Safety and efficacy of a novel transbronchial radiofrequency ablation system for lung tumours: One year follow-up from the first multi-centre large-scale clinical trial (BRONC-RFII).

BACKGROUND AND OBJECTIVE: Radiofrequency ablation (RFA) is an emerging treatment of lung cancer, yet it is accompanied by certain safety concerns and operational limitations. This first multi-centre, large-scale clinical trial aimed to investigate the technical performance, efficacy and safety of an innovative transbronchial RFA system for lung tumours. METHODS: The study enrolled patients with malignant lung tumours who underwent transbronchial RFA using an automatic saline microperfusion system between January 2021 and December 2021 across 16 medical centres. The primary endpoint was the complete ablation rate. The performance and safety of the technique, along with the 1-year survival rates, were evaluated. RESULTS: This study included 126 patients (age range: 23-85 years) with 130 lung tumours (mean size: 18.77 × 14.15 mm) who had undergone 153 transbronchial RFA sessions, with a technique success rate of 99.35% and an average ablation zone size of 32.47 mm. At the 12-month follow-up, the complete ablation rate and intrapulmonary progression-free survival rates were 90.48% and 88.89%, respectively. The results of patients with ground-glass nodules (GGNs) were superior to those of the patients with solid nodules (12-month complete ablation rates: solid vs. pure GGN vs. mixed GGN: 82.14% vs. 100% vs. 96.08%, p = 0.007). No device defects were reported. Complications such as pneumothorax, haemoptysis, pleural effusion, pulmonary infection and pleural pain were observed in 3.97%, 6.35%, 8.73%, 11.11% and 10.32% of patients, respectively. Two subjects died during the follow-up period. CONCLUSION: Transbronchial RFA utilizing an automatic saline microperfusion system is a viable, safe and efficacious approach for the treatment for lung tumours, particularly for patients with GGNs.

Bronchial thermoplasty decreases airway remodeling by inhibiting autophagy via the AMPK/mTOR signaling pathway.

Bronchial thermoplasty (BT), an effective treatment for severe asthma, requires heat to reach the airway to reduce the mass of airway smooth muscle cells (ASMCs). Autophagy is involved in the pathological process of airway remodeling in patients with asthma. However, it remains unclear whether autophagy participates in controlling airway remodeling induced by BT. In this study, we aim to elucidate the autophagy-mediated molecular mechanisms in BT. Our study reveal that the number of autophagosomes and the level of alpha-smooth muscle actin (α-SMA) fluorescence are significantly decreased in airway biopsy tissues after BT. As the temperature increased, BT causes a decrease in cell proliferation and a concomitant increase in the apoptosis of human airway smooth muscle cells (HASMCs). Furthermore, increase in temperature significantly downregulates cellular autophagy, autophagosome accumulation, the LC3II/LC3I ratio, and Beclin-1 expression, upregulates p62 expression, and inhibits the AMPK/mTOR pathway. Furthermore, cotreatment with AICAR (an AMPK agonist) or RAPA (an mTOR antagonist) abolishes the inhibition of autophagy and attenuates the increase in the apoptosis rate of HASMCs induced by the thermal effect. Therefore, we conclude that BT decreases airway remodeling by blocking autophagy induced by the AMPK/mTOR signaling pathway in HASMCs.

Photodynamic therapy for treatment of recurrent hemoptysis secondary to pulmonary endometriosis: a case report.

Pulmonary endometriosis (PEM) is rare, and drug therapy remains the primary treatment. However, patients with PEM frequently experience recurrent hemoptysis that is refractory to pharmacological intervention. We herein describe a patient with PEM who developed recurrent hemoptysis and was successfully treated with photodynamic therapy (PDT) after drug withdrawal. The patient was admitted to our hospital because of recurrent hemoptysis despite repeated drug treatments for more than 1 year. Given that PDT targets specific tissues and destroys vascular endothelial cells through the cytotoxic effect produced by the photodynamic reaction of the photosensitizer, we considered that it may effectively control hemoptysis secondary to vascular morphological changes in PEM. Therefore, we performed PDT in this case, and the patient's recurrent hemoptysis regressed. Approximately 2 years following PDT, the patient had recovered well and reported no discomfort. We recommend consideration of PDT as a treatment option for patients with PEM who develop recurrent hemoptysis after drug withdrawal. Notably, the patient's lung lesions should be superficial and limited, and no contraindications should be present.

Research on the effectiveness and safety of bronchial thermoplasty in patients with chronic obstructive pulmonary disease.

