Hydrogen therapy: recent advances and emerging materials.

Hydrogen therapy, leveraging its selective attenuation of hydroxyl radicals (˙OH) and ONOO-, has emerged as a pivotal pathophysiological modulator with antioxidant, anti-inflammatory, and antiapoptotic attributes. Hydrogen therapy has been extensively studied both preclinically and clinically, especially in diseases with an inflammatory nature. Despite the substantial progress, challenges persist in achieving high hydrogen concentrations in target lesions, especially in cancer treatment. A notable breakthrough lies in water/acid reactive materials, offering enhanced hydrogen generation and sustained release potential. However, limitations include hydrogen termination upon material depletion and reduced bioavailability at targeted lesions. To overcome these challenges, catalytic materials like photocatalytic and sonocatalytic materials have surfaced as promising solutions. With enhanced permeability and retention effects, these materials exhibit targeted delivery and sustained stimuli-reactive hydrogen release. The future of hydrogen therapy hinges on continuous exploration and modification of catalytic materials. Researchers are urged to prioritize improved catalytic efficiency, enhanced lesion targeting effects, and heightened biosafety and biocompatibility in future development.

Association between systemic inflammatory markers and chronic obstructive pulmonary disease: A population-based study.

Objective: To investigate whether inflammatory indices, including the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), product of platelet and neutrophil count (PPN), and lymphocyte-to-monocyte ratio (LMR), correlate with chronic obstructive pulmonary disease (COPD). Methods: This was a cross-sectional study from the National Health and Nutrition Examination Survey (NHANES) database 2007-2018. The SII, NLR, PLR, PPN and LMR were calculated based on blood cell counts and were log2-transformed. COPD was diagnosed via a questionnaire or spirometry examination. Multivariate logistic regression, sensitivity analysis, subgroup analyses, and interaction tests were performed to evaluate the relationships. Results: 23,875 participants, including 1000 COPD patients (453 diagnosed via spirometry examination, 547 diagnosed via a questionnaire), were enrolled in this study. Positive associations were observed between SII (OR 1.231, 95 % CI 1.081,1.401), NLR (OR 1.223, 95 % CI 1.064,1.405), PLR (OR 1.325, 95 % CI 1.086,1.617), PPN (OR 1.157, 95 % CI 1.031,1.298) and COPD, while a negative association was obtained between LMR and COPD (OR 0.794, 95 % CI 0.666,0.948) after covariate adjustments. When divided COPD patients into spirometry-based and questionnaire-based, only SII (OR 1.310, 95%CI 1.122,1.529), PLR (OR 1.669, 95%CI 1.272,2.191) and PPN (OR 1.218, 95%CI 1.050,1.412) significantly correlated with spirometry-based COPD, while only NLR (OR 1.303, 95%CI 1.055,1.609) and LMR (OR 0.524, 95%CI 0.406,0.677) significantly correlated with questionnaire-based COPD after covariate adjustments. Conclusion: Significant associations are observed between different inflammation indices and COPD. Heterogeneity exists between spirometry-based and questionnaire-based COPD patients. Future studies are needed to verify the results.

Prone positioning does not improve outcomes of intubated patients with pneumocystis pneumonia and moderate-severe acute respiratory distress syndrome: a single-center, retrospective, observational, cohort study.

BACKGROUND: Pneumocystis pneumonia is an uncommon precipitant of acute respiratory distress syndrome and is associated with high mortality. Prone positioning ventilation has been proven to reduce mortality in patients with moderate-severe acute respiratory distress syndrome. We investigated the effect of prone positioning on oxygenation and mortality in intubated patients with pneumocystis pneumonia comorbid with moderate-severe acute respiratory distress syndrome. METHODS: In this single-center, retrospective, observational, cohort study, eligible patients were enrolled at West China Hospital of Sichuan University from January 1, 2017, to December 31, 2021. Data on demographics, clinical features, ventilation parameters, arterial blood gas, and outcomes were collected. Patients were assigned to the prone cohort or supine cohort according to whether they received prone positioning ventilation. The main outcome was 28-day mortality. FINDINGS: A total of 79 patients were included in the study. Sixty-three patients were enrolled in the prone cohort, and 16 patients were enrolled in the supine cohort. The 28-day mortality was 61.9% in the prone cohort and 68.8% in the supine cohort (P = 0.26), and 90-day mortality was 66.7% in the prone cohort and 68.8% in the supine cohort (P = 0.55). Patients in the supine cohort had fewer invasive mechanical ventilation days and more ventilator-free days. The incidence of complications was higher in the prone cohort than in the supine cohort. CONCLUSIONS: In patients with pneumocystis pneumonia and moderate-severe acute respiratory distress syndrome, prone positioning did not decrease 28-day or 90-day mortality. Trial registration ClinicalTrials.gov number, ChiCTR2200063889. Registered on 20 September 2022, https://www.chictr.org.cn/showproj.html?proj=174886 .

