Non-invasive diagnosis of liver fibrosis via MRI using targeted gadolinium-based nanoparticles.

INTRODUCTION: Accurate diagnosis of liver fibrosis is crucial for preventing cirrhosis and liver tumors. Liver fibrosis is driven by activated hepatic stellate cells (HSCs) with elevated CD44 expression. We developed hyaluronic acid (HA)-coated gadolinium-based nanoprobes to specifically target CD44 for diagnosing liver fibrosis using T1-weighted magnetic resonance imaging (MRI). MATERIALS AND METHODS: NaGdF4 nanoparticles (NPs) were synthesized via thermal decomposition and modified with polyethylene glycol (PEG) to obtain non-targeting NaGdF4@PEG NPs. These were subsequently coated with HA to target HSCs, resulting in liver fibrosis-targeting NaGdF4@PEG@HA nanoprobes. Characterization includedd transmission electron microscopy and X-ray diffraction. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8). Internalization of NaGdF4@PEG@HA nanoprobes by mouse HSCs JS1 cells via ligand-receptor interaction was observed using flow cytometry and confocal laser scanning microscopy (CLSM). Liver fibrosis was induced in C57BL/6 mice using a methionine-choline deficient (MCD) diet. MRI performance and nanoprobe distribution in fibrotic and normal livers were analyzed using a GE Discovery 3.0T MR 750 scanner. RESULTS: NaGdF4@PEG@HA nanoprobes exhibited homogeneous morphology, low toxicity, and a high T1 relaxation rate (7.645 mM⁻¹s⁻¹). CLSM and flow cytometry demonstrated effective phagocytosis of NaGdF4@PEG@HA nanoprobes by JS1 cells compared to NaGdF4@PEG. MRI scans revealed higher T1 signals in fibrotic livers compared to normal livers after injection of NaGdF4@PEG@HA. NaGdF4@PEG@HA demonstrated higher targeting ability in fibrotic mice. CONCLUSIONS: NaGdF4@PEG@HA nanoprobes effectively target HSCs with high T1 relaxation rate, facilitating efficient MRI diagnosis of liver fibrosis.

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

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

Novel electromagnetic navigation bronchoscopy system for the diagnosis of peripheral pulmonary nodules: a prospective, multicentre study.

BACKGROUND: Traditional electromagnetic navigation bronchoscopy (ENB) is a real-time image-guided system and used with thick bronchoscopes for the diagnosis of peripheral pulmonary nodules (PPNs). A novel ENB that could be used with thin bronchoscopes was developed. This study aimed to evaluate the diagnostic yield and the experience of using this ENB system in a real clinical scenario. METHODS: This multicentre study enrolled consecutive patients with PPNs adopting ENB from March 2019 to August 2021. ENB was performed with different bronchoscopes, ancillary techniques and sampling instruments according to the characteristics of the nodule and the judgement of the operator. The primary endpoint was the diagnostic yield. The secondary endpoints included the diagnostic yield of subgroups, procedural details and complication rate. RESULTS: In total, 479 patients with 479 nodules were enrolled in this study. The median lesion size was 20.9 (IQR, 15.9-25.9) mm. The overall diagnostic yield was 74.9% (359/479). A thin bronchoscope was used in 96.2% (461/479) nodules. ENB in combination with radial endobronchial ultrasound (rEBUS), a guide sheath (GS) and a thin bronchoscope was the most widely used guided method, producing a diagnostic yield of 74.1% (254/343). The median total procedural time was 1325.0 (IQR, 1014.0-1676.0) s. No severe complications occurred. CONCLUSION: This novel ENB system can be used in combination with different bronchoscopes, ancillary techniques and sampling instruments with a high diagnostic yield and safety profile for the diagnosis of PPNs, of which the combination of thin bronchoscope, rEBUS and GS was the most common method in clinical practice. TRIAL REGISTRATION NUMBER: NCT03716284.

A nomogram strategy for identifying the subclassification of IDH mutation and ATRX expression loss in lower-grade gliomas.

