Coronary artery-bronchial artery fistula imaging characteristics and its correlation with pulmonary disease severity.

Hemoptysis is a common clinical emergency, bronchial arterial embolization is considered to be an effective treatment. The presence of coronary artery-bronchial artery fistula (CBF) may lead to recurrence of hemoptysis after treatment. It is necessary to investigate the imaging characteristics of a CBF and its correlation with the severity of pulmonary disease. With the development of multi-detector computed tomography, our study used the 320-slice CT bronchial artery angiography technology to observe and visualize blood vessels. The image and clinical data of 2015 hemoptysis patients with 320-slice CT bronchial artery angiography were retrospectively reviewed from January 2015 to December 2019. The axial and three-dimensional CT images were analyzed. The incidence, anatomical characteristics of CBF and pulmonary disease severity score were evaluated. A total of 12 CBF vessels were detected in 11 patients. We found that the incidence of CBF in this group was 0.55% (11/2015). Mean CBF diameter was 1.9 mm (1.2-2.5 mm). The course of CBF usually was relatively fixed. The proportions of CBF originated from the left circumflex artery, right coronary artery, and left anterior descending artery were 75%, 16.7% and 8.3%, respectively. Preliminarily analysis of the correlation between the trend of CBF and the pulmonary diseases severity score showed that CBF was more likely to communicate with a bronchial artery on the side with a higher severity score. CBF may occur in patients with chronic pulmonary disease and hemoptysis, and its origin, course and trend are characteristic. Detailed and comprehensive computed tomography angiography image analysis is helpful to improve the clinical treatment of hemoptysis with CBF.

Modification of neutralizing epitopes of hemagglutinin for the development of broadly protective H9N2 vaccine.

The H9N2 avian influenza viruses cause significant economic losses in poultry worldwide and could potentially cause human pandemic. Currently, the available vaccines have limited efficacy due to antigenic drift of H9N2. To improve vaccine efficacy, we developed monovalent vaccine strain via the modification of neutralizing epitopes on hemagglutinin (HA) to broaden the protection against H9N2 viruses. In this study, single and multiple mutation were introduced to amino acid at position 148, 150 (site I) and 183, 186, 188 (site II) on the full-length HA gene of H9N2 strain (A/Hong Kong/33982/2009). These mutant HA constructs were displayed on the baculovirus surface (BacH9), and evaluated for their cross-protective efficacy against H9N2 viruses in a mouse model. Our findings indicate that mice immunized with multiple BacH9 mutant constructs (148-150 183 and 186) induced cross-protective immunity against circulating H9N2 in the viral challenge study and prove to be a promising vaccine candidate for H9N2.

Incorporating G-C Pair-Recognizing Guanidinium into PNAs for Sequence and Structure Specific Recognition of dsRNAs over dsDNAs and ssRNAs.

Recognition of RNAs under physiological conditions is important for the development of chemical probes and therapeutic ligands. Nucleobase-modified dsRNA-binding PNAs (dbPNAs) are promising for the recognition of dsRNAs in a sequence and structure specific manner under near-physiological conditions. Guanidinium is often present in proteins and small molecules for the recognition of G bases in nucleic acids, in cell-penetrating carriers, and in bioactive drug molecules, which might be due to the fact that guanidinium is amphiphilic and has unique hydrogen bonding and stacking properties. We hypothesized that a simple guanidinium moiety can be directly incorporated into PNAs to facilitate enhanced molecular recognition of G-C pairs in dsRNAs and improved bioactivity. We grafted a guanidinium moiety directly into a PNA monomer (designated as R) using a two-carbon linker as guided by computational modeling studies. The synthetic scheme of the PNA R monomer is relatively simple compared to that of the previously reported L monomer. We incorporated the R residue into various dbPNAs for binding studies. dbPNAs incorporated with R residues are excellent in sequence specifically recognizing G-C pairs in dsRNAs over dsDNA and ssRNAs. We demonstrated that the R residue is compatible with unmodified T and C and previously developed modified L and Q residues in dbPNAs for targeting model dsRNAs, the influenza A viral panhandle duplex structure, and the HIV-1 frameshift site RNA hairpin. Furthermore, R residues enhance the cellular uptake of PNAs.

Sequence- And Structure-Specific Probing of RNAs by Short Nucleobase-Modified dsRNA-Binding PNAs Incorporating a Fluorescent Light-up Uracil Analog.

RNAs are emerging as important biomarkers and therapeutic targets. The strategy of directly targeting double-stranded RNA (dsRNA) by triplex-formation is relatively underexplored mainly due to the weak binding at physiological conditions for the traditional triplex-forming oligonucleotides (TFOs). Compared to DNA and RNA, peptide nucleic acids (PNAs) are chemically stable and have a neutral peptide-like backbone, and thus, they show significantly enhanced binding to natural nucleic acids. We have successfully developed nucleobase-modified dsRNA-binding PNAs (dbPNAs) to facilitate structure-specific and selective recognition of dsRNA over single-stranded RNA (ssRNA) and dsDNA regions at near-physiological conditions. The triplex formation strategy facilitates the targeting of not only the sequence but also the secondary structure of RNA. Here, we report the development of novel dbPNA-based fluorescent light-up probes through the incorporation of A-U pair-recognizing 5-benzothiophene uracil (btU). The incorporation of btU into dbPNAs does not affect the binding affinity toward dsRNAs significantly, in most cases, as evidenced by our nondenaturing gel shift assay data. The blue fluorescence emission intensity of btU-modified dbPNAs is sequence- and structure-specifically enhanced by dsRNAs, including the influenza viral RNA panhandle duplex and HIV-1-1 ribosomal frameshift-inducing RNA hairpin, but not ssRNAs or DNAs, at 200 mM NaCl, pH 7.5. Thus, dbPNAs incorporating btU-modified and other further modified fluorescent nucleobases will be useful biochemical tools for probing and detecting RNA structures, interactions, and functions.

