS < 0.001*
DOX + DUS DOX-NB 0.570
DOX-NB + DUS < 0.001*
DOX-NB DOX-NB + DUS < 0.001*

*p < 0.05.

Table A5

The expression of CD31 by Immunohistochemistry in differrence treatment group(n = 5/group)

Group Group P-value
Control DOX 0.869
DOX + DUS < 0.001*
DOX-NB < 0.001*
DOX-NB + DUS < 0.001*
DOX DOX + DUS < 0.001*
DOX-NB < 0.001*
DOX-NB + DUS < 0.001*
DOX + DUS DOX-NB 0.064
DOX-NB + DUS < 0.001*
DOX-NB DOX-NB + DUS < 0.001*

*p < 0.05.

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Received: 2023-08-25
Revised: 2024-01-19
Accepted: 2024-01-22
Published Online: 2024-02-13

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

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

Artikel in diesem Heft

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https://doi.org/10.1515/med-2024-0910
Schlagwörter für diesen Artikel
diagnostic ultrasound; nasopharyngeal carcinoma; carbonic anhydrase IX; doxorubicin nanobubbles; microvascular density
Creative Commons
BY 4.0

Artikel in diesem Heft

  1. Research Articles
  2. EDNRB inhibits the growth and migration of prostate cancer cells by activating the cGMP-PKG pathway
  3. STK11 (LKB1) mutation suppresses ferroptosis in lung adenocarcinoma by facilitating monounsaturated fatty acid synthesis
  4. Association of SOX6 gene polymorphisms with Kashin-Beck disease risk in the Chinese Han population
  5. The pyroptosis-related signature predicts prognosis and influences the tumor immune microenvironment in dedifferentiated liposarcoma
  6. METTL3 attenuates ferroptosis sensitivity in lung cancer via modulating TFRC
  7. Identification and validation of molecular subtypes and prognostic signature for stage I and stage II gastric cancer based on neutrophil extracellular traps
  8. Novel lumbar plexus block versus femoral nerve block for analgesia and motor recovery after total knee arthroplasty
  9. Correlation between ABCB1 and OLIG2 polymorphisms and the severity and prognosis of patients with cerebral infarction
  10. Study on the radiotherapy effect and serum neutral granulocyte lymphocyte ratio and inflammatory factor expression of nasopharyngeal carcinoma
  11. Transcriptome analysis of effects of Tecrl deficiency on cardiometabolic and calcium regulation in cardiac tissue
  12. Aflatoxin B1 induces infertility, fetal deformities, and potential therapies
  13. Serum levels of HMW adiponectin and its receptors are associated with cytokine levels and clinical characteristics in chronic obstructive pulmonary disease
  14. METTL3-mediated methylation of CYP2C19 mRNA may aggravate clopidogrel resistance in ischemic stroke patients
  15. Understand how machine learning impact lung cancer research from 2010 to 2021: A bibliometric analysis
  16. Pressure ulcers in German hospitals: Analysis of reimbursement and length of stay
  17. Metformin plus L-carnitine enhances brown/beige adipose tissue activity via Nrf2/HO-1 signaling to reduce lipid accumulation and inflammation in murine obesity
  18. Downregulation of carbonic anhydrase IX expression in mouse xenograft nasopharyngeal carcinoma model via doxorubicin nanobubble combined with ultrasound
  19. Feasibility of 3-dimensional printed models in simulated training and teaching of transcatheter aortic valve replacement
  20. miR-335-3p improves type II diabetes mellitus by IGF-1 regulating macrophage polarization
  21. The analyses of human MCPH1 DNA repair machinery and genetic variations
  22. Activation of Piezo1 increases the sensitivity of breast cancer to hyperthermia therapy
  23. Comprehensive analysis based on the disulfidptosis-related genes identifies hub genes and immune infiltration for pancreatic adenocarcinoma
  24. Changes of serum CA125 and PGE2 before and after high-intensity focused ultrasound combined with GnRH-a in treatment of patients with adenomyosis
  25. The clinical value of the hepatic venous pressure gradient in patients undergoing hepatic resection for hepatocellular carcinoma with or without liver cirrhosis
  26. Development and validation of a novel model to predict pulmonary embolism in cardiology suspected patients: A 10-year retrospective analysis
  27. Downregulation of lncRNA XLOC_032768 in diabetic patients predicts the occurrence of diabetic nephropathy
  28. Circ_0051428 targeting miR-885-3p/MMP2 axis enhances the malignancy of cervical cancer
  29. Effectiveness of ginkgo diterpene lactone meglumine on cognitive function in patients with acute ischemic stroke
  30. The construction of a novel prognostic prediction model for glioma based on GWAS-identified prognostic-related risk loci