Bibliometric analysis of the pirfenidone and nintedanib in interstitial lung diseases.

Background: At the beginning of 21st century, reclassification of fibrosing interstitial lung diseases (ILD) scored academic concerning, and then propelled development. Decade before, pifenidone and nintedanib were approved for idiopathic pulmonary fibrosis, but no more drugs are yet available. To evaluate the development traits of pirfenidone and nintedanib in fibrosing ILD, including the influential country, institution, authors, keywords, and the major problems or the priorities of the field emerge and evolve, bibliometric analysis was used to summarize and draw scientific knowledge maps. Methods: We confined the words to "pirfenidone", "nintedanib", "pulmonary fibrosis", and "lung disease, interstitial". Publications were retrieved from the Web of Science Core Collection on February 24, 2024 with the search strategies. Citespace and VOSviewer were adopted for bibliometric analysis. Results: For the knowledge map of pirfenidone, a total of 4359 authors from 279 institutions in 58 countries/regions contributed to 538 studies. The United States and Italy are way ahead. Genentech Inc and the University of Turin are the institutions with the strongest influence. AM J RESP CRIT CARE is the maximized influential periodical. Raghu G was the most frequently co-cited scholar. keywords cluster demonstrated that vital capacity, safety, outcome, effectiveness, acute exacerbation, pathway, cell, collagen were the hotspots. The burst timeline of hotspots and references revealed academic transitions of pirfenidone-related studies. About the knowledge map of nintedanib, 3297 authors from 238 institutions in 47 countries/regions published 374 studies. Japan, the United States, and Italy are the most productive countries. Boehringer Ingelheim is the overriding productive institution. New ENGL J MED have important roles in reporting milestones of nintedanib. Richeldi L carried numerous capital publications to support the anti-fibrotic effect of nintedanib. From the network of co-occurrence keywords, idiopathic pulmonary fibrosis, efficacy, and safety were the hotspots. Nintedanib for systemic sclerosis-related ILD and progressive pulmonary fibrosis is the hotspot with sharp evolution recently. Conclusions: We summarized and showed developmental alterations of pirfenidone and nintedanib in fibrosing ILD through bibliographic index-based analysis. Our findings showed just dozen years sharp development period of pirfenidone and nintedanib in ILD, and identifies potential partners for interested researchers. The burst of hotspots demonstrated the evolvement of research priorities and major problems, and we observed the transition of keywords from experimental terms like mouse, bleomycin, cell, pathway, collagen, gene expression, to clinical terms including efficacy, safety, survival, acute exacerbation, and progressive pulmonary fibrosis. In the future, exploration about disparity models of drug administration, differences between early and later initiate anti-fibrotic therapy, both short-term and long-term efficacy of pirfenidone and nintedanib in fibrosing ILD, specifically in connective disease associate ILD would be emphatically concerned by pulmonologists.

Association between gene polymorphisms and initial warfarin therapy in patients after heart valve surgery.

