A new integrative analysis of histopathology and single cell RNA-seq reveals the CCL5 mediated T and NK cell interaction with vascular cells in idiopathic pulmonary arterial hypertension.

BACKGROUND: Inflammation and dysregulated immunity play vital roles in idiopathic pulmonary arterial hypertension (IPAH), while the mechanisms that initiate and promote these processes are unclear. METHODS: Transcriptomic data of lung tissues from IPAH patients and controls were obtained from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA), differential expression analysis, protein-protein interaction (PPI) and functional enrichment analysis were combined with a hemodynamically-related histopathological score to identify inflammation-associated hub genes in IPAH. The monocrotaline-induced rat model of pulmonary hypertension was utilized to confirm the expression pattern of these hub genes. Single-cell RNA-sequencing (scRNA-seq) data were used to identify the hub gene-expressing cell types and their intercellular interactions. RESULTS: Through an extensive bioinformatics analysis, CXCL9, CCL5, GZMA and GZMK were identified as hub genes that distinguished IPAH patients from controls. Among these genes, pulmonary expression levels of Cxcl9, Ccl5 and Gzma were elevated in monocrotaline-exposed rats. Further investigation revealed that only CCL5 and GZMA were highly expressed in T and NK cells, where CCL5 mediated T and NK cell interaction with endothelial cells, smooth muscle cells, and fibroblasts through multiple receptors. CONCLUSIONS: Our study identified a new inflammatory pathway in IPAH, where T and NK cells drove heightened inflammation predominantly via the upregulation of CCL5, providing groundwork for the development of targeted therapeutics.

Adversarial attacks and adversarial training for burn image segmentation based on deep learning.

Deep learning has been widely applied in the fields of image classification and segmentation, while adversarial attacks can impact the model's results in image segmentation and classification. Especially in medical images, due to constraints from factors like shooting angles, environmental lighting, and diverse photography devices, medical images typically contain various forms of noise. In order to address the impact of these physically meaningful disturbances on existing deep learning models in the application of burn image segmentation, we simulate attack methods inspired by natural phenomena and propose an adversarial training approach specifically designed for burn image segmentation. The method is tested on our burn dataset. Through the defensive training using our approach, the segmentation accuracy of adversarial samples, initially at 54%, is elevated to 82.19%, exhibiting a 1.97% improvement compared to conventional adversarial training methods, while substantially reducing the training time. Ablation experiments validate the effectiveness of individual losses, and we assess and compare training results with different adversarial samples using various metrics.

[Effect and mechanism of Maxing Shigan Decoction on reducing inflammatory response in rats with cough variant asthma via TLR4/MyD88/NF-κB and p38 MAPK signaling pathways].

