[Retrospective Study of Bronchoscopic Intervention Therapy for Bronchopleural Fistula Induced by Pulmonary Surgery].

BACKGROUND: As a new technique developed in recent years, bronchoscopic intervention therapy has the advantages of minimal invasion, high safety and repeatability. The aim of this study is to investigate the clinical characteristics of bronchopleural fistula (BPF) induced by surgeries for lung malignancies or benign diseases and the effect of bronchoscopic intervention therapy for BPF, so as to provide support for prevention and treatment of BPF. METHODS: Data 64 patients with BPF who were treated by bronchoscopic intervention in Respiratory Disease Center of Dongzhimen Hospital, Beijing University of Chinese Medicine from June 2020 to September 2023 were collected. Patients with fistula diameter ≤5 mm were underwent submucous injection of macrogol, combined with blocking therapy with N-butyl cyanoacrylate, medical bioprotein glue or silicone prosthesis. Patients with fistula diameter >5 mm were implanted with different stents and cardiac occluders. Locations and characteristics of fistulas were summarized, meanwhile, data including Karnofsky performance status (KPS), shortbreath scale (SS), body temperature, pleural drainage volume and white blood cell count before and after operation were observed. RESULTS: For all 64 patients, 96 anatomic lung resections including pneumonectomy, lobectomy and segmentectomy were executed and 74 fistulas occurred in 65 fistula locations. The proportion of fistula in the right lung (63.5%) was significantly higher than that in the left (36.5%). Besides, the right inferior lobar bronchial fistula was the most common (40.5%). After operation, KPS was significantly increased, while SS, body temperature, pleural drainage volume and white blood cell count were significantly decreased compared to the preoperative values (P<0.05). By telephone follow-up or readmission during 1 month to 38 months after treament, median survival time was 21 months. 33 patients (51.6%) showed complete response, 7 patients (10.9%) showed complete clinical response, 18 patients (28.1%) showed partial response, and 6 patients (9.4%) showed no response. As a whole, the total effective rate of bronchoscopic intervention for BPF was 90.6%. CONCLUSIONS: BPF induced by pulmonary surgery can lead to severe symptoms and it is usually life-threating. Bronchoscopic intervention therapy is one of the fast and effective therapeutic methods for BPF.

Prediction of High-Risk Gastrointestinal Stromal Tumor Recurrence Based on Delta-CT Radiomics Modeling: A 3-Year Follow-up Study After Surgery.

Background: Medium- to high-risk classification-gastrointestinal stromal tumors (MH-GIST) have a high recurrence rate and are difficult to treat. This study aims to predict the recurrence of MH-GIST within 3 years after surgery based on clinical data and preoperative Delta-CT Radiomics modeling. Methods: A retrospective analysis was conducted on clinical imaging data of 242 cases confirmed to have MH-GIST after surgery, including 92 cases of recurrence and 150 cases of normal. The training set and test set were established using a 7:3 ratio and time cutoff point. In the training set, multiple prediction models were established based on clinical data of MH-GIST and the changes in radiomics texture of enhanced computed tomography (CT) at different time periods (Delta-CT radiomics). The area under curve (AUC) values of each model were compared using the Delong test, and the clinical net benefit of the model was tested using decision curve analysis (DCA). Then, the model was externally validated in the test set, and a novel nomogram predicting the recurrence of MH-GIST was finally created. Results: Univariate analysis confirmed that tumor volume, tumor location, neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), diabetes, spicy hot pot, CT enhancement mode, and Radscore 1/2 were predictive factors for MH-GIST recurrence (P < .05). The combined model based on these above factors had significantly higher predictive performance (AUC = 0.895, 95% confidence interval [CI] = [0.839-0.937]) than the clinical data model (AUC = 0.735, 95% CI = [0.6 62-0.800]) and radiomics model (AUC = 0.842, 95% CI = [0.779-0.894]). Decision curve analysis also confirmed the higher clinical net benefit of the combined model, and the same results were validated in the test set. The novel nomogram developed based on the combined model helps predict the recurrence of MH-GIST. Conclusions: The nomogram of clinical and Delta-CT radiomics has important clinical value in predicting the recurrence of MH-GIST, providing reliable data reference for its diagnosis, treatment, and clinical decision-making.