OBJECTIVES: To investigate the clinical efficacy and safety of bronchial thermoplasty (BT) in treating patients with chronic obstructive pulmonary disease (COPD). METHODS: Clinical data of 57 COPD patients were randomized into the control (n = 29, conventional inhalation therapy) or intervention group (n = 28, conventional inhalation therapy plus BT). Primary outcomes were differences in clinical symptom changes, pulmonary function-related indicators, modified Medical Research Council (mMRC), 6-min walk test (6MWT), COPD assessment test (CAT) score and acute exacerbation incidence from baseline to an average of 3 and 12 months. Safety was assessed by adverse events. RESULTS: FEV1, FEV1(%, predicted) and FVC in both groups improved to varying degrees post-treatment compared with those pre-treatment (P < 0.05). The Intervention group showed greater improving amplitudes of FEV1 (Ftime × between groups = 21.713, P < 0.001) and FEV1(%, predicted) (Ftime × between groups = 31.216, P < 0.001) than the control group, and there was no significant difference in FVC variation trend (Ftime × between groups = 1.705, P = 0.193). mMRC, 6MWT and CAT scores of both groups post-treatment improved to varying degrees (Ps < 0.05), but the improving amplitudes of mMRC (Ftime × between groups = 3.947, P = 0.025), 6MWT (Ftime × between groups = 16.988, P < 0.001) and CAT score (Ftime × between groups = 16.741, P < 0.001) in the intervention group were greater than the control group. According to risk assessment of COPD acute exacerbation, the proportion of high-risk COPD patients with acute exacerbation in the control and intervention groups at 1 year post-treatment (100% vs 65%, 100% vs 28.6%), inpatient proportion (100% vs 62.1%; 100% vs 28.6%), COPD acute exacerbations [3.0 (2.50, 5.0) vs 1.0 (1.0, 2.50); 3.0(3.0, 4.0) vs 0 (0, 1.0)] and hospitalizations [2.0 (2.0, 3.0) vs 1.0 (0, 2.0); 2.0 (2.0, 3.0) vs 0 (0, 1.0)] were significantly lower than those pre-treatment (P < 0.05). Besides, data of the intervention group were significantly lower than the control group at each timepoint after treatment (P < 0.05). CONCLUSIONS: Combined BT therapy is superior to conventional medical treatment in improving lung function and quality of life of COPD patients, and it also significantly reduces the COPD exacerbation risk without causing serious adverse events.

Rapid weaning from mechanical ventilation and bronchial thermoplasty for near-fatal asthma: A case report.

Background: The action mechanism of bronchial thermoplasty (BT) is poorly understood. Generally, patients with severe asthma who are in desperate need of treatment have relatively low baseline values. In this paper, we describe the case of an asthmatic patient who was saved by a combination of therapy and bronchial thermoplasty. Case information: A patient with near-fatal asthma was initially treated in our hospital with conventional medication, but his condition did not improve. The patient was next subjected to invasive mechanical ventilation, which did not provide significant relief. Additionally, he was treated with BT in conjunction with mechanical ventilation, which promptly reversed his status asthmaticus and stabilized his condition. Conclusion: Patients with near-fatal asthma who do not react effectively to aggressive therapy may benefit from BT.

Correlation of Activation Site and Number with the Clinical Response to Bronchial Thermoplasty.

Objective: To investigate the relation of activation site and number with clinical response to bronchial thermoplasty (BT) in refractory asthma patients. Methods: This work included 106 consecutive refractory asthma patients completing three BT sessions in our hospital from May 2016 to May 2019. Procedure details included recording delivery sites and those in BT. Asthma Control Questionnaire (ACQ) scores and spirometric measurements were recorded 1-day before treatment and 6 months post-treatment to explore the effects of BT activation number and site on clinical response. Results: ACQ score (3.19±1.14 vs 1.26±0.63), forced expiratory volume in 1 sec (FEV1)% predicted (55.53±21.66 vs 66.19±22.50), FEV1 (1.53±0.74 vs 1.93±0.82), and forced vital capacity (FVC) (2.49±0.86 vs 2.92±0.94) significantly increased after three BT sessions compared with pre-session. Major bronchial ablation did not significantly improve BT response in asthma patients. Multivariate logistic regression identified baseline ACQ score and baseline FEV1% predicted as independent factors affecting the clinical response to BT. Correlation and regression analysis revealed a significant linear relationship between baseline ACQ and ACQ improvement, as well as a linear relationship between the third session activation number and ACQ improvement. Based on subgroup analysis of activation number, cohort C (activations ≥ 200) had better lung function, lower non-responding rate, and better long-term effectiveness than the other two cohorts. The activation number in the third BT session showed the strongest predictive ability compared with the first two sessions. Conclusion: Main bronchial ablation did not markedly affect clinical response to BT. Baseline ACQ and baseline FEV1% predicted were independent factors affecting clinical response to BT. Increasing the activation number might promote the therapeutic efficacy of BT, and the activation number in the third BT session correlated with and predicted the BT response.

