Polyhydroxylated Spirostanol Saponins from the Rhizomes of Paris dulongensis.

Three new polyhydroxylated spirostanol steroidal saponins, dulongenosides B-D (2-4), along with 14 known compounds, dulongenoside A (1), padelaoside B (5), parisyunnanoside G (6), polyphyllin D (7), ophiopogonin C' (8), formosanin C (9), dioscin (10), paris saponin VII (11), paris H (12), parisyunnanoside I (13), protodioscin (14), proprotogracillin (15), crustecdysone (16), and stigmasterol-3-O-ß-d-glucopyranoside (17), were isolated from the rhizomes of Paris dulongensis (Melanthiaceae). Their chemical structures were elucidated based on extensive analyses of NMR and MS data and acidic hydrolyses. The isolates were evaluated for their cytotoxicity to five human cancer cell lines (HL-60, SW480, MDA-MB-231, A549, and A549/Taxol) and the normal human bronchial epithelial cell line BEAS-2B by the MTS test. Compounds 7-12 and 14 showed cytotoxic activity, with IC50 values ranging from 0.20 to 4.35 µM. Proprotogracillin selectively inhibited A549 (IC50=0.58 µM) and A549/Taxol (IC50=0.74 µM) cells, with no significant cytotoxic activity against HL-60, SW480, MDA-MB-231, or BEAS-2B cells, with IC50 values greater than 40 µM.

Destroyed lung contributes to the recurrence of hemoptysis after bronchial artery embolization in patients with post-tuberculosis bronchiectasis.

BACKGROUND: Bronchiectasis has high rates of hemoptysis and recurrent hemoptysis, which is inconsistent among various etiologies. Idiopathic bronchiectasis and post-tuberculous bronchiectasis are two important etiologies in China, but the differences in clinical features and risk factors of recurrent hemoptysis have not been elucidated. METHODS: Patients hospitalized for idiopathic bronchiectasis or post-tuberculosis bronchiectasis were included. Patients were followed up for at least 24 months post-BAE. Demographic characteristics and clinical data were collected and analyzed between idiopathic bronchiectasis and post-tuberculosis bronchiectasis. Based on the outcomes of recurrent severe hemoptysis in patients with post-tuberculosis bronchiectasis, Cox regression models were used to identify risk factors for recurrence. RESULTS: Among 417 patients including 352 idiopathic bronchiectasis and 65 post-tuberculous bronchiectasis, 209 (50.1%) were females. Compared with the idiopathic group, the proportion of patients with female (54.5% vs. 26.2%, p < 0.001), with sputum (79.5% vs. 36.9%, p < 0.001), isolation of Pseudomonas aeruginosa (28.7% vs. 7.7%, p < 0.001), and the number of bronchiectatic lobes≥ 3(98.3% vs 50.8%, p < 0.001) were lower, and the proportion of destroyed lung (4.5% vs. 26.6%, p < 0.001) and recurrence of severe hemoptysis (22.4% vs. 41.5%, p = 0.001) were higher in the post-tuberculous group. Among patients with post-tuberculosis bronchiectasis, destroyed lung [HR: 3.2(1.1,9.1), p = 0.026] and abnormal esophageal proper artery [HR: 2.8(1.1,7.0), p = 0.032] were two independent risk factors for the recurrence of hemoptysis. CONCLUSIONS: The recurrence rate of severe hemoptysis in patients with post-tuberculous bronchiectasis receiving BAE is high, and the proper esophageal artery should be actively evaluated and standardized treatment should be given.

Simultaneous electrocoagulation and E-peroxone coupled with ultrafiltration membrane for shale gas produced water treatment.

