Development and performance of SIAT bPET: a high-resolution and high-sensitivity MR-compatible brain PET scanner using dual-ended readout detectors.

PURPOSE: Positron emission tomography/magnetic resonance imaging (PET/MRI) is a powerful tool for brain imaging, but the spatial resolution of the PET scanners currently used for brain imaging can be further improved to enhance the quantitative accuracy of brain PET imaging. The purpose of this study is to develop an MR-compatible brain PET scanner that can simultaneously achieve a uniform high spatial resolution and high sensitivity by using dual-ended readout depth encoding detectors. METHODS: The MR-compatible brain PET scanner, named SIAT bPET, consists of 224 dual-ended readout detectors. Each detector contains a 26 × 26 lutetium yttrium oxyorthosilicate (LYSO) crystal array of 1.4 × 1.4 × 20 mm3 crystal size read out by two 10 × 10 silicon photomultiplier (SiPM) arrays from both ends. The scanner has a detector ring diameter of 376.8 mm and an axial field of view (FOV) of 329 mm. The performance of the scanner including spatial resolution, sensitivity, count rate, scatter fraction, and image quality was measured. Imaging studies of phantoms and the brain of a volunteer were performed. The mutual interferences of the PET insert and the uMR790 3 T MRI scanner were measured, and simultaneous PET/MRI imaging of the brain of a volunteer was performed. RESULTS: A spatial resolution of better than 1.5 mm with an average of 1.2 mm within the whole FOV was obtained. A sensitivity of 11.0% was achieved at the center FOV for an energy window of 350-750 keV. Except for the dedicated RF coil, which caused a ~ 30% reduction of the sensitivity of the PET scanner, the MRI sequences running had a negligible effect on the performance of the PET scanner. The reduction of the SNR and homogeneity of the MRI images was less than 2% as the PET scanner was inserted to the MRI scanner and powered-on. High quality PET and MRI images of a human brain were obtained from simultaneous PET/MRI scans. CONCLUSION: The SIAT bPET scanner achieved a spatial resolution and sensitivity better than all MR-compatible brain PET scanners developed up to date. It can be used either as a standalone brain PET scanner or a PET insert placed inside a commercial whole-body MRI scanner to perform simultaneous PET/MRI imaging.

A Novel Three-Channel Endorectal Coil for Prostate Magnetic Resonance Imaging at 3T.

OBJECTIVE: The purpose of this work is to develop a 3-channel endorectal coil (ERC-3C) structure to obtain higher signal-to-noise (SNR) and better parallel imaging performance for prostate magnetic resonance imaging (MRI) at 3T. METHODS: The coil performance was validated by in vivo studies and the SNR, g-factor, and diffusion-weighted imaging (DWI) were compared. A 2-channel endorectal coil (ERC-2C) with two orthogonal loops and a 12-channel external surface coil were employed for comparison. RESULTS: Compared with the ERC-2C with a quadrature configuration and the external 12-channel coil array, the proposed ERC-3C improved SNR performance by 23.9% and 428.9%, respectively. The improved SNR enables the ERC-3C to produce spatial high-resolution images of 0.24 mm × 0.24 mm × 2 mm (0.1152 µL) in the prostate area within 9 minutes. CONCLUSION: We developed an ERC-3C and validated its performance through in vivo MR imaging experiments. SIGNIFICANCE: The results demonstrated the feasibility of an ERC with more than two channels and that a higher SNR can be achieved using the ERC-3C compared with an orthogonal ERC-2C of the same coverage.

5T magnetic resonance imaging: radio frequency hardware and initial brain imaging.