  31. Evaluating the impact of childhood BMI on the risk of coronavirus disease 2019: A Mendelian randomization study
  32. Lactate dehydrogenase to albumin ratio is associated with in-hospital mortality in patients with acute heart failure: Data from the MIMIC-III database
  33. CD36-mediated podocyte lipotoxicity promotes foot process effacement
  34. Efficacy of etonogestrel subcutaneous implants versus the levonorgestrel-releasing intrauterine system in the conservative treatment of adenomyosis
  35. FLRT2 mediates chondrogenesis of nasal septal cartilage and mandibular condyle cartilage
  36. Challenges in treating primary immune thrombocytopenia patients undergoing COVID-19 vaccination: A retrospective study
  37. Let-7 family regulates HaCaT cell proliferation and apoptosis via the ΔNp63/PI3K/AKT pathway
  38. Phospholipid transfer protein ameliorates sepsis-induced cardiac dysfunction through NLRP3 inflammasome inhibition
  39. Postoperative cognitive dysfunction in elderly patients with colorectal cancer: A randomized controlled study comparing goal-directed and conventional fluid therapy
  40. Long-pulsed ultrasound-mediated microbubble thrombolysis in a rat model of microvascular obstruction
  41. High SEC61A1 expression predicts poor outcome of acute myeloid leukemia
  42. Comparison of polymerase chain reaction and next-generation sequencing with conventional urine culture for the diagnosis of urinary tract infections: A meta-analysis
  43. Secreted frizzled-related protein 5 protects against renal fibrosis by inhibiting Wnt/β-catenin pathway
  44. Pan-cancer and single-cell analysis of actin cytoskeleton genes related to disulfidptosis
  45. Overexpression of miR-532-5p restrains oxidative stress response of chondrocytes in nontraumatic osteonecrosis of the femoral head by inhibiting ABL1
  46. Autologous liver transplantation for unresectable hepatobiliary malignancies in enhanced recovery after surgery model
  47. Clinical analysis of incomplete rupture of the uterus secondary to previous cesarean section
  48. Abnormal sleep duration is associated with sarcopenia in older Chinese people: A large retrospective cross-sectional study
  49. No genetic causality between obesity and benign paroxysmal vertigo: A two-sample Mendelian randomization study
  50. Identification and validation of autophagy-related genes in SSc
  51. Long non-coding RNA SRA1 suppresses radiotherapy resistance in esophageal squamous cell carcinoma by modulating glycolytic reprogramming
  52. Evaluation of quality of life in patients with schizophrenia: An inpatient social welfare institution-based cross-sectional study
  53. The possible role of oxidative stress marker glutathione in the assessment of cognitive impairment in multiple sclerosis
  54. Compilation of a self-management assessment scale for postoperative patients with aortic dissection
  55. Left atrial appendage closure in conjunction with radiofrequency ablation: Effects on left atrial functioning in patients with paroxysmal atrial fibrillation
  56. Effect of anterior femoral cortical notch grade on postoperative function and complications during TKA surgery: A multicenter, retrospective study
  57. Clinical characteristics and assessment of risk factors in patients with influenza A-induced severe pneumonia after the prevalence of SARS-CoV-2
  58. Analgesia nociception index is an indicator of laparoscopic trocar insertion-induced transient nociceptive stimuli
  59. High STAT4 expression correlates with poor prognosis in acute myeloid leukemia and facilitates disease progression by upregulating VEGFA expression
  60. Factors influencing cardiovascular system-related post-COVID-19 sequelae: A single-center cohort study
  61. HOXD10 regulates intestinal permeability and inhibits inflammation of dextran sulfate sodium-induced ulcerative colitis through the inactivation of the Rho/ROCK/MMPs axis
  62. Mesenchymal stem cell-derived exosomal miR-26a induces ferroptosis, suppresses hepatic stellate cell activation, and ameliorates liver fibrosis by modulating SLC7A11
  63. Endovascular thrombectomy versus intravenous thrombolysis for primary distal, medium vessel occlusion in acute ischemic stroke
  64. ANO6 (TMEM16F) inhibits gastrointestinal stromal tumor growth and induces ferroptosis
  65. Prognostic value of EIF5A2 in solid tumors: A meta-analysis and bioinformatics analysis
  66. The role of enhanced expression of Cx43 in patients with ulcerative colitis
  67. Choosing a COVID-19 vaccination site might be driven by anxiety and body vigilance