Membrane fouling caused by the organics-coated particles was the main obstacle for the highly efficient shale gas produced water (SGPW) treatment and recycling. In this study, a novel hybrid electrocoagulation (EC) and E-peroxone process coupled with UF (ECP-UF) process was proposed to examine the efficacy and elucidate the mechanism for UF fouling mitigation in assisting SGPW reuse. Compared to the TMP (transmembrane pressure) increase of -15 kPa in the EC-UF process, TMP in ECP-UF system marginally increased to -1.4 kPa for 3 filtration cycles under the current density of 15 mA/cm2. Both the total fouling index and hydraulically irreversible fouling index of the ECP-UF process were significantly lower than those of EC-UF process. According to the extended Derjaguin-Landau-Verwey-Overbeek theory, the potential barriers was the highest for ECP-UF processes due to the substantial increase of the acid-base interaction energy in ECP-UF process, which was well consistent with the TMP and SEM results. Turbidity and TOC of ECP-UF process were 63.6% and 45.8% lower than those of EC-UF process, respectively. According to the MW distribution, the variations of compounds and their relative contents were probably due to the oxidation and decomposing products of the macromolecular organics. The number of aromatic compound decreased, while the number of open-chain compounds (i.e., alkenes, alkanes and alcohols) increased in the permeate of ECP-UF process. Notably, the substantial decrease in the relative abundance of di-phthalate compounds was attributed to the high reactivity of these compounds with ·OH. Mechanism study indicated that ECP could realize the simultaneous coagulation, H2O2 generation and activation by O3, facilitating the enhancement of ·OH and Alb production and therefore beneficial for the improved water quality and UF fouling mitigation. Therefore, the ECP-UF process emerges as a high-efficient and space-saving approach, yielding a synergistic effect in mitigating UF fouling for SGPW recycling.

The role of volatile organic compounds for assessing characteristics and severity of non-cystic fibrosis bronchiectasis: an observational study.

Background: Hypoxic conditions and Pseudomonas aeruginosa (P. aeruginosa) infection are significant factors influencing the prognosis and treatment of patients with bronchiectasis. This study aimed to explore the potential for breath analysis to detect hypoxic conditions and P. aeruginosa infection in bronchiectasis patients by analyzing of volatile organic compounds (VOCs) in exhaled breath condensate (EBC). Methods: EBC samples were collected from stable bronchiectasis patients and analyzed using solid phase microextraction-gas chromatography-mass spectrometry (SPME-GCMS). The association of VOCs with bronchiectasis patients' phenotypes including hypoxic conditions and P. aeruginosa isolation was analyzed, which may relate to the severity of bronchiectasis disease. Results: Levels of 10-heptadecenoic acid, heptadecanoic acid, longifolene, and decanol in the hypoxia group were higher compared to the normoxia group. Additionally, the levels of 13-octadecenoic acid, octadecenoic acid, phenol, pentadecanoic acid, and myristic acid were increased in P. aeruginosa (+) group compared to the P. aeruginosa (-) group. Subgroup analysis based on the bronchiectasis severity index (BSI)reveled that the levels of 10-heptadecenoic acid, heptadecanoic acid, decanol, 13-octadecenoic acid, myristic acid, and pentadecanoic acid were higher in the severe group compared to the moderate group. Multivariate linear regression showed that 10-heptadecenoic acid and age were independent prognostic factors for bronchiectasis patients with hypoxia. Furthermore, octadecenoic acid, phenol and gender were identified as independent prognostic factors for bronchiectasis patients with P. aeruginosa isolation. Conclusion: The study provides evidence that specific VOCs in EBC are correlated with the severity of bronchiectasis, and 10-heptadecenoic acid is shown to be a predictive marker for hypoxia condition in bronchiectasis patients.

New steroidal saponins from the aerial parts of Paris polyphylla var. yunnanensis and their effects on blood coagulation.

Five new steroidal saponins, paripolins D-H (1-5), and 6 known compounds (6-11) were isolated from the aerial parts of Paris polyphylla var. yunnanensis. The structures of 1-5 were determined using spectroscopic analyses in conjunction with acid hydrolysis. It is for the first time to report the 12-hydroxysteroidal saponins from the genus Paris. The effect of all isolated compounds on blood coagulation was determined in vitro using the plasma recalcification time method. Compounds 1 and 2 showed potent procoagulant activity, and 5-11 exhibited significant anticoagulant activity.

CNN-based multi-modal radiomics analysis of pseudo-CT utilization in MRI-only brain stereotactic radiotherapy: a feasibility study.

