ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

OBJECTIVE To study the efficacy of Tianjiang xueshuantong pills in the treatment of coronary heart disease. METHODS In accordance with the common pathogenesis of coronary heart disease， acute myocardial ischemia model， hyperlipidemia model， blood stasis model， and carotid artery thrombosis model were established using Wistar rats or SD rats as the experimental subjects. The effects of Tianjiang xueshuantong pills administered at high， medium， and low doses （0.6， 1.2 and 2.4 g/kg） on hemodynamic parameters and myocardial enzyme markers [lactate dehydrogenase （LDH）， creatine kinase-MB （CK- MB）]， oxidative stress factors [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione （GSH）]， inflammatory cytokines [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， monocyte chemotactic protein-1 （MCP-1）， intercellular adhesion molecule-1 （ICAM-1）]， myocardial infarction percentage， serum lipid indexes [total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）]， platelet aggregation function 话：022-84845240。E-mail：jiangx@tjipr.com [maximum aggregation rate （MAR）]， and thrombus formation indexes [thrombosis time， thrombus mass， thrombus protein content， plasminogen activator inhibitor-1 （PAI-1）， and tissue-type plasminogen activator （t-PA）] were evaluated in the rat models. RESULTS In myocardial ischemia tests， Tianjiang xueshuantong pills significantly reduced the percentage of myocardial infarction and the levels of CK-MB， LDH， MDA， GSH， IL-6， TNF-α， IL- 1β， and MCP-1 in serum （P＜0.05 or P＜0.01）. In hyperlipidemia tests， high dose of Tianjiang xueshuantong pills significantly reduced the serum levels of TC， LDL and significantly increased the level of HDL in rats after 2 weeks and 4 weeks of administration. In blood stasis tests， different doses of Tianjiang xueshuantong pills significantly reduced MAR of rats （P＜0.01）. In artery thrombosis tests， high dose of Tianjiang xueshuantong pills significantly prolonged the time of thrombosis formation （P＜ 0.01）， significantly reduced the weight and protein content of thrombus and the level of PAI-1 in serum （P＜0.01）. CONCLUSIONS Tianjiang xueshuantong pills exert therapeutic effects on coronary heart disease through multi-dimensional synergistic actions， including anti-myocardial ischemia， lipid-lowering， and anti-thrombotic effects.

Objective: To analyze the impact of parental sports concept and behavior on physical activity in preschool children, so as to provide a foundation for future guidance on fostering childrens physical activity within the family context. Methods: From November to December 2020, a clustered convenience sampling method was employed to conduct surveys, and a total of 283 children were selectal from one kindergarten each in Beijing, Shenyang, and Xian. Participating children wore ActiGraph GT9X accelerometers continuously for one week to collect data on different intensity levels of physical activity. Physical Activity afterschool Questionnaire for Preschooler (P-PAQ) was utilized to assess parental sports concept and behavior. The gender differences in physical activity level and physical activity compliance rate were analyzed by using ttest, Mann-Whitney U test, and Chisquare test; and the relationship between parental exercise concepts and behaviors and physical activity of preschool children was analyzed using Spearman rank correlation analysis and multiple linear regression analysis. Results: Parental sports concept was significantly positively correlated with average daily moderatetovigorous physical activity (MVPA) and total physical activity (TPA) in children (r=0.12-0.16, P<0.05). Parental sports behavior was significantly positively correlated with childrens average daily TPA (r=0.25, P<0.05). Multiple linear regression revealed that parental sports concept was positively correlated with average daily MVPA and TPA in both boys and girls (B=0.65-0.83), while parental sports behavior only was positively correlated with boys average daily MVPA and TPA (B=0.24-0.25)(P<0.05). Conclusions Parental sports concept and behavior can impact physical activity levels in preschool children, exhibiting gender differences. Future guidance on physical activity in family upbringing should consider both parental sports concept and behavior, and pay attention to the influence of childrens gender.

The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.