  68. Role of ICAM-1 in triple-negative breast cancer
  69. Cost-effectiveness of ambroxol in the treatment of Gaucher disease type 2
  70. HLA-DRB5 promotes immune thrombocytopenia via activating CD8+ T cells
  71. Efficacy and factors of myofascial release therapy combined with electrical and magnetic stimulation in the treatment of chronic pelvic pain syndrome
  72. Efficacy of tacrolimus monotherapy in primary membranous nephropathy
  73. Mechanisms of Tripterygium wilfordii Hook F on treating rheumatoid arthritis explored by network pharmacology analysis and molecular docking
  74. FBXO45 levels regulated ferroptosis renal tubular epithelial cells in a model of diabetic nephropathy by PLK1
  75. Optimizing anesthesia strategies to NSCLC patients in VATS procedures: Insights from drug requirements and patient recovery patterns
  76. Alpha-lipoic acid upregulates the PPARγ/NRF2/GPX4 signal pathway to inhibit ferroptosis in the pathogenesis of unexplained recurrent pregnancy loss
  77. Correlation between fat-soluble vitamin levels and inflammatory factors in paediatric community-acquired pneumonia: A prospective study
  78. CD1d affects the proliferation, migration, and apoptosis of human papillary thyroid carcinoma TPC-1 cells via regulating MAPK/NF-κB signaling pathway
  79. miR-let-7a inhibits sympathetic nerve remodeling after myocardial infarction by downregulating the expression of nerve growth factor
  80. Immune response analysis of solid organ transplantation recipients inoculated with inactivated COVID-19 vaccine: A retrospective analysis
  81. The H2Valdien derivatives regulate the epithelial–mesenchymal transition of hepatoma carcinoma cells through the Hedgehog signaling pathway
  82. Clinical efficacy of dexamethasone combined with isoniazid in the treatment of tuberculous meningitis and its effect on peripheral blood T cell subsets
  83. Comparison of short-segment and long-segment fixation in treatment of degenerative scoliosis and analysis of factors associated with adjacent spondylolisthesis
  84. Lycopene inhibits pyroptosis of endothelial progenitor cells induced by ox-LDL through the AMPK/mTOR/NLRP3 pathway
  85. Methylation regulation for FUNDC1 stability in childhood leukemia was up-regulated and facilitates metastasis and reduces ferroptosis of leukemia through mitochondrial damage by FBXL2
  86. Correlation of single-fiber electromyography studies and functional status in patients with amyotrophic lateral sclerosis
  87. Risk factors of postoperative airway obstruction complications in children with oral floor mass
  88. Expression levels and clinical significance of serum miR-19a/CCL20 in patients with acute cerebral infarction
  89. Physical activity and mental health trends in Korean adolescents: Analyzing the impact of the COVID-19 pandemic from 2018 to 2022
  90. Evaluating anemia in HIV-infected patients using chest CT
  91. Ponticulus posticus and skeletal malocclusion: A pilot study in a Southern Italian pre-orthodontic court
  92. Causal association of circulating immune cells and lymphoma: A Mendelian randomization study
  93. Assessment of the renal function and fibrosis indexes of conventional western medicine with Chinese medicine for dredging collaterals on treating renal fibrosis: A systematic review and meta-analysis
  94. Comprehensive landscape of integrator complex subunits and their association with prognosis and tumor microenvironment in gastric cancer
  95. New target-HMGCR inhibitors for the treatment of primary sclerosing cholangitis: A drug Mendelian randomization study
  96. Population pharmacokinetics of meropenem in critically ill patients
  97. Comparison of the ability of newly inflammatory markers to predict complicated appendicitis
  98. Comparative morphology of the cruciate ligaments: A radiological study
  99. Immune landscape of hepatocellular carcinoma: The central role of TP53-inducible glycolysis and apoptosis regulator
  100. Serum SIRT3 levels in epilepsy patients and its association with clinical outcomes and severity: A prospective observational study
  101. SHP-1 mediates cigarette smoke extract-induced epithelial–mesenchymal transformation and inflammation in 16HBE cells
  102. Acute hyper-hypoxia accelerates the development of depression in mice via the IL-6/PGC1α/MFN2 signaling pathway
  103. The GJB3 correlates with the prognosis, immune cell infiltration, and therapeutic responses in lung adenocarcinoma
  104. Physical fitness and blood parameters outcomes of breast cancer survivor in a low-intensity circuit resistance exercise program
