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.Quantitative CT measurement of bone mass density in different regions of the distal clavicle in reconstruction of acromioclavicular joint dislocation
Jian XU ; Wenzhi BI ; Yuncong JI ; Yunkang KANG ; Peiqi MA ; Jialiang WANG ; Zongxi ZHANG ; Fusheng GAN ; Haiyang YU ; Biao GUO
Chinese Journal of Tissue Engineering Research 2024;28(12):1920-1924
BACKGROUND:There is no consensus on the optimal bone tunnel position in the lateral clavicle,which guides coracoclavicular ligament reconstruction.Postoperative complications such as enlargement of the lateral clavicle bone tunnel,bone osteolysis,clavicle fracture,and failure of internal fixation are likely to occur.Bone mass density plays an important role in the strength and stability of endophytic fixation.Regional differences in the bone mass density of the distal clavicle should not be overlooked in the repair and reconstruction of acromioclavicular dislocation.Currently,there are no quantitative clinical studies in humans regarding the bone mass density of the distal clavicle. OBJECTIVE:To measure the magnitude of bone mass density in different regions of the distal clavicle by quantitative CT to provide a reference for surgeons to repair and reconstruct the coracoclavicular ligament. METHODS:101 patients undergoing quantitative CT checking in Fuyang People's Hospital Affiliated to Anhui Medical University from October to December 2022 were enrolled,from which 1 616 samples of subdivisional bone mass density of the distal clavicle were measured.For each of the quantitative CT samples,firstly,the distal clavicle was divided medially to laterally into the following four regions:conical nodal region(region A),inter-nodal region(region B),oblique crest region(region C)and distal clavicular region(region D).Secondly,each region was divided into the first half and the second half to determine eight subdivisions,then setting semiautomatic region of interest(ROI)in each subdivision:(ROI A1,A2,B1,B2,C1,C2,D1,and D2).Thirdly,each quantitative CT scan was transferred to the quantitative CT pro analysis workstation,and cancellous bone mass density was measured in the distal clavicle ROI.Finally,the clavicular cortex was avoided when measuring. RESULTS AND CONCLUSION:(1)There was no statistically significant difference in bone mineral density on the different sides of the shoulder(P>0.05).(2)The analysis of bone mineral density in eight sub-areas of the distal clavicle A1,A2,B1,B2,C1,C2,D1,and D2 showed statistically significant differences(P<0.05).It could be considered that there were differences in bone mineral density in different areas of the distal clavicle.After pairwise comparison,there was no statistically significant difference in bone mineral density between A1 and A2,D1 and D2,A2 and B1(P>0.05),and there was a statistically significant difference in bone mineral density between the other sub-areas(P<0.05).(3)The bone mineral density in the region A2 of the anatomical insertion of the conical ligament was significantly higher than that in the inter-nodular area(region B)(P<0.05).The bone mineral density in the region A1 was higher than that in the region A2,but the difference was not statistically significant(P>0.05).The bone mineral density in the region C1 of the anatomical insertion of the trapezium ligament was higher than that in regions C2,D1 and D2,and the bone mineral density in the inter-nodular area(region B)was significantly higher than that in regions C and D(P<0.05).(4)These results have suggested that there are differences in bone mass density in different regions of the distal clavicle;regional differences in bone mass density in the distal clavicle during repair and reconstruction of acromioclavicular dislocation cannot be ignored.Consideration should be given not only to biomechanical factors but also to the placement of implants or bone tunnels in regions of higher bone mass density,which could improve the strength and stability of implant fixation and reduce the risk of complications such as bone tunnel enlargement,osteolysis,fracture and implant failure.