Background: We aimed to demonstrate the feasibility of generating high-resolution human brain magnetic resonance imaging (MRI) at 5 Tesla (T) using a quadrature birdcage transmit/48-channel receiver coil assembly. Methods: A quadrature birdcage transmit/48-channel receiver coil assembly was designed for human brain imaging at 5T. The radio frequency (RF) coil assembly was validated by electromagnetic (EM) simulations and phantom imaging experimental studies. The simulated B1+ field inside a human head phantom and inside a human head model generated by the birdcage coils driven in circularly polarized (CP) mode at 3T, 5T and 7T was compared. Signal-to-noise ratio (SNR) maps, the inverse g-factor maps for evaluation of parallel imaging performance, anatomic images, angiography images, vessel wall images and susceptibility weighted images (SWI) were acquired using the RF coil assembly at 5T and compared to those acquired using a 32-channel head coil on a 3T MRI scanner. Results: For the EM simulations, 5T MRI provided less RF inhomogeneity compared to that of 7T. In the phantom imaging study, the distributions of the measured B1+ field were consistent with the distributions of the simulated B1+ field. In the human brain imaging study, the average SNR value of the brain in the transversal plane at 5T was 1.6 times of that at 3T. The 48-channel head coil at 5T had higher parallel acceleration capability than the 32-channel head coil at 3T. The anatomic images at 5T also showed higher SNR than those at 3T. Improved delineation of the hippocampus, lenticulostriate arteries, and basilar arteries was observed at 5T compared to 3T. SWI with a higher resolution of 0.3 mm ×0.3 mm ×1.2 mm could be acquired at 5T, which enabled better visualization of small blood vessels compared to that at 3T. Conclusions: 5T MRI can provide significant SNR improvement compared to that of 3T with less RF inhomogeneity than that of 7T. The ability to obtain high quality in vivo human brain images at 5T using the quadrature birdcage transmit/48-channel receiver coil assembly has significant in clinical and scientific research applications.

A 5-channel local B0 shimming coil combined with a 3-channel RF receiver coil for rat brain imaging at 3 T.

PURPOSE: We aimed to improve B0 magnetic field homogeneity and minimize the interference between RF coils and local B0 shimming coils with few channel numbers. METHODS: To design and construct the prototype for B0 shimming of the rat brain, we first evaluated the interferences of single shimming loops on RF receiver loops. Then, B0 shimming of the whole rat brain was implemented using an optimization procedure. The positions and currents of the local shimming coils with channel numbers from 3 to 6 were optimized to improve shimming performance. Based on the simulation results, a 5-channel local shimming coil, combined with a 3-channel RF receiver coil, was constructed and evaluated by animal experiments. RESULTS: There was marginal SNR loss within 5% after integrating the local shimming coil into the RF receiver coil. With respect to the Siemens standard shims up to second order, the B0 inhomogeneity in one whole rat brain was reduced from 39.6 Hz to 24.7 Hz by using the local shimming coil. A large portion of the EPI distortions was recovered after using the 5-channel local shimming coil. The temporal SNR using the local shimming coil was higher than that using the Siemens standard shims up to second order, with an improvement of more than 24%. CONCLUSIONS: The local shimming coil can improve B0 magnetic field homogeneity despite minor effects on the RF coil and can benefit a variety of applications that are sensitive to B0 inhomogeneity. Nevertheless, EPI for rat brain is still very challenging.

Patient Preferences for Rescue Medications in the Treatment of Breakthrough Cancer Pain.

OBJECTIVE: The discrete choice experiment (DCE) is conducted in this study to discuss Chinese cancer patients' risk-benefit preferences for rescue medications (RD) and their willingness to pay (WTP) in the treatment of breakthrough cancer pain (BTcP). METHOD: Through literature reviews, specialist consultation, and patient surveys, this work finally included five attributes in the DCE questionnaire, i.e., the remission time of breakthrough pain, adverse reactions of the digestive system, adverse reactions of the neuropsychiatric system, administration routes, and drug costs (estimating patients' WTP). The alternative-specific conditional logit model is used to analyze patients' preferences and WTP for each attribute and its level and to assess the sociodemographic impact and clinical characteristics. RESULTS: A total of 134 effective questionnaires were collected from January, 1 to April, 5 in 2022. Results show that the five attributes all have a significant impact on cancer patients' choice of "rescue medications" (P<0.05). Among these attributes, the remission time after drug administration (10.0; 95%CI 8.5-11.5) is the most important concern for patients, followed by adverse reactions of the digestive system (8.5; 95%CI 7.0-10.0), adverse reactions of the neuropsychiatric system (2.9; 95%CI 1.4-4.3), and administration routes (0.9; 95%CI 0-1.8). The respondents are willing to spend 1182 yuan (95%CI 605-1720 yuan) per month for "rescue medications" to take effect within 15 minutes and spend 1002 yuan (95%CI 605-1760 yuan) per month on reducing the incidence of drug-induced adverse reactions in the digestive system to 5%. CONCLUSION: For Chinese cancer patients, especially those with moderate/severe cancer pain, the priority is to relieve the BTcP more rapidly and reduce adverse drug reactions more effectively. This study indicates these patients' expectations for the quick control of breakthrough pain and their emphasis on the reduction of adverse reactions. These findings are useful for doctors, who are encouraged to communicate with cancer patients about how to better alleviate the BTcP.

