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The combination of photothermal therapy with chemotherapy has emerged as a promising therapeutic modality for addressing triple-negative breast cancer (TNBC). This manuscript describes a novel hybrid nanoplatform comprising ultrathin catalytic platinum/gold (Pt/Au) nanotubes encapsulated with docetaxel and phase-change materials (PCMs) for the photoacoustic imaging-guided synergistic chemo-photothermal therapy of TNBC. Upon irradiation of near-infrared laser, the photothermal heating of nanotubes converts solid-state PCM into liquid, triggering the controlled release of the encapsulated docetaxel. The thin Pt layer within nanotubes enhances the nanotube's thermal stability, thus prolonging the photothermal ablation of tumors. Furthermore, platinum effectively mitigates tumor hypoxia by catalyzing the decomposition of hydrogen peroxides to generate oxygen in the tumor microenvironment, thus improving the efficiency of chemotherapy. It is demonstrated that the drug-loaded nanotubes achieve significant tumor inhibition rates of 75.4% in vivo on 4T1 tumor-bearing mice, significantly surpassing control groups. These nanotubes also notably extend survival, attributable to the synergistic effects of prolonged photothermal therapy facilitated by platinum and oxygenation-enhanced chemotherapy. This combination leverages the unique properties of the Pt/Au NTs-DTX/PCM nanoplatform, optimizing therapeutic outcomes. It is envisioned that this nanoplatform may find important applications in managing superficial malignant solid tumors in general.
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Objective: To analyze the antibiotic resistance profile, virulence genes, and molecular typing of Staphylococcus aureus (S. aureus) strains isolated in skin and soft tissue infections at the First Affiliated Hospital, Gannan Medical University, to better understand the molecular epidemiological characteristics of S. aureus. Methods: In 2023, 65 S. aureus strains were isolated from patients with skin and soft tissue infections. Strain identification and susceptibility tests were performed using VITEK 2 and gram-positive bacteria identification cards. DNA was extracted using a DNA extraction kit, and all genes were amplified using polymerase chain reaction. Multilocus sequence typing (MLST) was used for molecular typing. Results: In this study, of the 65 S. aureus strains were tested for their susceptibility to 16 antibiotics, the highest resistance rate to penicillin G was 95.4%. None of the staphylococcal isolates showed resistance to ceftaroline, daptomycin, linezolid, tigecycline, teicoplanin, or vancomycin. fnbA was the most prevalent virulence gene (100%) in S. aureus strains isolated in skin and soft tissue infections, followed by arcA (98.5%). Statistical analyses showed that the resistance rates of methicillin-resistant S. aureus isolates to various antibiotics were significantly higher than those of methicillin-susceptible S. aureus isolates. Fifty sequence types (STs), including 44 new ones, were identified by MLST. Conclusion: In this study, the high resistance rate to penicillin G and the high carrying rate of virulence gene fnbA and arcA of S.aureus were determine, and 44 new STs were identified, which may be associated with the geographical location of southern Jiangxi and local trends in antibiotic use. The study of the clonal lineage and evolutionary relationships of S. aureus in these regions may help in understanding the molecular epidemiology and provide the experimental basis for pathogenic bacteria prevention and treatment.
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Ultrasound technology has been extensively used as one of the efficient and economic methodology to achieve the desired outcomes in many applications by harnessing the physico-chemical effects of acoustic cavitation. However, the cavitation-associated effects, primarily determined by the oscillatory dynamics of cavitation bubbles, are considerably complex and still remain poorly understood. The main objective of this study was to perform a numerical analysis of the acoustic cavitation (i.e., the cavitation dynamics, the resultant temperature, pressure and chemical yields within collapsing bubbles), particularly focusing on the influence of the interactions between bubbles. A comprehensive model was developed to simulate the acoustic cavitation dynamics via combining the influences of mass transfer, heat conduction and chemical reactions as well as the interaction effects between bubbles. The results demonstrated that only the large bubble exerts a greater impact on the small one in a two-bubble system. Specifically, within parameter ranges covered this study, there are noticeable decreases in the expansion ratio of the small bubble, the resultant temperature, pressure and molar yields of free radicals, hence weakening the cavitation intensity and cavitation- associated physico-chemical effects. Moreover, the influences of the interactions between bubbles were further assessed quantitatively under various parameters, such as the ultrasound amplitude PA and frequency f, the distance between bubbles d0, the initial radius of the large bubble R20, as well as the liquid properties (e.g., surface tension σ and viscosity µ). It was found that the suppression effect can be amplified when subjected to ultrasound with an increased PA and/or a decreased f, probably due to a stronger cavitation intensity under this condition. Additionally, the suppression effect is also enhanced with a decrease in d0, σ and µ, but with R20 increasing. This study can contribute to deepening knowledge about acoustic cavitation and the resultant physical and/or chemical effects, potentially further facilitating the ultrasound-assisted various applications involving acoustic cavitation.
