To enhance the specificity of anti-TNF-α single chain Fv antibody (TNF-scFv) to inflamed site, we constructed a bispecific antibody BsDb that targets TNF-α and ED-B-containing fibronectin (B-FN) by covalently linking TNF-scFv and the anti-ED-B scFv L19 at the gene level via a flexible peptide linker deriving from human serum albumin. BsDb was successfully secreted from Pichia pastoris as functional protein, identified by immunoblotting, and purified to homogeneity with affinity chromatography. BsDb retained the immunoreactivity of its original antibodies TNF-scFv and L19, and showed a marked gain in antigen-binding affinity and in TNF-α-neutralizing ability, when compared to TNF-scFv and L19 that were produced in Escherichia coli. In the adjuvant-induced arthritis (AIA) mice model, BsDb showed selective accumulation and retention in the inflamed paws but rapid clearance from blood, resulting in high arthritic paw to blood ratios. These data indicate that BsDb is endowed with high specificity to inflamed site and low toxicity to normal tissues and holds great potential for in vivo application for the targeted therapy of RA and other chronic inflammatory diseases.
Animals ; Antibodies, Bispecific ; biosynthesis ; immunology ; Antibodies, Neutralizing ; biosynthesis ; immunology ; Escherichia coli ; Fibronectins ; chemistry ; immunology ; Humans ; Mice ; Single-Chain Antibodies ; biosynthesis ; immunology ; Tumor Necrosis Factor-alpha ; immunology

Objective To discuss the feasibility and effect of labeled antibody on targeting therapy of systemic lupus erythematosus(SLE) associated thrombocytopenia.Methods MTX-IVIG conjugate was prepared by indirect and direct cross linking,and the binding ability of it to Fc fragment was detected by indirect immunofluor-escence.The killing activity of the conjugate was detected by MTT method using murine macrophage with Fc receptor and strain U937 of human monocytic leukemia cell as targets.Results Conjugation showed stronger cytotoxicity upon target cells than free MTX,and it showed less cytotoxic effect on Fc receptor negative cells compared with the positive ones.IVIG-HSA-MTX restrained the phagocyte of macrophage.The killing effect of IVIG-HSA-MTX was significantly stronger than that of IVIG-MTX.Conclusion The conjugation can show a highly specific cytotoxicity upon mononuclear-macrophage in vitro.

Objective To establish a patient-derived xenografts (PDX) mouse model of liver cancer (LC) and to explore its role in precision medicine.Methods PDX model was established by subcutaneous implantation of tumor tissues in NCG mice.The morphological structure of tumor tissue was exaimed using HE staining.Fifteen BALB/c nude mice were subcutaneously inoculated with tumor cell suspension from the PDX models.The xenograft mice were randomly divided into 5-fluorouracil (5-FU) group, sorafenib group and negative control group.The tumor volume and body weight of the tumor-bearing mice were measured regularly, the tumor inhibition rate was calculated and the curative effect was evaluated.Results The success rate was 33.3% (6/18) in the establishment of liver cancer PDX mouse model, and the model well retained the characteristics of the primary tumor.In one case of PDX mouse model, the tumor inhibition rates of 5-FU and sorafenib group were 63.7% and 29.6%, with a statistically significant differece between them (P< 0.05), and there was no significant difference between the sorafenib group and negative control group, consistent with clinical observation.Conclusions The PDX mouse model of liver cancer can maintain the histological structure of primary tumor, and can be applied to precision medicine for patients with liver cancer.

In recent years, the chimeric antigen receptor T-cell (CAR-T) therapy has achieved breakthrough progress in the treatment of hematologic malignancies. However, when it comes to solid tumors, numerous challenges persist.These include limited CAR-T cell infiltration, susceptibility to T cell exhaustion, off-target effects, and more.Thus, novel therapeutic strategies are imperative to enhance the efficacy of CAR-T therapy for solid tumors. In comparison to standalone CAR-T approaches, the combination of CAR-T with other tumor treatment modalities has demonstrated remarkable effectiveness in both preclinical and clinical research.This review article summarizes the advancements in combining CAR-T with various solid tumor treatments: antibody drugs, oncolytic viruses, tumor vaccines, and nanomedicines.The objective is to furnish a theoretical foundation and novel perspectives for the development of innovative CAR-T combination strategies tailored for solid tumor therapy.