TaNBR1, a Novel Wheat NBR1-like Domain Gene Negatively Regulates Drought Stress Tolerance in Transgenic Arabidopsis.

Drought stress is an important factor that severely affects crop yield and quality. Autophagy has a crucial role in the responses to abiotic stresses. In this study, we explore TaNBR1 in response to drought stress. Expression of the TaNBR1 gene was strongly induced by NaCl, PEG, and abscisic acid treatments. The TaNBR1 protein is localized in the Golgi apparatus and autophagosome. Transgenic Arabidopsis plants overexpressing TaNBR1 exhibited reduced drought tolerance. When subjected to drought stress, compared to the wild-type (WT) lines, the transgenic overexpressing TaNBR1 plants had a lower seed germination rate, relative water content, proline content, and reduced accumulation of antioxidant enzymes, i.e., superoxide dismutase, peroxidase, and catalase, as well as higher chlorophyll losses, malondialdehyde contents, and water loss. The transgenic plants overexpressing TaNBR1 produced much shorter roots in response to mannitol stress, in comparison to the WT plants, and they exhibited greater sensitivity to abscisic acid treatment. The expression levels of the genes related to stress in the transgenic plants were affected in response to drought stress. Our results indicate that TaNBR1 negatively regulates drought stress responses by affecting the expression of stress-related genes in Arabidopsis.

Liushen Capsules, a promising clinical candidate for COVID-19, alleviates SARS-CoV-2-induced pulmonary in vivo and inhibits the proliferation of the variant virus strains in vitro.

BACKGROUND: Coronavirus disease 2019 (COVID-19) causes a global pandemic and has devastating effects around the world, however, there are no specific antiviral drugs and vaccines for the constant mutation of SARS-CoV-2. PURPOSE: In this study, we evaluted the antiviral and anti-inflammatory activities of Liushen Capsules (LS) on different novel coronavirus in vitro, studied its therapeutic effects on novel SARS-CoV-2 infected mice and observed the LS's clinical efficacy and safety in COVID-19. METHODS: The antiviral and aiti-inflammatory effects of LS on the 501Y.V2/B.1.35 and G/478K.V1/ B.1.617.2 strains were determined in vitro. A hACE2 mouse model of novel SARS-CoV-2 pneumonia was established. Survival rates, histological changes, inflammatory markers, lung virus titers and the expression of the key proteins in the NF-κB/MAPK signaling pathway was detected by western blotting and immumohistochemical staining in the lungs were measured. Subsequently, the disease duration, prognosis of disease, time of negative nucleic acid and the cytokines levels in serum were used to assess the efficacy of treatment with LS in patients. RESULTS: The results showed that LS (2, 1, 0.5 µg/mL) could significantly inhibit the replication of the two SARS-CoV-2 variants and the expression of pro-inflammatory cytokines (IL-6, IL-8, IP-10, CCL-5, MIP-1α, IL-1α) induced by the virus in vitro. As for the survival experiment in mice, the survival rate of virus group was 20%, while LS-treatment groups (40, 80, 160 mg/kg) could increase the survival rate to 60, 100 and 100%, respectively. LS (40, 80, 160 mg/kg) could significantly decrease the lung titers in mice and it could improve the pathological changes, inhibit the excessive inflammatory mediators (IFN-α, IFN-γ, IP-10, MCP-1) and the protein expression of p-NF-κB p65 in mice. Moreover, LS could significantly decrease SARS-CoV-2-induced activation of p-NF-κB p65, p-IκBα, and p-p38 MAPK and increase the protein expression of the IκBα. In addition, the patient got complete relief of symptoms after being treated with LS for 6 days and was proven with negative PCR test after being treated for 23 days. Finally, treatment with LS could reduce the release of inflammatory cytokines (IL-6, PDGF-AA/BB, Eotaxin, MCP-1, MIP-1α, MIP-1ß, GRO, CCL-5, MCP-3, IP-10, IL-1α). CONCLUSION: LS effectively alleviated novel SARS-CoV-2 or variants induced pneumonia in vitro and in vivo, and improved the prognosis of COVID-19. In light of the efficacy and safety profiles, LS could be considered for the treatment of COVID-19 with a broad-spectrum antiviral and anti-inflammatory agent.