Prognostic modeling for nasopharyngeal carcinoma (NC) undergoing concurrent chemoradiotherapy using clinical and enhanced MRI-Delta radiomics data: A preliminary study.

BACKGROUND: Nasopharyngeal carcinoma (NC) is one of the prevalent malignancies of the head and neck region with poor prognosis. OBJECTIVE: The aim of this study is to establish a predictive model for assessing NC prognosis based on clinical and MR radiomics data, subsequently to develop a nomogram for practical application. METHODS: Retrospective analysis was conducted on clinical and imaging data collected between May 2010 and August 2018, involving 211 patients diagnosed with histologically confirmed NC who received concurrent chemoradiotherapy or radical surgery in Xiangyang No. 1 People's Hospital. According to 5-10 years of follow-up results, the patients were divided into two groups: the study group (n= 76), which experienced recurrence, metastasis, or death, and the control group (n= 135), characterized by normal survival. Training and testing subsets were established at a 7:3 ratio, with a predefined time cutoff. In the training set, three prediction models were established: a clinical data model, an imaging model, and a combined model using the integrated variation in clinical characteristics along with MR radiomics parameters (Delta-Radscore) observed before and after concurrent chemoradiotherapy. Model performance was compared using Delong's test, and net clinical benefit was assessed via decision curve analysis (DCA). Then, external validation was conducted on the test set, and finally a nomogram predicting NC prognosis was created. RESULTS: Univariate analysis identified that the risk factors impacting the prognosis of NC included gender, pathological type, neutrophil to lymphocyte ratio (NLR), degree of tumor differentiation, MR enhancement pattern, and Delta-Radscore (P< 0.05). The combined model established based on the abovementioned factors exhibited significantly higher predictive performance [AUC: 0.874, 95% CI (0.810-0.923)] than that of the clinical data model [AUC: 0.650, 95% CI (0.568-0.727)] and imaging model [AUC: 0.824, 95% CI (0.753-0.882)]. DCA also demonstrated superior clinical net benefit in the combined model, a finding further verified by results from the test set. The developed nomogram, based on the combined model, exhibited promising performance in clinical applications. CONCLUSION: The Delta-Radscore derived from MR radiomics data before and after concurrent chemoradiotherapy helps enhance the performance of the NC prognostic model. The combined model and resultant nomogram provide valuable support for clinical decision-making in NC treatment, ultimately contributing to an improved survival rate.

Ameliorative Effect of Coenzyme Q10 on Phenotypic Transformation in Human Smooth Muscle Cells with FBN1 Knockdown.

Mutations of the FBN1 gene lead to Marfan syndrome (MFS), which is an autosomal dominant connective tissue disorder featured by thoracic aortic aneurysm risk. There is currently no effective treatment for MFS. Here, we studied the role of mitochondrial dysfunction in the phenotypic transformation of human smooth muscle cells (SMCs) and whether a mitochondrial boosting strategy can be a potential treatment. We knocked down FBN1 in SMCs to create an MFS cell model and used rotenone to induce mitochondrial dysfunction. Furthermore, we incubated the shFBN1 SMCs with Coenzyme Q10 (CoQ10) to assess whether restoring mitochondrial function can reverse the phenotypic transformation. The results showed that shFBN1 SMCs had decreased TFAM (mitochondrial transcription factor A), mtDNA levels and mitochondrial mass, lost their contractile capacity and had increased synthetic phenotype markers. Inhibiting the mitochondrial function of SMCs can decrease the expression of contractile markers and increase the expression of synthetic genes. Imposing mitochondrial stress causes a double-hit effect on the TFAM level, oxidative phosphorylation and phenotypic transformation of FBN1-knockdown SMCs while restoring mitochondrial metabolism with CoQ10 can rapidly reverse the synthetic phenotype. Our results suggest that mitochondria function is a potential therapeutic target for the phenotypic transformation of SMCs in MFS.

The Isolation and Characterization of a Novel Psychrotolerant Cellulolytic Bacterium, Microbacterium sp. QXD-8T.