OBJECTIVES: To construct a radiomics nomogram based on multiparametric MRI data for predicting isocitrate dehydrogenase 1 mutation (IDH +) and loss of nuclear alpha thalassemia/mental retardation syndrome X-linked expression (ATRX -) in patients with lower-grade gliomas (LrGG; World Health Organization [WHO] 2016 grades II and III). METHODS: A total of 111 LrGG patients (76 mutated IDH and 35 wild-type IDH) were enrolled, divided into a training set (n = 78) and a validation set (n = 33) for predicting IDH mutation. IDH + LrGG patients were further stratified into the ATRX - (n = 38) and ATRX + (n = 38) subtypes. A total of 250 radiomics features were extracted from the region of interest of each tumor, including that from T2 fluid-attenuated inversion recovery (T2 FLAIR), contrast-enhanced T1 WI, ASL-derived cerebral blood flow (CBF), DWI-derived ADC, and exponential ADC (eADC). A radiomics signature was selected using the Elastic Net regression model, and a radiomics nomogram was finally constructed using the age, gender information, and above features. RESULTS: The radiomics nomogram identified LrGG patients for IDH mutation (C-index: training sets = 0.881, validation sets = 0.900) and ATRX loss (C-index: training sets = 0.863, validation sets = 0.840) with good calibration. Decision curve analysis further confirmed the clinical usefulness of the two nomograms for predicting IDH and ATRX status. CONCLUSIONS: The nomogram incorporating age, gender, and the radiomics signature provided a clinically useful approach in noninvasively predicting IDH and ATRX mutation status for LrGG patients. The proposed method could facilitate MRI-based clinical decision-making for the LrGG patients. KEY POINTS: • Non-invasive determination of IDH and ATRX gene status of LrGG patients can be obtained with a radiomics nomogram. • The proposed nomogram is constructed by radiomics signature selected from 250 radiomics features, combined with age and gender. • The proposed radiomics nomogram exhibited good calibration and discrimination for IDH and ATRX gene mutation stratification of LrGG patients in both training and validation sets.

A Modified Bowel Displacement Technique for Magnetic Resonance Imaging-Guided Focused Ultrasound Surgery in the Treatment of Uterine Fibroids and Adenomyosis.

OBJECTIVE: The clinical application of magnetic resonance imaging-guided focused ultrasound (MRgFUS) surgery for treatment of symptomatic uterine fibroids is often limited because of the bowel between the abdominal wall and uterus. If bowels are in the pathway of sonication path, firstly filling the bladder, then filling the rectum, and emptying the bladder subsequently can be used to avoid them in recent research. The purpose of this study was to evaluate whether the modified bowel displacement technique (rectal filling first and then bladder filling, with or without subsequent bladder emptying) was feasible to create secure acoustic window. METHODS: A total of 78 patients who had undergone MRgFUS treatment for uterine fibroids and adenomyosis from January 2020 to November 2020 were included in this retrospective study. Of the 78 patients, 19 patients were treated using a modified bowel displacement technique, whereas the rest of the patients did not require intestinal displacement. High-intensity focused ultrasound was performed using GE Sightec HDXT 1.5 Tesla MR and ExAblate high-intensity focused ultrasound system. RESULTS: Of the 19 patients requiring bowel displacement techniques, 17 patients successfully completed MRgFUS surgery. Magnetic resonance imaging-guided focused ultrasound surgery was feasible in 4 patients after rectal filling, bladder filling, and subsequent bladder emptying. The others received ablation through the extended bladder because of bowel descending after emptying the bladder. The surgery caused no intestinal or uterine complications and no serious discomfort to the patient. CONCLUSIONS: The modified bowel displacement technique was effective in displacing interposed bowels during MRgFUS treatment to create safe acoustic pathway for ablating uterine fibroids and adenomyosis.

Evaluation of Inferior Intercavernous Sinus in Patients With Pituitary Microadenoma by Contrast-Enhanced SPACE Imaging.