Simultaneous Head and Spine MR Imaging in Children Using a Dedicated Multichannel Receiver System at 3T.

OBJECTIVE: The purpose of this work was to enable simultaneous head and spine Magnetic Resonance imaging (MRI) in children at 3T by using a dedicated multichannel radiofrequency coil array system. METHODS: A 24-channel head and spine pediatric coil system was developed and constructed. The coil's performance was compared with a commercially available 24-channel adult head-neck coil and a spine coil (1-4 spine of 16-channel were selected). Signal-to-noise ratio (SNR) and parallel imaging capability were quantitatively evaluated by phantom studies and in vivo imaging experiments. With Institutional Review Board and Ethics Committee approval, the designed coil was used to acquire head and spine images on 27 children in clinical settings. RESULTS: The pediatric coil provided substantial SNR improvements with an increase of 32% to 40% in the brain region and up to a two-fold increase in the surface. SNR increased by at least 18% in the spine region. The coil enabled higher resolution and a faster imaging speed, owing to significantly improved SNR. Extensive coverage of the coil enabled high-quality fast imaging from head-neck to the whole spine. Good image quality with an average score 4.63 out of 5 was achieved using the developed pediatric coil in clinical studies. CONCLUSION: Simultaneous head and spine MRI with superior performance have been successfully acquired in children subjects at 3T using the dedicated 24-channel head and spine pediatric coil system. SIGNIFICANCE: The 24-channel pediatric coil system potentially can enhance pediatric head and spine MRI in clinical research and diagnosis.

Real-time volumetric MR thermometry using 3D echo-shifted sequence under an open source reconstruction platform.

PURPOSE: The aim of this work is to implement real-time 3D MR thermometry for high intensity focused ultrasound (HIFU) monitoring. METHODS: Volumetric MR thermometry was implemented based on a 3D echo-shifted sequence with short TR to improve temperature sensitivity. The 3D acquisition was accelerated in two phase encoding directions with controlled aliasing in volumetric parallel imaging (CAIPIRINHA). Image reconstruction was run in an open source reconstruction platform (Gadgetron). RESULTS: Phantom experiments showed the proposed volumetric thermometry was comparable to the fiber optical thermometer. In-vivo animal experiments in rabbit thigh showed that the temperature error before and after 4× acceleration was less than 0.65 °C. Finally, real-time 3D thermometry with temporal resolution ~3 s and spatial resolution 2 × 2 × 5 mm3 (spatial coverage 192 × 192 × 80 mm3) was achieved with Gadgetron reconstruction. CONCLUSION: Real-time temperature monitoring was achieved in-vivo by using parallel imaging accelerated 3D echo-shifted sequence with Gadgetron reconstruction.

Efficacy of indoor air purification in the treatment of Artemisia pollen-allergic rhinitis: A randomised, double-blind, clinical controlled trial.

OBJECTIVES: To evaluate the clinical efficacy of a high-efficiency air purifier in patients with allergic rhinitis. DESIGN: We conducted a randomised, double-blind, clinical controlled trial with active and inactive versions of an air purifier. Our study included patients with allergic rhinitis who were sensitive to Artemisia pollen and treatment of the indoor environment using air filtration at night. We evaluated the clinical efficacy of indoor air filtration during the Artemisia pollen scattering season in Yulin City in Shanxi Province, China. SETTING: The First Hospital of Yulin (Yulin City, Shanxi Province, China). PARTICIPANTS: A total of 90 patients with allergic rhinitis who were sensitive to allergens of Artemisia pollen were randomly assigned to one of two groups in equal numbers. MAIN OUTCOME MEASURES: The primary outcome measure was the difference in visual analogue scale scores from baseline. Secondary outcomes were changes from baseline in nasal symptoms, allergy symptom scores, responses to the Rhinoconjunctivitis Quality of Life Questionnaire, Epworth Sleepiness Scale scores and tolerability scores for the air purifier. RESULTS: Based on the allergy symptom score, we found significant differences in rhinitis symptoms between the groups who used the active versus the inactive air purifier. CONCLUSIONS: The results of our investigation demonstrated the health benefits of particle filtration.