Objective To compare the clinical efficacy of anti-vascular endothelial growth factor(VEGF)combined with pars plana vitrectomy(PPV)treatment for patients with proliferative diabetic retinopathy(PDR)of different traditional Chinese medicine(TCM)syndrome types in the real world.Methods A prospective real-world study was performed in the 36 patients(involving 42 eyes)with PDR treated by anti-VEGF combined with PPV in the Department of Ophthalmology of the First Affiliated Hospital of Guangzhou University of Chinese Medicine from March 2019 to December 2019.According to the TCM syndrome manifestations,the patients were differentiated as qi-yin deficiency complicated with blood stasis obstructing collaterals type(15 cases,involving 18 eyes;shorten as qi-yin deficiency type),liver-kidney deficiency and ocular collaterals failing in the nourishment type(14 cases,involving 17 eyes;shorten as liver-kidney deficiency type),and yin-yang deficiency complicated with blood stasis and phlegm coagulation type(7 cases,involving 7 eyes;shorten as yin-yang deficiency type).The patients were treated with anti-VEGF therapy first and then received PPV after 5-7 days.Aqueous humor was sampled during anti-VEGF therapy and PPV.After treatment,the efficacy of PDR patients with different TCM syndromes was compared.Moreover,the patients were observed in the best corrected visual acuity(BCVA)of the affected eyes before surgery and 3 months after surgery,levels of cytokines in the aqueous humor before and after anti-VEGF treatment,macular central retinal thickness(CRT),area of the foveal avascular zone(FAZ),the blood density of macular center,inner ring,outer ring and intact macula 3 months after surgery,and the postoperative complications.Results(1)The difference of the therapeutic efficacy of PDR patients with various TCM syndrome types was statistically significant(P＜0.05).Among 3 syndrome types,the best efficacy was found in the qi-yin deficiency type,followed by liver-kidney deficiency type,and then yin-yang deficiency type,with the total efficacy rate being 88.89%(16/18),52.94%(9/17),and 42.86%(3/7),respectively.(2)Three months after surgery,the logarithmic value of minimum angle of resolution(LogMAR)for BCVA of patients with qi-yin deficiency type was significantly superior to that of patients with yin-yang deficiency type,with the difference being statistically significant(P＜0.05).After the anti-VEGF treatment,the levels of cytokines in the aqueous humor of the patients varied in the 3 syndrome types:vascular endothelial growth factor A(VEGF-A)level in the patients with the 3 syndrome types was significantly lower,placental growth factor(PLGF)and angiopoietin-like protein 4(ANGPTL4)levels in the patients with qi-yin deficiency type were higher,and interleukin 8(IL-8)level in the patients with liver-kidney deficiency type was higher than those before treatment,and the differences were statistically significant(P＜0.05 or P＜0.01).The blood density of macular outer ring and intact macula in the patients with qi-yin deficiency type and liver-kidney deficiency type was larger than that in the patients with yin-yang deficiency type,and the differences were statistically significant(P＜0.05).However,the differences of CRT,FAZ area,and blood density of macular center and inner ring among the 3 syndrome types were not statistically significant(P＞0.05).(3)The incidence of postoperative complications in the patients with yin-yang deficiency type was relatively high,but the difference among the 3 syndrome types was not statistically significant(P＞0.05).Conclusion In the real world,the best efficacy of anti-VEGF combined with PPV treatment in PDR patients with different TCM syndrome types can be achieved in the patients differentiated as qi-yin deficiency type,followed by liver-kidney deficiency type,and then yin-yang deficiency type.After anti-VEGF treatment,the levels of cytokines in the aqueous humor of the patients vary in the 3 syndrome types.Three months after the operation,the patients with qi-yin deficiency type and liver-kidney deficiency type have larger blood density of macular outer ring and intact macula,and exert good prognosis.