OBJECTIVE: Inferior intercavernous sinus (iICS) is a venous channel below the pituitary gland. Inferior intercavernous sinus injury is predisposed to cause venous bleeding during dura incision in transsphenoidal surgery for pituitary adenomas. Therefore, this study aimed to perform a radiological assessment of iICS before transsphenoidal surgery for pituitary microadenoma. METHODS: A retrospective evaluation was performed on 156 patients who underwent magnetic resonance imaging examinations in our hospital before endoscopic transsphenoidal surgery for pituitary microadenoma. Both sagittal reformatted and coronal contrast-enhanced (CE) sampling perfection with application optimized contrast using different flip angle evolutions (SPACE) images were interpreted for the presence, shape, and size of the iICS. RESULTS: In CE SPACE, the iICS was identified in 72 patients (46.15%) with pituitary microadenoma. The iICS was appeared as a filiform-shaped hyperintense structure below the pituitary gland on coronal CE SPACE planes and a crescent-shaped hyperintense structure on sagittal CE SPACE planes. The mean ± SD width, depth, and height of iICS were 11.15 ± 3.47 mm, 5.29 ± 1.24 mm, and 1.41 ± 0.19 mm, respectively. CONCLUSIONS: Contrast-enhanced SPACE may serve as a promising technique in evaluating iICS and individualized preoperative planning before transsphenoidal surgery for pituitary microadenoma.

Deep learning shows good reliability for automatic segmentation and volume measurement of brain hemorrhage, intraventricular extension, and peripheral edema.

OBJECTIVES: To evaluate for the first time the performance of a deep learning method based on no-new-Net for fully automated segmentation and volumetric measurements of intracerebral hemorrhage (ICH), intraventricular extension of intracerebral hemorrhage (IVH), and perihematomal edema (PHE) in primary ICH on CT. METHODS: Three hundred and eighty primary ICH patients who underwent CT at hospital arrival were divided into a training cohort (n = 300) and a validation cohort (n = 80). An independent cohort with 80 patients was used for testing. Ground truth (segmentation masks) was manually generated by radiologists. Model performance on lesion segmentation and volumetric measurement of ICH, IVH, and PHE were evaluated by comparing the model results with the segmentations performed by radiologists. RESULTS: In the test cohort, the Dice scores of lesion segmentation were 0.92, 0.79, and 0.71 for ICH, IVH, and PHE, respectively. The sensitivities were 0.93 for ICH, 0.88 for IVH, and 0.81 for PHE. The positive predictive values were 0.92, 0.76, and 0.69 for ICH, IVH, and PHE, respectively. Excellent concordance (concordance correlation coefficients [CCCs] ≥ 0.98) of ICH and IVH and good concordance of PHE (CCCs ≥ 0.92) were demonstrated between manually and automatically measured volumes. The model took approximately 15 s to provide automatic segmentation and volume analysis for each patient. CONCLUSION: Our model demonstrates good reliability for automatic segmentation and volume measurement of ICH, IVH, and PHE in primary ICH, which can be useful to reduce the effort and time of doctors to calculate volumes of ICH, IVH, and PHE. KEY POINTS: • Deep learning algorithms can provide automatic and reliable assessment of intracerebral hemorrhage, intraventricular hemorrhage, and perihematomal edema on CT. • Non-contrast CT-based deep learning method can be helpful to provide efficient and accurate measurements of ICH, IVH, and PHE in primary ICH patients, thereby reducing the effort and time of doctors to segment and calculate volumes of ICH, IVH, and PHE in primary ICH patients.

Diffuse Tract Damage Correlates With Global Cognitive Impairment in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy: A Tract-Based Spatial Statistics Study.

PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common familial arteriopathy characterized by recurrent lacunar stroke, migraine, and depression. The mechanism of cognitive dysfunction in CADASIL is still uncertain. The aim of this study was to use tract-based spatial statistics (TBSS) to map voxelwise the spatial distribution of brain microstructural change revealed by DTI-derived indices in patients with CADASIL to further study the underlying neuropsychopathological mechanism of CADASIL. METHOD: Twelve patients with CADASIL and 11 age-, sex-matched healthy controls underwent magnetic resonance imaging at 3 T. Then we evaluated DTI-derived indices (fractional anisotropy [FA], mode of anisotropy [MO], mean diffusivity [MD], axial diffusivity [AD] and radial diffusivity [RD]) of brain white matter (WM) between CADASIL patients and healthy subjects through TBSS. RESULTS: Compared with healthy controls, patients with CADASIL showed extensive decreased FA, MO and increased RD, AD, and MD throughout the entire brain (mainly the WM of the temporal poles, inferior and superior longitudinal fasciculus, inferior fronto-occipital fasciculus, corpus callosum, uncinate fasciculus, internal capsule, external capsule, corona radiata, thalamic radiation, and cingulum). Furthermore, these WM microstructural alterations were significantly correlated with cognitive scores and Scheltens scores. Decreased FA values and MO values were positively correlated with Montreal Cognitive Assessment scores in CADASIL patients. Increased AD, RD, and MD values were significantly negatively correlated with Montreal Cognitive Assessment scores. CONCLUSIONS: Widespread WM abnormalities were clearly shown in CADASIL by using TBSS. Severity of microstructural changes correlates significantly with extension of T2 hyperintensity. Moreover, WM microstructural damage and cognitive impairment were significantly correlated. This study indicated that WM tract damage plays an important role in cognitive impairment in CADASIL.

Optimization of Contrast Agent Dosage on Contrast-Enhanced T2 Fluid-Attenuated Inversion Recovery: An In Vitro and In Vivo Study.

OBJECTIVE: This study aimed to ascertain the minimum gadolinium dosage on contrast-enhanced (CE) T2 fluid-attenuated inversion recovery (FLAIR) at appropriate imaging time. METHODS: Different dosages of gadodiamide were imaged with a 3.0-T magnetic resonance scanner for T2-FLAIR and T1WI. Twenty glioma-induced rat models were randomly assigned into 4 groups (1/2, 1/4, 1/6, 1/8 of routine dosage) and imaged for T2-FLAIR and T1WI preinjection and postinjection of gadodiamide. Contrast-enhanced T2-FLAIR was acquired for 8 repetitions postinjection. Enhancement effects were assessed by calculating contrast-noise ratio and contrast ratio using Kruskal-Wallis and Mann-Whitney rank sum test. RESULTS: The in vitro experiment showed that gadodiamide at 1/4 of the T1WI dosage presented the best contrast on CE-T2-FLAIR. For in vivo study, the best enhancement effect on CE-T2-FLAIR was achieved at 1/2 of the routine dosage at 8 to 12 minutes of delayed scanning. Compared with CE-T1WI at routine dosage, CE-T2-FLAIR at 1/2 gadodiamide dosage presented similar enhancement effects with no statistical difference (P = 0.244 and 0.090 for contrast-noise ratio and contrast ratio, respectively). CONCLUSIONS: Contrast-enhanced T2-FLAIR imaging with half of T1WI routine gadodiamide dosage can produce similar enhancement effects to CE-T1WI when characterizing brain gliomas. The cut-down of contrast agent dosage may help reduce gadolinium accumulation in certain tissues.

Iron Sucrose as MRI Contrast Agent in Ischemic Stroke Model.