A flexible 9-channel coil array for fast 3D MR thermometry in MR-guided high-intensity focused ultrasound (HIFU) studies on rabbits at 3 T.

Signal-to-noise ratio (SNR) is a critical factor in MR-guided high-intensity focused ultrasound (HIFU) for local heating, which can affect the accuracy of temperature measurement. In order to achieve high SNR and higher temporal resolution, dedicated coil arrays for MR-guided HIFU applications need to be developed. In this work, a flexible 9-channel coil array was designed, and constructed at 3 T to achieve fast temperature mapping for MR-guided HIFU applications on rabbit leg muscle. Coil performance was evaluated for SNR, and parallel imaging capability by in-vivo studies. Compared to a commercially available 4-channel flexible coil array, the dedicated 9-channel coil array has a much higher SNR, with at least a 2.6-fold increment in the region of interest (ROI). The inverse g-factors maps demonstrated that the dedicated 9-channel coil array has a better parallel imaging capability than the Flex Small 4. With accelerations normal to the array direction, both coil arrays showed much higher g-factors than those of accelerations along the array direction. Room temperature mapping was implemented to evaluate the temperature measurement accuracy by in-vivo experiments. The precisions of the 9-channel coil, ±0.18 °C for un-acceleration and ±â€¯0.56 °C for acceleration at R = 2 × 2, both improved by an order of magnitude than these of the 4-channel coil, which were ±â€¯1.45 °C for un-acceleration and ±â€¯3.52 °C for acceleration at R = 2 × 2. In the fast temperature imaging on the rabbit leg muscle with heating, a high temporal resolution of 3.3 s with a temperature measurement precision of ±0.56 °C has been achieved using the dedicated 9-channel coil. This study demonstrates that the dedicated 9-channel coil array for rabbit leg imaging provides improved performance in SNR, parallel imaging capability, and the accuracy of temperature measurement compared to a commercial 4-channel coil, and it also achieves fast temperature mapping in practical MR-guided HIFU applications.

One-Stop MR Neurovascular Vessel Wall Imaging With a 48-Channel Coil System at 3 T.

OBJECTIVE: The purpose of this article was to build a radio frequency (RF) coil system to achieve high vessel wall image quality with coverage extending from the aortic arch to the intracranial vessels. METHODS: A 48-channel coil system was built and characterized at a 3 tesla (T) Magnetic Resonance Imaging (MRI) scanner (uMR 790, Shanghai United Imaging Healthcare, Shanghai, China). The coil's performance was compared with a commercially available 36-channel coil system. By human studies, signal-to-noise ratio (SNR) units were evaluated and g-factors were calculated in the transverse planes of the brain and neck regions. RESULTS: The SNR was increased by at least 28% in the brain region and up to fourfold in the neck region. The average g-factor with the acceleration factor, R = 3, was lowered by 21% in the transverse plane of the neck region. Intracranial and carotid arterial wall images with an isotropic spatial resolution of 0.63 mm were acquired within 7.7 minutes and thoracic aorta wall images with an isotropic spatial resolution of 1.1 mm were acquired within 2.7 minutes with the 48-channel coil system. The vessel wall can be more clearly visualized with the 48-channel coil system compared with the 36-channel coil system. CONCLUSION: A 48-channel coil system was developed and demonstrated superior performance for vessel wall imaging at the intracranial and cervical carotid arteries compared with a commercial 36-channel coil. SIGNIFICANCE: The 48-channel coil system is potentially useful for clinical diagnostics, especially when attempting to diagnose ischemic stroke.

Design and testing of a 24-channel head coil for MR imaging at 3 T.