BACKGROUND: Warfarin is widely used for the prevention and treatment of thrombotic events. This study aimed to examine the influence of gene polymorphisms on the early stage of warfarin therapy in patients following heart valve surgery. METHODS: Nine single nucleotide polymorphisms were genotyped using microarray chips, categorizing patients into three groups: normal responders (Group I), sensitive responders (Group II), and highly sensitive responders (Group III). The primary clinical outcomes examined were time in therapeutic range (TTR) and international normalized ratio (INR) variability. To investigate potential influencing factors, a generalized linear regression model was employed. RESULTS: Among 734 patients, the prevalence of CYP2C9*3-1075A > C, CYP2C19*3-636G > A, and CYP2C19*17-806C > T variants were 11.2%, 9.9%, and 1.9% of patients, respectively. VKORC1-1639G > A or the linked -1173C > T variant was observed in 99.0% of the patients. Generalized linear model analysis revealed an impact of sensitivity grouping on INR variability. Compared to Group I, Group II showed higher TTR values (p = 0.023), while INR variability was poorer in Group II (p < 0.001) and Group III (p < 0.001). Individual gene analysis identified significant associations between CYP2C9*3-1075A > C (p < 0.001), VKORC1-1639G > A or the linked -1173 C > T (p = 0.009) and GGCX-3261G > A (p = 0.019) with INR variability. CONCLUSION: The genotypes of CYP2C9, VKORC1, and GGCX were found to have a significant impact on INR variability during the initial phase of warfarin therapy. However, no significant association was observed between TTR and gene polymorphisms. These findings suggest that focusing on INR variability is crucial in clinical practice, and preoperative detection of gene polymorphisms should be considered to assist in the initiation of warfarin therapy.

Roles of gender and smoking in the associations between urinary phytoestrogens and asthma/wheeze and lung function: evidence from a cross-sectional study.

BACKGROUND: The role of phytoestrogens in asthma/wheeze and lung function remains controversial. Thus, we aimed to examine whether phytoestrogens have beneficial effects on asthma/wheeze, lung function for subgroups and mortality. METHODS: Participants in this study were individuals aged 20 years or older from the National Health and Nutrition Examination Survey. Multivariate logistic regression models were fitted to examine the associations of urinary phytoestrogens with the risk of asthma/wheeze and lung function in individuals with and without asthma/wheeze. Cox proportional hazards regression was used to examine the relationship between urinary phytoestrogens and all-cause mortality. Stratified analyses were conducted based on gender and smoking status. RESULTS: We included 2465 individuals in this study. Enterolactone levels in the highest quartile were associated with a lower risk of asthma than those in the lowest quartile. As compared with the lowest quartile, the highest quartile of enterodiol and enterolactone was associated with a lower risk of wheeze. Significant associations were observed between subtypes of phytoestrogens (equol and enterolactone) and lung function (forced vital capacity (FVC) and forced expiratory volume in 1 s). Besides, FVC was higher in individuals with higher levels of enterodiol. The results were consistent in subpopulations without asthma/wheeze, while the significant difference was not observed in individuals with asthma/wheeze. The stratified analyses revealed that the associations between phytoestrogens and lung function differed by gender and smoking status among subgroups. No significant association was found between urinary phytoestrogens and all-cause mortality. CONCLUSION: In summary, subtypes of phytoestrogens were associated with lower risk of asthma/wheeze and beneficial for lung function improvement in individuals without asthma/wheeze. Furthermore, gender and smoking may interact in the relationship between phytoestrogens and asthma/wheeze, and lung function. Further researches are needed to confirm these associations and explain the results of stratified analyses.

Predictive value of NT-proBNP and hs-TnT for outcomes after pediatric congenital cardiac surgery.

BACKGROUND: The available evidence regarding the predictive value of troponins and natriuretic peptides for early postoperative outcomes in pediatrics is limited, controversial, and based on small sample sizes. The authors aimed to investigate the association of N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT) with the in-hospital adverse outcomes after congenital cardiac surgeries. METHODS: A secondary analysis based on a prospective study of pediatric congenital heart disease (CHD) patients was conducted to investigate the association of NT-proBNP and hs-TnT tested within 6 h postoperatively with in-hospital adverse events. A multivariate logistic regression analysis with a minimum P value approach was used to identify the optimal thresholds of NT-proBNP and hs-TnT for risk stratification. RESULTS: NT-proBNP and hs-TnT are positively correlated with cardiopulmonary bypass time, mechanical ventilation duration, and pediatric intensive care unit stay. The predictive performance of NT-proBNP is excellent for adverse events in both patients younger than 1 year [area under the curve (AUC): 0.771, 0.693-0.850] and those older than 1 year (AUC: 0.839, 0.757-0.922). However, hs-TnT exhibited a satisfactory predictive value solely in patients aged over 1 year. (AUC: 0.784, 0.717-0.852). NT-proBNP levels of 2000-10 000 ng/l [odds ratio (OR): 3.79, 1.47-9.76] and exceeding 10 000 ng/l (OR: 12.21, 3.66-40.80) were associated with a higher risk of postoperative adverse events in patients younger than 1 year. Patients older than 1 year, with NT-proBNP higher than 500 ng/l (OR: 15.09, 6.05-37.66) or hs-TnT higher than 1200 ng/l (OR: 5.50, 1.47-20.59), had a higher incidence of postoperative adverse events. CONCLUSIONS: NT-proBNP and hs-TnT tested within postoperative 6 h demonstrated significant predictive value for postoperative adverse events in CHD patients older than 1 year. However, among CHD patients younger than 1 year, only NT-proBNP exhibited commendable predictive performance for postoperative adverse events.

