1.Structural and Spatial Analysis of The Recognition Relationship Between Influenza A Virus Neuraminidase Antigenic Epitopes and Antibodies
Zheng ZHU ; Zheng-Shan CHEN ; Guan-Ying ZHANG ; Ting FANG ; Pu FAN ; Lei BI ; Yue CUI ; Ze-Ya LI ; Chun-Yi SU ; Xiang-Yang CHI ; Chang-Ming YU
Progress in Biochemistry and Biophysics 2025;52(4):957-969
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.
2.Role of sphingosine-1-phosphate signaling in the proliferation of breast cancer BT549 cells
Juan SONG ; Ming WANG ; Xin-Yang LIU ; Hao-Tian ZHANG ; Qi ZHANG ; Xue-Mei ZHAO ; Ying LIU ; Hong-Xia CUI
The Chinese Journal of Clinical Pharmacology 2024;40(11):1578-1582
Objective To study the role of sphingosine-1-phosphate(S1P)signal on the proliferation of breast cancer BT549 cells.Methods Cells were divided into control group and experimental group,experimental group were treated with 0.1,1.0,10.0 μmol·L-1 S1P receptor agonist SEW2871 for 72 h.Control group was cultured with 0.1%fetal bovine serum.Cell proliferation was detected by methyl thiazolyl tetrazolium(MTT)assay.Cell models of overexpressing S1P receptors in BT549 were divided into three groups:blank plasmid group(LUC),wild type S1P receptor overexpression group(WT),S1P receptor phosphorylation site mutation overexpression group(MUT);the proliferation ratio was detected by MTT,the number of cell clones was counted by colony formation experiment.S1P antagonist W146(10 μmol·L-1)and protein kinase(AKT)signaling inhibitor MK2206(90 nmol·L-1)were used to detect the role of S1P signaling in the proliferation of breast cancer cells.The expression of phosphorylate signal transducer and activator of transcription 3(p-STAT3),c-Myc proteins were detected by Western blot.Results The growth ratio of BT549 cells in control group and 0.1,1.0,10.0 μmol·L-1experimental groups were 1.00±0.03,1.13±0.06,1.06±0.10 and 1.07±0.03,0.1 μmol·L-1 SEW2871 promot the cell proliferation(P<0.05).Compared between WT group,MUT group and LUC group,the growth rate and the number of clonal colonies were increased after overexpression of S1P receptor(all P<0.05).The growth ratio of BT549 cells after treatment with W146 and MK2206 in the LUC group,WT group and MUT group were 1.25±0.12,1.31±0.03,1.43±0.14 and 0.87±0.15,0.77±0.03,0.88±0.02.Compared between MUT group,WT group and corresponding DMSO group,the differences were statistically significant(all P<0.01).The number of cell clony formation number after treatment with W146 were 65.65±5.12,141.48±5.63 and 93.64±5.14;compared between MUT,WT group and corresponding DMSO group,the differences were statistically significant(all P<0.05).The relative protein expression levels of p-STAT3 in LUC group,WT group and MUT group were 0.67±0.04,0.69±0.08 and 0.81±0.06,the relative protein expression levels of proto-oncogene c-Myc were 1.69±0.03,0.70±0.10 and 0.67±0.07,compared between WT group,MUT group and corresponding DMSO group,the difference was statistically significant(P<0.05).Conclusion S1P signaling can promote proliferation in breast cancer BT549 cells,and the mechanism could be related to AKT and STAT3 signaling pathway.
