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.Maintenance and improvement program for WYD2000 field surgical lamp
Ming-Ming ZHU ; Ji-Su CAO ; Ze-Rui ZHANG ; Jiang-Hui HAO ; Rui-Zhe WANG ; Feng ZHOU ; Lu-Chuan XUN
Chinese Medical Equipment Journal 2024;45(4):116-118
The steps for installation and withdrawal of WYD2000 field surgical lamp were introduced.The failures and causes of broken cross-arm connector of WYD2000 field surgical lamp were analyzed.The problems of WYD2000 field surgical lamp in vulnerability to breaking and difficulty in maintenance were solved by designing and manufacturing a special maintenance tool and optimizing the materials and fixing mode of cross-arm connection.References were provided for main-tenance and improvement of WYD2000 field surgical lamp.[Chinese Medical Equipment Journal,2024,45(4):116-118]
3.Morphological study of GABAergic neurons in the ventral zona incerta of mice involved in chronic itch
Shihao PENG ; Ze FAN ; Ziyi DAI ; Yiwen ZHANG ; Xiaotong SHI ; Yuanyuan ZHU ; Shengxi WU ; Jing HUANG
Chinese Journal of Neuroanatomy 2024;40(1):1-8
Objective:To detect itching,anxiety,depression behaviors in chronic itch models of mice and observe the activation of γ-aminobutiric acid(GABA)neurons in the ventral sector of the zona incerta(ZIv),and provide mor-phological evidence for their involvement in the modulation of itch information.Methods:Diphenylcyclopropenone(DCP)was used in glutamic acid decarboxylase 67-green fluorescent protein(GAD67-GFP)knock-in mice to establish chronic itch model.Itch behaviors were detected by video tracking system to verify whether the models were successfully established.The anxiety,depression behaviors of chronic itch model mice were detected by using elevated plus maze test(EPM)and tail suspention test(TST).By using GAD67-GFP mice,the distribution of GABAergic neurons in va-rious sectors of the zona incerta(ZI)was observed.And combined with immunofluorescence staining method,double labeling of GABAergic neurons with FOS in ZIv were observed respectively in control and DCP group mice.Results:In brain slices of GAD67-GFP mice,GABAergic neurons can be observed within all sectors of ZI and are more concentrat-ed in ZIv.Compared with control group mice,DCP group mice showed a significant increase in the bouts of scratching(P<0.001).The time of immobility in TST was significantly higher in DCP group mice than in control group mice,which displayed depression-like behavior.The EPM test showed that the numbers of entries and proportion of time in the cross region in DCP group mice were less than in control group mice.EPM test revealed that DCP group mice exhibited anxiety-like behavior.The results of immunofluorescence staining showed that the number of FOS-positive cells in ZIv was significantly higher in DCP group mice than in control group mice,and abundant co-labeled neurons of FOS and GABAergic neurons were observed in ZIv.Conclusion:GABAergic neurons were predominantly distributed in ZI,and were more concentrated in ZIv.The activation of GABAergic neurons in ZIv of DCP group mice provides morphological evidence on the involvement of GABAergic neurons in chronic itch and associated negative emotions.
4.A Case Report of Multidisciplinary Diagnosis and Treatment of a Patient with Tuberous Sclerosis Complex and Multi-Organ Involvement
Hua ZHENG ; Yunfei ZHI ; Lujing YING ; Lan ZHU ; Mingliang JI ; Ze LIANG ; Jiangshan WANG ; Haifeng SHI ; Weihong ZHANG ; Mengsu XIAO ; Yushi ZHANG ; Kaifeng XU ; Zhaohui LU ; Yaping LIU ; Ruiyi XU ; Huijuan ZHU ; Li WEN ; Yan ZHANG ; Gang CHEN ; Limeng CHEN
JOURNAL OF RARE DISEASES 2024;3(1):79-86
Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.
5.Research progress on drug resistance mechanism of sorafenib in radioiodine refractory differentiated thyroid cancer
En-Tao ZHANG ; Hao-Nan ZHU ; Zheng-Ze WEN ; Cen-Hui ZHANG ; Yi-Huan ZHAO ; Ying-Jie MAO ; Jun-Pu WU ; Yu-Cheng JIN ; Xin JIN
The Chinese Journal of Clinical Pharmacology 2024;40(13):1986-1990
Most patients with differentiated thyroid cancer have a good prognosis after radioiodine-131 therapy,but a small number of patients are insensitive to radioiodine-131 therapy and even continue to develop disease.At present,some targeted drugs can improve progression-free survival in patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC),such as sorafenib and levatinib,have been approved for the treatment of RAIR-DTC.However,due to the presence of primary and acquired drug resistance,drug efficacy in these patients is unsatisfactory.This review introduces the acquired drug resistance mechanism of sorafenib in the regulation of mitogen-activated protein kinase(MAPK)and phosphatidylinositol-3-kinase(PI3K)pathways and proposes related treatment strategies,in order to provide a reference for similar drug resistance mechanism of sorafenib and effective treatment of RAIR-DTC.
