Near-Infrared Light-Triggered NO Nanogenerator for Gas-Enhanced Photodynamic Therapy and Low-Temperature Photothermal Therapy to Eliminate Biofilms.

Purpose: Owing to its noninvasive nature, broad-spectrum effectiveness, minimal bacterial resistance, and high efficiency, phototherapy has significant potential for antibiotic-free antibacterial interventions and combating antibacterial biofilms. However, finding effective strategies to mitigate the detrimental effects of excessive temperature and elevated concentrations of reactive oxygen species (ROS) remains a pressing issue that requires immediate attention. Methods: In this study, we designed a pH-responsive cationic polymer sodium nitroside dihydrate/branched polyethylenimine-indocyanine green@polyethylene glycol (SNP/PEI-ICG@PEG) nanoplatform using the electrostatic adsorption method and Schiff's base reaction. Relevant testing techniques were applied to characterize and analyze SNP/PEI-ICG@PEG, proving the successful synthesis of the nanomaterials. In vivo and in vitro experiments were performed to evaluate the antimicrobial properties of SNP/PEI-ICG@PEG. Results: The morphology and particle size of SNP/PEI-ICG@PEG were observed via TEM. The zeta potential and UV-visible (UV-vis) results indicated the synthesis of the nanomaterials. The negligible cytotoxicity of up to 1 mg/mL of SNP/PEI-ICG@PEG in the presence or absence of light demonstrated its biosafety. Systematic in vivo and in vitro antimicrobial assays confirmed that SNP/PEI-ICG@PEG had good water solubility and biosafety and could be activated by near-infrared (NIR) light and synergistically treated using four therapeutic modes, photodynamic therapy (PDT), gaseous therapy (GT), mild photothermal therapy (PTT, 46 °C), and cation. Ultimately, the development of Gram-positive (G+) Staphylococcus aureus (S. aureus) and Gram-negative (G-) Escherichia coli (E. coli) were both completely killed in the free state, and the biofilm that had formed was eliminated. Conclusion: SNP/PEI-ICG@PEG demonstrated remarkable efficacy in achieving controlled multimodal synergistic antibacterial activity and biofilm infection treatment. The nanoplatform thus holds promise for future clinical applications.

Edge Detection Algorithm-Based Lung Ultrasound in Evaluation of Efficacy of High-Flow Oxygen Therapy on Critical Lung Injury.

The study focused on the therapeutic effects of high-flow oxygen therapy on patients with critical lung injury using edge detection-based ultrasound images. Firstly, the traditional Canny edge detection algorithm was improved, and the optimal threshold was obtained by optimizing the median filter and combining Otsu algorithm and threshold iteration method. Then, the optimized algorithm was compared with the traditional Canny edge detection algorithm and applied to process the lung ultrasound images of 120 cases of critical lung injury, to compare the efficacy of high-flow oxygen therapy and the traditional oxygen therapy. It was found that the peak signal-to-noise ratio (PSNR) (20.34~31.3), edge intensity value (17.89~27.34), and edge detection effect of the improved Canny algorithm were better than the traditional Canny algorithm (15.2~28.61, 9.44~18.56). The failure rate of extubation (4.1%), reintubation rate (0.8%), comfort (2.38 ± 0.15 points), dry humidity score (1.07 ± 0.21 points), antibiotic use (7.41 ± 0.74 days), and hospital stay (8.66 ± 1.02 days) in the experimental group were significantly lower than the corresponding indexes in the control group (11.7%, 5%, 4.25 ± 0.26 minutes, 4.94 ± 0.78 minutes, 19.29 ± 1.7 days, and 27.49 ± 2.22 days), and the difference was statistically significant (P < 0.05). In the experimental group, within 48 hours after extubation, the respiratory rate (RR), heart rate (HR), arterial partial pressure of carbon dioxide (PaCO2), and HCO3 - were significantly lower than those of the control group; and the values of transcutaneous oxygen saturation (SpO2), mean arterial pressure (MAP), arterial partial pressure of oxygen (PaO2), and pH were significantly higher than the control group, and the difference was statistically significant (P < 0.05). In conclusion, the algorithm in this study is superior to the traditional Canny algorithm, and the high-flow oxygen therapy can reduce the failure rate of extubation, strengthen patient comfort, improve the degree of gas humidification, stabilize the respiratory function and circulatory system, and shorten the time of antibiotic use and hospital stay.

