ObjectiveTo explore the mechanism by which Qidan Yifei Tongqiao granules （QDYF） alleviate nasal mucosal remodeling in allergic rhinitis （AR） via the interleukin-33 （IL-33）/growth stimulation expressed gene 2 （ST2）/interleukin-1 receptor accessory protein （IL-1RAP） signaling pathway from the perspective of Qi-replenishing and blood-activating therapy. MethodsFirst， according to the previous network pharmacology results， this study predicted the potential mechanisms of QDYF in treating AR by screening key pathways， components， and targets. Molecular docking was performed via AutoDock and PyMOL 2.5.5. Subsequently， a rat model of ovalbumin （OVA）-induced AR was used for validation through in vivo experiments. Forty-eight rats were assigned into 6 groups： Control， model， low-dose QDYF （QDYF-L， 4.04 g·kg^-1）， medium-dose QDYF （QDYF-M， 8.08 g·kg^-1）， high-dose QDYF （QDYF-H， 16.16 g·kg^-1）， and loratadine （0.9 mg·kg^-1）. After 14 days of intervention， behavioral scores of the rats were observed. The morphological changes of nasal mucosa tissue were observed by hematoxylin-eosin （HE） staining. Masson staining was used to observe collagen fiber deposition in the nasal mucosal tissue and to calculate the collagen volume fraction （CVF）. The expression of E-cadherin （E-cad） in the nasal mucosa tissue was detected by immunofluorescence. The serum levels of helper T cell 2 （Th2） cytokines interleukin-4 （IL-4）， interleukin-5 （IL-5）， and interleukin-13 （IL-13） as well as helper T cell 1 （Th1） cytokines interleukin-2 （IL-2） and interferon-γ （INF-γ） were quantified by enzyme-linked immunosorbent assay （ELISA）. The protein levels of transforming growth factor-beta 1 （TGF-β₁）， IL-33， ST2， and IL-1RAP in the nasal mucosa tissue were determined by Western blot. ResultsIL-33， ST2， and IL-1RAP had strong binding ability with the main active ingredients—wogonin， 7-methoxy-2-methylisoflavone， formononetin， naringenin， stigmasterol， and beta-sitosterol of QDYF， with the binding energy < -4.25 kcal⋅mol^-1（1 cal≈4.184 J）. The results of in vivo experiments showed that compared with the control group， the model group exhibited increased behavioral scores （P<0.05）， aggravated pathological damage of nasal mucosa， increased collagen fiber deposition and CVF （P<0.05）， elevated serum levels of IL-4， IL-5， and IL-13， up-regulated protein levels of TGF-β₁， IL-33， ST2， and IL-1RAP in the nasal mucosa （P<0.05）， down-regulated expression of E-cad， and declined serum levels of IL-2， IFN-γ， and IFN-γ/IL-4 ratio （P<0.05）. Compared with the model group， the QDYF groups and loratadine group showed reduced behavioral scores （P<0.05）， alleviated pathological damage of nasal mucosa， reduced collagen fiber deposition and CVF （P<0.05）， and up-regulated E-cad expression （P<0.05）. Compared with the model group， the QDYF-H group and the loratadine group showed raised levels of INF-γ and IFN-γ/IL-4 ratio （P<0.05）， declined serum levels of IL-4， IL-5， and IL-13， and down-regulated protein levels of TGF-β₁， IL-33， ST2， and IL-1RAP in the nasal mucosa （P<0.05）. In addition， the QDYF-H group exhibited an elevated serum IL-2 level （P<0.05）. The QDYF-M group showed down-regulated protein levels of TGF-β₁， IL-33 and IL-1RAP in the nasal mucosa （P<0.05）. The QDYF-L group demonstrated a down-regulated protein level of ST2 in the nasal mucosa （P<0.05）. ConclusionQDYF may regulate the Th1/Th2 balance through the IL-33/ST2/IL-1RAP signaling pathway， thereby ameliorating nasal mucosal tissue remodeling and alleviating AR.

