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.

Resection is one of the most important treatments for esophageal squamous cell carcinoma, and routine postoperative follow-up is an effective method for early detection and treatment of recurrent metastases, which can improve patients' quality of life and prognosis. This consensus aims to provide a reference for colleagues responsible for postoperative follow-up of esophageal squamous cell carcinoma patients in China, and further improve the standardization of the diagnosis and treatment of esophageal squamous cell carcinoma.

This study aimed to evaluate the sensitivity and specificity of the new clinical diagnostic and classification criteria for Kashin-Beck disease (KBD) using six clinical markers: flexion of the distal part of fingers, deformed fingers, enlarged finger joints, shortened fingers, squat down, and dwarfism. One-third of the total population in Linyou County was sampled by stratified random sampling. The survey included baseline characteristics and clinical diagnoses, and the sensitivity and specificity of the new criteria was evaluated. We identified 3,459 KBD patients, of which 69 had early stage KBD, 1,952 had stage I, 1,132 had stage II, and 306 had stage III. A screening test classified enlarged finger joints as stage I KBD, with a sensitivity and specificity of 0.978 and 0.045, respectively. Shortened fingers were classified as stage II KBD, with a sensitivity and specificity of 0.969 and 0.844, respectively, and dwarfism was classified as stage III KBD with a sensitivity and specificity of 0.951 and 0.992, respectively. Serial screening test revealed that the new clinical classification of KBD classified stages I, II, and III KBD with sensitivities of 0.949, 0.945, and 0.925 and specificities of 0.967, 0.970, and 0.993, respectively. The screening tests revealed that enlarged finger joints, shortened fingers, and dwarfism were appropriate markers for the clinical diagnosis and classification of KBD with high sensitivity and specificity.
Adolescent ; Adult ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Kashin-Beck Disease ; classification ; diagnosis ; epidemiology ; pathology ; Male ; Middle Aged ; Young Adult