Immunotherapy with radiotherapy fails to improve prognosis of patients with stage IV non-small cell lung cancer: a retrospective cohort analysis of the THUNDER-2 study.

Background: Radiotherapy (RT) may enhance the systemic antitumor reaction to immunotherapy (IT). Currently, the effect of RT in stage IV non-small cell lung cancer (NSCLC) patients treated with IT is uncertain. This study aimed to confirm the role of RT in these patients. Methods: We enrolled 120 stage IV NSCLC patients who had been treated with IT and had received external beam radiation therapy (EBRT) or radioactive particle implantation (RPI) at 3 oncology centers in Shandong province between 2019 and 2021. We assessed relevant clinical factors and regular follow-up was conducted via electronic medical records and telephone. The primary endpoint was overall survival (OS). Different combination models in various populations were compared by generating Kaplan-Meier curves and Cox regression analysis. Results: The OS for the overall population was 5 months (range, 0-31 months) and the overall survival rate was 47.5%. Patients receiving IT with RPI had the least favorable prognostic trend (median survival: 2 months) compared to those receiving IT without RT (median survival: 9 months) and IT with EBRT (median survival: 10 months), but this difference was not significant (P=0.148). In subgroup analysis, patients treated with IT with RPI appeared to have a worse prognosis in some specific cohorts, such as males [hazard ratio (HR) =2.433, P=0.031], non-squamous carcinoma histologies (HR =2.680, P=0.034), patients with oligometastases (HR =7.967, P=0.024), patients with liver metastases (HR =10.808, P=0.011) or brain metastases (HR =20.087, P=0.005), and those with Eastern Cooperative Oncology Group (ECOG) performance score ≥2 (HR =2.769, P=0.043). Multivariate Cox analysis of total population revealed that ECOG score and IT stage were the independent prognostic factors. IT combined with EBRT did not have a significant survival benefit in all subgroups. Concurrent IT with RT and first-line and second-line IT combined with RT trended toward improved long-term prognosis. Conclusions: While the robustness of the present conclusions is limited by relatively small sample size and retrospective nature of this research, the addition of EBRT or RPI to IT did not significantly improve patients' OS in stage IV NSCLC. Early combination IT after RT may benefit patients with long-term survival.

Association between IL-13 +1923C/T polymorphism and asthma risk: a meta-analysis based on 26 case-control studies.

Asthma is a serious and hereditary respiratory disorder affecting all age groups. Interleukin-13 (IL-13) is a central regulator of allergic inflammation. The purpose of the present study was to estimate the relationship between IL-13 +1923C/T polymorphism and asthma susceptibility. Relevant case-control studies published between January 2000 and July 2016 were searched in the online databases. Review Manage (RevMan) 5.3 was used to conduct the statistical analysis. The pooled odds ratio (OR) with its 95% confidence interval (CI) was employed to calculate the strength of association. A total of 26 articles were retrieved, including 17642 asthma patients and 42402 controls. Overall, our results found that IL-13 +1923C/T polymorphism was significantly associated with increased risk of asthma under each genetic model (P<0.00001). Subgroup analysis by ethnicity showed that alleles and genotypes of this variant correlated with asthma among Asians and Caucasians, but only TT genotype under the homozygote model in Africans. When stratified by age group, this variant highly correlated with asthma in children and moderately in adults. Furthermore, the TT, CT and CC genotypes in asthma group were all significantly associated with increased IgE levels in sera of asthma patients when compared with controls. Our results suggested that IL-13 +1923C/T polymorphism contributed to the development of asthma. Further case-control studies with more ethnicities are still needed.