  105. Exploring anesthetic-induced gene expression changes and immune cell dynamics in atrial tissue post-coronary artery bypass graft surgery
  106. Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism
  107. Analysis of the risk factors of the radiation-induced encephalopathy in nasopharyngeal carcinoma: A retrospective cohort study
  108. Reproductive outcomes in women with BRCA 1/2 germline mutations: A retrospective observational study and literature review
  109. Evaluation of upper airway ultrasonographic measurements in predicting difficult intubation: A cross-section of the Turkish population
  110. Prognostic and diagnostic value of circulating IGFBP2 in pancreatic cancer
  111. Postural stability after operative reconstruction of the AFTL in chronic ankle instability comparing three different surgical techniques
  112. Research trends related to emergence agitation in the post-anaesthesia care unit from 2001 to 2023: A bibliometric analysis
  113. Frequency and clinicopathological correlation of gastrointestinal polyps: A six-year single center experience
  114. ACSL4 mediates inflammatory bowel disease and contributes to LPS-induced intestinal epithelial cell dysfunction by activating ferroptosis and inflammation
  115. Affibody-based molecular probe 99mTc-(HE)3ZHER2:V2 for non-invasive HER2 detection in ovarian and breast cancer xenografts
  116. Effectiveness of nutritional support for clinical outcomes in gastric cancer patients: A meta-analysis of randomized controlled trials
  117. The relationship between IFN-γ, IL-10, IL-6 cytokines, and severity of the condition with serum zinc and Fe in children infected with Mycoplasma pneumoniae
  118. Paraquat disrupts the blood–brain barrier by increasing IL-6 expression and oxidative stress through the activation of PI3K/AKT signaling pathway
  119. Sleep quality associate with the increased prevalence of cognitive impairment in coronary artery disease patients: A retrospective case–control study
  120. Dioscin protects against chronic prostatitis through the TLR4/NF-κB pathway
  121. Association of polymorphisms in FBN1, MYH11, and TGF-β signaling-related genes with susceptibility of sporadic thoracic aortic aneurysm and dissection in the Zhejiang Han population
  122. Application value of multi-parameter magnetic resonance image-transrectal ultrasound cognitive fusion in prostate biopsy
  123. Laboratory variables‐based artificial neural network models for predicting fatty liver disease: A retrospective study
  124. Decreased BIRC5-206 promotes epithelial–mesenchymal transition in nasopharyngeal carcinoma through sponging miR-145-5p
  125. Sepsis induces the cardiomyocyte apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway
  126. Assessment of iron metabolism and iron deficiency in incident patients on incident continuous ambulatory peritoneal dialysis
  127. Tibial periosteum flap combined with autologous bone grafting in the treatment of Gustilo-IIIB/IIIC open tibial fractures
  128. The application of intravenous general anesthesia under nasopharyngeal airway assisted ventilation undergoing ureteroscopic holmium laser lithotripsy: A prospective, single-center, controlled trial
  129. Long intergenic noncoding RNA for IGF2BP2 stability suppresses gastric cancer cell apoptosis by inhibiting the maturation of microRNA-34a
  130. Role of FOXM1 and AURKB in regulating keratinocyte function in psoriasis
  131. Parental control attitudes over their pre-school children’s diet
  132. The role of auto-HSCT in extranodal natural killer/T cell lymphoma
  133. Significance of negative cervical cytology and positive HPV in the diagnosis of cervical lesions by colposcopy
  134. Echinacoside inhibits PASMCs calcium overload to prevent hypoxic pulmonary artery remodeling by regulating TRPC1/4/6 and calmodulin
  135. ADAR1 plays a protective role in proximal tubular cells under high glucose conditions by attenuating the PI3K/AKT/mTOR signaling pathway
  136. The risk of cancer among insulin glargine users in Lithuania: A retrospective population-based study
  137. The unusual location of primary hydatid cyst: A case series study
  138. Intraoperative changes in electrophysiological monitoring can be used to predict clinical outcomes in patients with spinal cavernous malformation
  139. Obesity and risk of placenta accreta spectrum: A meta-analysis
  140. Shikonin alleviates asthma phenotypes in mice via an airway epithelial STAT3-dependent mechanism
  141. NSUN6 and HTR7 disturbed the stability of carotid atherosclerotic plaques by regulating the immune responses of macrophages