BACKGROUND: Despite the growing concern about the safety of gadolinium-based contrast agents (GBCAs), they are still the most commonly used. Ferumoxytol, as an off-label alternative MRI contrast agent, cannot be administered by a rapid bolus for dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI). PURPOSE: To assess the feasibility of iron sucrose (IS) as a contrast agent for MR angiography (MRA) and DSC-PWI. STUDY TYPE: Prospective animal model. ANIMAL MODEL: Thirty-six normal rats (16 for MRA, 20 for biocompability tests) and 36 occlusion of the middle cerebral artery (MCAO) model rats. FIELD STRENGTH/SEQUENCE: 3.0T; head and neck angiography, using a fast spoiled gradient-recalled-echo (FSPGR) sequence and DSC-MRI using echo planar imaging(EPI) sequence. ASSESSMENT: MRA was performed on normal rats to examine the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of different doses of IS. DSC-PWI was performed on MCAO rats at 0, 24, 48, and 72 hours postreperfusion to investigate the lesion detectability of IS. Arterial spin labeling (ASL) and DSC-PWI enhanced by GBCAs were conducted on MCAO rats as controls. STATISTICAL TESTS: Kruskal-Wallis test was used to compare qualitative assessment. One-way analysis of variance (ANOVA) was used to compare the parametric data. Pearson's r values were evaluated between relative cerebral blood flow(rCBF)-ASL, rCBF-DSCIS , and rCBF obtained from DSC-PWI enhanced by GBCA. RESULTS: The mean SNR and CNR of the common carotid artery at doses of 10 mg Fe/kg of IS were comparable with the standard dose of GBCAs (SNR: 68.04 ± 12.55 vs. 67.72 ± 14.66; CNR: 23.78 ± 7.21vs. 21.63 ± 6.83). In MCAO rat models, rCBF and relative cerebral blood volume (rCBV) of ipsilateral striatum declined (0.72 ± 0.14, 0.86 ± 0.11) with prolonged relative mean transit time (rMTT) and relative time-to-peak (rTTP) (1.27 ± 0.24, 1.07 ± 0.03) following occlusion. Hyperperfusion was observed in all rats at 48 and 72 hours postreperfusion, in 4/6 rats at 24 hours postreperfusion for IS-mediated DSC-PWI. DATA CONCLUSION: IS may be an effective contrast agent for both MRA and DSC-PWI in ischemic stroke models. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1 J. Magn. Reson. Imaging 2020;52:836-849.

Research review on land development rights and its implications for China's national territory spatial planning.

Based on the China National Knowledge Infrastructure (CNKI) and Web of Science (WOS) databases, this article analyzes the deductive context, cooperation network, and research hotspots of land development rights (LDR) research in the Chinese and international literature by using CiteSpace software, and it also explores the implications of this research for the theory and practice of national territory spatial planning (NTSP) in China. The results show that (1) the literature on LDR in Chinese and international journal articles initially appeared in 1995 and 1973, respectively, researches in China experienced three stages: embryonic fluctuating development, rapid growth and stable development, and wave development, while international researches experienced two stages: embryonic fluctuating and a gradually increasing development. (2) Among these scholars and research institutions, there is no obvious difference between Chinese and international scholars, while the Renmin University of China and the State University System of Florida are the research institutions with the largest number of Chinese and international journal articles, respectively. (3) In terms of publishing journals, international journals mainly focus on land policy, cities, and resource fields, while Chinese journals mainly focus on the agricultural economy, civil and commercial law, economic systems, and macroeconomic management fields. (4) The direction and scale of thematic research vary greatly, with Chinese research mainly conducted from the perspectives of rights attribution and benefits distribution, while international research mainly focuses on the operation of the right-to-development system and its impact on the environment. In the future, studies focus on China's need to strengthen the research and institutional practice of LDR at the legal level, value level, and extension level following national conditions, formulate a land value-added benefit distribution system with efficiency and fairness, and strengthen the practice of LDR in China's NTSP based on the differences between urban and rural development.

A FAPα-activated MRI nanoprobe for precise grading diagnosis of clinical liver fibrosis.

Molecular imaging holds the potential for noninvasive and accurate grading of liver fibrosis. It is limited by the lack of biomarkers that strongly correlate with liver fibrosis grade. Here, we discover the grading potential of fibroblast activation protein alpha (FAPα) for liver fibrosis through transcriptional analysis and biological assays on clinical liver samples. The protein and mRNA expression of FAPα are linearly correlated with fibrosis grade (R2 = 0.89 and 0.91, respectively). A FAPα-responsive MRI molecular nanoprobe is prepared for quantitatively grading liver fibrosis. The nanoprobe is composed of superparamagnetic amorphous iron nanoparticles (AFeNPs) and paramagnetic gadoteric acid (Gd-DOTA) connected by FAPα-responsive peptide chains (ASGPAGPA). As liver fibrosis worsens, the increased FAPα cut off more ASGPAGPA, restoring a higher T1-MRI signal of Gd-DOTA. Otherwise, the signal remains quenched due to the distance-dependent magnetic resonance tuning (MRET) effect between AFeNPs and Gd-DOTA. The nanoprobe identifies F1, F2, F3, and F4 fibrosis, with area under the curve of 99.8%, 66.7%, 70.4%, and 96.3% in patients' samples, respectively. This strategy exhibits potential in utilizing molecular imaging for the early detection and grading of liver fibrosis in the clinic.