Activation of Bcl-2-Caspase-9 Apoptosis Pathway in the Testis of Asthmatic Mice.

BACKGROUND: Apoptosis plays a critical role in controlling the proliferation and differentiation of germ cells during spermatogenesis. Dysregulation of the fine-tuned balance may lead to the onset of testicular diseases. In this study, we investigated the activation status of apoptosis pathways in the testicular tissues under the background of an asthmatic mouse model. METHODS: Ten BALB/c mice were divided into two groups: the acute asthma group and the control group. In the acute asthma group, ovalbumin (OVA)-sensitized mice were challenged with aerosolized OVA for 7 days, while the control group was treated with physiological saline. After that, both epididymis and testis were collected to determine the sperm count and motility. Apoptosis in the testis was evaluated by DNA ladder, immunochemistry and further by PCR array of apoptosis-related genes. Finally, the cleavage of caspase-3 and poly ADP-ribose polymerase (PARP) was determined by western blot and the enzymatic activities of caspase-9 and 3/7 were assessed using Caspase-Glo kits. RESULTS: Compared with control mice, significant decreases in the body weight, testis weight, sperm count and motility were seen in the experimental group. DNA ladder and immunochemistry showed significant increase in apoptotic index of the asthmatic testis, whereas a decrease in mRNA expression of Bcl-2 and increases in Bax, BNIP3, caspase-9, and AIF were observed in the asthma group. Furthermore, protein levels of AIF were significantly upregulated, while the translational expression of Bcl-2 was downregulated markedly. Consistently, caspase-9 activity in the testis of asthma mice was significantly higher than that of the control group. CONCLUSION: Collectively, these results showed that Bcl-2-caspase-9 apoptosis pathway was clearly activated in the testis of asthmatic mice with the increased expression of apoptosis-related genes and proteins. To our knowledge, this is the first report demonstrating that asthma could lead to the activation of the mitochondrial apoptosis signaling pathway in the mouse testis.

Correlation between survivin genetic polymorphisms and lung cancer susceptibility.

AIMS: The purpose of the study was to analyze the relationship of survivin polymorphisms including -31G/C, -625G/C, 9194A/G and 9809T/C with the susceptibility to lung cancer. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to test the polymorphisms of -31G/C, -625G/C, 9194A/G and 9809T/C in 104 patients with lung cancer and 104 healthy controls. Then, linkage disequilibrium and haplotypes were analyzed by HaploView software. The differences of genotype, allele and haplotype frequencies in case and control group were assessed via chi-square test. Odds ratio (OR) with 95% CI were used to evaluate the correlation of survivin polymorphisms with lung cancer. RESULTS: Genotype distribution of each polymorphism site in control group was in agreement with Hardy-Weinberg equilibrium (HWE) (P>0.05). The frequency of -31G/C CC genotype and C allele in case group were much higher than that of controls, respectively (CC: 33.6% vs. 22.1%; C: 57.2% vs. 46.6%) and CC genotype as well as C allele were appeared to be risk factors for lung cancer. Meanwhile, 9194A/G GG genotype could increase the risk for lung cancer (OR=2.86, 95% CI=1.14-7.20). The risk of G allele carriers for lung caner was higher than that of A allele (OR=1.63, 95% CI=1.08-2.47). The haplotypes analysis indicated that CGGC and GCAT were associated with the susceptibility to lung cancer (OR=2.79, 95% CI=1.58-4.92; OR=2.36, 95% CI=1.29-4.30). CONCLUSIONS: Survivin -31G/C and 9194A/G polymorphisms were associated with the risk of lung cancer. The CGGC and GCAT haplotypes carriers were more likely to develop lung cancer.