  142. The effect of COVID-19 lockdown on admission rates in Maternity Hospital
  143. Temporal muscle thickness is not a prognostic predictor in patients with high-grade glioma, an experience at two centers in China
  144. Luteolin alleviates cerebral ischemia/reperfusion injury by regulating cell pyroptosis
  145. Therapeutic role of respiratory exercise in patients with tuberculous pleurisy
  146. Effects of CFTR-ENaC on spinal cord edema after spinal cord injury
  147. Irisin-regulated lncRNAs and their potential regulatory functions in chondrogenic differentiation of human mesenchymal stem cells
  148. DMD mutations in pediatric patients with phenotypes of Duchenne/Becker muscular dystrophy
  149. Combination of C-reactive protein and fibrinogen-to-albumin ratio as a novel predictor of all-cause mortality in heart failure patients
  150. Significant role and the underly mechanism of cullin-1 in chronic obstructive pulmonary disease
  151. Ferroptosis-related prognostic model of mantle cell lymphoma
  152. Observation of choking reaction and other related indexes in elderly painless fiberoptic bronchoscopy with transnasal high-flow humidification oxygen therapy
  153. A bibliometric analysis of Prader-Willi syndrome from 2002 to 2022
  154. The causal effects of childhood sunburn occasions on melanoma: A univariable and multivariable Mendelian randomization study
  155. Oxidative stress regulates glycogen synthase kinase-3 in lymphocytes of diabetes mellitus patients complicated with cerebral infarction
  156. Role of COX6C and NDUFB3 in septic shock and stroke
  157. Trends in disease burden of type 2 diabetes, stroke, and hypertensive heart disease attributable to high BMI in China: 1990–2019
  158. Purinergic P2X7 receptor mediates hyperoxia-induced injury in pulmonary microvascular endothelial cells via NLRP3-mediated pyroptotic pathway
  159. Investigating the role of oviductal mucosa–endometrial co-culture in modulating factors relevant to embryo implantation
  160. Analgesic effect of external oblique intercostal block in laparoscopic cholecystectomy: A retrospective study
  161. Elevated serum miR-142-5p correlates with ischemic lesions and both NSE and S100β in ischemic stroke patients
  162. Correlation between the mechanism of arteriopathy in IgA nephropathy and blood stasis syndrome: A cohort study
  163. Risk factors for progressive kyphosis after percutaneous kyphoplasty in osteoporotic vertebral compression fracture
  164. Predictive role of neuron-specific enolase and S100-β in early neurological deterioration and unfavorable prognosis in patients with ischemic stroke
  165. The potential risk factors of postoperative cognitive dysfunction for endovascular therapy in acute ischemic stroke with general anesthesia
  166. Fluoxetine inhibited RANKL-induced osteoclastic differentiation in vitro
  167. Detection of serum FOXM1 and IGF2 in patients with ARDS and their correlation with disease and prognosis
  168. Rhein promotes skin wound healing by activating the PI3K/AKT signaling pathway
  169. Differences in mortality risk by levels of physical activity among persons with disabilities in South Korea
  170. Review Articles
  171. Cutaneous signs of selected cardiovascular disorders: A narrative review
  172. XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis
  173. A narrative review on adverse drug reactions of COVID-19 treatments on the kidney
  174. Emerging role and function of SPDL1 in human health and diseases
  175. Adverse reactions of piperacillin: A literature review of case reports
  176. Molecular mechanism and intervention measures of microvascular complications in diabetes
  177. Regulation of mesenchymal stem cell differentiation by autophagy
  178. Molecular landscape of borderline ovarian tumours: A systematic review
  179. Advances in synthetic lethality modalities for glioblastoma multiforme
  180. Investigating hormesis, aging, and neurodegeneration: From bench to clinics
  181. Frankincense: A neuronutrient to approach Parkinson’s disease treatment
  182. Sox9: A potential regulator of cancer stem cells in osteosarcoma
  183. Early detection of cardiovascular risk markers through non-invasive ultrasound methodologies in periodontitis patients
  184. Advanced neuroimaging and criminal interrogation in lie detection
  185. Maternal factors for neural tube defects in offspring: An umbrella review
  186. The chemoprotective hormetic effects of rosmarinic acid
  187. CBD’s potential impact on Parkinson’s disease: An updated overview