3.Relationship between degeneration of paraspinal muscle and refractures in postmenopausal women treated by percutaneous vertebroplasty
Cekai YANG ; Zhuoyan CAI ; Ming CHEN ; Hao LIU ; Rui WENG ; Jianchao CUI ; Shuncong ZHANG ; Zhensong YAO
Chinese Journal of Tissue Engineering Research 2024;28(9):1414-1419
BACKGROUND:There are few studies on the effect of degeneration of paraspinal muscle on osteoporotic vertebral compression refractures treated by percutaneous vertebroplasty in postmenopausal women.This paper intends to reveal the relationship between them. OBJECTIVE:To investigate the relationship between degeneration of paraspinal muscle and osteoporotic vertebral compression refractures in postmenopausal women treated by percutaneous vertebroplasty. METHODS:The medical records of 81 postmenopausal female patients who were admitted to the First Affiliated Hospital of Guangzhou University of Chinese Medicine from May 2018 to March 2021 for osteoporotic vertebral compression fracture and received percutaneous vertebroplasty were retrospectively analyzed.The patients were divided into an osteoporotic vertebral compression refracture group(n=39)and a control group(n=42)according to whether they had osteoporotic vertebral compression refracture after percutaneous vertebroplasty.General data,vertebral bone mineral density,paravertebral cross-sectional area and mean CT value(Hu)of the two groups were analyzed. RESULTS AND CONCLUSION:(1)Univariate analysis showed that there was no significant difference in age and mean CT value of psoas major between the two groups(P>0.05).The body mass index,vertebral bone mineral density,paravertebral cross-sectional area and the mean CT value of the posterior vertebral muscle group in the control group were significantly higher than those in the osteoporotic vertebral compression refracture group(P<0.05).(2)Multivariate logistic regression analysis showed that low vertebral bone mineral density(OR=0.004,95%CI:0.000-0.555,P<0.05)and low mean CT value of posterior vertebral muscle group(OR=0.940,95%CI:0.894-0.988,P<0.05)were independent risk factors for postmenopausal osteoporotic vertebral compression refracture.(3)It is indicated that degeneration of paraspinal muscle will increase the risk of osteoporotic vertebral compression refractures in patients treated by percutaneous vertebroplasty,especially in postmenopausal women with a low mean CT value of low posterior vertebral muscle group.
4.Effects of antibiotics on energy metabolism and adipose tissue function in high-fat diet-induced obese mice
Yuanjie CUI ; Xinwen BI ; Fan BU ; Jia CUI ; Qiuxian LU ; Fang HE ; Hua YANG ; Ming LI
Journal of Public Health and Preventive Medicine 2024;35(6):6-10
Objective To study the effects of antibiotics and high-fat diet on energy metabolism and the browning of white adipose tissue (WAT) and brown adipose tissue (BAT) in mice, so as to provide new ideas for the possible mechanism of adipose tissue in the prevention and treatment of obesity. Methods A total of 80 10-week-old C57BL/6 male mice were fed with normal diet in the early stage, and the antibiotic gavage group (AG) and antibiotic high-fat group (AFG) were given mixed antibiotics by gavage. The blank group (BG) and the high-fat diet group (FG) were given normal saline intragastric solution for 2 weeks, and after the gavage operation, the FG group and the AFG group were given high-fat diet for obesity modeling, and the BG group and AG group continued to be fed with normal diet for 8 weeks (N=20). After the experiment, each group was injected with β3-adrenergic receptor agonists for 5 days, and the high-fat/ordinary diet remained unchanged. At the end of the experiment, basal metabolic rate (BMR), fasting blood glucose (FBG) and rectal temperature were measured, and feces, blood, subcutaneous white fat, epididymis and brown adipose tissue in the scapular area of mice were collected. The automatic biochemical analyzer was used to determine the blood biochemical indexes; reverse transcription polymerase chain reaction (RT-qPCR) was used to measure the expression of genes related to browning of WAT and BAT adipose tissue, respectively. Real-time quantitative polymerase chain reaction (qPCR) was used to determine the expression of WAT mitochondrial DNA (mt DNA). Results From the 4th week to the end of the experiment, the weight of the AFG group was significantly higher than that of the AG group and significantly lower than that of the FG group (P<0.05). The body weight, organ coefficient, serum TC level, rectal temperature and WAT cell diameter in the AFG group were significantly higher than those in the AG group. The serum levels of FBG, TC and LDL in the AFG group were significantly lower than those in the FG group (P<0.05). The overall BMR(mlO2/h) FG group was significantly higher than that of BG group, and the AFG group was significantly higher than that of AG. BMR per unit body weight (mlO2/h/g) AFG was significantly higher than that of FG group (P<0.05). The expressions of RIP140, PPAR-γ and UCP-1 in BAT in the AFG group were significantly higher than those in the FG group, and the mt DNA copy number of WAT in the AFG group was significantly higher than that in the FG group (P<0.05). Conclusion Antibiotic intervention can up-regulate the expression of brown fat-related genes in high-fat diet mice, increase brown fat activity, increase the relative mitochondrial number of white fat, increase the level of browning of white fat, promote thermogenesis, increase the BMR per unit body weight of adult obese mice, and then improve the overall energy metabolism of the body, and slow down the weight gain induced by high-fat diet to a certain extent.
