Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

Objective:To explore the application value of arthroscopic tunnel pulling and suturing methods in West type Ⅱ and Ⅲ lateral meniscus posterior root injuries.Methods:A total of 184 patients with West Ⅱ ( n=92) and Ⅲ ( n=92) lateral meniscus posterior root injuries who underwent surgical treatment in Second Affiliated Hospital of Xi′an Jiaotong University from May 2022 to June 2023 were selected as the study subjects, by adopting a retrospective controlled study method. Using a random number table method, West Ⅱ and Ⅲ patients were divided into a tunnel method group and a suture method group, with 46 patients in each group. There were 23 male and 23 female patients in the West Ⅱ tunnel method group, with an age of (48.36±2.52) years. There were 25 male and 21 female patients in the suture method group, with an age of (48.61±2.21) years. There were 24 male and 22 female patients in the West Ⅲ tunnel method group, with an age of (48.53±2.36) years. There were 24 male and 22 female patients in the suture method group, with an age of (46.38±2.67) years. The tunnel method group used arthroscopic tibial tunnel cable fixation method, while the suture method group used arthroscopic full internal meniscus suture method. Compared the surgical time, length of hospital stay, and first postoperative time of getting out of bed between the tunnel method group and the suture method group of patients with different subtypes. Compared the knee joint function scores (Lysholm, Tegner, IKDC, VAS) before and after surgery. Used MRI to examine the compression of the patient′s lateral meniscus. Compared the incidence of adverse reactions. Measurement data with normal distribution were represented as mean ± standard deviation( ± s), and the comparison between groups was conducted using the t-test; the comparison of count data were represented as [ n(%)] and was conducted by chi-square test or Fisher exact probability. The skewness data were expressed by M( Q1, Q3), and rank-sum test was used for inter-group comparison. Results:There was no significant difference in surgical time, length of hospital stay, and first postoperative bed time between the West type Ⅱ, Ⅲ tunel method group and the suture method group ( P>0.05). At 12 months after surgery, there was no statistically significant difference in the Lysholm score, Tegner score, IKDC score, and VAS score between the West Ⅱ type patients in the tunnel method group and the suture method group ( P>0.05). However, the Lysholm score and IKDC score in the West Ⅲ type tunnel method group were significantly higher than those in the suture method group, and the difference was statistically significant( P<0.05). However, there was no statistically significant difference in the Tegner score and VAS score ( P>0.05). At the 12th months after surgery, there was no statistically significant difference in the overall width of the meniscus between the tunnel method group and the suture method group for patients with different West classifications( P>0.05). However, the relative percentage of meniscus compression in the tunnel method group was significantly lower than that in the suture method group, and the difference was statistically significant ( P<0.05). There was no statistically significant difference in the incidence of postoperative complications between the tunnel method group and the suture method group in patients with different West subtypes ( P>0.05). Conclusions:The arthroscopic tibial tunnel wire fixation method is effective, safe, and reliable in treating patients with West Ⅱ and West Ⅲ lateral meniscus posterior root injuries promoting kneejoint function recovery. It is expected to become a high-quality treatment plan for patients with West Ⅱ and West Ⅲ meniscus injuries.

With the increasing global prevalence of tree pollen allergies, there has been a significant impact on the quality of life for populations. In North and Central China, birch pollen, cypress pollen, and plane tree pollen are the most common allergens for springtime pollen allergy sufferers. The distribution of plants and patterns of pollen transmission in different geographical areas result in varying pollen exposure outcomes, further complicating the challenges in diagnosis and individualized treatment. This article delves into the research progress and clinical application of tree pollen allergies based on the "Molecular Allergology User′s Guide 2.0 (MAUG 2.0) " published by the European Academy of Allergy and Clinical Immunology (EAACI). It discusses major allergen families and component proteins of tree pollen such as PR-10 proteins, profilins, polcalcins, as well as cross-reactive components that may cause pollen-food allergy syndrome. Allergen component diagnostics can distinguish true allergy sufferers from those with multiple allergen reactions, enabling more targeted selection of allergens for specific immunotherapy, thus enhancing treatment effectiveness. Bet v 1 and Cup a 1, for instance, are specific indicators for immunotherapy in birch and cypress allergy patients. Overall, this article provides cutting-edge information for professionals in the field of tree pollen allergies, offering in-depth exploration of tree pollen allergen component proteins, clinical manifestations, and treatment-related research, aiding in better understanding and addressing the challenges of tree pollen allergies.