3.Virulence determinants and genetic diversity of foodborne Yersinia enterocolitica isolated from Wenzhou
Ai-Rong XIE ; Yi LI ; Hui-Huang LOU ; Zhong-Bi XIE ; Le-Yi ZHANG ; Yu-Qin HU ; Yue-Jin WU
Chinese Journal of Zoonoses 2024;40(1):40-45
The aim of this study was to investigate the virulence determinants and genetic diversity of foodborne Yersinia enterocolitica from Wenzhou.A total of 71 strains of Yersinia enterocolitica were isolated from food and foodborne diarrhea ca-ses in Wenzhou,and their biotypes,serotypes,and drug resistance were analyzed.On the basis of whole genome sequencing,we assessed virulence gene profiles,and performed multilocus sequence typing(MLST)and core gene multilocus sequence typ-ing(cgMLST).A total of 94.4%(67/71)of isolates belonged to biotype 1A,and the highest proportion had serotype lA/O∶5(29.6%,21/71).The sensitivity rates of the isolates to 14 antibiotics exceeded 95.8%.A total of 16 categories and 126 viru-lence genes were identified,with two strains carrying the pYV plasmid and chromosome-related virulence genes.ST3(31.6%,12/38)was the most widespread MLST type,and cgMLST analysis revealed no dense clusters of genotypes except for strains sharing the same ST.In conclusion,pathogenic strains were identified from foodborne Yersinia enterocolitica in Wenzhou and were found to exhibit high genetic polymorphism.Enhanced regulatory supervision is essential to prevent the outbreak of food-borne diseases caused by Yersinia enterocolitica.
4.Current status and influencing factors of fear of surgery in patients with oral and maxillofacial tumors
Yu ZHANG ; Lixia KUANG ; Xiaoqin BI ; Xueli ZHAN ; Tianyu ZHANG
West China Journal of Stomatology 2024;42(4):494-501
Objective This study aimed to investigate the incidence and severity of surgical fear in patients with oral and maxillofacial tumors.Methods The survey participants were composed of patients with oral and maxillofacial tu-mors,who were scheduled to undergo surgery.A general information questionnaire,the Surgical Fear Questionnaire(SFQ),the Patient Health Questionnaire(PHQ)-9,and the Generalized Anxiety Disorder(GAD)-7 score were used for the investigation.Results A total of 203 patients were investigated.Among them,85.22%had fear of surgery.The me-dian score of SFQ was 20,and the quartile was(6,36).The patients were categorized into none,mild,moderate,and severe groups according fear level.Gender,diabetes,obvious discomfort before surgery,PHQ-9,and GAD-7 scores were the variables with statistical difference in each fear level.Multifactor analysis showed that women were more likely to have moderate and severe fear than men(OR=2.19,P=0.03;OR=2.72,P=0.01),patients with obvious preoperative discomfort symptoms were more inclined to have no fear(OR=4.73,P=0.02),and patients with diabetes were more likely to have severe fear(OR=3.33,P=0.02).The incidence rates of depression and anxiety were 31.03%and 24.63%,respectively.The incidence of anxiety and de-pression in patients with severe fear was 40.00%.Surgical fear was moderately positively correlated with anxiety(r=0.491,P<0.001)and depression(r=0.514,P<0.001).Conclusion The fear of surgery in patients with oral and maxillo-facial tumors is common and distributed in all levels.Medical staff can screen and assess patients with moderate and se-vere fear of surgery in accordance with the influencing factors and implement targeted interventions to reduce fear of sur-gery,anxiety,and depression on the basis of the source of fear.
5.The development of a framework on the need for elderly healthcare guidelines in China and related issues
Bi ZHANG ; Lingling YU ; Qiang GAO ; Pengjun ZHANG
Chinese Journal of Geriatrics 2024;43(9):1131-1136
Objective:Based on the serious situation of population aging and the need for geriatric healthcare guidelines in China, we constructed a framework on the need for national geriatric care guidelines and conducted relevant analysis, aiming to provide a reference for the formulation of guidelines for geriatric care.Methods:Literature review and expert consultations were used to construct a framework on the need for guidelines on geriatric care in China.Twenty-two experts were invited to form a consultation group, and two rounds of expert consultations and discussions were carried out using the Delphi method to update and adjust the framework.Hierarchical analysis was used to calculate the weight of each guideline direction.Results:A framework on the need for geriatric healthcare guidelines was developed, containing 7 first-level directions and 35 second-level directions, and the weights of the directions were derived, with the direction of guidelines on geriatric syndromes having the highest weight at 0.204, and the direction of guidelines on geriatric disease diagnosis and treatment having the second highest weight at 0.196.Conclusions:A preliminary framework on the need for geriatric healthcare guidelines has been established.It is fitting for the country's general conditions, takes into account the needs from multiple perspectives, has good coverage, and can be expected to solve a range of difficult and urgent issues in geriatric care and help promote the development of a set of high-quality guidelines in the field of geriatric healthcare.