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The cavitation dynamics of a two-bubble system in viscoelastic media excited by dual-frequency ultrasound is studied numerically with a focus on the effects of inter-bubble interactions. Compared to the isolated bubble cases, the enhancement or suppression effects can be exerted on the amplitude and nonlinearity of the bubble oscillations to different degrees. Moreover, the interaction effects are found to be highly sensitive to multiple paramount parameters related to the two-bubble system, the dual-frequency ultrasound and the medium viscoelasticity. Specifically, the larger bubble of a two-bubble system shows a stronger effect on the smaller one, and this effect becomes more pronounced when the larger bubble undergoes harmonic and/or subharmonic resonances as well as the two bubbles get closer (e.g., d0 < 100 µm). For the influences of the dual-frequency excitation, the results show that the bubbles can achieve enhanced harmonic and/or subharmonic oscillations as the frequency combinations with small frequency differences (e.g., Δf < 0.2 MHz) close to the corresponding resonance frequencies of bubbles, and the interaction effects are consequently intensified. Similarly, the bubble oscillations and the interaction effects can also be enhanced as the acoustic pressure amplitude of each frequency component is equal and the pressure amplitude pA increases. Above a pressure threshold (pA = 215 kPa), a larger bubble undergoes period 2 (P2) oscillations, which can force a smaller bubble to change its oscillation pattern from period 1 (P1) into P2 oscillations. In addition, it is found that the medium viscosity dampens the bubble oscillations while the medium elasticity affects the bubble resonances, accordingly exhibiting stronger interaction effects at smaller viscosities (e.g., µ < 4 mPa·s) or certain elasticities (approximately G = 70-120 kPa, G = 160-200 kPa and G = 640-780 kPa) at which the bubble resonances occur. The study can contribute to a better understanding of the complex dynamic behaviors of interacting cavitation bubbles in viscoelastic tissues for high efficient cavitation-mediated biomedical applications using dual-frequency ultrasound.
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BACKGROUND: Abnormal serum ferritin levels are associated with a variety of diseases. Meanwhile, abnormal serum ferritin is influenced by a variety of risk factors, but its correlation with obesity remains poorly described. OBJECTIVE: This study aimed to investigate the association of body mass index (BMI) and weight waist adjustment index (WWI) with serum ferritin in US adults. METHODS: Participants in this study took part in the National Health and Nutrition Examination Survey (NHANES) prior to the pandemic from 2017 to March 2020. Serum ferritin was used as the sole response variable and BMI and WWI were used as independent variables. Multiple linear regression was used to assess the relationship between serum ferritin and the independent variables, and smoothed curve fitting and threshold effects analysis were performed to assess the presence of non-linear relationships. To validate the sensitive individuals for the correlation between the independent and the dependent variables, a subgroup analysis was performed. RESULTS: A final total of 7552 participants were included in this study. Both independent variables had a positive relationship with serum ferritin, with effect values of (ß = 0.68, 95% CI: 0.17-1.19) when BMI was the independent variable and (ß = 8.62, 95% CI: 3.53-13.72) when WWI was the independent variable in the fully adjusted model. This positive association between the two obesity-related indexes and serum ferritin became more significant as BMI and WWI increased (P for trend < 0.001). In subgroup analyses, the positive association between the independent variables and serum ferritin was more pronounced in participants who were male, 40-59 years old, white, and had diabetes and hypertension. In addition, smoothed curve fitting and threshold effects analysis demonstrated a linear positive association of BMI and WWI with serum ferritin. CONCLUSIONS: In the US adult population, while there was a linear positive association of WWI and BMI with serum ferritin, the effect values between WWI and serum ferritin were more significant. Male, 40-59 years old, white, participants with diabetes and hypertension should be cautious that higher WWI might entail a risk of higher serum ferritin levels.