PURPOSE: To offer the new head coil option (with a lower channel count) of an RF coil array that provides comparable performance to the commercial 32-channel head coil. METHODS: The coil system comprised an upper shield (ten channels) and bottom section (fourteen channels). Signal-to-noise ratio (SNR) values for 2D unaccelerated imaging and the g-factor with an acceleration factor of 2-4 were evaluated in a phantom study. SNR performance and human brain and intracranial vessel wall imaging were conducted as part of the in vivo study. Both studies were conducted using the commercial head coil on the Siemens Tim Trio 3 T system for comparison. RESULTS: In the phantom study, the new head coil had an 8% higher SNR than the commercial head coil and demonstrated less than a 1% difference in the g-factor with the acceleration factor 2-4 in the right-to-left and anterior-to-posterior directions. In the in vivo study, the performance matched the results seen in the phantom study and showed high reproducibility in several human experiments. Structural images of the brain and intracranial vessel wall with an isotropic spatial resolution of 0.5 mm can be acquired with the new head coil. CONCLUSION: This study demonstrates that the new head coil is capable of providing good SNR performance in both phantom and human experiments, can achieve similar acceleration ability compared to the commercial head coil, and is capable of obtaining brain and intracranial vessel wall images.

A Dedicated 36-Channel Receive Array for Fetal MRI at 3T.

Due to a lack of fetal imaging coils, the standard commercial abdominal coil is often used for fetal imaging, the performance of which is limited by its insufficient coverage, element number, and Signal-to-noise ratio (SNR). In this paper, a dedicated 36-channel coil array, of which size can best fit the body sizes of pregnancy gestation from 20 to 37+ weeks, was designed for fetal imaging at 3T. SNR with full phase encoding and G-factor denoted as noise amplification for parallel imaging were quantitatively evaluated by phantom studies. Compared with a commercial abdominal coil array, the proposed 36-channel fetal array provides not only SNR improvements in full phase encoding (with 10% in the region where the whole fetal body was located, and up to 40% in the edge region where the fetal brain and heart may appear) but also an augmented parallel imaging capability and remarkable SNR improvements at high acceleration factors.

A low-cost home-built NMR using Halbach magnet.

The objective of this work is to develop a low-cost compact desktop NMR system based on Halbach magnets with the advantages of small size and ability to generate relatively high field strength. Considering the cost of manufacturing and assembling the magnetic blocks, the system utilized a 3-layer Halbach magnet and a wedge-shaped mechanical structure, which was designed for magnet rapid assembling. The comparison between simulation and calculation results of the initial magnetic field strength distribution showed that design theory and practice were in accordance. The initial homogeneity was 576 ppm in a square with a length of 5 mm. After passive shimming with two magnetic blocks and steel pieces, the uniformity reached 120 ppm in the same area. We developed and tested a compact single board spectrometer with digital modulation and demodulation in order to enhance the system mobility and improve the SNR. A self-made probe was used to carry out experiments with the spectrometer, and the spectral width at half-height reached 20 ppm in a cylinder with a diameter of 1.5 mm and a length of 1 mm. Compact structure and low cost of the system will facilitate and extend the application of desktop NMR system.

Efficacy of indoor air purification in treating Artemisia (mugwort) pollen allergic rhinitis: study protocol for a randomised controlled trial.

BACKGROUND: Allergic rhinitis (AR) is a worldwide health problem. Allergen avoidance is strongly recommended for AR patients. Air purification can reduce concentrations of particles in indoor air, including those of allergens. Air purifiers have been recommended by clinicians for AR patients, but few studies have focused on the removal of airborne allergens from home environments. Such studies have been limited by a lack of blinding, small samples, or a failure to measure allergen levels, disease activity, or a combination of these factors. This study investigates the efficacy of a high-efficiency air purifier in reducing disease activity in the homes of AR patients sensitive to the allergens produced by Artemisia (mugwort) pollen. METHODS: This is a randomized, double-blind, clinical controlled trial that will test active and inactive versions of an air purifier (Atmosphere®; Amway China). Sixty AR patients sensitive to the allergens produced by Artemisia pollen will be assigned randomly to two groups of equal numbers. All patients will undergo a 4-week treatment period and a 4-week observation period. Evaluation will be conducted at baseline (day 0) and on days 7, 14, 21, 28, and 56. The primary outcome measure will be the difference in visual analog scale scores from baseline. Secondary outcomes will be changes from baseline in nasal symptoms, allergy symptom scores, responses to the Rhinoconjunctivitis Quality of Life Questionnaire, Epworth Sleepiness Scale scores, and tolerability scores for the air purifier. Side effects of treatment will be recorded. DISCUSSION: Reducing exposure to allergens can reduce the risk of conditions such as AR. We hypothesise that AR patients sensitive to the allergens produced by Artemisia pollen will not suffer symptoms in a pollen-free environment. AR patients can remove pollen from their homes using air purifiers, decreasing the risk of symptoms. We expect that our study results will provide reliable evidence for determining the effects of air-purification therapy. TRIAL REGISTRATION: ChiCTR-INR-17012481 . (Retrospectively registered 26 August 2017).