6.Research status in application and safety research of preventive human papillomavirus vaccine
Yang LUO ; Xiao-Rui WANG ; Fang-Mei ZHANG ; Yu-Ze DONG ; Ying-Nan ZHU
The Chinese Journal of Clinical Pharmacology 2024;40(17):2586-2590
Objective Human papillomavirus(HPV)is a detriment virus to human health,because it can cause malignant tumors.HPV vaccine has been developed and plays an important role in preventing a range of diseases caused by HPV.HPV vaccine as a primary prevention measure,has demonstrated excellent protective efficacy and safety in preventing HPV-related infection and cervical cancer.This article summarizes the application of preventive HPV vaccine and its safety,and provides reference for the widespread vaccination of HPV vaccine in China.
7.Effect of Combined Frequency Stimulation on The Electrophysiology of Granule Neurons in The Hippocampal Dentate Gyrus Area of Hindlimb Unloading Mice
Jun-Qiao ZHAO ; Ming-Qiang ZHU ; Hai-Jun ZHU ; Rui FU ; Ze ZHANG ; Jia-Le WANG ; Chong DING
Progress in Biochemistry and Biophysics 2024;51(7):1670-1686
ObjectiveIn recent years, the negative impact of microgravity on astronauts’ nervous systems has received widespread attention. The repetitive transcranial magnetic stimulation (rTMS) technology has shown significant positive effects in the treatment of neurological and psychiatric disorders. The potential benefits of combined frequency stimulation (CFS) which combines different frequency stimulation patterns in ameliorating neurological dysfunctions induced by the microgravity environment, still require in-depth investigation. Exploring the therapeutic effects and electrophysiological mechanisms of CFS in improving various neurological disorders caused by microgravity holds significant importance for neuroscience and the clinical application of magnetic stimulation. MethodsThis study employed 40 C57BL/6 mice, randomly divided into 5 groups: sham group, hindlimb unloading (HU) group, 10 Hz group, 20 Hz group, and combined frequency stimulation (10 Hz+20 Hz, CFS) group. Mice in all groups except the sham group received 14 d of simulated microgravity conditions along with 14 d of repetitive transcranial magnetic stimulation. The effects of CFS on negative emotions and spatial cognitive abilities were assessed through sucrose preference tests and water maze experiments. Finally, patch-clamp techniques were used to record action potentials, resting membrane potentials, and ion channel dynamics of granule neurons in the hippocampal dentate gyrus (DG) region. ResultsCompared to the single-frequency stimulation group, behavioral results indicated that the combined frequency stimulation (10 Hz+20 Hz) significantly improved cognitive impairments and negative emotions in simulated microgravity mice. Electrophysiological experiments revealed a decrease in excitability of granule neurons in the hippocampal DG region after HU manipulation, whereas the combined frequency stimulation notably enhanced neuronal excitability and improved the dynamic characteristics of voltage-gated Na+ and K+ channels. ConclusionThe repetitive transcranial magnetic stimulation with combined frequencies (10 Hz+20 Hz) effectively ameliorates cognitive impairments and negative emotions in simulated microgravity mice. This improvement is likely attributed to the influence of combined frequency stimulation on neuronal excitability and the dynamic characteristics of Na+ and K+ channels. Consequently, this study holds the promise to provide a theoretical basis for alleviating cognitive and emotional disorders induced by microgravity environments.
8.The Influence of Family Adversities on Longitudinal Changes in Physical Inactivity Among Korean Adolescents During the COVID-19 Pandemic
Tae Kyoung LEE ; Jing ZHU ; Young Mi KIM ; Ze-Kai JIANG ; Meilin ZHANG ; Won Ha CHOI ; Tae-Young PAK ; Hana SONG
Journal of Preventive Medicine and Public Health 2024;57(5):443-450
Objectives:
Lack of physical activity has a critical effect on the physical and mental health of adolescents. This study examined the influence of family adversities on the longitudinal changes in physical inactivity among adolescents during the coronavirus disease 2019 (COVID-19) pandemic.
Methods:
The study used multi-wave data from the Korean Children and Youth Panel Survey, including 2590 Korean adolescents aged 12-14 years. The longitudinal trajectory of physical inactivity among adolescents and the effects of related factors were estimated using a latent growth modeling method.