ObjectiveTo investigate the effects and underlying mechanisms of Modified Yupingfeng Nasal Spray （玉屏风加味鼻喷剂， MYNS） on nasal mucosal tissue remodeling in allergic rhinitis （AR） model rats based on the Janus kinase 2 （JAK2）/ signal transducer and activator of transcription 3 （STAT3） signaling pathway. MethodsThe chemical constituents of MYNS were identified and analyzed using liquid chromatography-tandem mass spectrometry （LC-MS/MS）. Network pharmacology and molecular docking were integrated to identify the potential targets and signaling pathways of MYNS in the treatment of AR， and to verify the crucial role of the JAK2/STAT3 pathway. Forty rats were randomly divided into blank group， model group， MYNS group， and mometasone furoate nasal spray group， with 10 rats per group. Except for the blank group， the AR rat model was established by ovalbumin （OVA） induction. After successful modeling， rats in the MYNS group received an intranasal instillation of 50 μl of MYNS at concentration of 1.05 g·ml^-¹ in each nostril， while the mometasone furoate nasal spray group received 50 μl of corresponding spray per nostril， and the model group received 50 μl of normal saline per nostril. Treatments were administered once daily. After 14 consecutive days of intervention， the frequencies of nosal scratching and sneezing in rats within 15 minutes were recorded. Hematoxylin-eosin （HE） staining was used to assess morphological changes in the nasal mucosa and perform pathological scoring. Masson staining was used to evaluate collagen fiber deposition in nasal mucosal tissue and calculate the collagen volume fraction （CVF）. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） staining was performed to detect apoptosis in nasal mucosal cells and record the number of apoptotic cells. Immunofluorescence assay was used to detect the expression of E-cadherin （E-Cad） in the nasal mucosa. Enzyme-linked immunosorbent assay （ELISA） was used to determine the serum levels of interleukin-4 （IL-4）， interferon-γ （IFN-γ）， histamine （HIS）， immunoglobulin E （IgE）， superoxide dismutase （SOD）， and malondialdehyde （MDA）. Transmission electron microscopy was used to observe the ultrastructure of mitochondria in nasal mucosal epithelial cells. Flow cytometry was used to measure mitochondrial membrane potential （MMP） and reactive oxygen species （ROS） levels. Western Blot was used to determine the protein expression levels of collagen Ⅲ （Collagen Ⅲ）， α-smooth muscle actin （α-SMA）， Bcl-2-associated X protein （Bax）， Caspase-3， JAK2， phosphorylated JAK2 （p-JAK2）， STAT3， and phosphorylated signal transducer and activator of transcription 3 （p-STAT3）. ResultsA total of 626 chemical constituents were identified by LC-MS/MS. Network pharmacology screening identified 450 active ingredients. Nine intersecting components and 39 drug-AR intersecting targets were obtained. KEGG enrichment analysis indicated the involvement of signaling pathways including JAK2/STAT3. The animal experimental results showed that， compared with the blank group， rats in the model group exhibited significantly increased frequencies of nasal scratching and sneezing， as well as elevated CVF and the number of apoptotic cells， while the levels of E-Cad， MMP， and serum IFN-γ and SOD significantly decreased； meanwhile， the serum levels of IL-4， IgE， HIS， ROS， and MDA， along with the protein expression levels of Collagen Ⅲ， α-SMA， Bax， Caspase-3， p-JAK2， and p-STAT3 in the nasal mucosa， significantly increased （P＜0.05）， accompanied by aggravated pathological damage in the nasal mucosa， increased collagen fiber deposition， and abnormal mitochondrial morphology. Compared to the model group， rats in the MYNS group showed improvements in all the aforementioned indicators except for HIS （P＜0.05）， and those in the mometasone furoate nasal spray group showed improvements in all indicators except for IL-4， IgE， and SOD levels （P＜0.05）. ConclusionThe mechanism of MYNS in treating AR may be related to inhibiting the activation of the JAK2/STAT3 signaling pathway， reducing inflammatory responsesand oxidative stress， ameliorating mitochondrial damage， and suppressing nasal mucosal cell apoptosis， thereby improving nasal mucosal tissue pathological remodeling.