6.Rosmarinic acid ameliorates acute liver injury by activating NRF2 and inhibiting ROS/TXNIP/NLRP3 signal pathway
Jun-fu ZHOU ; Xin-yan DAI ; Hui LI ; Yu-juan WANG ; Li-du SHEN ; DU Xiao-bi A ; Shi-ying ZHANG ; Jia-cheng GUO ; Heng-xiu YAN
Acta Pharmaceutica Sinica 2024;59(6):1664-1673
Acute liver injury (ALI) is one of the common severe diseases in clinic, which is characterized by redox imbalance and inflammatory storm. Untimely treatment can easily lead to liver failure and even death. Rosmarinic acid (RA) has been proved to have anti-inflammatory and antioxidant activity, but it is not clear how to protect ALI through antioxidation and inhibition of inflammation. Therefore, this study explored the therapeutic effect and molecular mechanism of RA on ALI through
7.Effects of Different Proportions of Astragali Radix and Chuanxiong Rhizoma on the Extraction Kinetics of Flavonoids
Yu ZHANG ; Manyue ZHANG ; Yun BI ; Yali ZHAO ; Jingmei SONG ; Yuyan ZHANG
Chinese Journal of Modern Applied Pharmacy 2024;41(9):1192-1197
OBJECTIVE
To study the effect of different proportion compatibility of Astragali Radix and Chuanxiong Rhizoma on the extraction kinetics of flavonoids.
METHODS
The content determination method of flavonoids(with rutin as the control substance) was established, and the concentrations of flavonoids in the extracts of Astragali Radix membranicum and Chuanxiong Rhizoma in different proportions(1∶1, 1∶2, 1∶3, 1∶4, 1∶5, 2∶1, 3∶1, 4∶1, 5∶1) were determined dynamically within 2 h, respectively. The extraction kinetics model was established according to Feck's first diffusion law. The extraction rate constant was calculated and the difference of dissolution kinetics was compared.
RESULTS
The compatibility of different proportions of Astragali Radix and Chuanxiong Rhizoma had significant effects on the extraction rate and concentration of flavonoids. The extraction kinetics models of flavonoids were consistent with the characteristics of the first-order kinetic equation. The extraction rate was the fastest when Astragali Radix ∶ Chuanxiong Rhizoma was 3∶1, the extraction rate was the slowest when Chuanxiong Rhizoma∶ Astragali Radix was 2∶1. The equilibrium concentration of flavonoids was the highest when Chuanxiong Rhizoma∶ Astragali Radix was 3∶1, when the ratio of Astragali Radix∶Chuanxiong Rhizoma was 5∶1, it was the lowest.
CONCLUSION
The compatibility of different proportions of Astragali Radix and Chuanxiong Rhizoma has a significant effect on the extraction rate and concentration of flavonoids.