Cellulolytic microorganisms play a crucial role in agricultural waste disposal. Strain QXD-8T was isolated from soil in northern China. Similarity analyses of the 16S rRNA gene, as well as the 120 conserved genes in the whole-genome sequence, indicate that it represents a novel species within the genus Microbacterium. The Microbacterium sp. QXD-8T was able to grow on the CAM plate with sodium carboxymethyl cellulose as a carbon source at 15 °C, forming a transparent hydrolysis circle after Congo red staining, even though the optimal temperature for the growth and cellulose degradation of strain QXD-8T was 28 °C. In the liquid medium, it effectively degraded cellulose and produced reducing sugars. Functional annotation revealed the presence of encoding genes for the GH5, GH6, and GH10 enzyme families with endoglucanase activity, as well as the GH1, GH3, GH39, and GH116 enzyme families with ß-glucosidase activity. Additionally, two proteins in the GH6 family, one in the GH10, and two of nine proteins in the GH3 were predicted to contain a signal peptide and transmembrane region, suggesting their potential for extracellularly degrade cellulose. Based on the physiological features of the type strain QXD-8T, we propose the name Microbacterium psychrotolerans for this novel species. This study expands the diversity of psychrotolerant cellulolytic bacteria and provides a potential microbial resource for straw returning in high-latitude areas at low temperatures.

Antioxidant Minerals Modified the Association between Iron and Type 2 Diabetes in a Chinese Population.

Inconsistent findings exist regarding the relationship between heme iron intake and type 2 diabetes (T2D) among Western and Eastern populations. Easterners tend to consume a plant-based diet which is abundant in antioxidant minerals. To examine the hypothesis that antioxidant mineral may modify the relationship between iron and T2D, we performed a case-control study by measuring the serum mineral levels in 2198 Chinese subjects. A total of 2113 T2D patients and 2458 controls were invited; 502 T2D patients and 1696 controls were finally analyzed. In the total population, high serum iron showed a positive association with T2D odds (odds ratio [OR] = 1.27 [1.04, 1.55]); high magnesium (OR = 0.18 [0.14, 0.22]), copper (OR = 0.27 [0.21, 0.33]), zinc (OR = 0.37 [0.30, 0.46]), chromium (OR = 0.61 [0.50, 0.74]), or selenium concentrations (OR = 0.39 [0.31, 0.48]) were inversely associated with T2D odds. In contrast, in individuals with higher magnesium (>2673.2 µg/dL), zinc (>136.7 µg/dL), copper (>132.1 µg/dL), chromium (>14.0 µg/dL), or selenium concentrations (>16.8 µg/dL), serum iron displayed no association with T2D (p > 0.05). Serum copper and magnesium were significant modifiers of the association between iron and T2D in individuals with different physiological status (p < 0.05). Our findings support the idea that consuming a diet rich in antioxidant minerals is an effective approach for preventing T2D.

Members of the class Candidatus Ordosarchaeia imply an alternative evolutionary scenario from methanogens to haloarchaea.

The origin of methanogenesis can be traced to the common ancestor of non-DPANN archaea, whereas haloarchaea (or Halobacteria) are believed to have evolved from a methanogenic ancestor through multiple evolutionary events. However, due to the accelerated evolution and compositional bias of proteins adapting to hypersaline habitats, Halobacteria exhibit substantial evolutionary divergence from methanogens, and the identification of the closest methanogen (either Methanonatronarchaeia or other taxa) to Halobacteria remains a subject of debate. Here, we obtained five metagenome-assembled genomes with high completeness from soda-saline lakes on the Ordos Plateau in Inner Mongolia, China, and we proposed the name Candidatus Ordosarchaeia for this novel class. Phylogenetic analyses revealed that Ca. Ordosarchaeia is firmly positioned near the median position between the Methanonatronarchaeia and Halobacteria-Hikarchaeia lineages. Functional predictions supported the transitional status of Ca. Ordosarchaeia with the metabolic potential of nonmethanogenic and aerobic chemoheterotrophy, as did remnants of the gene sequences of methylamine/dimethylamine/trimethylamine metabolism and coenzyme M biosynthesis. Based on the similarity of the methyl-coenzyme M reductase genes mcrBGADC in Methanonatronarchaeia with the phylogenetically distant methanogens, an alternative evolutionary scenario is proposed, in which Methanonatronarchaeia, Ca. Ordosarchaeia, Ca. Hikarchaeia, and Halobacteria share a common ancestor that initially lost mcr genes. However, certain members of Methanonatronarchaeia subsequently acquired mcr genes through horizontal gene transfer from distantly related methanogens. This hypothesis is supported by amalgamated likelihood estimation, phylogenetic analysis, and gene arrangement patterns. Altogether, Ca. Ordosarchaeia genomes clarify the sisterhood of Methanonatronarchaeia with Halobacteria and provide new insights into the evolution from methanogens to haloarchaea.

