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.Inhibition of HDAC3 Promotes Psoriasis Development in Mice Through Regulating Th17
Fan XU ; Xin-Rui ZHANG ; Yang-Chen XIA ; Wen-Ting LI ; Hao CHEN ; An-Qi QIN ; Ai-Hong ZHANG ; Yi-Ran ZHU ; Feng TIAN ; Quan-Hui ZHENG
Progress in Biochemistry and Biophysics 2025;52(4):1008-1017
ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4+ T lymphocytes, CD8+ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4+ T lymphocytes. Additionally, spleen CD4+ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4+ and CD8+ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4+ and CD8+ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4+ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4+ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.
3.Effect of salidroside combined with rosavin on ischemic brain injury in rats
Wen-Fang LAI ; Yu-Ting JIANG ; Hui-Ling WU ; Qing-Qing WU ; Jing-Quan CHEN ; Xue-Rui ZHENG ; Gui-Zhu HONG
Chinese Pharmacological Bulletin 2024;40(12):2303-2311
Aim To study the effect of salidroside combined with rosavin on ischemic stroke in rats.Methods The model of MCAO was established by u-sing thread-embolic method.The rats were divided into the sham group,MCAO group,salidroside combined with rosavin group,positive control group,and the drug was given continuously for seven days.The infarct volume was measured by MRI and neurological deficit score was evaluated by Zea-Longa.The levels of Ne-uN,BDNF,TGF-β1,p-Smad were observed by West-ern blot and immunofluorescence staining.The expres-sions of IL-1β,TNF-α and IL-6 were performed by RT-qPCR/ELISA.The primary cortical neurons were isolated,OGD/R inducted,divided into the normal group,OGD/R group,salidroside combined with rosa-vin group,and TGF-β1 inhibitor+salidroside com-bined with rosavin group,the drug was given for 24 hours,and the expressions of NeuN,BDNF,IL-1β,TNF-α and IL-6 were measured.Results Salidroside combined with rosavin could decrease the infarct vol-ume,improve the neurological function,promote the levels of Neun,BDNF,TGF-β1,p-Smad,and inhibit the expressions of IL-1β,TNF-α and IL-6.Salidroside combined with rosavin could promote NeuN,BDNF,inhibit IL-1β,TNF-α,IL-6 in primary nerve cells in-duced by OGD/R,and these effects were blocked by TGF-β1 inhibitor.Conclusions Salidroside combined with rosavin has neuroprotective effects on MCAO rats,and primary neurons are induced by OGD/R,and these effects are closely related to the TGF-β pathway.
4.Establishment and evaluation of non-obese polycystic ovary syndrome rat model
Shiqing QIAO ; Ting WANG ; Yonghuang YAN ; Jiusi YANG ; Yuling YU ; Yanmin WANG ; Yateng SUN ; Yujie WU ; Peixuan ZHU ; Min LI ; Cong CHEN ; Zeqi SU ; Cai ZHANG
Acta Laboratorium Animalis Scientia Sinica 2024;32(8):965-975
Objective To establish a stable rat model of non-obese polycystic ovary syndrome(PCOS)with clinical characteristics.Methods Dehydroepiandrosterone(DHEA)was used to establish a PCOS rat model by subcutaneous injection.Three-week-old female SD rats were divided into a normal group,6 mg/kg DHEA model group,and 60 mg/kg DHEA model group.The model groups were subcutaneously injected with the corresponding dose of DHEA daily,while the normal group was subcutaneously injected with glycerol daily for 21 consecutive days.The model was evaluated with ovarian histopathology as the gold standard to determine the optimal dosage of DHEA to induce a PCOS rat model.On this basis,the optimal DHEA modeling dose was selected,and stop and continue modeling groups were set up to observe the model for 28 days and evaluate its maintenance.The stop modeling group was no longer given DHEA,and the continued modeling group was subcutaneously injected with 60 mg/kg DHEA every 48 h.The evaluation indicators