5.Incidence and influencing factors of depression in family caregivers of Alzheimer's disease patients: a meta-analysis
LIU Xingyu ; YANG Zhilan ; CUI Liping ; JIA Ming ; SHI Hongrui ; ZHAO Huimin ; YAN Zhili
Journal of Preventive Medicine 2024;36(4):322-327
Objective:
To systematically evaluate the incidence and influencing factors of depression in family caregivers of Alzheimer's disease (AD) patients, so as to provide the basis for the prevention and treatment of depression among the family caregivers of AD patients.
Methods:
Publications pertaining to depression in family caregivers of AD patients were retrieved from CNKI, Wanfang Data, PubMed and other databases from the time of their establishment to June 15, 2023. The evaluation criteria recommended by the Agency for Healthcare Research and Quality (AHRQ) and the Newcastle-Ottawa Scale were used to assess the quality of cross-sectional and cohort studies, respectively. Stata 16.0 and Revman 5.4 softwares were used to conduct a meta-analysis on the incidence and influencing factors of depression in family caregivers of AD patients. Sensitivity analysis and publication bias assessment were also performed on the results.
Results:
A total of 2 324 articles were retrieved, and ultimately 14 articles were included, with a total sample size of 8 313 individuals. There were 6 high-quality articles and 8 moderate-quality articles. Meta-analysis showed that the incidence of depression in family caregivers of AD patients was 37.5% (95%CI: 30.2%-45.1%). Factors associated with depression included patients' high degree of dementia (OR=1.718, 95%CI: 1.059-2.789), patients' low scores on Activities of Daily Living Scale (OR=1.344, 95%CI: 1.059-1.706), patients' psychobehavioral abnormalities (OR=1.248, 95%CI: 1.155-1.348), long duration of caregiving (OR=1.998, 95%CI: 1.637-2.437), less involvement of other family members in caregiving (OR=1.597, 95%CI: 1.237-2.061), low educational level (OR=1.191, 95%CI: 1.044-1.359), poor caregiving skills (OR=3.060, 95%CI: 2.257-4.149), poor self-rated health (OR=2.536, 95%CI: 1.114-5.771) and social support (OR=0.424, 95%CI: 0.232-0.774). The results of depression incidence demonstrated good stability with no significant publication bias. However, publication bias was observed in the influencing factors for depression, which were patients' high degree of dementia and patients' low scores on Activities of Daily Living Scale.
Conclusions
The incidence of depression in family caregivers of AD patients ranges from 30.2% to 45.1%. It is primarily influenced by the severity of patients' symptoms and ability to perform daily activities, and caregivers' educational level, caregiving skills, health status, caregiving duration and social support.