Activated non-neuronal cholinergic system correlates with non-type 2 inflammation and exacerbations in severe asthma.

BACKGROUND: Non-neuronal cholinergic system (NNCS) contributes to various inflammatory airway diseases. However, the role of NNCS in severe asthma (SA) remains largely unexplored. OBJECTIVE: To explore airway NNCS in SA. METHODS: In this prospective cohort study based on the Australasian Severe Asthma Network in a real-world setting, patients with SA (n = 52) and non-SA (n = 104) underwent clinical assessment and sputum induction. The messenger RNA (mRNA) levels of NNCS components and proinflammatory cytokines in the sputum were detected using real-time quantitative polymerase chain reaction, and the concentrations of acetylcholine (Ach)-related metabolites were evaluated using liquid chromatography coupled with tandem mass spectrometry. Asthma exacerbations were prospectively investigated during the next 12 months. The association between NNCS and future asthma exacerbations was also analyzed. RESULTS: Patients with SA were less controlled and had worse airway obstruction, a lower bronchodilator response, higher doses of inhaled corticosteroids, and more add-on treatments. The sputum mRNA levels of NNCS components, such as muscarinic receptors M1R-M5R, OCT3, VACHT, and ACHE; proinflammatory cytokines; and Ach concentration in the SA group were significantly higher than those in the non-SA group. Furthermore, most NNCS components positively correlated with non-type (T) 2 inflammatory profiles, such as sputum neutrophils, IL8, and IL1B. In addition, the mRNA levels of sputum M2R, M3R, M4R, M5R, and VACHT were independently associated with an increased risk of moderate-to-severe asthma exacerbations. CONCLUSION: This study indicated that the NNCS was significantly activated in SA, leading to elevated Ach and was associated with clinical features, non-T2 inflammation, and future exacerbations of asthma, highlighting the potential role of the NNCS in the pathogenesis of SA. CLINICAL TRIAL REGISTRATION: ChiCTR-OOC-16009529 (http://www.chictr.org.cn).

Gut microbiota and metabolic biomarkers in metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD), a replacement of the nomenclature employed for NAFLD, is the most prevalent chronic liver disease worldwide. Despite its high global prevalence, NAFLD is often under-recognized due to the absence of reliable noninvasive biomarkers for diagnosis and staging. Growing evidence suggests that the gut microbiome plays a significant role in the occurrence and progression of NAFLD by causing immune dysregulation and metabolic alterations due to gut dysbiosis. The rapid advancement of sequencing tools and metabolomics has enabled the identification of alterations in microbiome signatures and gut microbiota-derived metabolite profiles in numerous clinical studies related to NAFLD. Overall, these studies have shown a decrease in α-diversity and changes in gut microbiota abundance, characterized by increased levels of Escherichia and Prevotella, and decreased levels of Akkermansia muciniphila and Faecalibacterium in patients with NAFLD. Furthermore, bile acids, short-chain fatty acids, trimethylamine N-oxide, and tryptophan metabolites are believed to be closely associated with the onset and progression of NAFLD. In this review, we provide novel insights into the vital role of gut microbiome in the pathogenesis of NAFLD. Specifically, we summarize the major classes of gut microbiota and metabolic biomarkers in NAFLD, thereby highlighting the links between specific bacterial species and certain gut microbiota-derived metabolites in patients with NAFLD.