Objective The scope of related research on ethical conflicts in the interprofessional collaboration in nursing was reviewed,so as to summarize the obstacles and coping strategies that lead to ethical conflicts in interprofessional collaboration and provide references for promoting nurse engagement in interprofessional collaboration.Methods Based on the methodological framework of the scope review,we systematically searched domestic and foreign databases including the Cochrane Library,CINAHL,Embase,PubMed,Web of Science,CNKI,VIP,Wanfang and SinoMed.The time limit for database retrieval was from the establishment of each database to March 2023.The selected studies were summarized and analyzed.Results Totally 13 articles published between 1991 and 2022 were included.The obstacle factors that lead to ethical conflicts in nurse engagement of interprofessional collaboration can be divided into 3 categories,including personal factors(insufficient professional knowledge,differences in professional values),interprofessional factors(imbalanced power between professions,lack of respect and collaboration between cooperators)and environmental factors(insufficient resources and staffing,high-intensity workload,and high-pressure work environment).At the same time,in view of these 3 aspects,it puts forward some countermeasures,such as enhancing professional knowledge,strengthening interprofessional education,improving understanding and cooperation among medical workers in different wards,providing medical practitioners with a team-based,ethical work environment that facilitates interprofessional collaborations and open dialogues.Conclusion It is of great significance for nurses to get involved in interprofessional collaborations,in order to ensure high-quality nursing services.Further studies are needed for the development of education and the core competency framework construction for interprofessional collaborations in nursing.More attention should be paid to develop the organizational atmosphere at the same time,so as to continuously improve nurse'capabilities in interprofessional collaborations.

Objective To understand the current status of nurses'health promotion lifestyle in tertiary comprehensive hospitals,explore the category characteristics of nurses'health promotion lifestyle,and analyze the influencing factors under different categories.Methods From March to April 2023,a multi-stage sampling method was used to select 1326 nurses from 10 tertiary comprehensive hospitals in Hunan Province as the research subjects.A cross-sectional survey was conducted by General Information Questionnaire,Health Promotion Lifestyle Profile Scale,Self-Rated Abilities for Health Practices Scale,Health Behavior Self-Efficacy Assessment Scale,and Nursing Work Environment Scale.Latent profile analysis(LPA)of nurses'health promotion lifestyle was conducted,and the influencing factors of different profiles were explored through univariate analysis and logistic regression analysis.Results A total of 1220 nurses were included,and the score of Health Promotion Lifestyle Profile Scale was(62.61±18.67)points.Nurses'health promotion lifestyle in tertiary comprehensive hospitals can be divided into 3 profiles,namely survival type(25.41％),vitality type(21.97％)and normal type(52.62％).The results of logistic regression analysis showed that coping strategies for stress,non-occupational physical activity,perceived health status,health behavior self-efficacy,and nursing work environment are the influencing factors of nurses'health promotion lifestyle in tertiary comprehensive hospitals(P＜0.05).Conclusion Nurses'health promotion lifestyle in tertiary comprehensive hospitals exhibit significant heterogeneity.It is recommended that nursing managers carry out individualized interventions based on the characteristics of nurses in different categories.Health behavior self-efficacy can be used as the core of intervention to improve nurses'health promotion lifestyles.

Objective To compare ablation ranges of single and double needle microwave ablation(MWA)of pig lung in vivo.Methods Five healthy Bama miniature pigs were enrolled.Single needle(single needle group)and parallel double needle MWA(double needle group)were performed successively on bilateral lungs,respectively.Adverse event during MWA was evaluated according to common terminology criteria for adverse events(CTCAE).The long diameter(D1CT),short diameter(D2CT),longitudinal diameter(D3CT)and volume(V)of ablation foci were measured and calculated based on CT images immediately after MWA,whereas D1,s D2s and sphericity of ablation foci were also obtained based on specimen and compared between groups.Results D1CT,D2CT,D3CT and V,as well as D1S,D2S and sphericity of ablation foci in single needle group were all significantly smaller than those in double needle group(all P＜0.01).Mild pneumothorax(CTCAE grade 1)was found in 1 pig(1/5,20.00%)in single needle group,while mild pneumothorax and pulmonary hemorrhage(both CTCAE grade 1)occurred in 1 pig(1/5,20.00%)in double needle group.No other adverse event was observed.Conclusion Compared with single needle MWA,double needle MWA of pig lung in vivo resulted larger ablation range and more spherically shaped ablation foci.

