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 investigate the clinical effect of the first dorsal metatarsal-dorsal phalangeal artery flap in repairing large area of soft tissue defect on the palmar side of finger.Methods:From February, 2016 to June, 2018, 11 fingers of 11 patients (7 males and 4 females, aged 19-46 years old with an average of 32.5 years old) with large area of soft tissue defect on the palmar side of the finger were repaired with the first dorsal metatarsal-dorsal phalangeal artery flap. These included 3 with the first dorsal metatarsal-first dorsal phalangeal artery blood supply, and 8 with the first dorsal metatarsal-second dorsal phalangeal artery blood supply. In which 3 with retained finger pulp was for repairing the defects and bridging arteries, including 1 flexor tendon defect repaired by the extensor digitorum brevis tendon of the second toe with the flap. The type of blood vessel was Gilbert I detected by CDU before surgery. The area of the flaps was from 1.5 cm×5.0 cm to 3.0 cm×8.0 cm. The donor area of the flaps was compressed with full thickness skin grafts of the shank. The follow-up data was collected by outpatient clinic visits and telephone interviews.Results:All the 11 flaps survived and were followed-up for an average of 14 months, ranged from 6 months to 24 months. The colour and texture of the flaps were good. Sensing of temperature, pain and touch restored, without swelling. Function of the fingers was well restored. The range of motion of distal and proximal interphalangeal joints was closed to normal. The TPD of the flaps was 5-11 mm, with an average of 8 mm. Ten had primary wound healing in the donor sites of foot. One case had necrosis of the proximal toe of the skin graft and healed after dressing change. Long-term follow-up of the skin grafting area was wear-resistant, and does not hinder walking without rupture.Conclusion:Application of the first dorsal metatarsal-dorsal toe artery flap to repair large area of soft tissue defect on the palmar side of finger has number of advantages such as it, covers the wound and carry the tendons, bridges the arteries at the same time, plus delivers satisfactory outcome.

Energy metabolism is significantly reprogrammed in many human cancers, and these alterations confer many advantages to cancer cells, including the promotion of biosynthesis, ATP generation, detoxification and support of rapid proliferation. The pentose phosphate pathway (PPP) is a major pathway for glucose catabolism. The PPP directs glucose flux to its oxidative branch and produces a reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), an essential reductant in anabolic processes. It has become clear that the PPP plays a critical role in regulating cancer cell growth by supplying cells with not only ribose-5-phosphate but also NADPH for detoxification of intracellular reactive oxygen species, reductive biosynthesis and ribose biogenesis. Thus, alteration of the PPP contributes directly to cell proliferation, survival and senescence. Furthermore, recent studies have shown that the PPP is regulated oncogenically and/or metabolically by numerous factors, including tumor suppressors, oncoproteins and intracellular metabolites. Dysregulation of PPP flux dramatically impacts cancer growth and survival. Therefore, a better understanding of how the PPP is reprogrammed and the mechanism underlying the balance between glycolysis and PPP flux in cancer will be valuable in developing therapeutic strategies targeting this pathway.
Animals ; Energy Metabolism ; Glucose ; metabolism ; Glycolysis ; Humans ; Neoplasms ; metabolism ; pathology ; Pentose Phosphate Pathway ; physiology