Grasses are extensively cultivated worldwide, with the three most common allergenic grass pollen subfamilies being Pooideae in temperate regions, Chloridoideae and Panicoideae in subtropical areas. This article delves into the research progress and clinical applications of grass pollen allergy as delineated in the "Molecular Allergology User′s Guide 2.0" issued by the European Academy of Allergy and Clinical Immunology (EAACI). It compiles epidemiological data on grass pollen, allergenic components, clinical manifestations, and treatment guidelines from both domestic and international sources, providing cutting-edge insights and scientific perspectives for professionals in the field of pollen allergy. The aim is to enhance the understanding of allergenic components, distinguishing between grass pollen allergy and pan-allergen responses with precision through advanced component-resolved diagnostic techniques. This serves to foster novel approaches to characterizing the unique sensitization patterns of grass pollen allergens in China, thereby offering more personalized and targeted diagnostic and therapeutic strategies for clinical practice in the region.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Objective:To compare the biomechanical properties of the modified and traditional iliolumbar pedicle screw-rod system for the fixation of vertically unstable posterior pelvic ring dislocation.Methods:The CT images of the lumbar spine, pelvis, and femur from a 31-year-old healthy male volunteer were used to establish models of posterior pelvic ring dislocation and unilateral and bilateral fixation models of modified and traditional iliolumbar pedicle screw-rod systems with the three-dimensional virtual software using the finite element method. By restraining the distal ends of the femurs of both sides and applying a vertical load of 500 N to the L 1 vertebral body, the maximum stress of the intact pelvis model and the stiffness of the posterior pelvic ring dislocation model were evaluated to validate the reliability of the models. After the validation of the models, a follower load of 400 N was applied in the direction of the L 1 vertebral curve to simulate the upper body weight; the maximum vertical displacement, the maximum posterior displacement, the maximum right displacement, and the overall maximum displacement of the sacrum of the modified and traditional iliolumbar pedicle screw-rod system models were compared. Additionally, stress distributions of the implant and the pelvis were also compared. Results:(1) The maximum stress of the intact pelvis model was 22.0 MPa, with the stiffness of the posterior pelvic ring dislocation model as 180.03 N/mm. (2) In terms of the maximum vertical displacement of the sacrum, the bilateral modified iliolumbar pedicle screw-rod system was similar to the bilateral traditional iliolumbar pedicle screw-rod system. However, the maximum posterior displacement, the maximum right displacement, and the overall maximum displacement of the sacrum in the bilateral modified iliolumbar pedicle screw-rod system were 0.57 mm, 0.19 mm and 0.68 mm respectively, which were markedly smaller than those of the bilateral traditional iliolumbar pedicle screw-rod system (1.38 mm, 0.26 mm and 1.41 mm respectively). (3) The maximum vertical displacement, the maximum posterior displacement, the maximum right displacement, and the overall maximum displacement of the sacrum in the unilateral modified iliolumbar pedicle screw-rod system were 0.70 mm, 0.73 mm, 0.17 mm and 0.88 mm respectively, which were markedly smaller than those of the unilateral traditional iliolumbar pedicle screw-rod system (1.17 mm, 2.21 mm, 0.31 mm and 2.29 mm respectively). (4) The stress of the implant was concentrated on the connecting rod between the iliac pedicle screw-rod and the lumbar pedicle screw-rod in the modified iliolumbar pedicle screw-rod system, but it was mainly concentrated on the connecting rod at the upper edge of the iliac screw in the traditional iliolumbar pedicle screw-rod system. The maximum stress of the implant was 340.84 MPa in the bilateral modified iliolumbar pedicle screw-rod system, which was 30.4% less than that in the bilateral traditional iliolumbar pedicle screw-rod system (489.77 MPa), and was 351.23 MPa in the unilateral modified iliolumbar pedicle screw-rod system, which was 15.5% less than that in the unilateral traditional iliolumbar pedicle screw-rod system (415.82 MPa). (5) In both modified and traditional iliolumbar pedicle screw-rod systems, the stress of the pelvis was concentrated on the contact area between the iliac screw and the cortical bone. The maximum stress of the pelvis was 19.21 MPa in the bilateral modified iliolumbar pedicle screw-rod system, which was 78.1% less than that in the bilateral traditional iliolumbar pedicle screw-rod system (87.59 MPa), and was 39.91 MPa in the unilateral modified iliolumbar pedicle screw-rod system, which was 70.4% less than that in the unilateral traditional iliolumbar pedicle screw-rod system (134.98 MPa).Conclusion:Compared with the traditional iliolumbar pedicle screw-rod system, the modified iliolumbar pedicle screw-rod system can effectively reduce the displacements of all directions in vertically unstable posterior pelvic ring dislocation and significantly reduce the stress of the implant and the pelvis, thus having good biomechanical stability.