A multicentre, randomised, double-blind, double-dummy, parallel-controlled, phase 3 clinical trial assessing the efficacy and safety of intravenous nemonoxacin malate vs. levofloxacin for community-acquired pneumonia in adult patients.

BACKGROUND: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3, multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin vs. levofloxacin for the treatment of community-acquired pneumonia (CAP) in adult patients. METHODS: Eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at the test-of-cure (TOC) visit in the modified intent-to-treat (mITT) population. Secondary efficacy and safety were also compared between nemonoxacin and levofloxacin. RESULTS: Overall, 525 patients were randomised and treated with nemonoxacin (n = 349) or levofloxacin (n = 176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P > 0.05). The clinical efficacy of nemonoxacin was non-inferior to levofloxacin for treatment of CAP. Microbiological success rate with nemonoxacin was 88.8% (95/107) and with levofloxacin was 87.8% (43/49) (P > 0.05) at the TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in the nemonoxacin group and 22.2% in the levofloxacin group. These AEs were mostly local reactions at the infusion site, nausea, elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST), and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin. CONCLUSIONS: Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and non-inferior to levofloxacin for treating CAP in adult patients.

Endometriosis-targeted MRI imaging using bevacizumab-modified nanoparticles aimed at vascular endothelial growth factor.

Endometriosis is a tumor-like disease with high recurrence. In this case, the accurate imaging-based diagnosis of endometriosis can help clinicians eradicate it by improving their surgical plan. However, although contrast agents can improve the visibility of the tissue of interest in vivo via magnetic resonance imaging (MRI), the lack of biomarkers in endometriosis hinders the development of agents for its targeted imaging and diagnosis. Herein, aiming at the enriched vascular endothelial growth factor (VEGF) in endometriosis, we developed a targeting MRI contrast agent modified with bevacizumab, i.e., NaGdF4@PEG@bevacizumab-Cy5.5 nanoparticles (NPBCNs), to detect endometriosis. NPBCNs showed negligible cytotoxicity and high affinity towards VEGF in endometrial cells in vitro. Furthermore, NPBCNs generated a strong signal enhancement in vivo in endometriosis lesions in rats in T1-weighted images via MRI at 3 days post-injection, as confirmed by the histopathological staining results and fluorescence imaging on the same day. Our approach can enable NPBCNs to target endometriosis effectively, thus avoiding missed diagnoses.

Chinese expert consensus on interventional diagnosis and management of acquired digestive-respiratory tract fistulas (second edition).

Acquired digestive-respiratory tract fistulas occur with abnormal communication between the respiratory tract and digestive tract caused by a variety of benign or malignant diseases, leading to the alimentary canal contents in the respiratory tract. Although various departments have been actively exploring advanced fistula closure techniques, including surgical methods and multimodal therapy, some of which have gotten good clinical effects, there are few large-scale evidence-based medical data to guide clinical diagnosis and treatment. The guidelines update the etiology, classification, pathogenesis, diagnosis, and management of acquired digestive-respiratory tract fistulas. It has been proved that the implantation of the respiratory and digestive stent is the most important and best treatment for acquired digestive-respiratory tract fistulas. The guidelines conduct an in-depth review of the current evidence and introduce in detail the selection of stents, implantation methods, postoperative management and efficacy evaluation.

Central nervous system efficacy of rezivertinib (BPI-7711) in advanced NSCLC patients with EGFR T790M mutation: A pooled analysis of two clinical studies.