ObjectiveTo investigate the effects and underlying mechanisms of Modified Yupingfeng Nasal Spray （玉屏风加味鼻喷剂， MYNS） on nasal mucosal tissue remodeling in allergic rhinitis （AR） model rats based on the Janus kinase 2 （JAK2）/ signal transducer and activator of transcription 3 （STAT3） signaling pathway. MethodsThe chemical constituents of MYNS were identified and analyzed using liquid chromatography-tandem mass spectrometry （LC-MS/MS）. Network pharmacology and molecular docking were integrated to identify the potential targets and signaling pathways of MYNS in the treatment of AR， and to verify the crucial role of the JAK2/STAT3 pathway. Forty rats were randomly divided into blank group， model group， MYNS group， and mometasone furoate nasal spray group， with 10 rats per group. Except for the blank group， the AR rat model was established by ovalbumin （OVA） induction. After successful modeling， rats in the MYNS group received an intranasal instillation of 50 μl of MYNS at concentration of 1.05 g·ml^-¹ in each nostril， while the mometasone furoate nasal spray group received 50 μl of corresponding spray per nostril， and the model group received 50 μl of normal saline per nostril. Treatments were administered once daily. After 14 consecutive days of intervention， the frequencies of nosal scratching and sneezing in rats within 15 minutes were recorded. Hematoxylin-eosin （HE） staining was used to assess morphological changes in the nasal mucosa and perform pathological scoring. Masson staining was used to evaluate collagen fiber deposition in nasal mucosal tissue and calculate the collagen volume fraction （CVF）. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） staining was performed to detect apoptosis in nasal mucosal cells and record the number of apoptotic cells. Immunofluorescence assay was used to detect the expression of E-cadherin （E-Cad） in the nasal mucosa. Enzyme-linked immunosorbent assay （ELISA） was used to determine the serum levels of interleukin-4 （IL-4）， interferon-γ （IFN-γ）， histamine （HIS）， immunoglobulin E （IgE）， superoxide dismutase （SOD）， and malondialdehyde （MDA）. Transmission electron microscopy was used to observe the ultrastructure of mitochondria in nasal mucosal epithelial cells. Flow cytometry was used to measure mitochondrial membrane potential （MMP） and reactive oxygen species （ROS） levels. Western Blot was used to determine the protein expression levels of collagen Ⅲ （Collagen Ⅲ）， α-smooth muscle actin （α-SMA）， Bcl-2-associated X protein （Bax）， Caspase-3， JAK2， phosphorylated JAK2 （p-JAK2）， STAT3， and phosphorylated signal transducer and activator of transcription 3 （p-STAT3）. ResultsA total of 626 chemical constituents were identified by LC-MS/MS. Network pharmacology screening identified 450 active ingredients. Nine intersecting components and 39 drug-AR intersecting targets were obtained. KEGG enrichment analysis indicated the involvement of signaling pathways including JAK2/STAT3. The animal experimental results showed that， compared with the blank group， rats in the model group exhibited significantly increased frequencies of nasal scratching and sneezing， as well as elevated CVF and the number of apoptotic cells， while the levels of E-Cad， MMP， and serum IFN-γ and SOD significantly decreased； meanwhile， the serum levels of IL-4， IgE， HIS， ROS， and MDA， along with the protein expression levels of Collagen Ⅲ， α-SMA， Bax， Caspase-3， p-JAK2， and p-STAT3 in the nasal mucosa， significantly increased （P＜0.05）， accompanied by aggravated pathological damage in the nasal mucosa， increased collagen fiber deposition， and abnormal mitochondrial morphology. Compared to the model group， rats in the MYNS group showed improvements in all the aforementioned indicators except for HIS （P＜0.05）， and those in the mometasone furoate nasal spray group showed improvements in all indicators except for IL-4， IgE， and SOD levels （P＜0.05）. ConclusionThe mechanism of MYNS in treating AR may be related to inhibiting the activation of the JAK2/STAT3 signaling pathway， reducing inflammatory responsesand oxidative stress， ameliorating mitochondrial damage， and suppressing nasal mucosal cell apoptosis， thereby improving nasal mucosal tissue pathological remodeling.

Dual-energy CT enables acquisition of multi-parametric information beyond conventional CT through various post-processing techniques.Among these,virtual monoenergetic imaging has demonstrated outstanding performance in improving image quality,facilitating diagnosis,detecting isodense and small lesions,optimizing angiographic protocols,and reducing contrast medium dosage and radiation exposure.This article reviews the fundamental principles,technical advantages,and emerging clinical applications of virtual monoenergetic imaging.