This study aims to investigate the effect and mechanism of Maxingshigan Decoction on inflammation in the rat model of cough variant asthma(CVA). The SPF-grade SD rats of 6-8 weeks were randomized into normal, model, Montelukast sodium, and low-, medium-, and high-dose Maxing Shigan Decoction groups, with 8 rats in each group. The CVA rat model was induced by ovalbumin(OVA) and aluminum hydroxide sensitization and ovalbumin stimulation. The normal group and model group were administrated with equal volume of normal saline by gavage, and other groups with corresponding drugs by gavage. After the experiment, the number of white blood cells in blood and the levels of interleukin-6(IL-6), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α) in the serum were measured. The lung tissue was stained with hematoxylin-eosin(HE). Western blot was employed to determine the protein levels of nuclear factor-κB(NF-κB), Toll-like receptor 4(TLR4), myeloid differentiation protein(MyD88), and mitogen-activated protein kinase(MAPK) in the lung tissue. Real-time PCR was carried out to measure the mRNA levels of TLR4 and MyD88 in the lung tissue. Compared with the normal group, the model group showed increased white blood cells, elevated IL-6 and TNF-α levels(P<0.01), lowered IL-10 level(P<0.01), up-regulated protein levels of TLR4, MyD88, p-p65/NF-κB p65, and p-p38 MAPK/p38 MAPK(P<0.01) and mRNA levels of TLR4 and MyD88(P<0.01) in the lung tissue. HE staining showed obvious infiltration of inflammatory cells around the airway and cell disarrangement in the model group. Compared with the model group, Montelukast sodium and high-dose Maxing Shigan Decoction reduced the white blood cells, lowered the IL-6 and TNF-α levels(P<0.01), and elevated the IL-10 level(P<0.01). Moreover, they down-regulated the protein levels of TLR4, MyD88, p-p65/NF-κB p65, p-p38 MAPK/p38 MAPK in the lung tissue(P<0.01) and the mRNA levels of TLR4 and MyD88 in the lung tissue(P<0.01). HE staining showed that Montelukast sodium and high-dose Maxing Shigan Decoction reduced inflammatory cell infiltration and cell disarrangement. The number of white blood cells, the levels of IL-10 and TNF-α in the serum, the protein levels of TLR4, MyD88, p-p65/NF-κB p65, and p-p38 MAPK/p38 MAPK, and the mRNA levels of TLR4 and MyD88 in the lung tissue showed no significant differences between the Montelukast sodium group and high-dose Maxing Shigan Decoction group. Maxing Shigan Decoction can inhibit airway inflammation in CVA rats by inhibiting the activation of TLR4/MyD88/NF-κB and p38 MAPK signaling pathways.

Serum proteome profiling reveals heparanase as a candidate biomarker for chronic thromboembolic pulmonary hypertension.

Determining novel biomarkers for early identification of chronic thromboembolic pulmonary hypertension (CTEPH) could improve patient outcomes. We used the isobaric tag for relative and absolute quantitation approach to compare the serum protein profiles between CTEPH patients and the controls. Bioinformatics analyses and ELISA were also performed. We identified three proteins including heparanase (HPSE), gelsolin (GSN), and secreted protein acidic and rich in cysteine (SPARC) had significant changes in CTEPH. The receiver operating characteristic curve analysis showed that the areas under the curve of HPSE in CTEPH diagnosis were 0.988. Furthermore, HPSE was correlated with multiple parameters of right ventricular function. HPSE concentrations were significantly higher in patients with a low TAPSE/sPAP ratio (≤0.31 mm/mmHg) (65.4 [60.5,68.0] vs. 59.9 [35.9,63.2] ng/mL, p < 0.05). The CTEPH patients treated by balloon pulmonary angioplasty had significantly lower HPSE levels. The study demonstrates that HPSE may be a promising biomarker for noninvasive detection of CTEPH.

Safety and efficacy of balloon pulmonary angioplasty for technically operable chronic thromboembolic pulmonary hypertension.

Balloon pulmonary angioplasty (BPA) has been proven effective for addressing technically inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, the effectiveness of BPA in technically operable CTEPH patients who, for various reasons, did not undergo the procedure remains an area requiring exploration. This study sought to assess the safety and efficacy of BPA in such cases. We collected and reviewed data from CTEPH patients who underwent BPA in a consecutive manner. Following multidisciplinary team (MDT) decisions, patients were classified into two groups: technically inoperable (group A) and operable (group B). Group B comprised patients deemed technically suitable for pulmonary endarterectomy (PEA) but who did not undergo the procedure for various reasons. All patients underwent a comprehensive diagnostic work-up, including right heart categorization at baseline and the last intervention. This study compared changes in hemodynamic parameters, functional capacity, and quality of life between the two groups. In total, 161 patients underwent 414 procedures at our center, with Group A comprising 112 patients who underwent 282 BPA sessions and group B comprising 49 patients who underwent 132 BPA sessions. Significantly, both groups exhibited improvements in hemodynamics, functional capacity, and quality of life. The occurrence rate of complications, including hemoptysis and lung injury, was similar [12 (63.2%) vs. 7 (36.8%), p = 0.68]. BPA demonstrated favorable outcomes in patients with proximal CTEPH who did not undergo pulmonary endarterectomy. However, the clinical impact of BPA in technically operable CTEPH was found to be less significant than in inoperable cases.