BACKGROUND: Rezivertinib (BPI-7711) is a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) which revealed the systematic and central nervous system (CNS) antitumor activities for EGFR T790M-mutated advanced NSCLC in previous clinical studies and is further analyzed here. METHODS: Eligible patients from the previous phase I and phase IIb studies of rezivertinib were included for pooled analysis. Post-progressive patients who received a prescribed dosage (≥180 mg) of rezivertinib orally once daily were included in full analysis set (FAS), while those with stable, asymptomatic CNS lesions, including measurable and non-measurable ones at baseline were included in CNS full analysis set (cFAS). Patients with measurable CNS lesions were included in CNS evaluable for response set (cEFR). BICR-assessed CNS objective response rate (CNS-ORR), CNS disease control rate (CNS-DCR), CNS duration of response (CNS-DoR), CNS progression-free survival (CNS-PFS), and CNS depth of response (CNS-DepOR) were evaluated. RESULTS: 355 patients were included in FAS, among whom 150 and 45 patients were included in cFAS and cEFR. This pooled analysis showed the CNS-ORR was 32.0% (48/150; 95% CI: 24.6-40.1%) and the CNS-DCR was 42.0% (63/150; 95% CI: 34.0-50.3%) in cFAS, while that in cEFR were 68.9% (31/45; 95% CI: 53.4-81.8%) and 100% (45/45; 95% CI: 92.1-100.0%). In cEFR, the median CNS-DepOR and the mean of CNS-DepOR were -52.0% (range: -100.0 to 16.1%) and -46.8% (95% CI: -55.5 to -38.1%). In cFAS, the median CNS-DoR and CNS-PFS were 13.8 (95% CI: 9.6-not calculable [NC]) and 16.5 (95% CI: 13.7-NC) months. CONCLUSIONS: Rezivertinib demonstrated encouraging clinical CNS efficacy among advanced NSCLC patients with EGFR T790M mutation and CNS metastases.

[Airway remodeling assessed by high-resolution computed tomography in patients with asthma: relationship to biological markers in induced sputum].