PEEP-Induced Lung Recruitment Maneuver Combined with Prone Position for ARDS: A Single-Center, Prospective, Randomized Clinical Trial.

Background: Prone position (PP) and the positive end-expiratory pressure (PEEP)-induced lung recruitment maneuver (LRM) are both efficient in improving oxygenation and prognosis in patients with ARDS. The synergistic effect of PP combined with PEEP-induced LRM in patients with ARDS remains unclear. We aim to explore the effects of PP combined with PEEP-induced LRM on prognosis in patients with moderate to severe ARDS and the predicting role of lung recruitablity. Methods: Patients with moderate to severe ARDS were consecutively enrolled. The patients were prospectively assigned to either the intervention (PP with PEEP-induced LRM) or control groups (PP). The clinical outcomes, respiratory mechanics, and electric impedance tomography (EIT) monitoring results for the two groups were compared. Lung recruitablity (recruitment-to-inflation ratio: R/I) was measured during the PEEP-induced LRM procedure and was used for predicting the response to LRM. Results: Fifty-eight patients were included in the final analysis, among which 28 patients (48.2%) received PEEP-induced LRM combined with PP. PEEP-induced LRM enhanced the effect of PP by a significant improvement in oxygenation (∆PaO2/FiO2 75.8 mmHg vs. 4.75 mmHg, p < 0.001) and the compliance of respiratory system (∆Crs, 2 mL/cmH2O vs. -1 mL/cmH2O, p = 0.02) among ARDS patients. Based on the EIT measurement, PP combined with PEEP-induced LRM increased the ventilation distribution mainly in the dorsal region (5.0% vs. 2.0%, p = 0.015). The R/I ratio was measured in 28 subjects. The higher R/I ratio was related to greater oxygenation improvement after LRM (Pearson's r = 0.4; p = 0.034). Conclusions: In patients with moderate to severe ARDS, PEEP-induced LRM combined with PP can improve oxygenation and dorsal ventilation distribution. R/I can be useful to predict responses to LRM.

Resolving the heterogeneous tumour microenvironment in cardiac myxoma through single-cell and spatial transcriptomics.

BACKGROUND: Cardiac myxoma (CM) is the most common (58%-80%) type of primary cardiac tumours. Currently, there is a need to develop medical therapies, especially for patients not physically suitable for surgeries. However, the mechanisms that shape the tumour microenvironment (TME) in CM remain largely unknown, which impedes the development of targeted therapies. Here, we aimed to dissect the TME in CM at single-cell and spatial resolution. METHODS: We performed single-cell transcriptomic sequencing and Visium CytAssist spatial transcriptomic (ST) assays on tumour samples from patients with CM. A comprehensive analysis was performed, including unsupervised clustering, RNA velocity, clonal substructure inference of tumour cells and cell-cell communication. RESULTS: Unsupervised clustering of 34 759 cells identified 12 clusters, which were assigned to endothelial cells (ECs), mesenchymal stroma cells (MSCs), and tumour-infiltrating immune cells. Myxoma tumour cells were found to encompass two closely related phenotypic states, namely, EC-like tumour cells (ETCs) and MSC-like tumour cells (MTCs). According to RNA velocity, our findings suggest that ETCs may be directly differentiated from MTCs. The immune microenvironment of CM was found to contain multiple factors that promote immune suppression and evasion, underscoring the potential of using immunotherapies as a treatment option. Hyperactive signals sent primarily by tumour cells were identified, such as MDK, HGF, chemerin, and GDF15 signalling. Finally, the ST assay uncovered spatial features of the subclusters, proximal cell-cell communication, and clonal evolution of myxoma tumour cells. CONCLUSIONS: Our study presents the first comprehensive characterisation of the TME in CM at both single-cell and spatial resolution. Our study provides novel insight into the differentiation of myxoma tumour cells and advance our understanding of the TME in CM. Given the rarity of cardiac tumours, our study provides invaluable datasets and promotes the development of medical therapies for CM.

Research Bronchoscopies in Critically Ill Research Participants: An Official American Thoracic Society Workshop Report.