Chemical profile and quantitative comparison of constituents in different medicinal parts of Lactuca indica during varied harvest periods using UPLC-MS/MS method.

Lactuca indica L. cv. Mengzao (LIM), acknowledged as a pivotal "One Root of Medicine and Food", boasts dual applications in both culinary and medicinal domains. This research delves into the influence of various harvest periods (vegetative, budding, blossom, and fruiting) on distinct medicinal parts (roots, stems, leaves, flowers, and seeds) of LIM, employing plant metabolomics to assess its chemical constituents. A total of 66 chemical constituents were identified in LIM, with 11 chemical components emerging as potential markers for distinguish medicinal parts. Notably, nutritional organs exhibited elevated levels of cichoric acid, rutin and chlorogenic acid. Specifically, leaves during the budding stage displayed the highest chicoric acid content at 11.70 mg·g-1. Conversely, reproductive organs showed heightened concentrations of cichoric acid, rutin and chlorogenic acid, with seeds exhibiting the peak cichoric acid content at 4.53 mg g-1. This study enriches our understanding of LIM by offering novel insights into quality assessment and the comprehensive utilization of its diverse parts.

Pharmacokinetic-pharmacodynamic modeling of the active components of Shenkang injection in rats with chronic renal failure and its protective effect on damaged renal cells.

The study aimed to explore the pharmacokinetic and pharmacodynamic alterations of the active components of Shenkang injection (i.e. hydroxy saffron yellow pigment A [HSYA], tanshinol, rheum emodin, and astragaloside IV) in rats with chronic renal failure (CRF), and establish a pharmacokinetic-pharmacodynamic model (PK-PD model) in order to provide a scientific and theoretical basis for the rational clinical use of Shenkang injection. Sprague-Dawley (SD) rats were randomly divided into a normal group, model group, and Shenkang injection group. A rat model of CRF was induced by adenine gavage and then followed by drug administration via tail vein injection. Orbital blood was collected at different timepoints and the blood concentrations of the four active components were measured by UHPLC-Q-Orbitrap HRMS. Serum levels of creatinine (Scr), urea nitrogen (BUN), and uric acid (UA) were determined using an automatic biochemical analyzer. A PK-PD model was established, and DAS 3.2.6 software was used for model fitting as well as statistical analysis. TGF-ß1 was utilized to induce normal rat kidney cells to construct a renal fibrosis model to investigate the protective effect of the pharmacological components on renal fibrosis. The pharmacokinetic analysis of hydroxy saffron yellow pigment A, tanshinol, rheum emodin, and astragaloside IV based on UHPLC-Q-Orbitrap HRMS was stable. The linear regression equations for the four active components were as follows: Y = 0.031X + 0.0091 (R2  = 0.9986) for hydroxy saffron yellow pigment A, Y = 0.0389X + 0.164 (R2  = 0.9979) for tanshinol, Y = 0.0257X + 0.0146 (R2  = 0.9973) for rheum emodin, and Y = 0.0763X + 0.0139 (R2  = 0.9993) for astragaloside IV, which indicated good linear relationships. The methodological investigation was stable, with the interday and intraday precision RSD <10%. Meanwhile, the recoveries ranged between 90% and 120%, in accordance with the requirements for in vivo analysis of drugs. Compared with the model group, the levels of Scr, BUN, and UA were significantly decreased after 20 min in the Shenkang injection group (p < 0.01). The PK-PD model showed that the four active components in the Shenkang injection group could fit well with the three effect measures (i.e. Scr, BUN, and UA), with the measured values similar to the predicted values. The cell model of renal fibrosis showed that the connective tissue growth factor and FN1 protein expression levels were significantly lower in the Shenkang injection group than those in the model group, and the cell fibrosis was improved. The established method for in vivo analysis of Shenkang injection was highly specific, with good separation of the components and simple operation. The total statistical moment could well integrate the pharmacokinetic parameters of the four active components. After treatment with Shenkang injection, all indexes in the administered group improved and showed significant inhibition of renal cell fibrosis in vitro. This study could provide scientific reference ideas for the clinical rational use of traditional Chinese medicine.