Objective To analyze the clinical and immunological characteristics of a rare case of CHARGE syndrome,we summarize the genotype and phenotype in the Chinese patient population,and explore the underlying immunopathogenic mechanisms.Methods Clinical data from a pediatric patient with CHARGE syndrome were collected and analyzed.A comprehensive analysis of the Chinese patient population was conducted.Gene analysis and immunological characterization were performed using flow cytometry,deep sequencing,and quantitative PCR.Results The proband was a premature female infant whose primary clinical manifestations included congenital heart disease,recurrent respiratory infections,respiratory failure,airway dysplasia,hearing impairment,and bilateral choroidal coloboma.Whole-exome sequencing revealed a de novo heterozygous nonsense mutation in the CHD7 gene,c.5122C＞T(p.Gln1708Ter),classified as pathogenic according to ACMG criteria.Immunological studies indicated impaired thymic output of T cells,significant alterations in the number and proportion of CD8+T cell subsets,increased apoptosis,and defective activation and production of key effector cytokines such as IFN-γ by CD8+T cells.However,no significant abnormalities were observed in peripheral lymphocyte proliferation.Conclusion CHARGE syndrome is a rare autosomal dominant genetic disorder primarily caused by mutations in the CHD7 gene.The main clinical features include ocular defects,cardiac disease,choanal atresia/cleft lip and palate,growth retardation,gonadal hypoplasia,and ear anomalies.This case study suggests that CHARGE syndrome is associated with abnormalities in the development,apoptosis,and effector functions of immune cells.

Dual-energy CT enables acquisition of multi-parametric information beyond conventional CT through various post-processing techniques.Among these,virtual monoenergetic imaging has demonstrated outstanding performance in improving image quality,facilitating diagnosis,detecting isodense and small lesions,optimizing angiographic protocols,and reducing contrast medium dosage and radiation exposure.This article reviews the fundamental principles,technical advantages,and emerging clinical applications of virtual monoenergetic imaging.

Objective To analyze the clinical and immunological characteristics of a rare case of CHARGE syndrome,we summarize the genotype and phenotype in the Chinese patient population,and explore the underlying immunopathogenic mechanisms.Methods Clinical data from a pediatric patient with CHARGE syndrome were collected and analyzed.A comprehensive analysis of the Chinese patient population was conducted.Gene analysis and immunological characterization were performed using flow cytometry,deep sequencing,and quantitative PCR.Results The proband was a premature female infant whose primary clinical manifestations included congenital heart disease,recurrent respiratory infections,respiratory failure,airway dysplasia,hearing impairment,and bilateral choroidal coloboma.Whole-exome sequencing revealed a de novo heterozygous nonsense mutation in the CHD7 gene,c.5122C＞T(p.Gln1708Ter),classified as pathogenic according to ACMG criteria.Immunological studies indicated impaired thymic output of T cells,significant alterations in the number and proportion of CD8+T cell subsets,increased apoptosis,and defective activation and production of key effector cytokines such as IFN-γ by CD8+T cells.However,no significant abnormalities were observed in peripheral lymphocyte proliferation.Conclusion CHARGE syndrome is a rare autosomal dominant genetic disorder primarily caused by mutations in the CHD7 gene.The main clinical features include ocular defects,cardiac disease,choanal atresia/cleft lip and palate,growth retardation,gonadal hypoplasia,and ear anomalies.This case study suggests that CHARGE syndrome is associated with abnormalities in the development,apoptosis,and effector functions of immune cells.

Objective To explore the value of multiparameter MRI for follow-up observation on changes of spinal cord microstructures in patients with hereditary spastic paraplegias type 5.Methods Eleven patients with SPG5 who underwent cervico-thoracic spinal cord MR examination and spastic paraplegia rating scale(SPRS)were prospectively enrolled.The second MR examination and SPRS were completed after 1 year follow-up,and the changes of SPRS score,the overall structures and microstructures of spinal cord were compared.Results No significant difference of SPRS scores was found(P＞0.05).Compared to the first cervico-thoracic spinal cord MR examination,atrophy of spinal cord aggravated in the second time MRI.Significant difference of axial diffusivity of C4 right corticospinal tract(CST)was found(t=3.987,P＜0.01),but not of the other parameters of C4(all P＞0.05)between the first and the second time MRI.No significant difference of fractional anisotropy(FA),mean diffusivity(MD),AD,radial diffusivity(RD)nor T1 value of the other centrums'white matter,posterior funiculus or bilateral CST in spinal cord was found between the first and the second time MRI(all P＞0.05).Meanwhile,no significant difference of CSA,left and right diameter nor anteroposterior diameter of C1-T9 was found between the first and second time MRI(all P＞0.05).FA value of white matter,posterior funiculus and bilateral corticospinal tract in cervical spinal cord were all lower,whereas RD value at the above position were all higher in the second time MRI than those in the first time MRI(all P＞0.05).Conclusion Multiparameter MRI could be used for follow-up observation on changes of microstructure spinal cord in patients with hereditary spastic paraplegias type 5.