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Hipertensión , Humanos , Adulto , Masculino , Persona de Mediana Edad , Femenino , Índice de Masa Corporal , Encuestas Nutricionales , Obesidad/epidemiología , FerritinasRESUMEN
The importance of serum ferritin has been demonstrated in many liver diseases, but its relationship with liver stiffness remains unclear. The objective of this study was to investigate the association between serum ferritin levels and participants' liver stiffness measurement (LSM) in the United States population. We conducted a screening of participants from National Health and Nutrition Examination Survey (NHANES) 2017.1 to 2020.3 to ensure that participants included in this study had complete serum ferritin and LSM information. Association between the independent variable (serum ferritin) and the dependent variable (LSM) was investigated by multiple linear regression and subgroup analysis was performed to identify sensitive individuals, and we subsequently assessed whether there was a non-linear relationship between the 2 using smoothed curve fitting and threshold effect models. The final 7143 participants were included in this study. There was a positive association between participants' serum ferritin concentration and LSM, with an effect value of (ß = 0.0007, 95% confidence interval (CI): 0.0002-0.0011) in the all-adjusted model. The smoothing curve and threshold effect models indicated a non-linear positive correlation between serum ferritin and LSM, which was more pronounced when serum ferritin concentration exceeded 440 ng/mL. Subsequent subgroup analysis showed that this positive correlation was more pronounced in males (ß = 0.0007, 95% CI: 0.0001-0.0012), age >60 years (ß = 0.00015, 95% CI: 0.0007-0.0023), black participants (ß = 0.00018, 95% CI: 0.0009-0.0026), and participants with body mass index (BMI) <25 kg/m2 (ß = 0.00012, 95% CI: 0.0005-0.0020). In U.S. adults, there was a positive correlation between serum ferritin levels and liver stiffness, which was more pronounced when serum ferritin exceeded 440 ng/mL. Our study suggested that regular serum ferritin testing would be beneficial in monitoring changes in liver stiffness. Male, age >60 years, black participants, and those with a BMI < 25 kg/m2 should be of greater consideration.
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Ferritinas , Hígado , Adulto , Humanos , Masculino , Estudios Transversales , Ferritinas/sangre , Hígado/diagnóstico por imagen , Encuestas Nutricionales , Femenino , Persona de Mediana Edad , Negro o AfroamericanoRESUMEN
Background: Coarctation of the aorta (CoA) is a common congenital cardiovascular malformation, and improvements in the diagnostic process for surgical decision-making are important. We sought to compare the diagnostic accuracy of transthoracic echocardiography (TTE) with computed tomographic angiography (CTA) to diagnose CoA. Methods: We retrospectively reviewed 197 cases of CoA diagnosed by TTE and CTA and confirmed at surgery from July 2009 to August 2019. Results: The surgical findings confirmed that 19 patients (9.6%) had isolated CoA and 178 (90.4%) had CoA combined with other congenital cardiovascular malformations. The diagnostic accuracy of CoA by CTA was significantly higher than that of TTE (χ2 = 6.52, p = 0.01). In contrast, the diagnostic accuracy of TTE for associated cardiovascular malformations of CoA was significantly higher than that of CTA (χ2 = 15.36, p < 0.0001). Infants and young children had more preductal type of CoA, and PDA was the most frequent cardiovascular lesion associated with CoA. The pressure gradient was significantly decreased after the first operation, similar at 6 months, 1 year, and 3 years follow-ups by TTE. Conclusions: CTA is more accurate as a clinical tool for diagnosing CoA; however, TTE with color Doppler can better identify associated congenital cardiovascular malformations. Therefore, combining TTE and CTA would benefit clinical evaluation and management in patients suspected of CoA. TTE was valuable for post-operation follow-up and clinical management.
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Objective: This study aimed to explore the safety and efficacy of simultaneous interventional therapy for compound congenital heart disease (CCHD) in children. Methods: In total, 155 children with CCHD who received simultaneous interventional therapy at the Children's Hospital of Chongqing Medical University between January 2007 and December 2021 were included in study. Data on clinical manifestations, transthoracic echocardiography, electrocardiogram, and follow-up were retrospectively analyzed. Results: The most common type of CCHD was atrial septal defect (ASD) combined with ventricular septal defect (VSD), accounting for 32.3% of the patients. Simultaneous interventional therapy was successfully administered to 151 children (97.4%). The pulmonary gradient of patients with pulmonary stenosis decreased from 47.3 ± 21.9â mmHg to 15.2 ± 12.2â mmHg (P < 0.05) immediately after the procedure. One patient had failed PBPV as he had residual PS >40â mmHg post procedure. The right ventricular dimension and left ventricular end-diastolic dimension significantly decreased in the first month after the procedure in patients with ASD combined with VSD. Twenty-five (16.1%) patients had mild residual shunt, which spontaneously disappeared in more than half of these patients 6 months after the procedure. The major adverse events were minimal (n = 4, 2.58%), including one patient requiring drug treatment for complete atrioventricular block and three patients receiving surgical treatment because of cardiac erosion, anterior tricuspid valve chordae rupture, and hemolysis, respectively. Conclusions: ASD combined with VSD is the most common type of CCHD in children, and simultaneous interventional therapy for CCHD in children is safe and effective with satisfactory results. Ventricular remodeling can be reversed in patients with ASD combined with VSD 1 month after the procedure. Most adverse events associated with interventional therapy are mild and manageable.