The application of transbronchial cryobiopsy in interstitial lung disease: a prospective, multicenter, real-world study.

BACKGROUND: Transbronchial cryobiopsy (TBCB) has been widely used to diagnose interstitial lung disease (ILD). Existing reports on TBCB in ILD are mostly single-center prospective or retrospective studies but rarely multicenter prospective real-world studies. We explored the diagnostic efficiency and safety of TBCB in ILD in a real world setting. METHODS: A prospective, multicenter, real-world study was conducted to analyze the data of patients with unclarified ILD who underwent TBCB in 20 hospitals in China from October 2018 to October 2019. The results of the pathological and multidisciplinary discussion (MDD) diagnosis and complications related to TBCB were then analyzed. RESULTS: A total of 373 patients were enrolled in this study, including 194 males and 179 females, with an average age of 52.6±12.4 years. None of the patients had severe hemorrhaging, and the incidence of pneumothorax was 4.8%. The proportions of definitive, possible, and unclassified pathological diagnoses were 62.5%, 5.6%, and 31.9%, respectively. The overall diagnostic yield of MDD was 63.5%. There were 237 patients with a definitive diagnosis of MDD and 136 patients with an unclarified MDD diagnosis. The cooling gas pressure, freezing durations, number of specimens, maximum lengths of specimens, and specimen sizes varied significantly between the definitive and unclarified MDD diagnoses. CONCLUSIONS: In China, the application of TBCB in ILD is generally safe, and its diagnostic efficiency is acceptable. Using a 1.9-mm cryoprobe to collect five samples would achieve a better positive diagnostic rate for TBCB in ILD, without a significant increase in complication risk. TRIAL REGISTRATION: ClinicalTrials.gov; date of registration: 09/25/2018; registration number: NCT03704233; URL: clinicaltrials.gov.

LncRNA SNHG12 ameliorates brain microvascular endothelial cell injury by targeting miR-199a.

Long non-coding RNAs regulate brain microvascular endothelial cell death, the inflammatory response and angiogenesis during and after ischemia/reperfusion and oxygen-glucose deprivation/reoxygenation (OGD/R) insults. The long non-coding RNA, SNHG12, is upregulated after ischemia/reperfusion and OGD/R in microvascular endothelial cells of the mouse brain. However, its role in ischemic stroke has not been studied. We hypothesized that SNHG12 positively regulates ischemic stroke, and therefore we investigated its mechanism of action. We established an OGD/R mouse cell model to mimic ischemic stroke by exposing brain microvascular endothelial cells to OGD for 0, 2, 4, 8, 16 or 24 hours and reoxygenation for 4 hours. Quantitative real-time polymerase chain reaction showed that SNHG12 levels in brain microvascular endothelial cells increased with respect to OGD exposure time. Brain microvascular endothelial cells were transfected with pcDNA-control, pcDNA-SNHG12, si-control, or si-SNHG12. After exposure to OGD for 16 hours, these cells were then analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, trypan blue exclusion, western blot, and capillary-like tube formation assays. Overexpression of SNHG12 inhibited brain microvascular endothelial cell death and the inflammatory response but promoted angiogenesis after OGD/R, while SNHG12 knockdown had the opposite effects. miR-199a was identified as a target of SNHG12, and SNHG12 overexpression reversed the effect of miR-199a on brain microvascular endothelial cell death, the inflammatory response, and angiogenesis. These findings suggest that SNHG12 suppresses endothelial cell injury induced by OGD/R by targeting miR-199a.

Dodecahedral W@WC Composite as Efficient Catalyst for Hydrogen Evolution and Nitrobenzene Reduction Reactions.

Core-shell composites with strong phase-phase contact could provide an incentive for catalytic activity. A simple, yet efficient, H2O-mediated method has been developed to synthesize a mesoscopic core-shell W@WC architecture with a dodecahedral microstructure, via a one-pot reaction. The H2O plays an important role in the resistance of carbon diffusion, resulting in the formation of the W core and W-terminated WC shell. Density functional theory (DFT) calculations reveal that adding W as core reduced the oxygen adsorption energy and provided the W-terminated WC surface. The W@WC exhibits significant electrocatalytic activities toward hydrogen evolution and nitrobenzene electroreduction reactions, which are comparable to those found for commercial Pt/C, and substantially higher than those found for meso- and nano-WC materials. The experimental results were explained by DFT calculations based on the energy profiles in the hydrogen evolution reactions over WC, W@WC, and Pt model surfaces. The W@WC also shows a high thermal stability and thus may serve as a promising more economical alternative to Pt catalysts in these important energy conversion and environmental protection applications. The current approach can also be extended or adapted to various metals and carbides, allowing for the design and fabrication of a wide range of catalytic and other multifunctional composites.