BACKGROUND: Pseudo-computed tomography (pCT) quality is a crucial issue in magnetic resonance image (MRI)-only brain stereotactic radiotherapy (SRT), so this study systematically evaluated it from the multi-modal radiomics perspective. METHODS: 34 cases (< 30 cm³) were retrospectively included (2021.9-2022.10). For each case, both CT and MRI scans were performed at simulation, and pCT was generated by a convolutional neural network (CNN) from planning MRI. Conformal arc or volumetric modulated arc technique was used to optimize the dose distribution. The SRT dose was compared between pCT and planning CT with dose volume histogram (DVH) metrics and gamma index. Wilcoxon test and Spearman analysis were used to identify key factors associated with dose deviations. Additionally, original image features were extracted for radiomic analysis. Tumor control probability (TCP) and normal tissue complication probability (NTCP) were employed for efficacy evaluation. RESULTS: There was no significant difference between pCT and planning CT except for radiomics. The mean value of Hounsfield unit of the planning CT was slightly higher than that of pCT. The Gadolinium-based agents in planning MRI could increase DVH metrics deviation slightly. The median local gamma passing rates (1%/1 mm) between planning CTs and pCTs (non-contrast) was 92.6% (range 63.5-99.6%). Also, differences were observed in more than 85% of original radiomic features. The mean absolute deviation in TCP was 0.03%, and the NTCP difference was below 0.02%, except for the normal brain, which had a 0.16% difference. In addition, the number of SRT fractions and lesions, and lesion morphology could influence dose deviation. CONCLUSIONS: This is the first multi-modal radiomics analysis of CNN-based pCT from planning MRI for SRT of small brain lesions, covering dosiomics and radiomics. The findings suggest the potential of pCT in SRT plan design and efficacy prediction, but caution needs to be taken for radiomic analysis.

Quality-of-Life Bronchiectasis Respiratory Symptom Scale Predicts the Risk of Exacerbations in Adults with Bronchiectasis: A Prospective Observational Study.

Rationale: The relationship between symptoms, measured using a validated disease-specific questionnaire, and longitudinal exacerbation risk has not been demonstrated in bronchiectasis. Objectives: The aim of this study is to investigate whether baseline symptoms, assessed using the Quality-of-Life Bronchiectasis Respiratory Symptom Scale (QoL-B-RSS) and its individual component scores, could predict future exacerbation risk in patients with bronchiectasis. Methods: The study included 436 adults with bronchiectasis from three tertiary hospitals. Symptoms were measured using the QoL-B-RSS, with scores ranging from 0 to 100, where lower scores indicated more severe symptoms. We examined whether symptoms as continuous measures were associated with the risk of exacerbation over 12 months. The analysis was also repeated for individual components of the QoL-B-RSS score. Results: The baseline QoL-B-RSS score was associated with an increased risk of exacerbations (rate ratio, 1.25 for each 10-point decrease; 95% confidence interval [CI], 1.15-1.35; P < 0.001), hospitalizations (rate ratio, 1.24; 95% CI, 1.05-1.43; P = 0.02), and reduced time to the first exacerbation (hazard ratio, 1.12; 95% CI, 1.03-1.21; P = 0.01) over 12 months, even after adjusting for relevant confounders, including exacerbation history. The QoL-B-RSS score was comparable to exacerbation history in its association with future frequent exacerbations (defined as three or more exacerbations per year) and hospitalization (area under the curve, 0.86 vs. 0.84; P = 0.46; and area under the curve, 0.81 vs. 0.83; P = 0.41, respectively). Moreover, patients with more severe symptoms in the majority of individual components of the QoL-B-RSS were more likely to experience exacerbations. Conclusions: Symptoms can serve as useful indicators for identifying patients at increased risk of exacerbation in bronchiectasis. Beyond relying solely on exacerbation history, a comprehensive assessment of symptoms could facilitate timely and cost-effective implementation of interventions for exacerbation prevention.

Isoproterenol induces MD2 activation by ß-AR-cAMP-PKA-ROS signalling axis in cardiomyocytes and macrophages drives inflammatory heart failure.

Cardiac inflammation contributes to heart failure (HF) induced by isoproterenol (ISO) through activating ß-adrenergic receptors (ß-AR). Recent evidence shows that myeloid differentiation factor 2 (MD2), a key protein in endotoxin-induced inflammation, mediates inflammatory heart diseases. In this study, we investigated the role of MD2 in ISO-ß-AR-induced heart injuries and HF. Mice were infused with ISO (30 mg·kg-1·d-1) via osmotic mini-pumps for 2 weeks. We showed that MD2 in cardiomyocytes and cardiac macrophages was significantly increased and activated in the heart tissues of ISO-challenged mice. Either MD2 knockout or administration of MD2 inhibitor L6H21 (10 mg/kg every 2 days, i.g.) could prevent mouse hearts from ISO-induced inflammation, remodelling and dysfunction. Bone marrow transplantation study revealed that both cardiomyocyte MD2 and bone marrow-derived macrophage MD2 contributed to ISO-induced cardiac inflammation and injuries. In ISO-treated H9c2 cardiomyocyte-like cells, neonatal rat primary cardiomyocytes and primary mouse peritoneal macrophages, MD2 knockout or pre-treatment with L6H21 (10 µM) alleviated ISO-induced inflammatory responses, and the conditioned medium from ISO-challenged macrophages promoted the hypertrophy and fibrosis in cardiomyocytes and fibroblasts. We demonstrated that ISO induced MD2 activation in cardiomyocytes via ß1-AR-cAMP-PKA-ROS signalling axis, and induced inflammatory responses in macrophages via ß2-AR-cAMP-PKA-ROS axis. This study identifies MD2 as a key inflammatory mediator and a promising therapeutic target for ISO-induced heart failure.