6.Influence of CICARE communication mode on patients with acute heart failure
Yin YU ; Yang-Hui CUI ; Ai-Xia LI ; Ming-Zhen DUAN
Chinese Journal of cardiovascular Rehabilitation Medicine 2024;33(1):89-93
Objective:To study influence of Connect-Introduce-Communicate-Ask-Respond-Exit(CICARE)communication mode on patients with acute heart failure(AHF).Methods:A total of 156 AHF patients treated in our hospital were randomly and equally divided into routine nursing group and CICARE group(received CICARE communication mode based on routine nursing group).Both groups were intervened for one month.General clinical data,hospitalization indexes,scores of Hamilton rating scale for depression(HAMD),Hamilton rating scale for anxiety(HAMA),general self-efficacy scale(GSES)and quality of life scale(QOL-35)before and after inter-vention and incidence of complications were compared between two groups.Results:Compared with routine nursing group,there were significant reductions in first aid time[(42.06±9.77)s vs.(20.27±3.77)s],visit time[(95.67±23.18)min vs.(50.07±11.21)min],admission time[(3.22±0.36)min vs.(2.60±0.67)min]and hospital stay[(22.33±4.82)d vs.(14.13±2.42)d];and scores of HAMD[(14.02±1.42)scores vs.(6.04± 1.57)scores]and HAMA[(13.24±2.07)scores vs.(7.16±2.17)scores]after intervention,and significant rise in scores of GSES[(14.25±3.14)scores vs.(32.03±6.06)scores]and QOL-35[(70.67±5.75)scores vs.(86.93±5.51)scores]in CICARE group after intervention(P=0.001 all).Incidence rate of complications in CICARE group was significantly lower than that of CICARE group(5.13%vs.20.51%,P=0.004).Conclusion:CICARE communication mode can significantly alleviate adverse emotions and improve self-efficacy in patients with acute heart failure.
7.Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine (version 2024)
Xiao CHEN ; Hao ZHANG ; Man WANG ; Guangchao WANG ; Jin CUI ; Wencai ZHANG ; Fengjin ZHOU ; Qiang YANG ; Guohui LIU ; Zhongmin SHI ; Lili YANG ; Zhiwei WANG ; Guixin SUN ; Biao CHENG ; Ming CAI ; Haodong LIN ; Hongxing SHEN ; Hao SHEN ; Yunfei ZHANG ; Fuxin WEI ; Feng NIU ; Chao FANG ; Huiwen CHEN ; Shaojun SONG ; Yong WANG ; Jun LIN ; Yuhai MA ; Wei CHEN ; Nan CHEN ; Zhiyong HOU ; Xin WANG ; Aiyuan WANG ; Zhen GENG ; Kainan LI ; Dongliang WANG ; Fanfu FANG ; Jiacan SU
Chinese Journal of Trauma 2024;40(3):193-205
Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.
8.Risk factors for recurrent intussusception in children after ultrasound-guided saline enema reduction
Xiangyu ZHANG ; Heying YANG ; Yan'an LI ; Ming YUE ; Fei GUO ; Mingxia CUI ; Dazhi REN ; Yan LI ; Beibei SUN
Chinese Journal of General Surgery 2024;39(2):126-130
Objective:To explore the risk factors for recurrence of intussusception in children after successful ultrasound-guided saline enema reduction.Methods:The clinical and follow up data of 355 hospitalized children with intussusception at the First Affiliated Hospital of Zhengzhou University from Feb 2018 to Feb 2023 were reviewed.Patients were divided into two groups by recurrence develped and the differences were compared, Data with significant differences were incorporated into multi-factor logistic analysis.Results:The overall recurrence rate was 15.8% (56/355). By univariate variable analysis model, there were statistically significant differences between the two groups in age, previous intussusception history, vomiting, maximum diameter of concentric circles shown by ultrasound, and concurrent bowel organic diseases (lead points) (all P<0.05). In multivariate Logistic regression model, age, previous intussusception history, maximum diameter of concentric circles, and lead points were independent risk factors for recurrent intussusception after saline enema.The optimal cut-off values for age and maximum diameter of concentric circles were 2 years and 33.5 mm, respectively, according to ROC curve analysis. Conclusion:Age older than 2 years, previous intussusception history, maximum diameter of concentric circles longer than 33.5 mm, and lead points are independent risk factors for recurrence after saline enema.