Inhibition of the infectivity and inflammatory response of influenza virus by Arbidol hydrochloride in vitro and in vivo (mice and ferret).

Influenza virus infections are the main contagious respiratory disease with high levels of morbidity and mortality worldwide. Antiviral drugs are indispensable for the prophylaxis and treatment of influenza and other respiratory viral infections. In this study, the Arbidol hydrochloride (ARB), which has been licensed in Russia and China, is used to investigate its anti-viral and anti-inflammatory efficacy in vitro and in vivo. The antiviral results in vitro showed that ARB had a better inhibition on Influenza virus A/PR/8/34 (H1N1), A/Guangdong/GIRD07/09 (H1N1), A/Aichi/2/68 (H3N2), A/HK/Y280/97 (H9N2) with IC50 ranging from 4.4 to 12.1µM. The further mechanisms study demonstrated that ARB is able to inhibit hemagglutinin-mediated hemolysis at concentration of 3.91-15.63µg/mL. The anti-inflammatory efficacy in vitro indicated that IL-6, IP-10, MCP-1, RANTES and TNF-α levels were diminished by ARB at concentrations of 22.6 and 18.8µM. The in vivo results in mice model displayed that the survival rates of mice administered 25mg/mL and 45mg/mL ARB were 40% and 50% respectively. And also, ARB can inhibit the decrease of body weight at 45mg/mL and inhibit the increase of mice lung index at 25mg/mL and 45mg/mL comparing to virus group. In ferret model, the ARB-treated ferrets showed a fever that peaked at 2 dpi and gradually decreased beginning at 3 dpi while relatively high temperatures were observed until 4 dpi in the virus group. The ARB-treated group scored 0-1 in the activity level at 2 dpi and 3 dpi at all time points. The transcription levels of cytokines in the respiratory tract of ferrets were detected at 3 dpi. Several proinflammatory cytokines induced by influenza (IL-10, TNF-α, IL-8 and IL-6) were down-regulated by post-treatment with ARB. The histopathological results of ferret lung displayed that ARB can alleviate the influenza virus induced lung lesions. Our results clarified the activity of ARB in both suppressing virus propagation and modulating the expression of inflammatory cytokines in vitro and in vivo, it can be as an effective drug to treat the influenza virus infection.

The Chinese prescription lianhuaqingwen capsule exerts anti-influenza activity through the inhibition of viral propagation and impacts immune function.

BACKGROUND: Lianhuaqingwen Capsule (LH-C) is a traditional Chinese medicine (TCM) formula used to treat respiratory tract infectious diseases in Chinese. The aim of this study was to determine the antiviral activity of LH-C and its immunomodulatory effects on viral infection. METHOD: The in vitro cytotoxicity and antiviral activity of LH-C was determined by MTT and Plaque reduction assays. Time course study under single-cycle virus growth conditions were used to determine which stage of viral replication was blocked. The effect of LH-C on the nuclear export of the viral nucleoprotein was examined using an indirect immunofluorescence assay. The regulation to different signaling transduction events and cytokine/chemokine expression of LH-C was evaluated using Western blotting and real-time RT-PCR. After virus inoculation, BALB/c mice were administered with LH-C of different concentrations for 5 days. Body-weight, viral titers and lung pathology of the mice were measured, the level of inflammatory cytokines were also examined using real-time RT-PCR. RESULTS: LH-C inhibited the proliferation of influenza viruses of various strain in vitro, with the 50% inhibitory concentration (IC50) ranging from 0.35 to 2 mg/mL. LH-C blocked the early stages (0-2 h) of virus infection, it also suppressed virus-induced NF-kB activation and alleviated virus-induced gene expression of IL-6, IL-8, TNF-a, IP-10, and MCP-1 in a dose-dependent manner. LH-C treatment efficiently impaired the nuclear export of the viral RNP. A decrease of the viral titers in the lungs of mice were observed in groups administered with LH-C. The level of inflammatory cytokines were also decreased in the early stages of infection. CONCLUSIONS: LH-C, as a TCM prescription, exerts broad-spectrum effects on a series of influenza viruses, including the newly emerged H7N9, and particularly regulates the immune response of virus infection. Thus, LH-C might be a promising option for treating influenza virus infection.