Application of 3D computed tomography in emphysematous parenchyma patients scheduled for bronchoscopic lung volume reduction.

Bronchoscopic lung volume reduction (BLVR) is a feasible, safe, effective and minimally invasive technique to significantly improve the quality of life of advanced severe chronic obstructive pulmonary disease (COPD). In this study, three-dimensional computed tomography (3D-CT) automatic analysis software combined with pulmonary function test (PFT) was used to retrospectively evaluate the postoperative efficacy of BLVR patients. The purpose is to evaluate the improvement of lung function of local lung tissue after operation, maximize the benefits of patients, and facilitate BLVR in the treatment of patients with advanced COPD. All the reported cases of advanced COPD patients treated with BLVR with one-way valve were collected and analysed from 2017 to 2020. Three-dimensional-CT image analysis software system was used to analyse the distribution of low-density areas <950 Hounsfield units in both lungs pre- and post- BLVR. Meanwhile, all patients performed standard PFT pre- and post-operation for retrospective analysis. We reported six patients that underwent unilateral BLVR with 1 to 3 valves according to the range of emphysema. All patients showed a median increase in forced expiratory volume in 1 second (FEV1) of 34%, compared with baseline values. Hyperinflation was reduced by 16.6% (range, 4.9%-47.2%). The volumetric measurements showed a significant reduction in the treated lobe volume among these patients. Meanwhile, the targeted lobe volume changes were inversely correlated with change in FEV1/FEV1% in patients with heterogeneous emphysematous. We confirm that 3D-CT analysis can quantify the changes of lung volume, ventilation and perfusion, to accurately evaluate the distribution and improvement of emphysema and rely less on the observer.

Pretreatment patient-specific quality assurance prediction based on 1D complexity metrics and 3D planning dose: classification, gamma passing rates, and DVH metrics.

PURPOSE: Highly modulated radiotherapy plans aim to achieve target conformality and spare organs at risk, but the high complexity of the plan may increase the uncertainty of treatment. Thus, patient-specific quality assurance (PSQA) plays a crucial role in ensuring treatment accuracy and providing clinical guidance. This study aims to propose a prediction model based on complexity metrics and patient planning dose for PSQA results. MATERIALS AND METHODS: Planning dose, measurement-based reconstructed dose and plan complexity metrics of the 687 radiotherapy plans of patients treated in our institution were collected for model establishing. Global gamma passing rate (GPR, 3%/2mm,10% threshold) of 90% was used as QA criterion. Neural architecture models based on Swin-transformer were adapted to process 3D dose and incorporate 1D metrics to predict QA results. The dataset was divided into training (447), validation (90), and testing (150) sets. Evaluation of predictions was performed using mean absolute error (MAE) for GPR, planning target volume (PTV) HI and PTV CI, mean absolute percentage error (MAPE) for PTV D95, PTV D2 and PTV Dmean, and the area under the receiver operating characteristic (ROC) curve (AUC) for classification. Furthermore, we also compare the prediction results with other models based on either only 1D or 3D inputs. RESULTS: In this dataset, 72.8% (500/687) plans passed the pretreatment QA under the criterion. On the testing set, our model achieves the highest performance, with the 1D model slightly surpassing the 3D model. The performance results are as follows (combine, 1D, and 3D transformer): The AUCs are 0.92, 0.88 and 0.86 for QA classification. The MAEs of prediction are 0.039, 0.046, and 0.040 for 3D GPR, 0.018, 0.021, and 0.019 for PTV HI, and 0.075, 0.078, and 0.084 for PTV CI. Specifically, for cases with 3D GPRs greater than 90%, the MAE could achieve 0.020 (combine). The MAPE of prediction is 1.23%, 1.52%, and 1.66% for PTV D95, 2.36%, 2.67%, and 2.45% for PTV D2, and 1.46%, 1.70%, and 1.71% for PTV Dmean. CONCLUSION: The model based on 1D complexity metrics and 3D planning dose could predict pretreatment PSQA results with high accuracy and the complexity metrics play a leading role in the model. Furthermore, dose-volume metric deviations of PTV could be predicted and more clinically valuable information could be provided.