An adaptive weighted ensemble learning network for diabetic retinopathy classification.

Diabetic retinopathy (DR) is one of the leading causes of blindness. However, because the data distribution of classes is not always balanced, it is challenging for automated early DR detection using deep learning techniques. In this paper, we propose an adaptive weighted ensemble learning method for DR detection based on optical coherence tomography (OCT) images. Specifically, we develop an ensemble learning model based on three advanced deep learning models for higher performance. To better utilize the cues implied in these base models, a novel decision fusion scheme is proposed based on the Bayesian theory in terms of the key evaluation indicators, to dynamically adjust the weighting distribution of base models to alleviate the negative effects potentially caused by the problem of unbalanced data size. Extensive experiments are performed on two public datasets to verify the effectiveness of the proposed method. A quadratic weighted kappa of 0.8487 and an accuracy of 0.9343 on the DRAC2022 dataset, and a quadratic weighted kappa of 0.9007 and an accuracy of 0.8956 on the APTOS2019 dataset are obtained, respectively. The results demonstrate that our method has the ability to enhance the ovearall performance of DR detection on OCT images.

Efficacy of Bifidobacterium animalis subsp. lactis BL-99 in the treatment of functional dyspepsia: a randomized placebo-controlled clinical trial.

Current treatment for functional dyspepsia (FD) has limited and unsustainable efficacy. Probiotics have the sustainable potential to alleviate FD. This randomized controlled clinical trial (Chinese Clinical Trial Registry, ChiCTR2000041430) assigned 200 FD patients to receive placebo, positive-drug (rabeprazole), or Bifidobacterium animalis subsp. lactis BL-99 (BL-99; low, high doses) for 8-week. The primary outcome was the clinical response rate (CRR) of FD score after 8-week treatment. The secondary outcomes were CRR of FD score at other periods, and PDS, EPS, serum indicators, fecal microbiota and metabolites. The CRR in FD score for the BL-99_high group [45 (90.0%)] was significantly higher than that for placebo [29 (58.0%), p = 0.001], BL-99_low [37 (74.0%), p = 0.044] and positive_control [35 (70.0%), p = 0.017] groups after 8-week treatment. This effect was sustained until 2-week after treatment but disappeared 8-week after treatment. Further metagenomic and metabolomics revealed that BL-99 promoted the accumulation of SCFA-producing microbiota and the increase of SCFA levels in stool and serum, which may account for the increase of serum gastrin level. This study supports the potential use of BL-99 for the treatment of FD.

Cycl[2,2,4]azine-embedded non-alternant nanographenes containing fused antiaromatic azepine ring.

The development of non-alternant nanographenes has attracted considerable attention due to their unique photophysical properties. Herein, we reported a novel aza-doped, non-alternant nanographene (NG) 1 by embedding the cycl[2,2,4]azine unit into the benzenoid NG framework. Single-crystal X-ray diffractometry suggests saddle or twisted nonplanar geometry of the entire backbone of 1 and coplanar conformation of the cycl[2,2,4]azine unit. DFT calculation together with solid structure indicates that NG 1 possesses significant local antiaromaticity in the azepine ring. By oxidative process or trifluoroacetic acid treatment, this nanographene can transform into a mono-radical cation, which was confirmed by UV/Vis absorption, 1H NMR, and electron paramagnetic resonance (EPR) spectroscopy. The antiaromaticity/aromaticity switching of the azepine ring on 1˙+ from 1 enables the high stability of this radical cation, which remained intact for over 1 day. Due to the electron-donating nature of the nitrogen and the unique electronic structure, NG 1 exhibits strong electron-donating properties, as proved by the intermolecular charge transfer towards C60 with a high association constant. Furthermore, selective modification of NG 1 was accomplished by Vilsmeier reaction, and the derivatives 7 and 8 with substituted benzophenone were obtained. The photophysical and electronic properties can be tuned by the introduction of different electronic groups in benzophenone.