  188. Progress in cytokine research for ARDS: A comprehensive review
  189. Utilizing reactive oxygen species-scavenging nanoparticles for targeting oxidative stress in the treatment of ischemic stroke: A review
  190. NRXN1-related disorders, attempt to better define clinical assessment
  191. Lidocaine infusion for the treatment of complex regional pain syndrome: Case series and literature review
  192. Trends and future directions of autophagy in osteosarcoma: A bibliometric analysis
  193. Iron in ventricular remodeling and aneurysms post-myocardial infarction
  194. Case Reports
  195. Sirolimus potentiated angioedema: A case report and review of the literature
  196. Identification of mixed anaerobic infections after inguinal hernia repair based on metagenomic next-generation sequencing: A case report
  197. Successful treatment with bortezomib in combination with dexamethasone in a middle-aged male with idiopathic multicentric Castleman’s disease: A case report
  198. Complete heart block associated with hepatitis A infection in a female child with fatal outcome
  199. Elevation of D-dimer in eosinophilic gastrointestinal diseases in the absence of venous thrombosis: A case series and literature review
  200. Four years of natural progressive course: A rare case report of juvenile Xp11.2 translocations renal cell carcinoma with TFE3 gene fusion
  201. Advancing prenatal diagnosis: Echocardiographic detection of Scimitar syndrome in China – A case series
  202. Outcomes and complications of hemodialysis in patients with renal cancer following bilateral nephrectomy
  203. Anti-HMGCR myopathy mimicking facioscapulohumeral muscular dystrophy
  204. Recurrent opportunistic infections in a HIV-negative patient with combined C6 and NFKB1 mutations: A case report, pedigree analysis, and literature review
  205. Letter to the Editor
  206. Letter to the Editor: Total parenteral nutrition-induced Wernicke’s encephalopathy after oncologic gastrointestinal surgery
  207. Erratum
  208. Erratum to “Bladder-embedded ectopic intrauterine device with calculus”
  209. Retraction
  210. Retraction of “XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis”
  211. Corrigendum
  212. Corrigendum to “Investigating hormesis, aging, and neurodegeneration: From bench to clinics”
  213. Corrigendum to “Frankincense: A neuronutrient to approach Parkinson’s disease treatment”
  214. Special Issue The evolving saga of RNAs from bench to bedside - Part II
  215. Machine-learning-based prediction of a diagnostic model using autophagy-related genes based on RNA sequencing for patients with papillary thyroid carcinoma
  216. Unlocking the future of hepatocellular carcinoma treatment: A comprehensive analysis of disulfidptosis-related lncRNAs for prognosis and drug screening
  217. Elevated mRNA level indicates FSIP1 promotes EMT and gastric cancer progression by regulating fibroblasts in tumor microenvironment
  218. Special Issue Advancements in oncology: bridging clinical and experimental research - Part I
  219. Ultrasound-guided transperineal vs transrectal prostate biopsy: A meta-analysis of diagnostic accuracy and complication rates
  220. Assessment of diagnostic value of unilateral systematic biopsy combined with targeted biopsy in detecting clinically significant prostate cancer
  221. SENP7 inhibits glioblastoma metastasis and invasion by dissociating SUMO2/3 binding to specific target proteins
  222. MARK1 suppress malignant progression of hepatocellular carcinoma and improves sorafenib resistance through negatively regulating POTEE
  223. Analysis of postoperative complications in bladder cancer patients
  224. Carboplatin combined with arsenic trioxide versus carboplatin combined with docetaxel treatment for LACC: A randomized, open-label, phase II clinical study
  225. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part I
  226. Comprehensive pan-cancer investigation of carnosine dipeptidase 1 and its prospective prognostic significance in hepatocellular carcinoma
  227. Identification of signatures associated with microsatellite instability and immune characteristics to predict the prognostic risk of colon cancer
  228. Single-cell analysis identified key macrophage subpopulations associated with atherosclerosis
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Heruntergeladen am 24.10.2025 von https://www.degruyterbrill.com/document/doi/10.1515/med-2024-0910/html?srsltid=AfmBOoox9WnhU9g0lxzeDDVydNeZSr5hUR8didTA81cvfTrwNU_xK6TT
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