Long non-coding RNA PRR7-AS1 promotes osteosarcoma progression via binding RNF2 to transcriptionally suppress MTUS1.

Introduction: Osteosarcoma is a common bone malignant tumor in adolescents with high mortality and poor prognosis. At present, the progress of osteosarcoma and effective treatment strategies are not clear. This study provides a new potential target for the progression and treatment of osteosarcoma. Methods: The relationship between lncRNA PRR7-AS1 and osteosarcoma was analyzed using the osteosarcoma databases and clinical sample testing. Cell function assays and tumor lung metastasis were employed to study the effects of PRR7-AS1 on tumorigenesis in vivo and in vitro. Potential downstream RNF2 of PRR7-AS1 was identified and explored using RNA pulldown and RIP. The GTRD and KnockTF database were used to predict the downstream target gene, MTUS1, and ChIP-qPCR experiments were used to verify the working mechanismy. Rescue experiments were utilized to confirm the role of MTUS1 in the pathway. Results: Deep mining of osteosarcoma databases combined with clinical sample testing revealed a positive correlation between lncRNA PRR7-AS1 and osteosarcoma progression. Knockdown of PRR7-AS1 inhibited osteosarcoma cell proliferation and metastasis in vitro and in vivo. Mechanistically, RNA pulldown and RIP revealed that PRR7-AS1 may bind RNF2 to play a cancer-promoting role. ChIP-qPCR experiments were utilized to validate the working mechanism of the downstream target gene MTUS1. RNF2 inhibited the transcription of MTUS1 through histone H2A lysine 119 monoubiquitin. Rescue experiments confirmed MTUS1 as a downstream direct target of PRR7-AS1 and RNF2. Discussion: We identified lncRNA PRR7-AS1 as an important oncogene in osteosarcoma progression, indicating that it may be a potential target for diagnosis and prognosis of osteosarcoma.

Long non-coding RNA NRSN2-AS1 promotes ovarian cancer progression through targeting PTK2/ß-catenin pathway.

As a common malignant tumor among women, ovarian cancer poses a serious threat to their health. This study demonstrates that long non-coding RNA NRSN2-AS1 is over-expressed in ovarian cancer tissues using patient sample and tissue microarrays. In addition, NRSN2-AS1 is shown to promote ovarian cancer cell proliferation and metastasis both in vitro and in vivo. Mechanistically, NRSN2-AS1 stabilizes protein tyrosine kinase 2 (PTK2) to activate the ß-catenin pathway via repressing MG-53-mediated ubiquitinated degradation of PTK2, thereby facilitating ovarian cancer progression. Rescue experiments verify the function of the NRSN2-AS1/PTK2/ß-catenin axis and the effects of MG53 on this axis in ovarian cancer cells. In conclusion, this study demonstrates the key role of the NRSN2-AS1/PTK2/ß-catenin axis for the first time and explores its potential clinical applications in ovarian cancer.

Alveolar type II epithelial cell FASN maintains lipid homeostasis in experimental COPD.

Alveolar epithelial type II (AEC2) cells strictly regulate lipid metabolism to maintain surfactant synthesis. Loss of AEC2 cell function and surfactant production are implicated in the pathogenesis of the smoking-related lung disease chronic obstructive pulmonary disease (COPD). Whether smoking alters lipid synthesis in AEC2 cells and whether altering lipid metabolism in AEC2 cells contributes to COPD development are unclear. In this study, high-throughput lipidomic analysis revealed increased lipid biosynthesis in AEC2 cells isolated from mice chronically exposed to cigarette smoke (CS). Mice with a targeted deletion of the de novo lipogenesis enzyme, fatty acid synthase (FASN), in AEC2 cells (FasniΔAEC2) exposed to CS exhibited higher bronchoalveolar lavage fluid (BALF) neutrophils, higher BALF protein, and more severe airspace enlargement. FasniΔAEC2 mice exposed to CS had lower levels of key surfactant phospholipids but higher levels of BALF ether phospholipids, sphingomyelins, and polyunsaturated fatty acid-containing phospholipids, as well as increased BALF surface tension. FasniΔAEC2 mice exposed to CS also had higher levels of protective ferroptosis markers in the lung. These data suggest that AEC2 cell FASN modulates the response of the lung to smoke by regulating the composition of the surfactant phospholipidome.

Catalpol Prevents Glomerular Angiogenesis Induced by Advanced Glycation End Products via Inhibiting Galectin-3.