Prevalence and prognostic role of PD-L1 in patients with gynecological cancers: A systematic review and meta-analysis.

OBJECTIVE: Our study aims to evaluate programmed cell death ligand-1 (PD-L1) expression and its prognostic significance in cervical cancer (CC), endometrial cancer (EC) and ovarian cancer (OC). METHODS: Several electronic databases were searched. Fixed effects models or random effects models were employed to calculate the pooled prevalence of PD-L1 positivity and pooled hazard ratios (HRs) as appropriate. Heterogeneity and publication bias were also assessed. RESULTS: The pooled prevalence of PD-L1 positivity was 58.1%, 33.8% and 37.5% for CC, EC and OC patients, respectively. There were significant differences in the pooled estimates after stratification by PD-L1-positive assessment criteria and antibody clones. PD-L1 positivity was associated with worse OS in CC and EC patients and poorer progression-free survival (PFS) in CC patients. CONCLUSIONS: The prevalence of PD-L1-positive expression was considerably high in CC and modestly high in EC and OC patients. PD-L1 expression has the potential to be a prognostic biomarker for predicting the clinical outcomes of patients with CC and EC but not OC.

Optimization of ultrasonic-assisted extraction of flavonoids from Lactuca indica L. cv. Mengzao and their antioxidant properties.

In this study, the ultrasound-assisted extraction (UAE) conditions of flavonoids from Lactuca indica L.cv. Mengzao (LIM) leaves was optimized, and the flavonoids content and their antioxidant potential in different parts were analyzed. The optimal extraction parameters to obtain the highest total flavonoids content (TFC) were a a ratio of liquid to solid of 24.76 mL/g, ultrasonic power of 411.43 W, ethanol concentration of 58.86% and an extraction time of 30 min, the average TFC of LIM leaves could reach 48.01 mg/g. For the yield of flavonoids, the UAE method had the best extraction capacity compared with solvent extraction and microwave-assisted extraction (MAE). In general, the TFC in different parts of LIM followed the order flower > leaf > stem > root, the flowering period is the most suitable harvesting period. From ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) quantification, the flower samples showed significantly higher six flavonoids and had the highest radical scavenging capacities compared to other samples. A high positive correlation was observed between the antioxidant activity and TFC, luteolin-7-O-glucoside and rutin were significantly (p < 0.05) correlated with all antioxidant evaluations. This study provides valuable information for the development and utilization of flavonoids in Lactuca indica as ingredients in food, feed and nutritional health products.

[Huazhi Rougan Granules attenuates steatosis in cell model of nonalcoholic fatty liver disease by inducing autophagy].

To investigate the effect of Huazhi Rougan Granules(HZRG) on autophagy in a steatotic hepatocyte model of free fatty acid(FFA)-induced nonalcoholic fatty liver disease(NAFLD) and explore the possible mechanism. FFA solution prepared by mixing palmitic acid(PA) and oleic acid(OA) at the ratio of 1∶2 was used to induce hepatic steatosis in L02 cells after 24 h treatment, and an in vitro NAFLD cell model was established. After termination of incubation, cell counting kit-8(CCK-8) assay was performed to detect the cell viability; Oil red O staining was employed to detect the intracellular lipid accumulation; enzyme-linked immunosorbnent assay(ELISA) was performed to measure the level of triglyceride(TG); to monitor autophagy in L02 cells, transmission electron microscopy(TEM) was used to observe the autophagosomes; LysoBrite Red was used to detect the pH change in lysosome; transfection with mRFP-GFP-LC3 adenovirus was conducted to observe the autophagic flux; Western blot was performed to determine the expression of autophagy marker LC3B-Ⅰ/LC3B-Ⅱ, autophagy substrate p62 and silent information regulator 1(SIRT1)/adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway. NAFLD cell model was successfully induced by FFA at 0.2 mmol·L~(-1) PA and 0.4 mmol·L~(-1) OA. HZRG reduced the TG level(P<0.05, P<0.01) and the lipid accumulation of FFA-induced L02 cells, while elevated the number of autophagosomes and autophagolysosomes to generate autophagic flux. It also affected the functions of lysosomes by regulating their pH. Additionally, HZRG up-regulated the expression of LC3B-Ⅱ/LC3B-Ⅰ, SIRT1, p-AMPK and phospho-protein kinase A(p-PKA)(P<0.05, P<0.01), while down-regulated the expression of p62(P<0.01). Furthermore, 3-methyladenine(3-MA) or chloroquine(CQ) treatment obviously inhibited the above effects of HZRG. HZRG prevented FFA-induced steatosis in L02 cells, and its mechanism might be related to promoting autophagy and regulating SIRT1/AMPK signaling pathway.