9. Study on spleen strengthening effects and mechanisms of Atractylodes chinensis and Atractylodes coreana
Ming-Yang CUI ; Yi-Hui DING ; Yang QU ; Zhi-Li XU ; Qian CAI
Chinese Pharmacological Bulletin 2024;40(1):181-188
Aim To analyze the differences in plasma biomarkers and metabolic pathways between Atractylodes chinensis and Atractylodes coreana after intervention in spleen deficiency rats, and discuss the spleen strengthening mechanism of the two from a non targeted metabolomics perspective. Methods A spleen deficiency model was established in SD rats using a composite factor method of improper diet, excessive fatigue, and bitter cold diarrhea. To determine the content of gastrointestinal and immunological indicators, UHPLC-QE-MS technology was used, combined with principal component analysis (PC A) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA) methods to search for biomarkers in plasma of spleen deficiency rats, and metabolic pathways were induced using the Pathway database. Results After administration of Atractylodes chinensis and Atractylodes coreana, various indicators in plasma of spleen deficiency rats showed varying degrees of regression. Metabolomics analysis showed that Atractylodes chinensis and Atractylodes coreana respectively recalled 70 and 82 plasma differential metabolites. Atractylodes chinensis mainly regulated two metabolic pathways : "Glycine, serine, and threonine metabolism, and "Thiamine metabolism". Atractylodes coreana mainly regulated five metabolic pathways, "Glycine, serine, and threonine metabolism", "Thiamine metabolism, "Pyrimidine metabolism", "Butanoate metabolism", and "Riboflavin metabolism". Conclusions Both Atractylodes chinensis and Atractylodes coreana have certain regulatory effects on spleen deficiency rats, and their mechanism of action may be related to regulating metabolic pathways such as "Glycine, serine, and threonine metabolism, and "Thiamine metabolism"in spleen deficiency.
10.Aptasensor for Detection of Small Molecules Based on Displacement Fluorescent Probe
Cheng YANG ; Sheng-Nan CUI ; Yue WANG ; Guo-Feng WANG ; Cheng-Ming LI ; Shuang-Chao GU ; Chang-Ying XUE
Chinese Journal of Analytical Chemistry 2024;52(5):674-684,中插10-中插13
By using thioflavin T(ThT)as displacement-based fluorescent probes,three kinds of aptasensors were constructed for rapid detection of three kinds of small molecules such as ochratoxin A(OTA),aflatoxin B1(AFB1)and adenosine.In the absence of target molecule,ThT bound with the aptamer to form an aptamer-ThT complex and exhibited a significant fluorescence response.Upon the addition of target molecule,because of the higher affinity between target and aptamer than that between ThT and the aptamer,ThT was displaced by the target molecule from the aptamer-ThT complex,resulting in weakened fluorescence signal.Based on this principle,the target molecule could be detected quantitatively.Further study through circular dichroism spectra showed that there was no significant change in the conformation of the aptamer after addition of ThT or target molecules.The stoichiometric ratios of ThT to OTAapt,AFB1apt and Adeapt measured through the method of equimolar continuous variation was 1∶1,1∶1 and 2∶1,respectively,and their dissociation constants were all larger than those between the target molecule and its aptamer.Therefore,the principle of this detection method was the displacement of fluorescent probe(ThT)in aptamer-ThT complex by target molecule,resulting in decrease of fluorescence intensity.Under optimal experimental conditions,the limits of detection(LODs)were 0.8 nmol/L for OTA,1.3 nmol/L for AFB1,and 0.10 μmol/L for adenosine,respectively.This method was label-free,simple to operate,with low cost,good selectivity and high sensitivity.The developed assay kit based on this method could be used for actual sample detection.


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