OBJECTIVE: The main characteristics of diabetic nephropathy (DN) at the early stage are abnormal angiogenesis of glomerular endothelial cells (GECs) and macrophage infiltration. Galectin-3 plays a pivotal role in the pathogenesis of DN via binding with its ligand, advanced glycation end products (AGEs). Catalpol, an iridoid glucoside extracted from Rehmannia glutinosa, has been found to ameliorate vascular inflammation, reduce endothelial permeability, and protect against endothelial damage in diabetic milieu. However, little is known about whether catalpol could exert an anti-angiogenesis and anti-inflammation effect induced by AGEs. METHODS: Mouse GECs (mGECs) and RAW 264.7 macrophages were treated with different concentrations of AGEs (0, 50, 100, 200 and 400 µg/mL) for different time (0, 6, 12, 24 and 48 h) to determine the optimal concentration of AGEs and treatment time. Cells were treated with catalpol (10 µmol/L), GB1107 (1 µmol/L, galectin-3 inhibitor), PX-478 (50 µmol/L, HIF-1α inhibitor), adenovirus-green fluorescent protein (Ad-GFP) [3×107 plaque-forming unit (PFU)/mL] or Ad-galectin-3-GFP (2×108 PFU/mL), which was followed by incubation with 50 µg/mL AGEs. The levels of galectin-3, vascular endothelial growth factor A (VEGFA) and pro-angiogenic factors angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), tunica interna endothelial cell kinase-2 (Tie-2) were detected by enzymelinked immunosorbent assay (ELISA). Cell counting kit-8 (CCK-8) assay was used to evaluate the proliferation of these cells. The expression levels of galectin-3, vascular endothelial growth factor receptor 1 (VEGFR1), VEGFR2, and hypoxia-inducible factor-1α (HIF-1α) in mGECs and those of galectin-3 and HIF-1α in RAW 264.7 macrophages were detected by Western blotting and immunofluorescence (IF) staining. The rat DN model was established. Catalpol (100 mg/kg) or GB1107 (10 mg/kg) was administered intragastrically once a day for 12 weeks. Ad-galectin-3-GFP (6×107 PFU/mL, 0.5 mL) or Ad-GFP (6×106 PFU/mL, 0.5 mL) was injected into the tail vein of rats 48 h before the sacrifice of the animals. The expression of galectin-3, VEGFR1, VEGFR2, and HIF-1α in renal cortices was analyzed by Western blotting. The expression of galectin-3, F4/80 (a macrophage biomarker), and CD34 (an endothelium biomarker) in renal cortices was detected by IF staining, and collagen accumulation by Masson staining. RESULTS: The expression levels of galectin-3 and VEGFA were significantly higher in mGECs and RAW 264.7 macrophages treated with 50 µg/mL AGEs for 48 h than those in untreated cells. Catalpol and GB1107 could block the AGEs-induced proliferation of mGECs and RAW 264.7 macrophages. Over-expression of galectin-3 was found to reduce the inhibitory effect of catalpol on the proliferation of cells. Catalpol could significantly decrease the levels of Ang-1, Ang-2 and Tie-2 released by AGEs-treated mGECs, which could be reversed by over-expression of galectin-3. Catalpol could significantly inhibit AGEs-induced expression of galectin-3, HIF-1α, VEGFR1, and VEGFR2 in mGECs. The inhibitory effect of catalpol on galectin-3 in AGEs-treated mGECs was impaired by PX-478. Moreover, catalpol attenuated the AGEs-activated HIF-1α/galectin-3 pathway in RAW 264.7 macrophages, which was weakened by PX-478. Additionally, catalpol significantly inhibited the expression of galectin-3, macrophage infiltration, collagen accumulation, and angiogenesis in the kidney of diabetic rats. Over-expression of galectin-3 could antagonize these inhibitory effects of catalpol. CONCLUSION: Catalpol prevented the angiogenesis of mGECs and macrophage proliferation via inhibiting galectin-3. It could prevent the progression of diabetes-induced renal damage.

Optimal fractionation and timing of weekly cone-beam CT in daily surface-guided radiotherapy for breast cancer.

