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.A Meta-analysis of radiomics in differential diagnosis of small cell lung cancer and non-small cell lung cancer
Fujun YANG ; Fang SHEN ; Xiaoyang BI ; Yanlong TANG
Journal of Practical Radiology 2024;40(4):552-556
Objective To explore the value of radiomics in differential diagnosis of small cell lung cancer(SCLC)and non-small cell lung cancer(NSCLC).Methods Literature on the differential diagnosis of SCLC and NSCLC using radiomics was searched in Chinese and English databases.After literature screening and data extraction,Meta-DiSc1.4 and State16.0 SE software were used for analysis.Results A total of 910 patients were included in 8 studies.Meta-analysis results showed that the radiomics differential diag-nosis of SCLC and NSCLC had high co-sensitivity(Sen)and specificity(Spe),0.87[95%confidence interval(CI)0.83-0.91]and 0.88(95%CI 0.85-0.90),respectively.Meta-regression analysis showed that heterogeneity was not caused by feature extraction software type,joint machine learning,image pattern,brain metastasis,and sample size.Publication bias results didn't show any sig-nificant publication bias.Conclusion The radiomics method can differentiate and diagnose SCLC from NSCLC more accurately.When Matlab software is used to extract MRI image features combined with machine learning,and the sample size is large enough,the radiomics can differentiate and diagnose SCLC from NSCLC more accurately.
3.Role of intestinal flora in hypertension complicated with osteoporosis
Mei-Long SI ; Hua JIN ; Min-Ke LIU ; Shuang-Fang LIU ; Bi-Shi LING ; Shang-Wen QI ; Xue-Li MA
The Chinese Journal of Clinical Pharmacology 2024;40(3):449-453
Hypertension and osteoporosis(OP)are common diseases in middle-aged and elderly people,and the number of patients with both diseases has gradually increased in recent years.Because the onset of the disease is hidden,it is easy to cause fractures and serious complications of heart,brain and kidney in the later stage,which not only seriously damages the quality of life of patients,but also increases the difficulty of clinical treatment.Therefore,it is particularly necessary to strengthen the research on this disease.More and more studies have found that the disorder of intestinal flora will lead to the occurrence of OP,while the intestinal flora of patients with hypertension is obviously out of balance.Therefore,this paper thinks that intestinal flora may be the key influencing factor of hypertension complicated with OP,and the imbalance of intestinal flora will lead to the imbalance of short-chain fatty acid metabolism,immune inflammatory reaction and increased sympathetic nerve activity,thus causing the imbalance of bone homeostasis and promoting the occurrence of OP.Therefore,it is suggested that regulating intestinal flora may be a new way to intervene hypertension complicated with OP.
4.Effects of Zhengan Xifeng decoction on bile acid spectrum of bile and sterol 12 α hydroxylase in spontaneously hypertensive rats
Bi-Shi LING ; Hua JIN ; Shang-Wen QI ; Shuang-Fang LIU ; Zhi-Jun LIU
The Chinese Journal of Clinical Pharmacology 2024;40(15):2212-2216
Objective To observe the effects of Zhengan Xifeng decoction on bile acid spectrum of bile and sterol 12α hydroxylase(CYP8B1)in spontaneously hypertensive rats(SHR).Methods Fifty SHR were randomly divided into model group,control group(1.0 mg·kg-1·d-1 benazepril by gavage)and experimental-L,-M,-H groups(8.63,17.25 and 34.50 g·kg-1·d-1 Zhengan Xifeng decoction by gavage),another 10 homologous male Wistar-Kyoto(WKY)rats were taken as the normal group.The model group and the normal group were given the same amount of distilled water.The rats in the 6 groups were administered once a day for 8 weeks.The animal non-invasive sphygmomanometer was used to measure the blood pressure of rats in each group by tail-cuff method;the bile acid spectrum of rats in each group was detected by UPLC-MS/MS;the expression of CYP8B1 mRNA in rat liver tissue was detected by real-time fluorescence quantitative polymerase chain reaction.Results The systolic blood pressure at the 8th week of the experimental-M,-H groups,control group,model group,normal group were(169.63±12.10),(170.32±9.64),(175.95±15.47),(189.47±7.42)and(146.40±9.45)mmHg;the diastolic blood pressure at the 8th week were(135.10±11.99),(129.73±15.10),(135.18±17.62),(149.20±8.83)and(110.53±10.92)mmHg;the relative expression levels of CYP8B1 mRNA were 3.36±0.94,5.45±1.46,4.29±0.95,0.89±0.14 and 1.00±0.00,respectively.Compared with the model group,the above indexes in the experimental-M,-H groups were statistically significant(P<0.01,P<0.05).Compared with the model group,the bile acid spectrum of experimental-L,-M,-H groups bile changed significantly,and a total of 9 different bile acids were found,which were hyodeoxycholic acid,glycohyodeoxycholic acid,glycochenodeoxycholic acid,glycoursodeoxycholic acid,α-muricholic acid,ursodeoxycholic acid,cholic acid,β-muricholic acid and glycocholic acid.Conclusion Zhengan Xifeng decoction may correct bile acid spectrum disorder of bile and reduce blood pressure by up-regulating liver CYP8B1 expression.