BACKGROUND:SMAD family member 4(SMAD4)can promote bone remodeling in osteoporotic rats,but it is unclear whether SMAD4 interferes with the expression of iron metabolism related proteins in osteoporotic rats. OBJECTIVE:To explore the effect of SMAD4 overexpression on the expression of iron metabolism related proteins in osteoporotic rats. METHODS:Rats were randomized into sham group,ovariectomy group,transfection control group and SMAD4 overexpression group.Animal models of osteoporosis were established in the latter three groups by ovariectomy,and only adipose tissue was removed in the sham group.One week later,adenovirus was injected into the femoral bone marrow cavity.SMAD4 overexpression group and transfection control group were injected with adenovirus overexpressing SMAD4 gene and control empty virus,respectively.Index detection was performed at 1 month after injection.Micro-CT,hematoxylin-eosin staining and tartrate resistant acid phosphatase staining were used to detect bone formation and bone resorption in osteoporotic rats.ELISA was used to detect serum ferritin and hepcidin levels.Immunohistochemical staining was used to detect alkaline phosphatase,osteocalcin,receptor activator for nuclear factor-κB ligand and tartrate resistant acid phosphatase levels in femoral tissue.RT-qPCR was used to detect SMAD4,hepcidin,divalent metal transporter 1,transferrin receptor1 and ferroportin1 mRNA levels in femoral tissue.Western blot was used to detect SMAD4,alkaline phosphatase,osteocalcin,osteoprotegerin,receptor activator for nuclear factor-κB ligand,tartrate resistant acid phosphatase,β-Crosslaps,hepcidin,divalent metal transporter 1,transferrin receptor 1,and ferroportin 1 protein levels. RESULTS AND CONCLUSION:In the sham group,bone trabeculae in femur tissue were intact,and almost no osteoclasts were found.In the ovariectomy and transfection control groups,the bone trabeculae were sparse and a large number of osteoclasts were present.In the SMAD4 overexpression group,the number of bone trabeculae was increased and the number of osteoclasts was decreased.Compared with the sham group,the ovariectomy group showed a significant reduction in the protein expression of SMAD4,alkaline phosphatase,osteocalcin,and osteoprotegerin in femoral tissue and hepcidin levels in serum and femoral tissue,while receptor activator for nuclear factor-κB ligand,tartrate resistant acid phosphatase,β-Crosslaps protein levels,divalent metal transporter 1,transferrin receptor1,ferroportin1 mRNA and protein levels were significantly increased(P＜0.05).Compared with the transfection control group,the SMAD4 overexpression showed a significant increase in SMAD4,alkaline phosphatase,osteocalcin,and osteoprotegerin protein levels in femoral tissue and hepcidin levels in serum and femoral tissue,while the expressions of receptor activator for nuclear factor-κB ligand,tartrate resistant acid phosphatase,β-Crosslaps protein levels,divalent metal transporter 1,transferrin receptor1,and ferroportin 1 at mRNA and protein levels were significantly decreased(P＜0.05).To conclude,overexpression of SMAD4 promotes bone remodeling in osteoporotic rats by interfering with the expression of iron metabolism related proteins.

Objective:To investigate the effects of different tube voltages combined with artificial intelligence reconstruction algorithm(CI)on the computed tomography(CT)imaging quality and radiation dose of chest phantom on the basis of the CT scan for an adult male simulated chest phantom(PH-N1).Methods:A 512-slice CT scanner of ultrahigh-end was adopted to conduct scan,and the images were divided into 70 kV group,80 kV group,100 kV group and 120 kV group according to different tube voltage.For 4 groups of CT scan images with different tube voltages,the 10%,30%,50%,70%and 90%CI were adopted to reconstruct 1mm thin layer image.The CT volume dose index(CTDIvol)and the dose-length product(DLP)of the scans of 4 groups were compared.The CT values and standard deviation(SD)values of the aorta,abdominal wall fat and erector spine muscle were measured.Two senior diagnostic physicians with more than 5 years of work experience independently and double-blindly evaluated the image quality by using 5-point scale.A Kappa consistency test was conducted.One-way analysis of variance was adopted to compare the differences of CT values and SD values of the tissues of image targets.The Friedman rank-sum test was adopted to compare the differences of subjective image qualities among different groups.Results:The differences of CTDIvol and DLP among 4 groups with different tube voltages were significant(F=1855.617,3996.118,P<0.05),respectively.Under 70 kV tube voltage,there were no significant differences in CT values of the aorta,abdominal wall fat and erector spine muscle,which were reconstructed by using 10%,30%,50%,70%and 90%CI(P>0.05),while the differences of SD values among them were statistically significant(F=32.267,53.327,14.873,P<0.05),respectively.Under the different tube voltages of 4 groups,which were reconstructed by 90%CI,the CT values of aorta,abdominal wall fat and erector spine muscle gradually decreased with decreasing of tube voltage,the differences were significant(F=139.899,2563.93,219.231,P<0.05),respectively.The consistency of subjective scores between two diagnostic physicians was better for each group of images(Kappa=0.712～0.869).Conclusion:Compared with 80 kV,90 kV and 120 kV images,the reconstructed images with 90%CI algorithm under 70 kV tube voltage can significantly reduce the radiation dose,and the images have a favorable signal-to-noise ratio at the same time.