PURPOSE: Surface-guided radiotherapy (SGRT) has been demonstrated to be a promising supplement to cone-beam computed tomography (CBCT) in adjuvant breast cancer radiotherapy, but a rational combination mode is lacking in clinical practice. The aim of this study was to explore this mode and investigate its impact on the setup and dose accuracy. METHODS AND MATERIALS: Daily SGRT and weekly CBCT images were acquired for 23 patients with breast cancer who received conventional fractionated radiotherapy after lumpectomy. Sixteen modes were acquired by randomly selecting one (CBCT1), two (CBCTij), three (CBCTijk), four (CBCTijkl), and five (CBCT12345) images from the CBCT images for fusion with the SGRT. The CTV-PTV margins, OAR doses, and dose coverage (V95%) of PTV and CTV was calculated based on SGRT setup errors with different regions of interest (ROIs). Dose correlations between these modalities were investigated using Pearson and Spearman's methods. Patient-specific parameters were recorded to assess their impact on dose. RESULTS: The CTV-PTV margins decreased with increasing CBCT frequencies and were close to 5 mm for CBCTijkl and CBCT12345. For the ipsilateral breast ROI, SGRT errors were larger in the AP direction, and target doses were higher in all modes than in the whole breast ROI (P < 0.05). In the ipsilateral ROI, the target dose correlations between all modes increased with increasing CBCT time intervals, decreased, and then increased with increasing CBCT frequencies, with the inflection point being CBCT participation at week 5. The dose deviations in CBCT123, CBCT124, CBCT125, CBCTijkl, and CBCT12345 were minimal and did not differ significantly (P > 0.05). There was excellent agreement between CBCT124 and CBCT1234, and between (CBCTijkl, CBCT12345) and CBCT125 in determining the classification for the percentage of PTV deviation (Kappa = 0.704-0.901). In addition, there were weak correlations between the patient's Dips_b (ipsilateral breast diameter with bolus) and CTV doses in modes with CBCT participation at week 4 (R = 0.270 to 0.480). CONCLUSIONS: Based on weekly CBCT, these modes with ipsilateral ROI and a combination of daily SGRT and a CBCT frequency of ≥ 3 were recommended, and CBCT was required at weeks 1 and 2 for CBCTijk.

[Chronic Injury of Mice Bone Marrow Multipotent Hematopoietic Progenitor Cells Induced by Ionizing Radiation].

OBJECTIVE: To explore the chronic injury and its possible mechanism of ionizing radiation on multipotent hematopoietic progenitor cells (MPPs) by determining the related indicators of MPPs in bone marrow of mice post-radiation. METHODS: Sixteen C57BL/6 adult mice were randomly divided into normal control and irradiation groups, 8 mice in each group. The mice in irradiation group were exposed to 6 Gy X-ray. The proportion of bone marrow MPPs, their apoptosis and proliferation 2 months after irradiation were detected by flow cytometry. Mitochondrial activity and levels of reactive oxygen species (ROS) in each MPPs population were detected by Mitotracker Red and DCFDA probes, and the senescent state of MPPs in the bone marrow was analyzed. RESULTS: Ionizing radiation could reduce the proportion of MPPs in mouse bone marrow. The proportions and numbers of MPP1, MPP3 and MPP4 in the bone marrow were significantly decreased after whole-body irradiation with 6 Gy X-ray (P<0.05). In addition, radiation significantly reduced the colony-forming capacity of MPPs in bone marrow (P<0.05), the proportions of apoptotic cells in the MPP1 and MPP4 cell populations increased significantly in the bone marrow (P<0.05). The activity of mitochondria was significantly reduced in the bone marrow MPP2, MPP3 and MPP4 cell populations compared with that of the control group (P<0.05). It was also found that the radiation could significantly increase the ROS levels of MPPs in bone marrow, and the content of ROS in the MPP2, MPP3 and MPP4 cell population of the bone marrow was significantly increased(P<0.05). The senescent cells ratios of MPP1, MPP3 and MPP4 cells in the bone marrow after irradiation were significantly higher than those in the control group (P<0.05). CONCLUSION: Ionizing radiation can cause chronic MPPs damage in mice, which is closely associated with persistent oxidative stress, cells apoptosis, and cellular senescence.

Steroidal sapogenins from the aerial parts of Paris polyphylla var. yunnanensis and activity evaluation.

Phytochemical investigation of an extract of the aerial parts of Paris polyphylla var. yunnanensis resulted in the identification of three new steroidal sapogenins, namely as paripolins A-C (1-3). With the aid of comprehensive spectroscopic techniques (NMR, IR, UV, MS), the structures of all isolated compounds were elucidated and subsequently screened for anti-inflammatory activity.

Pseudomonas aeruginosa isolation is an important predictor for recurrent hemoptysis after bronchial artery embolization in patients with idiopathic bronchiectasis: a multicenter cohort study.