Objective:To investigate the effects of subcutaneous immunotherapy (SCIT) on patients′ immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers.Methods:A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using t-test and Mann-Whitney U-test. Results:After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT: Z=-2.298, P<0.05; DM-SCIT: Z=-3.411, P<0.001); total ACT score (SM-SCIT: Z=-2.054, P<0.05; DM-SCIT: Z=-2.014, P<0.05) and total medication scores (SM-SCIT: Z=-3.799, P<0.000 1; DM-SCIT: Z=-3.474, P<0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group ( t=-2.253, P<0.05). There was no significant change in sIgE in the SM-SCIT group ( P>0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated ( Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all P<0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions( Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all P<0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions ( Z=-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all P<0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment ( Z of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all P<0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment ( Z=-1.988, -2.090, -2.497, -1.988, respectively, all P<0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 ( r=-0.499, P<0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 ( r=0.451, 0.420, 0.474, respectively; all P<0.05). Conclusion:Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.

Cockroaches are one of the most common indoor allergens worldwide, and exposure to cockroach allergens (such as the insect body, debris, and secretions) can trigger severe allergic rhinitis and(or) asthma. Currently, the World Health Organization (WHO)/International Union of Immunological Societies (IUIS) has identified 32 allergenic components in cockroaches, but none of these allergens have shown a clear immunodominance. The sensitization rate to cockroach allergens shows significant variability across different regions and populations and exhibits cross-reactivity with various invertebrates, increasing the complexity of clinical diagnosis and treatment. This article delves into the "Molecular Allergology User′s Guide 2.0"(MAUG 2.0) published by the European Academy of Allergy and Clinical Immunology (EAACI) and the research progress on cockroach allergies both domestically and internationally. It elucidates the crucial role of allergen component diagnostic technology in enhancing the diagnosis and treatment of cockroach-induced allergic diseases, efficiently assisting clinicians in identifying common sensitizations and cross-reactivities, thereby offering patients more accurate diagnoses and personalized treatment plans.

Food allergy are triggered by an abnormal immune response to specific food components, with milk and eggs being the most common food allergens, especially in children. Food allergy can cause various symptoms such as rashes, difficulty breathing, and digestive issues. Allergen component diagnostics is a technique used to identify specific allergenic proteins, aiding doctors in providing more precise treatment and management recommendations for patients. This article analyzes the latest research developments and clinical significance of milk and egg allergen components based on the " Molecular Allergology User′s Guide 2.0 (MAUG 2.0)" issued by the European Academy of Allergy and Clinical Immunology (EAACI), including their applications in clinical diagnosis, treatment, and management. This article aims to enhance healthcare professionals′ understanding of milk and egg allergies, offering new perspectives and practical guidelines for research and clinical practice to promote accurate diagnosis and personalized treatment strategies.