[Application of Gemstone Spectrum Imaging for anterior spinal artery in patients with cervical spinal injury].

OBJECTIVE: To discuss the value of Gemstone Spectrum Imaging (GSI) CT anterior spinal artery angiography in the patients with cervical spinal cord injury, and to evaluate the correlation between the change of the blood flow of the anterior spinal artery and the postoperative recovery of nerve function. METHODS: From January 2014 to June 2016, thirty patients who underwent cervical open door laminoplasty for spinal cord injury were retrospective analyzed and included 21 males and 9 females with an average age of (46.4±9.7) years old ranging from 33 to 59 years. Within 2 weeks after injury, open door laminoplasty was performed through cervical posterior approach. Among them, there were 8 cases of 3 segments of open door decompression, 18 cases of 4 segments, 4 cases of 5 segments. GSI CT were performed at 3 days before operation and 5 days after operation. The anterior spinal artery was reconstructed and evaluated the improvement of blood flow after operation. The cervical JOA score was calculated at 1 day before operation, 5 days after operation and 1, 6 and 12 months after operation, and the JOA score improvement rate of the corresponding follow-up points was calculated. RESULTS: All patients were followed up for 12 to 30 months with an average of (17.4±7.6) months. The iodine content ratio (ASA/VA) of the anterior spinal artery before and after operation was 0.75±0.20 and 0.89±0.02 respectively, the postoperative improvement was significantly higher than that before operation(P<0.01). The average ASA/VA improvement rate was(21.05±12.45)% after operation. There was a positive linear correlation between the improvement of blood flow and the improvement of JOA score at 1, 6 and 12 months after operation. CONCLUSIONS: GSI CT anterior spinal artery angiography is safe and feasible, the imaging is satisfactory, it can quantitatively evaluated the blood flow of the anterior spinal artery. There was a positive linear correlation between the improvement of blood flow in anterior spinal artery and the recovery of neurological function. Early postoperative improvement of blood flow in the anterior spinal artery can be used as a reference index for predicting the recovery of neurological function in patients.

Is the Cervical Anterior Spinal Artery Compromised in Cervical Spondylotic Myelopathy Patients? Dual-Energy Computed Tomography Analysis of Cervical Anterior Spinal Artery.

OBJECTIVE: Cervical myelopathy is a common, acquired cause of spinal cord dysfunction in older patients. It is postulated that a hypoxic or ischemic environment secondary to chronic spinal cord compression plays an important role in the pathogenesis of myelopathy. This study aims to use dual-energy computed tomography (DECT) to assess the altered blood flow to the spinal cord in patients with cervical spondylotic myelopathy (CSM). To our knowledge, this study is the first to use DECT in identifying comprised anterior spinal artery blood flow in patients with CSM. METHODS: Fifty patients with single disc level CSM and 10 volunteers without CSM underwent DECT of the cervical spine to analyze and compare the ASA. The neurologic status of each patient was evaluated preoperatively and postoperatively at 5 days, 1 month, and 6 months using the Japanese Orthopedic Association (JOA) score. All the patients with CSM underwent single-level anterior cervical discectomy and fusion, and at postoperative day 5, each patient underwent repeated DECT. The anterior spinal artery before and after surgery was compared in patients with CSM. The blood flow in terms of iodine content at a specific region of interest was measured in the axial CT of the volunteers group and in the preoperative and postoperative axial CT of patients with CSM. Correlations between change in blood flow and clinical improvement at each follow-up point were analyzed statistically. RESULTS: Iodine content (100 mg/mL) was 14.2800 ± 1.89527 at the C3/C4 disc level, 14.8280 ± 1.83820 at the C4/C5 disc level, and 15.5000 ± 2.41048 at the C5/C6 level. In patients with CSM, the preoperative iodine content (100 mg/mL) measured was 10.2621 ± 2.37396 in C3/C4 disc-level compression, 12.1438 ± 1.63447 in C4/C5 disc-level compression, and 14.0620 ± 2.44390 in C5/C6 disc-level compression. Postoperative iodine content (100 mg/mL) measurement changed to 13.78 ± 2.77 for the C3/C4 disc level, 14.16 ± 1.90 for the C4/C5 disc level, and 15.14 ± 2.62 for the C5/C6 disc level. The JOA score was 13.650 preoperatively, 14.010 at 5 days postoperatively, 14.630 at 1 month postoperatively, and 15.000 at 6 months postoperatively. The 1- and 6-month correlation ratios between the JOA and change in blood flow were statistically significant, with an r value of 0.746 (P < 0.05) and 0.760 (P < 0.05), respectively. CONCLUSIONS: This study provided evidence for the benefit of DECT as a radiographic tool for identifying the compromised cervical anterior spinal artery in patients with CSM. We believe that DECT is the one of the best radiographic tools available to provide an objective screening tool to detect compromised blood flow in patients with CSM.