Results:
Our results revealed a significant increase in physical inactivity among adolescents over time. At the onset of the pandemic, approximately one-seventh of Korean middle schoolers reported a lack of physical activity. However, 3 years later, during the quarantine, nearly one-fifth of these adolescents reported a significant increase in their physical inactivity. Initially, low level parental education was predictive of adolescents’ physical inactivity, but this effect diminished over time, becoming statistically insignificant by the end of the 3-year period. Moreover, the increase in physical inactivity over the 3 years was significantly influenced by parental rejection.
Conclusions
These findings suggest that adolescents who experience parental rejection are more likely to report an increase in sedentary behaviors in contexts such as the COVID-19 pandemic.
9.LncRNA DRAIC regulates the proliferation, apoptosis, migration and invasion of lung adenocarcinoma cells by targeting let-7i-5p.
Bao Lin LIU ; Yi Shuang CUI ; Ya Ping TIAN ; Ying Ze ZHU ; Zi Qian HONG ; Xue Mei ZHANG ; Guo Gui SUN
Chinese Journal of Oncology 2023;45(6):471-481
Objective: To investigate the effects of lncRNA DRAIC on proliferation, apoptosis, migration and invasion of lung adenocarcinoma cells and its mechanism. Methods: Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression of DRAIC in lung cancer tissues and corresponding adjacent normal tissues of 40 patients with lung adenocarcinoma who underwent surgery in Tangshan People's Hospital from 2019 to 2020. Lung adenocarcinoma cells A549 and H1299 were cultured in vitro and divided into si-NC group, si-DRAIC group, miR-NC group, let-7i-5p mimics group, si-DRAIC+ inhibitor-NC group, and si-DRAIC+ let-7i-5p inhibitor group. CCK-8 method and clone formation experiment were used to detect cell proliferation. Flow cytometry was used to detect cell apoptosis. Transwell array was used to detect the cell migration and invasion. Western blot was used to detect the protein expressions of Caspase-3, Caspase-9, Bcl-2 and Bax. The double luciferase reporter gene experiment was used to verify the regulatory relationship between DRAIC and let-7i-5p. Independent sample t test was used for comparison between two groups, one-way ANOVA was used for comparison between multiple groups, and Pearson correlation analysis was used for correlation analysis. Results: Compared with adjacent tissues, the expression level of DRAIC in lung adenocarcinoma tissues increased (P<0.05), but the expression level of let-7i-5p decreased (P<0.05). The expression levels of DRAIC and let-7i-5p in lung adenocarcinoma tissues were negatively correlated (r=-0.737, P<0.05). The absorbance value of A549 and H1299 cells in the si-DRAIC group at 48, 72 and 96 hours were lower than those in the si-NC group (P<0.05), the number of clones formed [(91.00±6.08 vs. 136.67±6.51); (50.67±1.53 vs. 76.67±4.51)], the number of migration [(606.67±31.34 vs. 960.00±33.06); (483.33±45.96 vs. 741.67±29.67)], the number of invasion [(185.00±8.19 vs. 447.33±22.05); (365.00±33.87 vs. 688.00±32.97)] were lower than those in the si-NC group (P<0.05). However, the apoptosis rates of cells [(13.43±2.79)% vs. (4.53±0.42)%; (23.77±1.04)% vs. (6.60±1.42)%] were higher than those in the si-NC group (P<0.05). The protein expressions of Caspase-3, Caspase-9 and Bax in si-DRAIC group were higher than those in si-NC group, and the protein expression of Bcl-2 was lower than that in si-NC group (P<0.05). DRAIC is located in the cytoplasm. DRAIC targeted and negatively regulated the expression of let-7i-5p. The absorbance values of A549 and H1299 cells in the let-7i-5p mimics group at 48, 72 and 96 hours were lower than those in the miR-NC group (P<0.05), the number of clones formed [(131.33±14.47 vs. 171.33±6.11); (59.33±4.93 vs. 80.33±7.09)], the number of migration [(137.67±3.06 vs. 579.33±82.03); (425.00±11.14 vs. 669.33±21.13)], the number of invasion [(54.00±4.36 vs. 112.67±11.59); (80.00±4.58 vs. 333.33±16.80)] were lower than those in the miR-NC group (P<0.05). However, the apoptosis rates of cells [(14.57±1.10)% vs. (6.97±1.11)%; (23.97±0.42)% vs. (7.07±1.21)%] were higher than those in the miR-NC group (P<0.05). The protein expressions of Caspase-3, Caspase-9 and Bax in let-7i-5p mimics group were higher than those in miR-NC group, and the protein expression of Bcl-2 was lower than that in miR-NC group (P<0.05). The absorbance values of A549 and H1299 cells in the si-DRAIC+ let-7i-5p inhibitor group at 48, 72 and 96 hours were higher than those in the si-DRAIC+ inhibitor-NC group (P<0.05), the number of clones formed [(82.00±5.29 vs. 59.00±5.57); (77.67±4.93 vs. 41.33±7.57)], the number of migration [(774.33±35.81 vs. 455.67±19.04); (569.67±18.72 vs. 433.67±16.77)], the number of invasion [(670.33±17.21 vs. 451.00±17.52); (263.67±3.06 vs. 182.33±11.93)] were higher than those in the si-DRAIC+ inhibitor-NC group (P<0.05). However, the apoptosis rates of cells [(7.73±0.45)% vs. (19.13±1.50)%; (8.00±0.53)% vs. (28.40±0.53)%] were lower than those in the si-NC group (P<0.05). The protein expressions of Caspase-3, Caspase-9 and Bax in si-DRAIC+ let-7i-5p inhibitor group were higher than those in si-DRAIC+ inhibitor-NC group, and the protein expression of Bcl-2 was lower than that in si-DRAIC+ inhibitor-NC group (P<0.05). Conclusion: DRAIC is highly expressed in lung adenocarcinoma, and DRAIC promotes the proliferation, migration and invasion of lung adenocarcinoma cells and inhibits apoptosis by targeting let-7i-5p.