included body mass,estrous cycle,fasting blood glucose,serum insulin,histopathologic morphology of the ovaries,and serum sex hormone levels.Results(1)Compared with the normal group,the 6 mg/kg and 60 mg/kg DHEA model groups showed no significant difference in body mass,and their estrous cycles were irregular.There were more cystically dilated large follicles in the ovaries;fewer mature follicles;reduced layers of granulosa cells,which were arranged in a sparse and disorganized manner;and fewer lutea in the 6 mg/kg and 60 mg/kg DHEA model groups than the normal group.Furthermore,serum T and E2 levels were significantly higher in the 60 mg/kg DHEA model group(P<0.05)than the normal group.(2)The stop modeling group(A2 group)resumed regular estrous cycles after 2 weeks,various growth follicles and corpora lutea were observed in the ovarian tissues,the number of cystic follicles was reduced,the number of granulosa cell layers increased,mature follicles were visible,oocyte morphology was locally intact,and the levels of E2 and AMH were reduced compared with the normal group(A1 group)(P<0.05).(3)The continue model group(B2 group)was in the late stage of estrous cycle for a long period,and there were more large follicles with cystic dilatation,fewer mature follicles,fewer layers of granulosa cells with a sparse and disordered arrangement,and significantly fewer corpus lutea in the ovaries compared with the normal group(B1 group).The levels of serum LH,LH/FSH,and T were elevated(P<0.05).Conclusions Subcutaneous injection of 60 mg/kg DHEA for 21 consecutive days can be used to successfully construct a non-obese PCOS rat model that possesses clinical characteristics.Subcutaneous injection of 60 mg/kg DHEA every 48 hours maintains the stability of the model.
5.Dilemmas in decision-making:a qualitative study of family surrogate decision-makers of severe stroke patients
Zining GUO ; Keyu LING ; Shufan CHEN ; Haihan LI ; Ting YAO ; Sining ZENG ; Ling XU ; Xiaoping ZHU
Chinese Journal of Nursing 2024;59(14):1746-1751
Objective To explore the dilemmas faced by surrogate decision-makers of severe stroke patients in treatment decision-making,and to provide a basis for developing decision support strategies.Methods From April to December 2023,through phenomenological qualitative research with 16 surrogate decision-makers with severe stroke patients from ICU of the department of neurology in a tertiary hospital in Jing'an District,Shanghai.semi-structured in-depth interviews were used to examine the perceptions of decision-making on surrogate.Data were analyzed via Braun's style of thematic analysis.Results 4 themes and 10 sub-themes were identified.Theme 1:negative emotional dilemmas(urgent decision-making leads to anxiety,fear,and unknown stroke trajectory increases the sense of uncertainty).Theme 2:supportive environment dilemmas(lack of information support delays decision-making;lack of family support increases decision-making stress;insufficient economic support increases the burden of decision-making).Theme 3:the dilemma of weighing the pros and cons(difficult trade-offs between risk and reward,tough decisions between reality and ethics,conflicting choices of life and dignity).Theme 4:preference management dilemmas(practical difficulties in adhering to patient preferences,impediments to decision-making due to unknown patient preferences).Conclusion Surrogate decision-makers of severe stroke patients face multiple decision-making dilemmas.Healthcare professionals should provide emotional support in multiple ways and comprehensive support to reduce the decision-making dilemmas experienced by surrogate decision-makers,as well as implement death education for surrogate decision-makers and promote advance care planning to reduce their decision-making stress.