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The cavitation dynamics of an air-vapor mixture bubble with ultrasonic excitation can be greatly affected by the equation of state (EOS) for the interior gases. To simulate the cavitation dynamics, the Gilmore-Akulichev equation was coupled with the Peng-Robinson (PR) EOS or the Van der Waals (vdW) EOS. In this study, the thermodynamic properties of air and water vapor predicted by the PR and vdW EOS were first compared, and the results showed that the PR EOS gives a more accurate estimation of the gases within the bubble due to the less deviation from the experimental values. Moreover, the acoustic cavitation characteristics predicted by the Gilmore-PR model were compared to the Gilmore-vdW model, including the bubble collapse strength, the temperature, pressure and number of water molecules within the bubble. The results indicated that a stronger bubble collapse was predicted by the Gilmore-PR model rather than the Gilmore-vdW model, with higher temperature and pressure, as well as more water molecules within the collapsing bubble. More importantly, it was found that the differences between both models increase at higher ultrasound amplitudes or lower ultrasound frequencies while decreasing as the initial bubble radius and the liquid parameters (e.g., surface tension, viscosity and temperature of the surrounding liquid) increase. This study might offer important insights into the effects of the EOS for interior gases on the cavitation bubble dynamics and the resultant acoustic cavitation-associated effects, contributing to further optimization of its applications in sonochemistry and biomedicine.
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[This corrects the article DOI: 10.1016/j.gendis.2018.04.003.].
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[This corrects the article DOI: 10.1016/j.gendis.2018.02.001.].
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[This corrects the article DOI: 10.1016/j.gendis.2018.04.006.].
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The resonance behaviors of a few lipid-coated microbubbles acoustically activated in viscoelastic media were comprehensively examined via radius response analysis. The size polydispersity and random spatial distribution of the interacting microbubbles, the rheological properties of the lipid shell and the viscoelasticity of the surrounding medium were considered simultaneously. The obtained radius response curves present a successive occurrence of linear resonances, nonlinear harmonic and sub-harmonic resonances with the acoustic pressure increasing. The microbubble resonance is radius-, pressure- and frequency-dependent. Specifically, the maximum bubble expansion ratio at the main resonance peak increases but the resonant radius decreases as the ultrasound pressure increases, while both of them decrease with the ultrasound frequency increasing. Moreover, compared to an isolated microbubble case, it is found that large microbubbles in close proximity prominently suppress the resonant oscillations while slightly increase the resonant radii for both harmonic and subharmonic resonances, even leading to the disappearance of the subharmonic resonance with the influences increasing to a certain degree. In addition, the results also suggest that both the encapsulating shell and surrounding medium can substantially dampen the harmonic and subharmonic resonances while increase the resonant radii, which seem to be affected by the medium viscoelasticity to a greater degree rather than the shell properties. This work offers valuable insights into the resonance behaviors of microbubbles oscillating in viscoelastic biological media, greatly contributing to further optimizing their biomedical applications.
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BACKGROUND: Gasdermin (GSDM) B is a member of the GSDM family, which is a protein that may be involved in the cell pyroptosis process and is associated with inflammatory diseases. OBJECTIVE: To explore the correlation between GSDMB and psoriasis vulgaris. METHODS: Skin lesions from 33 patients with psoriasis vulgaris and 69 normal controls were collected. ELISA and Western blot were adopted to detect proteins. The HaCaT cell line was transfected with 3 sets of interfering sequence siRNA, and the mRNA and protein levels before and after the transfection were measured by qPCR and Western blot respectively, so as to establish a cell model with low GSDMB gene expression; the MTT method was used to detect cells viability, flow cytometry to detect cell apoptosis. RESULTS: The level of GSDMB protein in the skin lesions of patients with psoriasis vulgaris was lower than that in normal skin tissues (P < 0.05). The mRNA and protein expression levels of the target gene in the siRNA-GSDMB-3 group were lower than those in the control group (P < 0.05). The proliferation of HaCaT cells was decreased by MTT method and flow cytometry, and the apoptosis rate was increased (P < 0.05). CONCLUSION: The expression level of GSDMB in psoriasis vulgaris lesion tissue is lower than that of normal skin tissue. The down-regulation of GSDMB expression can inhibit cell proliferation and promote cell apoptosis. GSDMB may play a role in the pathogenesis of psoriasis by affecting the differentiation of keratinocytes and the function of T cells.