Humans
;
Adenocarcinoma/genetics*
;
Apoptosis/genetics*
;
bcl-2-Associated X Protein/metabolism*
;
Caspase 3/metabolism*
;
Caspase 9/metabolism*
;
Cell Line, Tumor
;
Cell Proliferation/genetics*
;
Lung/metabolism*
;
MicroRNAs/metabolism*
;
Proto-Oncogene Proteins c-bcl-2/metabolism*
;
RNA, Long Noncoding/genetics*
10.Differential diagnosis and surgical management in chondrosarcoma of the jugular foramen.
Da LIU ; Jian Ze WANG ; Jian Bin SUN ; Zhong LI ; Tong ZHANG ; Na SAI ; Yu Hua ZHU ; Wei Dong SHEN ; De Liang HUANG ; Pu DAI ; Shi Ming YANG ; Dong Yi HAN ; Wei Ju HAN
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(6):544-551
Objective: To explore the diagnosis, surgical management and outcome of jugular foramen chondrosarcoma (CSA). Methods: Fifteen patients with jugular foramen CSA hospitalized in the Department of Otorhinolaryngology Head and Neck Surgery of Chinese PLA General Hospital from December 2002 to February 2020 were retrospectively collected,of whom 2 were male and 13 were female, aging from 22 to 61 years old. The clinical symptoms and signs, imaging features, differential diagnosis, surgical approaches, function of facial nerve and cranial nerves IX to XII, and surgical outcomes were analyzed. Results: Patients with jugular foramen CSA mainly presented with facial paralysis, hearing loss, hoarseness, cough, tinnitus and local mass. Computed tomography (CT) and magnetic resonance (MR) could provide important information for diagnosis. CT showed irregular destruction on bone margin of the jugular foramen. MR demonstrated iso or hypointense on T1WI, hyperintense on T2WI and heterogeneous contrast-enhancement. Surgical approaches were chosen upon the sizes and scopes of the tumors. Inferior temporal fossa A approach was adopted in 12 cases, inferior temporal fossa B approach in 2 cases and mastoid combined parotid approach in 1 case. Five patients with facial nerve involved received great auricular nerve graft. The House Brackmann (H-B) grading scale was used to evaluate the facial nerve function. Preoperative facial nerve function ranked grade Ⅴ in 4 cases and grade Ⅵ in 1 case. Postoperative facial nerve function improved to grade Ⅲ in 2 cases and grade Ⅵ in 3 cases. Five patients presented with cranial nerves Ⅸ and Ⅹ palsies. Hoarseness and cough of 2 cases improved after operation, while the other 3 cases did not. All the patients were diagnosed CSA by histopathology and immunohistochemistry, with immunohistochemical staining showing vimentin and S-100 positive, but cytokeratin negative in tumor cells. All patients survived during 28 to 234 months' follow-up. Two patients suffered from tumor recurrence 7 years after surgery and received revision surgery. No complications such as cerebrospinal fluid leakage and intracranial infection occurred after operation. Conclusions: Jugular foramen CSA lacks characteristic symptoms or signs. Imaging is helpful to differential diagnosis. Surgery is the primary treatment of jugular foramen CSA. Patients with facial paralysis should receive surgery in time as to restore the facial nerve. Long-term follow-up is necessary after surgery in case of recurrence.
Humans
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Male
;
Female
;
Young Adult
;
Adult
;
Middle Aged
;
Facial Paralysis/etiology*
;
Diagnosis, Differential
;
Jugular Foramina
;
Retrospective Studies
;
Cough
;
Hoarseness
;
Neoplasm Recurrence, Local
;
Chondrosarcoma/surgery*

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