6.Application progress of Satir communication model in nursing from the perspective of family support
Yimeng CHEN ; Yinning GUO ; Hanfei ZHU ; Kang ZHAO ; Ting XU ; Lidong HUANG ; Lingyu DING ; Jieman HU ; Qin XU
Chinese Journal of Nursing 2024;59(19):2413-2419
As a type of experiential psychotherapy,Satir communication model can help the individual system and the family system achieve a state from dysfunction to healthy function,which can enrich the intervention connotation of family support and provide a new direction for the realization of full-life circle care.This paper aims to introduce the concept,core elements,common treatment techniques,application and effects,current challenges and relevant suggestions of Satir communication model in the nursing field from the perspective of family support,in order to provide references for the localization development and clinical integration of Satir communication model in the field of nursing in China.
7.Efficiency of different large language models in China in response to consultations about PCa-related perioperative nursing and health education
Xiao-Wen TAN ; Wen-Fang CHEN ; Na-Na WANG ; Hui-Yu LI ; Juan LI ; Yu-Mei CAO ; Meng-Qi ZHU ; Kun LI ; Ting-Ling ZHANG ; Dian FU
National Journal of Andrology 2024;30(2):151-156
Objective:To evaluate the efficiency of the four domestic language models,ERNIE Bot,ChatGLM2,Spark Desk and Qwen-14B-Chat,all with a massive user base and significant social attention,in response to consultations about PCa-related perio-perative nursing and health education.Methods:We designed a questionnaire that includes 15 questions commonly concerned by patients undergoing radical prostatectomy and 2 common nursing cases,and inputted the questions into each of the four language models for simulation consultation.Three nursing experts assessed the model responses based on a pre-designed Likert 5-point scale in terms of accuracy,comprehensiveness,understandability,humanistic care,and case analysis.We evaluated and compared the performance of the four models using visualization tools and statistical analyses.Results:All the models generated high-quality texts with no mis-leading information and exhibited satisfactory performance.Qwen-14B-Chat scored the highest in all aspects and showed relatively sta-ble outputs in multiple tests compared with ChatGLM2.Spark Desk performed well in terms of understandability but lacked comprehen-siveness and humanistic care.Both Qwen-14B-Chat and ChatGLM2 demonstrated excellent performance in case analysis.The overall performance of ERNIE Bot was slightly inferior.All things considered,Qwen-14B-Chat was superior to the other three models in con-sultations about PCa-related perioperative nursing and health education.Conclusion:In PCa-related perioperative nursing,large language models represented by Qwen-14B-Chat are expected to become powerful auxiliary tools to provide patients with more medical expertise and information support,so as to improve the patient compliance and the quality of clinical treatment and nursing.
8.Surgical treatment of isolated pulmonary mucormycosis
Weipeng ZHU ; Fan YANG ; Jiashun CAO ; Xianming HOU ; Ting ZHOU ; Zimu ZHANG ; Donghong CHEN
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(10):612-617
Objective:To retrospectively analyze the surgical treatment of isolated pulmonary mucormycosis, explore the timing and effect of operation.Methods:Clinical data of patients with isolated pulmonary mucormycosis who underwent surgical treatment from April 2019 to April 2024 were collected and retrospectively analyzed, combined with literature review.Results:The clinical data of 13 patients with pulmonary mucormycosis who underwent operation were collected, including 9 males and 4 females, aged 22~64(45.4±15.4)years old. The basic diseases included diabetes mellitus in 10 cases and hematological malignancy in 3 cases. Seven patients had hemoptysis during the course of the disease. All 13 patients received adequate antifungal therapy before surgery, and 12 patients received bronchoscopic interventional therapy. Ten patients underwent lobectomy, two underwent pneumonectomy, and one underwent a right sleeve pneumonectomy. All patients were cured except one patient with bronchopleural fistula after operation. All patients achieved complete elimination of mucor and also discontinuation of antifungal drug.Conclusion:For isolated pulmonary mucormycosis, on the basis of systemic antifungal treatment, actively seek the opportunity of surgical intervention, can shorten the course of the disease and achieve good therapeutic results.