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Psoriasis , Humanos , Psoriasis/patología , Piel/metabolismo , Queratinocitos/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Proliferación Celular , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Citotóxicas Formadoras de Poros/metabolismoRESUMEN
Incontinentia pigmenti (IP), an X-chromosome dominant genodermatosis caused by mutations in the IKBKG/NEMO gene, is a rare disease affecting the skin, teeth, eyes, and central nervous system. Here, we report two pedigrees of IP and detection of two novel mutations in the IKBKG gene associated with IP via genetic analysis. In addition, different gene mutation types can present with different clinical phenotypes, and the same gene mutation type can show different clinical phenotypes. This study provides clinical cases for further study of the genotype and phenotype of IP and enriches the mutation spectrum of IKBKG gene, which provides a basis for genetic counseling and genetic diagnosis of IP in the future.
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[This corrects the article DOI: 10.3389/fbioe.2022.903385.].
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Objective: The aim of this study was to explore the hemodynamic changes of hepatic artery and portal vein detected by Doppler ultrasound (DU) in infants who underwent living donor liver transplantation (LDLT). Methods: The data of 41 infant patients (22 Males, 19 Females, median age of 5 months) were collected in the Children's Hospital affiliated to the Chongqing Medical University from May 2018 to December 2019. The patients underwent left lateral segment LDLT (LLS -LDLT) because of biliary atresia (BA). Hemodynamic parameters, including the peak systolic velocity (PSV), resistivity index (RI) of the hepatic artery (HA), portal vein velocity (PVV), and portal vein flow (PVF) were recorded from Doppler ultrasound on the day before the operation, and on the 1st, the 7th, the 14th and the 30th day after LDLT procedures. The changes of PSVHA, RIHA, PVV and PVF before and on the 1st day after transplantation were analyzed by paired t-test. The comparison of the data between different postoperative time points were assessed by ANOVA. Results: Compared with the parameters measured before LDLT, PSVHA, and RIHA decreased, and PVV and PVF increased significantly (p < 0.001) on the 1st day after LLS-LDLT. As for PSV, there was no significant difference between the 7th day and the 1st day after transplantation (POD7 VS POD1, p = 0.167) while there was a substantial difference between the 14th, 30th and 1st day after LT (POD14 vs. POD1, p = 0.003) (POD30 vs. POD1, p < 0.001). And there was a significant difference between the 14th, 30th, and 7th days after LT (POD14 vs. POD7, p = 0.014) (POD30 vs. POD7, p < 0.001). There was no significant difference between 30th and 14th after transplantation (POD30 vs. POD14, p = 0.092). As for RIHA and PVV, the decrease was slow within the first month after the operation, and there was no significant difference at different times. Conclusion: We have identified major hepatic flow changes that occurred in 41 infants who underwent LLS -LDLT due to BA. The data could be used for future studies of LDLT in infants including hemodynamic modeling, liver regeneration and clinical management.
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Background: Although pulmonary arterial hypertension (PAH) is a fatal disease, specific drugs have been used to treat PAH. These drugs predominantly target these three pathobiological pathways: Endothelin receptor antagonist (ERA), nitric oxide (NO), and prostanoids pathways. In this review, we aimed to analyze the efficacy and safety of oral targeted treatments for PAH. Methods: The national library of medicine (MEDLINE), excerpta medica database (EMBASE), and Cochrane Central Register of Controlled Trials databases were searched. Randomized controlled trials that compared the oral targeted drugs with placebos were selected. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) for variables with dichotomous outcomes, and standardized mean differences with continuous outcomes variables. Additionally, the mean of the differences for the 6-min walk distance (6MWD) was analyzed. Results: In total, 23 studies involving 7,121 patients were included in this study. These studies show that orally PAH-specific drugs could decrease the risk of clinical worsening events, with an OR of 0.55 (p < 0.001). Furthermore, these drugs could improve exercise capacity, showing a 21.74-m increase in 6MWD (95% CI: 17.53-25.95 m) and cause a greater amelioration of functional class (OR = 0.60, 95% CI: 0.47-0.76). Additionally, subgroup analysis indicated that compared with placebo, ERAs, and drugs in the NO pathway were most effective and safe, which are associated with an improvement in exercise capacity, 6MWD, and worsening events-free survival rate. Conclusion: Nitric oxide exhibited the most prominent clinical effect on exercise tolerance. However, in the subgroup analysis, oral targeted drugs of different pathways show applicability to different populations, which highlights the need for precise treatment in the clinical setting. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=297946], identifier [CRD 42022297946].