5.Statistical methods for extremely unbalanced data in genome-wide association study (1)
Ning XIE ; Wenjian BI ; Zhongwen ZHANG ; Fang SHAO ; Yongyue WEI ; Yang ZHAO ; Ruyang ZHANG ; Feng CHEN
Chinese Journal of Epidemiology 2024;45(11):1582-1589
Extremely unbalanced data here refers to datasets where the values of independent or dependent variables exhibit severe unbalance in proportions, such as extremely unbalanced case-control ratio, very low incidence rate of disease, heavily censored time-to-event data, and low-frequency or rare variants. In such scenarios, the statistic derived from hypothesis test using the classical statistical method, e.g., logistic regression model and Cox proportional hazard regression model, might deviate from theoretical asymptotic distribution, resulting in inflation or deflation of type I error. With the increased availability and exploration of resources from large-scale population cohorts in genome-wide association study (GWAS), there is a growing demand for effective and accurate statistical approaches to handle extremely unbalanced data in independent and non-independent samples. Our study introduces classical statistical methods in genetic statistics firstly, then, summarizes the failure of classical statistical methods in dealing with extremely unbalanced data through simulation experiments to draw researchers' attention to the extremely unbalanced data in GWAS.
6.Application of Bi's intestinal loop binding in treating patients with critical esophagojejunal anastomosis leakage
Baoqing REN ; Zhiqiang FANG ; Xiaogang BI
Chinese Journal of Gastrointestinal Surgery 2024;27(5):507-510
Objective:To assess the safety and feasibility of Bi's intestinal loop binding treatment of esophageal jejunal anastomotic leak after total gastrectomy.Methods:Bi's Intestinal loop binding are suitable for patients who underwent radical total gastrectomy+Roux-en-Y anastomosis and were confirmed by upper gastrointestinal angiography to have esophageal jejunal anastomotic leakage and whose conservative or endoscopic treatment was ineffective. The operation procedure is as follows: take the original central incision of the upper abdomen, remove the abscess around the anastomoses after ventral incision, and place drainage tube inside the abscess, which is convenient to rinse and drain after operation. A double 1-0 VICRYL is applied to the loop of gastrointestinal surrogate 10-15 cm proximal to the jejuno-jejunal anastomosis. The knot tension is tight to prevent regurgitation of digestive juices, but too much force should be avoided to cut the intestinal tract. Nutritional jejunostomy fistula was performed at 10?15 cm distal to the jejuno-jejunal anastomosis and gastric tube was retained during the operation. The preoperative and postoperative data from 12 patients with jejunal esophageal anastomotic leak after total radical gastrectomy and Roux-en-Y anastomosis were retrospectively analyzed from October 2016 to January 2023 in gastrointestinal surgery and pancreas surgery at Shanxi People's Hospital, and observed the curative effect.Results:12 patients were managed with Bi's Intestinal loop binding, operative time (60.0±20.8) minutes, median bleeding (50±10.8) ml, median hospital stay 20(12~28) days, and median reviewing upper and mid Gastrointestinal Contrast time postoperatively 61(52~74) days. The results showed that the anastomoses healed well, all the small intestine showed good imaging, the binding wire fell off by itself, and two patients had incision infection.Conclusions:It is safe and feasible for patients with esophageal jejunostomy fistulae after total gastrectomy to use the method of Bi's Intestinal loop binding.