Objective To evaluate the clinical efficacy of prophylactic cranial irradiation (PCI) in the treatment of surgically resected small cell lung cancer (SCLC).Methods Clinical data of SCLC patients undergoing radical resection surgery in Zhejiang Cancer Hospital from 2003 to 2015 were retrospectively analyzed.According to the treatment modality,all patients were allocated into the PCI and non-PCI groups.A total of 52 patients were finally included,including 19 patients in the PCI group (5 cases of stage Ⅰ,5 stage Ⅱ and 9 stage Ⅲ) and 33 in the non-PCI group (12 cases of stage Ⅰ,5 stage Ⅱ and 16 stage Ⅲ).Kaplan-Meier method was utilized for survival analysis.Cox proportional hazards model was adopted to analyze clinical prognosis.Results The median survival time was 32.9 months in the PCI group,and 20.4 months in the non-PCI group.The 2-year overall survival rate was 72％ in the PCI group,significantly higher than 38％ in the non-PCI group (P=0.023).The median brain metastasis-free survival (BMFS) was 32.5 months in the PCI group,and 17.1 months in the non-PCI group.In the PCI group,the 2-year BMFS rate was 89％,significantly better than 53％ in the non-PCI group (P=0.026).Subgroup analysis demonstrated that PCI could confer survival benefit to patients with p-stage Ⅲ (p=0.031) rather than p-stage Ⅰ (P=0.924) and Ⅱ (P=0.094) counterparts.Multivariate analysis revealed that PCI (HR=0.330,P=0.041) was an independent prognostic factor of the overall survival.Conclusions PCI can reduce thr risk of brain metastasis rate and improve the overall survival of patients with surgically resected SCLC.

OBJECTIVE：To study the prot ective effects of crocin （CR）against triptolide （TP）-induced visceral organ injury in mice，and to provide reference for the studying TP compatibility and detoxification. METHODS ：Fifty mice were randomly divided into normal group ，TP low-dose and high-dose groups （i.e. TP-L group ，TP-H group ，with 300，600 μg/kg），TP low-dose and high dose combined with CR groups （i.e. TP-L+CR group ，TP-H+CR group ，with 300 μg/kg TP+100 mg/kg CR ，600 μg/kg TP+ 100 mg/kg CR ），with 10 mice in each group. Except for normal group ，other groups were given relevant medicine intragastrically ， once a day ，for consecutive 7 d. The body weight of mice was weighted every day ，and their death was recorded. After last administration，the mice were sacrificed ，and the heart ，liver，kidney and testis were taken ，and the organ index was calculated ； serum levels of ALT ，AST，BUN and Scr ，the activity of T-SOD and the contents of MDA were all determined. The pathological changes of heart ，liver，kidney and testis were observed ；mRNA expression of Bcl- 2，Bax and caspase- 3 in liver tissue were determined. RESULTS ：Three，five，two and three mice in TP-L group ，TP-H group ，TP-L+CR group and TP-H+CR group died respectively，and the survival rates were 70％，50％，80％ and 70％，respectively. Compared with normal group ，the body weight （7th day of experiment ），heart index ，liver index ，kidney index （except for TP-L group ），testicular index ，T-SOD activity and mRNA expression of Bcl- 2 in liver tissue ，serum levels of ALT （except for TP-L group ），AST（except for TP-L group ），BUN and Scr，MDA content and mRNA expression of Bax ，mRNA expression of caspase- 3 in liver tissue were increased significantly （P＜ 0.05 or P＜0.01）. There were obvious pathological changes in heart ，liver，kidney and testis tissue. Compared with the same dose of TP alone group ，the above indexes of TP combined with CR group were improved in varying degrees. Except for the renal index and serum ALT level of TP-L+CR group ，there was statistical significance for all indexes （P＜0.05 or P＜0.01）；the pathological injuries of heart ，liver，kidney and testis were significantly improved. CONCLUSIONS ：CR can relieve the damage of heart ， liver，kidney and testis induced by TP ，which may be related to the antioxidant stress of CR.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.