Bronchoscopy for research purposes is a valuable tool to understand lung-specific biology in human participants. Despite published reports and active research protocols using this procedure in critically ill patients, no recent document encapsulates the important safety considerations and downstream applications of this procedure in this setting. The objectives were to identify safe practices for patient selection and protection of hospital staff, provide recommendations for sample procurement to standardize studies, and give guidance on sample preparation for novel research technologies. Seventeen international experts in the management of critically ill patients, bronchoscopy in clinical and research settings, and experience in patient-oriented clinical or translational research convened for a workshop. Review of relevant literature, expert presentations, and discussion generated the findings presented herein. The committee concludes that research bronchoscopy with bronchoalveolar lavage in critically ill patients on mechanical ventilation is valuable and safe in appropriately selected patients. This report includes recommendations on standardization of this procedure and prioritizes the reporting of sample management to produce more reproducible results between laboratories. This document serves as a resource to the community of researchers who endeavor to include bronchoscopy as part of their research protocols and highlights key considerations for the inclusion and safety of research participants.

Birt-Hogg-Dubé syndrome with c.1579_1580insA variant in a Chinese family: a case report.

Birt-Hogg-Dubé (BHD) syndrome, is a rare genetic disease with heterogeneous manifestations in different populations. In this study, we reported a Chinese female BHD case and her family members with c.1579_1580insA variant in FLCN gene, who were characterized by diffused pulmonary cysts/bulla, and reviewed another five familial BHD cases in China. Based on these cases, recurrent spontaneous pneumothorax is likely to be the first symptom for BHD in Chinese patients, with particularly but not limited to c.1579_1580insA variant. Therefore, attention to the early diagnosis of BHD in China should focus on pulmonary signs, but skin or kidney lesions still can not be neglected.

Airway Stents from Now to the Future: A Narrative Review.

Airway stent insertion is important for patients with airway stenosis. Currently, the most widely used airway stents in clinical procedures are silicone and metallic stents, which offer patients effective treatment. However, these stents composed of permanent materials need to be removed, subjecting patients to invasive manipulation once more. As a result, there is a growing demand for biodegradable airway stents. Biodegradable materials for airway stents are now available in two types: biodegradable polymers and biodegradable alloys. Polymers that include poly (l-lactic acid), poly (D, l-lactide-co-glycolide), polycaprolactone, and polydioxanone are the ultimate metabolites which are generally carbon dioxide and water. Magnesium alloys are the most often utilized metal biodegradable materials for airway stents. The stent's mechanical properties and rate of degradation vary as a result of the different materials, cutting techniques, and structural configurations. We summarized the information above from recent studies on biodegradable airway stents conducted in both animals and humans. There is great potential for clinical applications for biodegradable airway stents. They avoid damage to the trachea during removal and reduce complications to some extent. However, several significant technical difficulties slow down the development of biodegradable airway stents. The efficacy and safety of different biodegradable airway stents still need to be investigated and proved.

Clinical characteristics and predictors of pulmonary hypertension in chronic obstructive pulmonary disease at different altitudes.

BACKGROUND: Pulmonary hypertension (PH) is a common complication in patients with chronic obstructive pulmonary disease (COPD) and is closely associated with poor prognosis. However, studies on the predictors of PH in COPD patients are limited, especially in populations living at high altitude (HA). OBJECTIVES: To investigate the differences in the clinical characteristics and predictors of patients with COPD/COPD and PH (COPD-PH) from low altitude (LA, 600 m) and HA (2200 m). METHODS: We performed a cross-sectional survey of 228 COPD patients of Han nationality admitted to the respiratory department of Qinghai People's Hospital (N = 113) and West China Hospital of Sichuan University (N = 115) between March 2019 and June 2021. PH was defined as a pulmonary arterial systolic pressure (PASP) > 36 mmHg measured using transthoracic echocardiography (TTE). RESULTS: The proportion of PH in COPD patients living at HA was higher than that in patients living at LA (60.2% vs. 31.3%). COPD-PH patients from HA showed significantly different in baseline characteristics, laboratory tests and pulmonary function test. Multivariate logistic regression analysis indicated that the predictors of PH in COPD patients were different between the HA and LA groups. CONCLUSIONS: The COPD patients living at HA had a higher proportion of PH than those living at LA. At LA, increased B-type natriuretic peptide (BNP) and direct bilirubin (DB) were predictors for PH in COPD patients. However, at HA, increased DB was a predictor of PH in COPD patients.