Optimization of Extraction Process and Dynamic Changes in Triterpenoids of Lactuca indica from Different Medicinal Parts and Growth Periods.

In this study, the triterpenoids in the leaves of Lactuca indica L.cv. Mengzao (LIM) were extracted via microwave-assisted ethanol extraction, and the optimum extraction conditions for triterpenoids were determined through single-factor experiments and the Box-Behnken method. The effects of three factors (solid-liquid ratio, microwave power and extraction time) on the total triterpenoids content (TTC) were evaluated. The TTC of different parts (roots, stems, leaves and flowers) of LIM in different growth stages was studied, and the scavenging effects of the highest TTC parts on DPPH, ABTS and hydroxyl free radicals were investigated. The results showed that the optimum extraction conditions for microwave-assisted extraction of total triterpenoids from LIM leaves were as follows: solid-liquid ratio of 1:20 g/mL; microwave power of 400 W; and extraction time of 60 min. Under these conditions, the TTC was 29.17 mg/g. Compared with the fresh raw materials, the TTC of the materials increased after freeze drying. The leaves of LIM had the highest TTC, and the flowering stage was the best time. The triterpenoids from the leaves had a strong ability to eliminate DPPH and ABTS free radicals, and the elimination effect of dried leaves was better than that of fresh leaves, while the elimination effect of hydroxyl free radicals was not obvious. The tested method was used to extract total triterpenoids from LIM using a simple process at low cost, which provides a reference for developing intensive processing methods for L. indica.

Changes in the oral and nasal microbiota in pediatric obstructive sleep apnea.

Background: Several clinical studies have demonstrated that pediatric obstructive sleep apnea (OSA) is associated with dysbiosis of airway mucosal microbiota. However, how oral and nasal microbial diversity, composition, and structure are altered in pediatric OSA has not been systemically explored. Methods: 30 polysomnography-confirmed OSA patients with adenoid hypertrophy, and 30 controls who did not have adenoid hypertrophy, were enrolled. Swabs from four surface oral tissue sites (tongue base, soft palate, both palatine tonsils, and adenoid) and one nasal swab from both anterior nares were collected. The 16S ribosomal RNA (rRNA) V3-V4 region was sequenced to identify the microbial communities. Results: The beta diversity and microbial profiles were significantly different between pediatric OSA patients and controls at the five upper airway sites. The abundances of Haemophilus, Fusobacterium, and Porphyromonas were higher at adenoid and tonsils sites of pediatric patients with OSA. Functional analysis revealed that the differential pathway between the pediatric OSA patients and controls involved glycerophospholipids and amino acid metabolism. Conclusions: In this study, the oral and nasal microbiome of pediatric OSA patients exhibited certain differences in composition compared with the controls. However, the microbiota data could be useful as a reference for studies on the upper airway microbiome.

Clonal integration systemically regulates leaf microstructure of Bouteloua dactyloides interconnected ramets to better adapt to different levels of simulated insect herbivory.