Objective:To explore whether the food additive sodium benzoate(NAB) induces pancreatic inflammation and β cell apoptosis through the benzoylation(Kbz) modification pathway.Methods:In vivo experiments: C57BL/6J male mice(8 weeks old, 18-20 g) were randomly divided into normal control group(double distilled water feeding) and NAB feeding group(1 g/kg NAB feeding). Blood glucose were measured. After 20 weeks, fasting serum insulin, interleukin(IL)-18, IL-1β, and benzoyl-CoA levels were detected by ELISA method. Bax, IL-18, Pan-Kbz and Pan-Kac were detected by immunohistochemistry staining. In vitro experiments: β-TC-6 cells were cultured with NAB(6 mmol/L) or benzoyl-CoA(100 μmol/L) as stimulator and acyltransferase P300 inhibitor A485(10 μmol/L) as intervention factor. 24 hours later, inflammation, apoptosis, insulin secretion and Pan-Kbz level were detected by qRT-PCR, ELISA and Western blotting.Results:In the in vivo experiments, compared to the NC group, mice in the NAB group exhibited impaired glucose tolerance, decreased fasting insulin levels, significantly increased serum benzoyl coenzyme A concentrations, relatively elevated pancreatic IL-1β, IL-18, and Bax protein expressions, increased levels of Pan-Kbz, while Pan-Kac levels were downregulated(all P<0.05); In vitro experiments, NAB dose-dependently inhibited insulin secretion, promoted the release of Pan-Kbz and inflammatory factors IL-18 and TNF- α, inhibited Bcl-2 expression and up-regulated Bax expression, A485 reversed NAB-induced Pan-Kbz modification, improved NAB-induced inflammation and apoptosis, and promoted insulin secretion(all P<0.05). Conclusion:NAB may induce pancreatic inflammation, β-cell apoptosis, and impair insulin secretion through Kbz modification pathway.

Objective:To investigate the feasibility of using spectral CT chest enhancement venous phase images to obtain virtual non-contrast (VNC) images and virtual arterial phase images to achieve one phase scan instead of three phase scans.Methods:Imaging data of 100 patients who underwent spectral CT chest plain and dual-phase enhancement scans at the First Affiliated Hospital of Kunming Medical University from January to May 2022 were analyzed retrospectively. The venous phase images of all patients were post-processed to obtain virtual non contrast (VNC) and 40 keV virtual mono-energy images (VMI) for simulated arterial phase images (Vart). Image quality and lesion detection were compared between true non-contrast (TNC) and VNC images, and conventional arterial phase (CIart) and Vart images by paired t-test, Wilcoxon test and McNemar test. Objective evaluation indexes of image quality included thoracic aorta, all levels of pulmonary artery, T4 vertebral bone cancellous, chest wall fat CT value, background noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR); the subjective score of image quality was assessed by double-blind method on a 5-point scale; the assessment of lesion detection included the detection rate of calcified foci and pulmonary nodules size, density, volume, percentage of solid components and imaging characteristics. Results:Except for chest wall fat and T4 vertebral bone cancellous, the differences in CT values between VNC and TNC images were not statistically significant ( P>0.05); Except for right upper pulmonary artery and right lower pulmonary artery, the differences in background noise values and SNR between TNC images and VNC images were statistically significant ( P<0.05). Compared with CIart images, the CT values of chest wall fat were lower in Vart images ( P<0.05), and the CT values of the remaining sites were significantly higher ( P<0.05); the background noise values of all sites on Vart images were smaller than those on CIart images, and the SNR and CNR values were higher than those on CIart images ( P<0.05).The differences of subjective scores of images quality were not statistically significant between TNC and VNC images, between CIar and Vart images ( P>0.05). Taking TNC as the standard, the overall detection rate of VNC for calcification was 88.53% (301/340). Except for the short diameter of partially solid nodules, the differences of qualitative and quantitative assessment indexes of lung nodules between TNC and VNC images were not statistically significant ( P>0.05). Conclusions:Spectral CT chest venous phase 40 keV VMI can simulate arterial phase images in the diagnosis of vascular lesions, and venous phase VNC basically meets the standard of conventional plain scan, so it is feasible to replace plain scan, arterial phase and venous phase images in a certain range.