9.Professor LIN Xianming's Academic Thoughts on the Treatment of Atopic Dermatitis with Combination of Acupuncture and Medication
Ke'an ZHU ; Ting CHEN ; Yang CHEN
Journal of Zhejiang Chinese Medical University 2024;48(10):1279-1283
[Objective]To summarize Professor LIN Xianming's clinical experience in treating atopic dermatitis(AD)with combination of acupuncture and medication,and to provide clinical reference.[Methods]Through the following-up of Professor LIN's treatment of AD,collection and analysis of cases,it is clear that AD is mostly caused by congenital or acquired disorders,combined with the infection of external pathogens.Professor LIN's clinical experience in the treatment of AD is explained from the two aspects of"acupuncture and moxibustion for relieving itching and calming the mind"and"regulating body with classical prescription",and a medical case was attached as proof.[Results]Professor LIN believes that the key of the pathogenesis of AD lies in the innate constitution,and the feeling of"dampness"and"heat"and other diseases depressed in the skin,resulting in itching symptoms.With the progression of the disease,severe pruritus affects patients'emotions,and abnormal emotions aggravate itching at the same time,forming an itch-scratch cycle.In clinical treatment,Professor LIN believes that correcting idiosyncratic constitution is the key to no recurrence of the disease,and advocates"acupuncture and moxibustion for relieving itching and calming the mind"and"regulating body with classical prescription".Acupuncture and moxibustion can relieve itching and regulate the mind,relieve the abnormal itching mood of patients,and prevent the generation of itching-scratching cycle;classical prescription can improve the specific constitution of patients,from the idea of"person-disease-prescription",and treat the patients according to their different physical characteristics.In this case,the patient had a history of allergy for many years,and the disease was prolonged,with severe pruritus and abnormal mood coexisting.Acupuncture can relieve the itch and regulate the mind to improve the pruritus and abnormal mood.At the same time,the constitution was identified as Xiaochaihu Decoction,the prescription used Xiaochaihu Decoction to regulate immune function,regulate the body,and obtain good effect.[Conclusion]Professor LIN treats AD with the principle of"relieving itching""regulating the mind"and"regulating the body"as the principles of diagnosis and treatment,using acupuncture to relieve itching,regulating the body to strengthen the foundation,treating both internal and external symptoms and root causes,with outstanding clinical efficacy.It broadens the thinking of traditional Chinese medicine diagnosis and treatment,and its experience is worthy of clinical application and promotion.
10.Clinical effectiveness of dynamic joint mobilization combined with core stability training for nonspecific low back pain treatment
Lingling ZHU ; Yanchun CHEN ; Liang FANG ; Chengyan CAI ; Ting LIU
The Journal of Practical Medicine 2024;40(18):2602-2606
Objective To observe the clinical efficacy of dynamic joint mobilization combined with core stability training in the treatment of nonspecific low back pain.Methods 60 patients with nonspecific low back pain were randomly assigned into either the treatment group or control group.Each group had 30 patients.The treatment group received a therapeutic regimen combining dynamic joint mobilization and core stability training,while the control group only received core stability training.Both groups were evaluated for therapeutic effectiveness using the Visual Analogue Scale(VAS)for pain,the Oswestry Disability Index(ODI),and the range of motion(ROM)of the lumbar spine before treatment,and at the 1st,3rd,and 6th weeks after treatment.At the conclusion of the treatment,a thorough assessment of the overall therapeutic efficacy was performed.Results At the 1st,3rd,and 6th weeks post-treatment,both groups showed statistically significant differences in VAS scores,ODI scores,and ROM scores over time(P<0.05).The improvements in these indices were significantly greater in the treatment group compared to the control group(P<0.05).The treatment group had considerably higher therapeutic effective-ness compared to the control group(P<0.05).Conclusions Dynamic joint mobilization combined with core stabil-ity training is effective in treating nonspecific low back pain.It can help with pain relief,lumbar and back function restoration,and lumbar and back mobility improvement.This approach is worthy of clinical application and promotion.

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