Radix isatidis Polysaccharides Inhibit Influenza a Virus and Influenza A Virus-Induced Inflammation via Suppression of Host TLR3 Signaling In Vitro.

Influenza remains one of the major epidemic diseases worldwide, and rapid virus replication and collateral lung tissue damage caused by excessive pro-inflammatory host immune cell responses lead to high mortality rates. Thus, novel therapeutic agents that control influenza A virus (IAV) propagation and attenuate excessive pro-inflammatory responses are needed. Polysaccharide extract from Radix isatidis, a traditional Chinese herbal medicine, exerted potent anti-IAV activity against human seasonal influenza viruses (H1N1 and H3N2) and avian influenza viruses (H6N2 and H9N2) in vitro. The polysaccharides also significantly reduced the expression of pro-inflammatory cytokines (IL-6) and chemokines (IP-10, MIG, and CCL-5) stimulated by A/PR/8/34 (H1N1) at a range of doses (7.5 mg/mL, 15 mg/mL, and 30 mg/mL); however, they were only effective against progeny virus at a high dose. Similar activity was detected against inflammation induced by avian influenza virus H9N2. The polysaccharides strongly inhibited the protein expression of TLR-3 induced by PR8, suggesting that they impair the upregulation of pro-inflammatory factors induced by IAV by inhibiting activation of the TLR-3 signaling pathway. The polysaccharide extract from Radix isatidis root therefore has the potential to be used as an adjunct to antiviral therapy for the treatment of IAV infection.

Lariciresinol-4-O-ß-D-glucopyranoside from the root of Isatis indigotica inhibits influenza A virus-induced pro-inflammatory response.

ETHNOPHARMACOLOGICAL RELEVANCE: Isatis indigotica is a traditional Chinese medicine. Its dried roots named "ban lan gen" in Chinese, are used for clinical treatment of virus infection, tumor, inflammation with a long history. However, its anti-influenza active ingredient and the underlying mechanism remain unclear. In this study, the anti-influenza and anti-inflammatory effects of a lignan glycoside: lariciresinol-4-O-ß-D-glucopyranoside isolated from the root of I. indigotica on human alveolar epithelial cell line A549 infected with influenza A virus were investigated. MATERIALS AND METHODS: Chemical and spectroscopic methods were employed to identify the structure of the lignan glycoside. Cytotoxicity of the lignan glycoside was analyzed using methylthiazolyltetrazolium (MTT) assay. The inhibitory activity against influenza virus of the lignan was determined by CPE inhibition assay. HEK-293 cells stably co-transfected with NF-κB responsive firefly luciferase and constitutively expressing GFP were employed for monitoring the effect of the lignan on NF-κB signal pathway activation. Nuclear export of viral ribonucleoprotein (RNP) complexes was monitored by indirect immunofluorescence. Quantitative real-time PCR was used to quantify the expression profiling of cytokines and chemokines after infection with influenza virus. RESULTS: We showed that the lignan glycoside treatment was effective against the influenza A virus-induced cytopathic effect (CPE) in MDCK cells. Further study demonstrated the lignan glycoside attenuated virus-induced NF-κB activation, but did not affect export of viral ribonucleoprotein (RNP) complexes from the nucleus in late stages of infection. We revealed that the lignan glycoside suppressed influenza A virus (H1N1)-induced expression of the pro-inflammatory molecules IL-6, TNF-α, IL-8, MCP-1, IP-10 and IFN-α. Moreover, the cytokines and chemokines profiles induced by H9N2 virus resembled those of influenza virus H1N1, but the lignan glycoside reduced the expression of IP-10 and TNF-α. CONCLUSIONS: Our results suggest that the lignan glycoside is a bioactive component of I. indigotica which may contribute an adjunct to pharmacotherapy for influenza virus infection.