Preparation and antibacterial activity of the oligosaccharides derived from Rhizoma Phragmites.

In this study, we prepared Rhizoma Phragmites derived oligosaccharides (ROs) by hydrolysis with hydrogen peroxide (H2O2). The ROs yield was affected by reaction time, temperature, and H2O2 concentration. Too long reaction time and too high temperature decreased the ROs yield. Maximum ROs yield (11.26%) was obtained at reaction time 4h, temperature 75 °C, and H2O2 concentration 3.5% (v/v). The oligosaccharides sample contained 93.16% sugar, of which the average degree was approximately 11, was water-soluble, and showed white. The ROs had the highest antibacterial activity against Staphylococcus aureus, followed by Bacillus subtilis and Escherichia coli at the concentration of 100 µg/mL.

Cellulase-assisted extraction and antioxidant activity of polysaccharides from Rhizoma imperata.

In this study, the cellulase-assisted extraction and antioxidant activity of the polysaccharides from Rhizoma imperata were investigated. To improve the yield of R. Imperata polysaccharides (RPs), the extraction conditions were optimized as follows: time, 69.48 min; temperature, 45.36°C; pH, 4.58; cellulase amount, 1,200 U/g. Under these optimum conditions, the yield of RPs reached 0.67% (w/w), and was higher than that of the traditionally aqueous extraction method. The sugar content in the RPs product reached up to 93.25% (w/w). The RPs product has high antioxidant activity including hydroxyl radical scavenging activity and 2,2-diphenyl-ß-picrylhydrazyl radical scavenging activity at the concentration of 100mg/mL.

The polysaccharides from porphyra yezoensis suppress the denaturation of bighead carp myofibrillar protein.

In this study, investigated was the effect of the porphyra yezoensis polysaccharides (PPs) on the denaturation of bighead carp (Aristichthys nobilis) myofibrillar protein (Mf) during frozen storage at -18°C for 90d. The PPs (2.5%, 5%, and 7.5%, respectively) was added to 100g of Mf. The changes in the Ca-adenylpyrophosphatase (ATPase) activity and unfrozen water content in Mf were examined to evaluate he denaturation of Mf during frozen storage. Ca-ATPase activity decreased gradually during frozen storage at -18°C upon addition of PPs. By contrast, Ca-ATPase activity in the control group dropped drastically during the first 45d of storage and then further decreased gradually for up to 90d of storage, indicating a biphasic denaturation pattern. PPs addition significantly increased sulfhydryl contents in the Mf of the treatment groups compared with that of the control group (p<0.05) during frozen storage at -18°C.

Preparation and antioxidant activity of Lycium barbarum oligosaccharides.

In this study, the Lycium barbarum oligosaccharides (LBO) were prepared by hydrolysis using hydrogen peroxide (H2O2). The yield of the LBO was monitored during the hydrolysis process. The hydrolysis conditions were optimized as follows: time, 4h; temperature, 70 °C; and H2O2 concentration, 2.5% (v/v). The hydrolysates were filtered, concentrated to ∼20% (w/v), precipitated with 6 volumes of absolute ethanol, freeze-dried, and ground to yield a water soluble and white powder. The sugar content of the product was 95.8%, and the yield was 21.05% (w/w), respectively. The LBO show higher hydroxyl radical scavenging activity (86.46%) than Vc (40.96) at the concentration of 100 µg/mL.

[Tetrasulfophthalocyaninatozinc-sensitized titania synthesized by a novel in-situ and self-assembly process and photocatalytic activity under visible-light irradiation].

Tetrasulfophthalocyaninatozinc/titanium dioxide (ZnTsPc/TiO2) was synthesized by a novel in-situ and self-assembly process. The prepared products, including pure TiO2 and ZnTsPc, were characterized by XRD, UV-Vis, FTIR, Zeta potential and fluorescence spectroscopic techniques. The results indicated that ZnTsPc was indeed synthesized during the in-situ method and sol-gel process. A chemical bond (--SO2--O--Ti--) was also formed between the sensitizer (ZnTsPc) and the surface of titanium dioxide particles. The photocatalyst of ZnTsPc/TiO2 reveals greatly enhanced activity for the degradation of organic pollutant, Rhodamine B, under visible-light irradiation as compared with pure TiO2 and P25. The sensitization mechanism is that photo-generated charge carriers are separated by the chemical bond between ZnTsPc and TiO2.