7.Tracking observation of fine motor development in children aged 6-8 with attention deficit hyperactivity disorder
Chinese Journal of School Health 2024;45(6):831-834
Objective:
To examine the developmental trajectory of fine motor ability in schoolage children with attention deficit hyperactivity disorder (ADHD) for two years, so as to provide scientific evidence to promote motor development in ADHD children.
Methods:
From April to June 2019, 31 children aged 6-8 years old were selected from a public elementary school. They were diagnosed with ADHD by two psychiatric professionals according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria. Additionally, 31 typical developmental children, matched for age, sex and IQ with the ADHD group, were recruited as the control group. Fine motor ability was assessed with tasks of hand manual dexterity in Movement Assessment Battery for Children-2 (MACB-2), and a followup assessment was conducted from April to June 2021. The development changes of fine motor ability between two groups of children were compared by using t test and repeated measures analysis of variance.
Results:
Between baseline and followup periods after two years, the total score of hand fine motor in the ADHD group did not show significant improvement (7.4±3.0, 8.0±3.4; t=-1.05, P>0.05), while there was a small effect size improvement in typically developing control group (9.5±2.1, 10.5±2.4; t=-2.12, effect size=0.38, P<0.05). Followup after two years, coin/peg throwing scores with dominant hand improved between ADHD group and control group (7.0±3.3, 9.5±3.2; 8.4±2.8, 11.6±1.6) (t=-3.74, -6.33, P<0.01; effect size=0.67, 1.14), with a smaller improvement in the ADHD group. The score for threading beads/threads decreased in between ADHD group and control group (7.9±2.4, 5.8±3.1; 9.2±1.1, 8.2±1.9) (t=3.89, 2.78, P<0.01; effect size=0.70, 0.50), with a greater decrease in the ADHD group.
Conclusions
The development speed of fine motor ability in children with ADHD aged 6-8 is slow and continues to lag behind normal developmental children. Fine motor development in children with ADHD should be closely monitored, and targeted interventions should be implemented when necessary.
8.KCNQ3 gene mutation-associated familial cortical myoclonic tremor and epilepsy:A family case report and litera-ture review
Fang WANG ; Bi WANG ; Xiaoli WANG
Journal of Apoplexy and Nervous Diseases 2024;41(8):735-740
Objective To study the clinical,electrophysiological,and genetic characteristics of familial cortical myoclonic tremor and epilepsy(FCMTE),and to review relevant literature for the potential pathogenic genes of the dis-ease.Methods We analyzed the clinical presentations and neuroelectrophysiological and second-generation whole exome gene sequencing results of a patient with FCMTE and her family members.Results The 72-year-old female proband com-plained of paroxysmal tremor of the upper limbs for more than 30 years and convulsions of the upper and lower limbs for 13 years.The somatosensory evoked potential test showed large potentials.Video electroencephalography detected a pattern of sharp waves with fast waves at 7-8 Hz during attacks.She was diagnosed as FCMTE.The symptoms almost disappeared after treatment with sodium valproate.The condition occurred across the three successive generations of the family.Next-generation whole exome sequencing detected a heterozygous mutation each in the exon region of the GFAP gene and KCNQ3 gene.Protein stability analysis found that the two variants had no significant effects on the spatial structures of the proteins encoded by the GFAP gene and KCNQ3 gene.Conclusion FCMTE features an autosomal dominant inheritance pattern,and presents in adulthood with tremor and/or epileptic seizures.KCNQ3 mutations may be implicated in the patho-genesis of this disease.
9.Antibacterial activity of turmeric (Curcuma longa L ) extract and effect on bacterial cell membranes
Lu HAN ; Chao ZHOU ; Xiu-fang BI ; Mei-gui HUANG ; Gang HAO
Acta Pharmaceutica Sinica 2024;59(8):2265-2272
In the present study, the antibacterial spectrum of turmeric extract was analyzed by measuring the minimum inhibitory concentration (MIC), and the antibacterial mechanism of turmeric extract was elaborated by determining its effects on the permeability and integrity of the cytoplasmic membrane, energy metabolism, and the morphology of the tested bacteria (
10.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.


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