The activator protein-1 complex governs a vascular degenerative transcriptional programme in smooth muscle cells to trigger aortic dissection and rupture.

BACKGROUND AND AIMS: Stanford type A aortic dissection (AD) is a degenerative aortic remodelling disease marked by an exceedingly high mortality without effective pharmacologic therapies. Smooth muscle cells (SMCs) lining tunica media adopt a range of states, and their transformation from contractile to synthetic phenotypes fundamentally triggers AD. However, the underlying pathomechanisms governing this population shift and subsequent AD, particularly at distinct disease temporal stages, remain elusive. METHODS: Ascending aortas from nine patients undergoing ascending aorta replacement and five individuals undergoing heart transplantation were subjected to single-cell RNA sequencing. The pathogenic targets governing the phenotypic switch of SMCs were identified by trajectory inference, functional scoring, single-cell regulatory network inference and clustering, regulon, and interactome analyses and confirmed using human ascending aortas, primary SMCs, and a ß-aminopropionitrile monofumarate-induced AD model. RESULTS: The transcriptional profiles of 93 397 cells revealed a dynamic temporal-specific phenotypic transition and marked elevation of the activator protein-1 (AP-1) complex, actively enabling synthetic SMC expansion. Mechanistically, tumour necrosis factor signalling enhanced AP-1 transcriptional activity by dampening mitochondrial oxidative phosphorylation (OXPHOS). Targeting this axis with the OXPHOS enhancer coenzyme Q10 or AP-1-specific inhibitor T-5224 impedes phenotypic transition and aortic degeneration while improving survival by 42.88% (58.3%-83.3% for coenzyme Q10 treatment), 150.15% (33.3%-83.3% for 2-week T-5224), and 175.38% (33.3%-91.7% for 3-week T-5224) in the ß-aminopropionitrile monofumarate-induced AD model. CONCLUSIONS: This cross-sectional compendium of cellular atlas of human ascending aortas during AD progression provides previously unappreciated insights into a transcriptional programme permitting aortic degeneration, highlighting a translational proof of concept for an anti-remodelling intervention as an attractive strategy to manage temporal-specific AD by modulating the tumour necrosis factor-OXPHOS-AP-1 axis.

Preliminary Application of a Continuous Functional Contrast Visual Acuity System in the Assessment of Visual Function in Dry Eye Patients.

Purpose: To investigate the feasibility and efficacy of a continuous functional contrast visual acuity (CFCVA) system in the assessment of visual function in dry eye disease (DED). Methods: Twenty patients with DED and 15 normal controls were recruited. Subjective symptoms were evaluated using the Ocular Surface Disease Index (OSDI) questionnaire, and tear film stability was assessed by a noninvasive corneal topographer. Under natural blinking conditions, the custom-built CFCVA system was used to take serial visual acuity measurements at 100%, 25%, 10%, and 5% contrast for 60 seconds. A 5-minute measurement at a 100% contrast level was defined as the stress test (ST). Mean CFCVA was defined, and visual maintenance ratio (VMR) was the ratio of mean CFCVA divided by baseline visual acuity. Results: In both groups, VMR decreased and mean CFCVA (logarithm of the minimum angle of resolution) increased with decreasing optotype contrast (from 100% to 5%). In ST, the ST VMR at the fourth and fifth minutes (VMR54 and VMR55) showed the strongest correlations with OSDI total, ocular symptoms, and vision-related function (-0.646 and -0.598, -0.688 and -0.693, and -0.599 and -0.555, respectively, P < 0.05). VMR54 and VMR55 also demonstrated the best discriminating ability for detecting DED, with areas under the curve of 0.903 and 0.867, respectively. Conclusions: Extending the continuous measuring time was more effective for detecting vision-related functional abnormalities in patients with DED than simply decreasing the optotype contrast level. Translational Relevance: The proposed CFCVA system and associated parameters offer a potential method for quantifying and interpreting the visual symptoms of DED in clinical care.