Stolon connection of clonal plants can translocate resources and signalling molecules between interconnected ramets to enhance resistance. Plants are well known to enhance leaf anatomical structure and vein density to respond to insect herbivory. Herbivory signalling molecules are transferred through vascular system to alert distant undamaged leaves, which is called systemic defence induction. Here, we investigated how clonal integration modulates leaf vasculature and anatomical structure of Bouteloua dactyloides ramets to cope with different levels of simulated herbivory. Ramet pairs were subject to six treatments, daughter ramets were exposed to three defoliation levels (0 %, 40 % or 80 % leaf removal) and their stolon connections to mother ramets were either severed or kept intact. Local 40 % defoliation increased vein density and adaxial/abaxial cuticle thickness, decreased leaf width and areolar area of daughter ramets. However, such effects of 80 % defoliation were much smaller. Compared with remote 40 % defoliation, remote 80 % defoliation increased leaf width and areolar area and decreased vein density of interconnected undefoliated mother ramets. Without simulated herbivory, stolon connection negatively affected most leaf microstructural traits of both ramets except from denser veins of mother ramets and more bundle sheath cells of daughter ramets. The negative effect of stolon connection on leaf mechanical structures of daughter ramets was ameliorated in the 40 % defoliation treatment, but not in the 80 % defoliation treatment. Stolon connection increased vein density and decreased areolar area of daughter ramets in the 40 % defoliation treatment. In contrast, stolon connection increased areolar area and decreased bundle sheath cell number of 80 % defoliated daughter ramets. Defoliation signals were transmitted from younger ramets to older ramets to change their leaf biomechanical structure. Clonal integration can adjust leaf microstructure of younger ramets according to the degree of herbivory stress, especially leaf vasculature.

"Guidezilla" extension catheter combined with balloon technique for treating pulmonary artery stenosis caused by Takayasu arteritis.

Takayasu arteritis (TA) is a rare systemic vasculitis of the aorta and its primary branches, which usually occurs in young women. Due to its insidious onset and lack of specific symptoms, this disease can be easily misdiagnosed or missed. Approximately 50 â€‹% of the patients having TA with pulmonary artery involvement develop pulmonary hypertension (PH). The 3-year survival rate among patients with TA-related PH is lower than that among patients with TA alone. Early balloon pulmonary angioplasty (BPA) can improve the clinical symptoms and survival of patients with stable TA. To the best of our knowledge, this is the first case reported in the English literature in which a "Guidezilla" catheter was used during BPA to treat stenosis and occlusion of the pulmonary artery caused by Takayasu arteritis (TA).

Clinical features and metabolic reprogramming of atherosclerotic lesions in patients with chronic thromboembolic pulmonary hypertension.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) patients may present with atherosclerotic lesions in their pulmonary arteries, but their clinical characteristics remain unclear. The metabolic pathways associated with the atherosclerotic lesions may explain their occurrence and have implications for interventions, but they have not been investigated. Methods: We collected pulmonary endarterectomy (PEA) samples of CTEPH patients from December 2016 to August 2021. Following a detailed pathological examination of the PEA specimen, the patients were divided into those with and without lesions, and age- and sex matching were performed subsequently using propensity score matching (n = 25 each). Metabolomic profiling was used to investigate the metabolites of the proximal lesions in the PEA specimens. Results: In our study population, 27.2% of all PEA specimens were found to contain atherosclerotic lesions. CTEPH patients with atherosclerotic lesions were more likely to have a history of symptomatic embolism and had a longer timespan between embolism and surgery, whereas the classic risk factors of systemic and coronary circulation could not distinguish CTEPH patients with or without atherosclerotic lesions. Metabolomic profiling revealed that the formation of atherosclerotic lesions in CTEPH was closely related to altered glycine, serine, and threonine metabolic axes, possibly involved in cellular senescence, energy metabolism, and a proinflammatory microenvironment. Conclusion: The occurrence of atherosclerotic lesions in the pulmonary arteries of CTEPH was associated with symptomatic thromboembolic history and prolonged disease duration. The results revealed a new link between atherosclerotic lesions and aberrant amino acid metabolism in the context of CTEPH for the first time. This study has characterized the clinical and metabolic profiles of this distinct group of CTEPH patients, providing new insights into disease pathogenesis and potential interventions.