OBJECTIVE: To explore the significance of assessing asthma control by high-resolution computed tomography (HRCT) and biological markers in induced sputum. METHODS: Forty-eight patients with asthma (asthma group) and 10 healthy subjects (control group) were retrospectively analyzed. The asthma patients were divided into 4 groups based on severity: 6 with near-fatal attacks, 12 with severe, 14 with moderate and 16 with mild asthma. These patients received step therapy for 6 months based on the guidelines for the prevention and treatment of asthma. After achieving asthma control or partial control, HRCT, lung function and cytokine levels in induced sputum were measured. The ratio of wall area to total airway area (WA%), the ratio of 2 airway wall thickness to outer diameter (2T/D) and lung densities in both the inspiratory and expiratory phases were measured. Matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), and transformation growth factor-ß(1) (TGF-ß(1)) levels in the sputum were assessed by enzyme-linked immunosorbent assay. RESULTS: There were significant differences in forced vital capacity and forced expiratory volume in 1 second as the percentage of predicted value (FVC% and FEV(1)%, respectively), the ratio of FEV(1)/FVC, and diffusing capacity of the lung for carbon monoxide (D(LCO)) among groups (F = 5.526, 15.064, 16.326, 2.945, respectively, P < 0.05). Sputum levels of MMP-9, TIMP-1 and TGF-ß(1) were significantly increased in the near-fatal asthma, severe asthma, moderate asthma and mild asthma groups [MMP-9: (80 ± 16), (70 ± 9), (59 ± 6), and (52 ± 7) µg/L, respectively; TIMP-1: (212 ± 95), (258 ± 167), (28 ± 51), and 98 ± 60 µg/L, respectively; TGF-ß(1): (586 ± 81), (513 ± 54), (401 ± 45) and (351 ± 57) µg/L, respectively]compared with the control group [MMP9: (46 ± 5) µg/L; TIMP: (19 ± 13) µg/L; and TGF-ß(1): (258 ± 29) µg/L]. These parameters were progressively increased in the asthma groups with the severity of disease (F = 11.179, 49.914, 9.286, respectively, P < 0.05). The ratio of MMP-9/TIMP-1 in sputum was decreased in the near-fatal attack, severe, moderate and mild asthma groups (0.50 ± 0.28, 0.34 ± 0.13, 0.53 ± 0.22, and 0.87 ± 0.75, respectively) compared with the control group (2.93 ± 1.13). The MMP-9/TIMP-1 ratio in the severe asthma group was lowest among the asthma groups (F = 43.335, P < 0.05). 2T/D and WA% were higher in both the near-fatal asthma group (0.51 ± 0.01 and 0.75 ± 0.01, respectively) and the severe asthma group (0.53 ± 0.03 and 0.77 ± 0.03, respectively) as compared to the moderate asthma group (0.43 ± 0.04 and 0.67 ± 0.04, respectively) or the mild group (0.42 ± 0.04 and 0.66 ± 0.04, respectively). 2T/D and WA% were higher in the asthma groups than in the control group (0.35 ± 0.03 and 0.57 ± 0.04, respectively), (F = 40.224, 41.294, respectively, P < 0.05). Lung densities in both the inspiratory and expiratory phases were lower in the near-fatal attack group as compared to those in the other asthma groups or the control group; and the lung density differences between the two phases in the near-fatal attack group were smaller than those in the other asthma groups or the control group (F = 5.048, 13.247, 11.541, respectively, P < 0.05). 2T/D and WA% were correlated positively with MMP-9, TIMP-1 and TGF-ß(1) levels, but negatively with the MMP-9/TIMP-1 ratio, respectively. CONCLUSIONS: HRCT and biological markers in induced sputum could be used to accurately evaluate asthma control. These findings suggest that the severity of asthma, especially, near-fatal attack of asthma, is correlated not only with the degree of airway remodeling, but also with the degree of air trapping.

Analysis of the Dynamic Relationship between Green Economy Efficiency and Urban Land Development Intensity in China.

The improvement of green economic efficiency (GEE) should be realized under reasonable urban land development intensity (ULDI). Improving GEE can also help alleviate the negative externalities of excessive or unreasonable ULDI. Clarifying the interactive response mechanism between GEE and ULDI is a key link in regional sustainable development. Therefore, this paper uses the super-efficiency slack-based model (SBM) method, panel entropy method, and panel vector auto regression model to comprehensively analyze the interactive response relationship between GEE and ULDI in 283 prefecture-level cities in China from 2003 to 2019. This paper finds that: (1) during the research period, both the GEE and ULDI showed a relatively obvious upward trend, which is manifested in the fact that ULDI increased year by year while GEE overall increased in volatility. The growth and evolution trend of ULDI and GEE has the characteristics of interaction and coordination; (2) there is a two-way interactive Granger causality between ULDI and GEE, showing a positive interactive response effect; and (3) both ULDI and GEE have positive inertial growth and self-enhancement mechanisms. In the long run, GEE has a greater impact on the change of ULDI.

Chemical Factory-Guaranteed Enhanced Chemodynamic Therapy for Orthotopic Liver Cancer.

In the field of nanomedicine, there is a tendency of matching designed nanomaterials with a suitable type of orthotopic cancer model, not just a casual subcutaneous one. Under this condition, knowing the specific features of the chosen cancer model is the priority, then introducing a proper therapy strategy using designed nanomaterials. Here, the Fenton chemistry is combined with zinc peroxide nanoparticles in the treatment of orthotopic liver cancer which has a "chemical factory" including that liver is the main place for iron storage, metabolism, and also the main metabolic sites for the majority of ingested substances, guaranteeing customized and enhanced chemodynamic therapy and normal liver cells protection as well. The good results in vitro and in vivo can set an inspiring example for exploring and utilizing suitable nanomaterials in corresponding cancer models, ensuring well-fitness of nanomaterials for disease and satisfactory therapeutic effect.