Objective To investigate the effect of AU-rich element RNA-binding factor 1(AUF1)on the proliferation,apoptosis,and migration abilities of hepatocellular carcinoma(HCC)cells and possible mechanisms,and to clarify the role and molecular mechanism of AUF1 in the progression of HCC.Methods The UALCAN and TCGA-HCC databases were used to analyze the expression of AUF1 in pan-cancer and investigate the association of the expression level of AUF1 with the clinicopathological features and prognosis of HCC patients.CCK-8 assay,cell apoptosis assay,and Transwell chamber assay were used to investigate the function of AUF1 at the cellular level,and RNA-seq assay was used to investigate transcriptome changes in HCC cells after AUF1 knockdown.The t-test was used for comparison of continuous data between two groups;the Kaplan-Meier method was used to plot survival curves,and the log-rank test was used for comparison of survival rates.Results There were abnormal mRNA and protein expression levels of AUF1 in various tumor tissues compared with normal tissue(P<0.05).The mRNA expression level of AUF1 was positively correlated with the degree of HCC malignancy and the poor prognosis of early-stage HCC(P<0.05).Compared with the control group,the overexpression of exogenous AUF1 in HCC cells promoted the proliferation of HCC cells and inhibited the apoptosis and migration of HCC cells,while AUF1 knockdown inhibited HCC cell proliferation and promoted the apoptosis and migration of HCC cells.The RNA-seq analysis showed that AUF1 knockdown mainly affected the Wnt/β-catenin pathway and downregulated the protein expression level of β-catenin.Conclusion The abnormal expression of AUF1 is associated with the prognosis of early-stage HCC,and AUF1 may exert an oncogenic effect by activating the Wnt signaling pathway.

Objective To observe the distribution of atypical memory B cells in peripheral blood of children with frequently relapsing nephrotic syndrome(FRNS).Methods A total of 60 children with primary ne-phrotic syndrome(PNS)admitted to the hospital from October 2020 to March 2023 were selected as the re-search objects.According to the response to glucocorticoid(GC),they were divided into non-frequently relap-sing nephrotic syndrome(NFRNS)group(25 cases)and FRNS group(35 cases).A total of 20 age-and gen-der-matched healthy children were enrolled as the control group.The changes of atypical memory B cells in each group before and after GC treatment were compared,and the correlation between the changes and clinical data was analyzed.Results Before GC treatment,The percentages of total B cells(CD19+CD20+),total memory B cells(CD19+CD20+CD27+),resting memory B cells(CD19+CD20+CD21+CD27+)and atypical memory B cells(CD19+CD20+CD21-CD27-)in FRNS group and NFRNS group were significantly higher than those in control group.And the FRNS group was significantly higher than the NFRNS group(P＜0.05).After GC treatment,the percentages of total B cells,total memory B cells,resting memory B cells,acti-vated memory B cells(CD19+CD20+CD21-CD27+)and atypical memory B cells in FRNS group and NFRNS group were lower than those before GC treatment(P＜0.05).The FRNS group had a significantly higher pro-portion of atypical memory B cells than the NFRNS group and the control group(P＜0.05).Before GC treat-ment,the 24 h urinary protein in FRNS group and NFRNS group were higher than those in control group,and the levels of immunoglobulin G and albumin were lower than those in control group.The 24 h urinary protein in FRNS group was significantly higher than that in NFRNS group(P＜0.05).Before GC treatment,there was a positive correlation between 24 h urinary protein and the proportion of atypical memory B cells in FRNS group(P＜0.05).Conclusion There is abnormal distribution of atypical memory B cells in peripheral blood of FRNS children.The increase of atypical memory B cells can be used as a marker of recurrence of FRNS af-ter GC treatment.

Hallux valgus is a common disorder of the forefeet,and its diagnosis and treatment have always drawn the attention of the practitioners.This article introduced the minimally-invasive diagnosis and treatment system for hallux valgus of integrated traditional Chinese and western medicine,which was established by Professor WEN Jian-Min after more than 40 years of in-depth clinical practice and research based on the theory of yin-yang balance and theory of tendons and bones in traditional Chinese medicine(TCM)and through the combination of modern surgical experience.The minimally-invasive diagnosis and treatment system for hallux valgus embodies the principles of balancing yin and yang,laying equal stress on tendons and bones,unifying the fixation and functional exercises,and treating the fractures and the whole body simultaneously,and includes the key technologies such as minimally-invasive osteotomy for the first metatarsal bone,curtain-wrapped external fixation,perioperative Chinese medicine therapy based on syndrome differentiation,and rehabilitation and nursing of TCM.The system will provide a systematic guide for the standardized minimally-invasive treatment of hallux valgus,and will supply an important approach to the treatment of other orthopedic diseases with integrated traditional Chinese and western medicine.The minimally-invasive diagnosis and treatment system for hallux valgus reflects the scientific research achievements and clinical experience of Professor WEN Jian-Min,which exerts high significance of reference and application value.