Different response of the oxygen pathway in patients with chronic thromboembolic pulmonary hypertension treated with pulmonary endarterectomy versus balloon pulmonary angioplasty.

Background: Oxygen pathway limitation exists in chronic thromboembolic pulmonary hypertension (CTEPH). Pulmonary endarterectomy (PEA) and balloon pulmonary angioplasty (BPA) are two effective interventions for CTEPH, but their effects and comparison of these two interventions on the oxygen pathway are not well demonstrated. Methods: CTEPH patients with available pulmonary function test, hemodynamics, and blood gas analysis before and after the interventions were included for comparison of oxygen pathway in terms of lung ventilation, lung gas exchange, oxygen delivery, and oxygen extraction between these two interventions. Results: The change in the percentage of the predicted forced expiratory volume in the 1 s (-3.4 ± 12.7 vs. 3.8 ± 8.7%, P = 0.006) and forced vital capacity (-5.5 ± 13.0 vs. 4.2 ± 9.9%, P = 0.001) among the PEA group (n = 24) and BPA group (n = 46) were significantly different. Patients in the PEA group had a significant increase in their arterial oxygen saturation (from 92.5 ± 3.6 to 94.6 ± 2.4%, P = 0.022), while those in the BPA group had no change, which could be explained by a significant improvement in ventilation/perfusion (-0.48 ± 0.53 vs. -0.17 ± 0.41, P = 0.016). Compared with patients post-BPA, patients post-PEA were characterized by higher oxygen delivery (756.3 ± 229.1 vs. 628.8 ± 188.5 ml/min, P = 0.016) and higher oxygen extraction (203.3 ± 64.8 vs. 151.2 ± 31.9 ml/min, P = 0.001). Conclusion: Partial amelioration of the oxygen pathway limitations could be achieved in CTEPH patients treated with PEA and BPA. CTEPH patients post-PEA had better performance in lung gas exchange, oxygen delivery, and extraction, while those post-BPA had better lung ventilation. Cardiopulmonary rehabilitation may assist in improving the impairment of the oxygen pathway.

Fasting blood glucose as a predictor of progressive infarction in men with acute ischemic stroke.

OBJECTIVE: Blood glucose is related to early neurological deterioration in acute ischemic stroke, but multiple mechanisms are involved in early neurological deterioration, such as progressive infarction. This study aimed to determine whether fasting blood glucose (FBG) is an independent predictor of progressive infarction. METHODS: From April 2017 to December 2020, we retrospectively enrolled 477 patients with acute ischemic stroke within 48 hours of onset. Demographic characteristics, clinical information, neuroimaging characteristics, and laboratory data were collected after admission. RESULTS: We found that 147 (30.8%) patients had progressive infarction. Multiple regression analysis showed that high FBG concentrations (>7.66 mmol/L) were independently associated with progressive infarction. Sex subgroup analysis showed that high FBG concentrations were an independent predictor of progressive infarction in male patients (odds ratio, 2.559; 95% confidence interval, 1.279-5.121). In a receiver operating characteristic curve analysis, FBG concentrations were a predictor of progressive infarction in all cases, especially in male patients. The cutoff value of FBG in all patients and men was 7.155 mmol/L. CONCLUSIONS: FBG is an independent predictor of progressive infarction in patients with acute ischemic stroke within 48 hours of onset, especially in men. Patients with FBG concentrations ≥7.155 mmol/L are more likely to develop progressive infarction.

Effects of different harvest frequencies on microbial community and metabolomic properties of annual ryegrass silage.