8.Clinical efficacy of endovascular interventional therapy for spontaneous isolated superior mesen-teric artery dissection
Yu LI ; Rongjie ZHANG ; Wei SUN ; Yuxuan XIAO ; Xianru BI ; Yingxue HAO
Chinese Journal of Digestive Surgery 2024;23(6):845-852
Objective:To investigate the clinical efficacy of endovascular interventional therapy for spontaneous isolated superior mesenteric artery dissection(SISMAD).Methods:The retrospective cohort study was conducted. The clinical data of 87 patients with SISMAD who were admitted to The First Affiliated Hospital of Army Medical University from March 2012 to March 2023 were collected. There were 80 males and 7 femals, aged 54(49,61)years. Of 87 patients, 55 cases undergoing conservative therapy were allocated into conservative therapy group and 32 cases under-going endovascular interventional therapy were allocated into endovascular interventional therapy group. Observation indicators: (1) clinical characteristics; (2) treatment; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were represented as absolute numbers and comparison between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) clinical characteristics. There were significant differences in the cases with symptoms, percentage of neutrophils between the conservative therapy group and the endovascular interventional therapy group ( P<0.05). There was no significant difference in the proportion of Yun classification between the two groups ( P>0.05). (2)Treatment. There were significant differences in the complete vascular remodeling, duration of hospital stay, and total expenses between the conservative therapy group and the endovascular interventional therapy group ( χ2=23.752, t=-4.213, -16.421, P<0.05). There were 34 patients in the conservative therapy group and 24 patients in the endovascular interventional therapy group with relieved abdominal pain, respectively, showing no significant difference between the two groups ( P>0.05). For symptomatic patients in the conservative therapy group, symptoms including abdominal pain, nausea, vomiting, diarrhea, hematochezia were relieved or disappeared, and no intestinal ischemia or rupture occurred. For patients in the endovascular interventional therapy group, 30 cases were implanted stents, the operation time was 115(86,155)minutes, volume of intraoperative blood loss was 5(5,10)mL, dose of contrast media was (200±51)mL. There were 23, 8 and 1 cases with the contrast medium as Iodoxanol, Ioprosamide, Iodohexanol, respectively. About the surgical methods, 14 patients received single bare stent implantation, 3 cases received bare stent-assisted coil embolization, 10 cases received multiple bare stent implantation, 3 cases received covered stent implantation, 2 cases received angiography alone. A total of 39 self-expandable bare metal stents and 3 self-expandable covered stents were implanted. The diameter and length of the stents were (6.5±1.0)mm and (69±23)mm, respectively. Two asymptomatic patients had failure in endovascular interventional therapy and underwent superior mesenteric artery angiography. For the endovascular interventional therapy group, 92.3%(24/26) of patients were relieved abdominal pain and 2 patients with abdominal pain were improved after symptomatic treatment. (3) Follow-up. All the 87 patients were followed up for 12(4,24)months, without recurrent abdominal pain or secondary intervention. During the follow-up, 82 patients underwent computed tomography angiography or ultrasonography, and 5 patients had no available results. There was no SISMAD related death or superior mesenteric artery rupture. Eight patients in the conservative therapy group achieved complete vascular remodeling, versus 21 cases in the endovascular interventional therapy group, showing a significant difference between the two groups ( χ2=23.752, P<0.05). Conclusions:Compared with conservative therapy, patients undergoing endovascular interventional therapy for SISMAD has loner hospital stay, higher total costs, higher complete vascular remodeling rate. There is no recurrent abdominal pain in two methods.
9.Thoughts and suggestions on digital services to enhance the level of vaccination management
Lin LUAN ; Na LIU ; Benfeng ZHENG ; Zhuoyu ZHANG ; Yifan SONG ; Li LI ; Ming GAN ; Lei CAO ; Zhuoying HUANG ; Jiakai YE ; Zhaonan ZHANG ; Xiaoxue LIU ; Junlei CHEN ; Changshuang WANG ; Bi CAI ; Wenzhou YU
Chinese Journal of Preventive Medicine 2024;58(2):159-165
With the development of information technology and the increasing demand for vaccination services among the people, it is a definite trend to enhance the quality of vaccination services through digitization. This article starts with a clear concept of digital services for vaccination, introduces the current development status in China and abroad, analyzes the advantages and disadvantages of existing models in leading regions, takes a glean from the summation, and proposes targeted solutions. This study suggests establishing a departmental coordination mechanism for data interconnection and sharing, formulating data standards and functional specifications, enhancing the functionalities of the immunization planning information system, strengthening data collection and analytical usage, and intensifying appointment management and science and health education to provide expert guidance for the construction of digital vaccination services across the country in the future.
10.Tildrakizumab for moderate-to-severe plaque psoriasis in Chinese patients: A 12-week randomized placebo-controlled phase III trial with long-term extension
Chen YU ; Songmei GENG ; Bin YANG ; Yunhua DENG ; Fuqiu LI ; Xiaojing KANG ; Mingye BI ; Furen ZHANG ; Yi ZHAO ; Weili PAN ; Zhongwei TIAN ; Jinhua XU ; Zhenghua ZHANG ; Nan YU ; Xinsuo DUAN ; Shuping GUO ; Qing SUN ; Weiquan LI ; Juan TAO ; Zhijun LIU ; Yuanyuan YIN ; Gang WANG
Chinese Medical Journal 2024;137(10):1190-1198
Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.


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