BACKGROUND: Nearly half of bronchiectasis patients receiving bronchial artery embolization (BAE) still have recurrent hemoptysis, which may be life-threatening. Worse still, the underlying risk factors of recurrence remain unknown. METHODS: A retrospective cohort was conducted of patients with idiopathic bronchiectasis who received BAE from 2015 to 2019 at eight centers. Patients were followed up for at least 24 months post BAE. Based on the outcomes of recurrent hemoptysis and recurrent severe hemoptysis, a Cox regression model was used to identify risk factors for recurrence. RESULTS: A total of 588 individuals were included. The median follow-up period was 34.0 months (interquartile range: 24.3-53.3 months). The 1-month, 1-year, 2-year, and 5-year cumulative recurrent hemoptysis-free rates were 87.2%, 67.5%, 57.6%, and 49.4%, respectively. The following factors were relative to recurrent hemoptysis: 24-h sputum volume (hazard ratio [HR] = 1.99 [95% confidence interval [95% CI]: 1.25-3.15, p = 0.015]), isolation of Pseudomonas aeruginosa (HR = 1.50 [95% CI: 1.13-2.00, p = 0.003]), extensive bronchiectasis (HR = 2.00 [95% CI: 1.29-3.09, p = 0.002]), and aberrant bronchial arteries (AbBAs) (HR = 1.45 [95% CI: 1.09-1.93, p = 0.014]). The area under the receiver operating characteristic curve of the nomogram was 0.728 [95% CI: 0.688-0.769]. CONCLUSIONS: Isolation of Pseudomonas aeruginosa is an important independent predictor of recurrent hemoptysis. The clearance of Pseudomonas aeruginosa might effectively reduce the hemoptysis recurrence rate.

A novel dose fall-off index and preliminary application in brain and lung stereotactic radiotherapy.

BACKGROUND: Stereotactic radiotherapy (SRT) has been widely used for the treatment of brain metastases and early stage non-small-cell lung cancer (NSCLC). Excellent SRT plans are characterized by steep dose fall-off, making it critical to accurately and comprehensively predict and evaluate dose fall-off. PURPOSE: A novel dose fall-off index was proposed to ensure high-quality SRT planning. METHODS: The novel gradient index (NGI) had two different modes: NGIx V for three-dimensions and NGIx r for one-dimension. NGIx V and NGIx r were defined as the ratios of the decreased percentage dose (x%) to the corresponding isodose volume and equivalent sphere radii, respectively. A total of 243 SRT plans at our institution between April 2020 and March 2022 were enrolled, including 126 brain and 117 lung SRT plans. Measurement-based verifications were performed using SRS MapCHECK. Ten plan complexity indexes were calculated. Dosimetric parameters related to radiation injuries were also extracted, including the normal brain volume exposed to 12 Gy (V12 ) and 18 Gy (V18 ) during single-fraction SRT (SF-SRT) and multi-fraction SRT (MF-SRT), respectively, and the normal lung volume exposed to 12 Gy (V12 ). The performance of NGI and other common dose fall-off indexes, gradient index (GI), R50% and D2cm were evaluated using Spearman correlation analysis to explore their correlations with the PTV size, gamma passing rate (GPR), plan complexity indexes, and dosimetric parameters. RESULTS: There were statistically significant correlations between NGI and PTV size (r = -0.98, P < 0.01 for NGI50 V and r = -0.93, P < 0.01 for NGI50 r), which were the strongest correlations compared with GI (r = 0.11, P = 0.13), R50% (r = -0.08, P = 0.19) and D2cm (r = 0.84, P < 0.01). The fitted formulas of NGI50 V = 23.86V-1.00 and NGI50 r = 113.5r-1.05 were established. The GPRs of enrolled SRT plans were 98.6 ± 1.7%, 94.2 ± 4.7% and 97.1 ± 3.1% using the criteria of 3%/2 mm, 3%/1 mm, and 2%/2 mm, respectively. NGI50 V achieved the strongest correlations with various plan complexity indexes (|r| ranged from 0.67 to 0.91, P < 0.01). NGI50 V also showed the highest r values with V12 (r = -0.93, P < 0.01) and V18 (r = -0.96, P < 0.01) of the normal brain during SF-SRT and MF-SRT, respectively, and V12 (r = -0.86, P < 0.01) of the normal lung during lung SRT. CONCLUSIONS: Compared with GI, R50% and D2cm , the proposed dose fall-off index, NGI, had the strongest correlations with the PTV size, plan complexity and V12 /V18 of the normal tissues. These correlations established on NGI are more helpful and reliable for SRT planning, quality control, and reducing the risk of radiation injuries.