In this study, we analyzed the fermentation quality, microbial community, and metabolome characteristics of ryegrass silage from different harvests (first harvest-AK, second harvest-BK, and third harvest-CK) and analyzed the correlation between fermentative bacteria and metabolites. The bacterial community and metabolomic characteristics were analyzed by single-molecule real-time (SMRT) sequencing and ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS/MS), respectively. After 60 days of ensiling, the pH of BK was significantly lower than those of AK and CK, and its lactic acid content was significantly higher than those of AK and CK. Lactiplantibacillus and Enterococcus genera dominate the microbiota of silage obtained from ryegrass harvested at three different harvests. In addition, the BK group had the highest abundance of Lactiplantibacillus plantarum (58.66%), and the CK group had the highest abundance of Enterococcus faecalis (42.88%). The most annotated metabolites among the differential metabolites of different harvests were peptides, and eight amino acids were dominant in the composition of the identified peptides. In the ryegrass silage, arginine, alanine, aspartate, and glutamate biosynthesis had the highest enrichment ratio in the metabolic pathway of KEGG pathway enrichment analysis. Valyl-isoleucine and glutamylvaline were positively correlated with Lactiplantibacillus plantarum. D-Pipecolic acid and L-glutamic acid were positively correlated with Levilactobacillus brevis. L-phenylalanyl-L-proline, 3,4,5-trihydroxy-6-(2-methoxybenzoyloxy) oxane-2-carboxylic acid, and shikimic acid were negatively correlated with Levilactobacillus brevis. In conclusion, this study explains the effects of different harvest frequencies on the fermentation quality, microbial community, and metabolites of ryegrass, and improves our understanding of the ensiling mechanisms associated with different ryegrass harvesting frequencies.

Mannose-decorated ginsenoside Rb1 albumin nanoparticles for targeted anti-inflammatory therapy.

Ginsenoside Rb1 is a potential anti-inflammatory natural molecule, but its therapeutic efficacy was tremendously hampered by the low solubility and non-targeted delivery. In this study, we innovatively developed a mannose (Man)-modified albumin bovine serum albumin carrier (Man-BSA) to overcome the previously mentioned dilemmas of Rb1. The constructed Man-BSA@Rb1 NPs could improve the solubility and increase the cellular uptake of Rb1, finally leading to the enhanced anti-inflammatory effects. The robust therapeutics of Man-BSA@Rb1 NPs were measured in terms of nitrite, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels, which might be achieved by potently inhibiting nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in lipopolysaccharide (LPS)-induced Raw264.7 cells. Moreover, the therapeutic efficacy of Man-BSA@Rb1 NPs was further confirmed in the d-Gal/LPS-induced liver injury model. The results indicated that Man-BSA may offer a promising system to improve the anti-inflammatory therapy of Rb1.

Rib Fracture Detection with Dual-Attention Enhanced U-Net.

Rib fractures are common injuries caused by chest trauma, which may cause serious consequences. It is essential to diagnose rib fractures accurately. Low-dose thoracic computed tomography (CT) is commonly used for rib fracture diagnosis, and convolutional neural network- (CNN-) based methods have assisted doctors in rib fracture diagnosis in recent years. However, due to the lack of rib fracture data and the irregular, various shape of rib fractures, it is difficult for CNN-based methods to extract rib fracture features. As a result, they cannot achieve satisfying results in terms of accuracy and sensitivity in detecting rib fractures. Inspired by the attention mechanism, we proposed the CFSG U-Net for rib fracture detection. The CSFG U-Net uses the U-Net architecture and is enhanced by a dual-attention module, including a channel-wise fusion attention module (CFAM) and a spatial-wise group attention module (SGAM). CFAM uses the channel attention mechanism to reweight the feature map along the channel dimension and refine the U-Net's skip connections. SGAM uses the group technique to generate spatial attention to adjust feature maps in the spatial dimension, which allows the spatial attention module to capture more fine-grained semantic information. To evaluate the effectiveness of our proposed methods, we established a rib fracture dataset in our research. The experimental results on our dataset show that the maximum sensitivity of our proposed method is 89.58%, and the average FROC score is 81.28%, which outperforms the existing rib fracture detection methods and attention modules.