Objective: To analyze the association of strength quality of junior high school students with comorbid depressive and anxiety (CDA) and its subtypes, so as to provide reference for mental health improvement among junior high students. Methods: A convenient sampling method was used to select 10 007 junior high students aged 13-16 from four cities (Nanchang, Ganzhou, Jiujiang, Shangrao) in Jiangxi Province during September to November 2023. A questionnaire survey and physical fitness tests were employed to collect basic information and assess students depressive and anxiety status, as well as strength quality. The χ 2 test was used to compare the distribution differences of CDA and its subtypes among different demographic characteristics, sleep, physical activity, and overweight/obesity conditions. Logistic regression models were applied to infer the association strength between strength quality and CDA and its subtypes. Results: The overall detection rate of CDA among junior high students was 11.04%. Among the CDA subtypes, the detection rates for mild depression-mild anxiety type, anxiety dominant type, depressiondominant type, and severe depression-severe anxiety type were 3.67%, 3.35%, 0.39% and 3.64%, respectively. Compared to the grip strength and standing long jump scores in the > P 75 group, the risk of CDA occurrence increased in other groups (grip strength: P 25 - P 75 , OR =1.20; < P 25 , OR =1.28; standing long jump: P 25 - P 75 , OR =1.31; < P 25 , OR =1.51; P <0.05). In stratified analysis of different CDA subtypes, compared to the grip strength > P 75 group, the risks for mild depression-mild anxiety type increased in the P 25 - P 75 and < P 25 groups ( OR=1.32, 1.44, P <0.05). Compared to the standing long jump > P 75 group, the risks for anxiety dominant type and severe depression-severe anxiety type increased in other groups (anxiety dominant type: P 25 - P 75 , OR =1.32; severe depression-severe anxiety type: < P 25 , OR =1.87; P < 0.05 ). Conclusions Lower levels of grip strength and standing long jump performance among junior high students are positively correlated with CDA and its subtypes. Lower levels of lower limb strength may be an important predictor of CDA in severe depression and anxiety.

Objective:To understand the current situation of nursing staff's salary satisfaction and job performance in Henan Province,and to explore the mechanism of salary satisfaction's influence on job performance.Methods:Electronic questionnaire was used to investigate the salary satisfaction,job performance and job involvement of nursing staff in sample public hospitals in Henan Province,and structural equation model was used to analyze the influence path of salary satisfaction on job performance.Results:The scores of nurses'salary satisfaction,job performance and job involvement were(68.59±19.99),(48.95±6.53)and(82.27±18.22)respectively.Nursing salary satisfaction was significantly and positively correlated with job performance(r= 0.594,P＜0.01)and work engagement(r= 0.600,P＜0.01).The standardized path coefficient of nursing staff's salary satisfaction on job performance was 0.637(P= 0.002).Conclusion:Pay satisfaction for caregivers has a significant positive impact on job outcomes,and job engagement serves as a mediator between reward satisfaction and job outcomes.It is suggested to improve the salary satisfaction and job involvement of nursing staff in order to promote the improvement of job performance.

Objective:To understand the current situation of nursing staff's salary satisfaction and job performance in Henan Province,and to explore the mechanism of salary satisfaction's influence on job performance.Methods:Electronic questionnaire was used to investigate the salary satisfaction,job performance and job involvement of nursing staff in sample public hospitals in Henan Province,and structural equation model was used to analyze the influence path of salary satisfaction on job performance.Results:The scores of nurses'salary satisfaction,job performance and job involvement were(68.59±19.99),(48.95±6.53)and(82.27±18.22)respectively.Nursing salary satisfaction was significantly and positively correlated with job performance(r= 0.594,P＜0.01)and work engagement(r= 0.600,P＜0.01).The standardized path coefficient of nursing staff's salary satisfaction on job performance was 0.637(P= 0.002).Conclusion:Pay satisfaction for caregivers has a significant positive impact on job outcomes,and job engagement serves as a mediator between reward satisfaction and job outcomes.It is suggested to improve the salary satisfaction and job involvement of nursing staff in order to promote the improvement of job performance.

Objective:To understand the current situation of nursing staff's salary satisfaction and job performance in Henan Province,and to explore the mechanism of salary satisfaction's influence on job performance.Methods:Electronic questionnaire was used to investigate the salary satisfaction,job performance and job involvement of nursing staff in sample public hospitals in Henan Province,and structural equation model was used to analyze the influence path of salary satisfaction on job performance.Results:The scores of nurses'salary satisfaction,job performance and job involvement were(68.59±19.99),(48.95±6.53)and(82.27±18.22)respectively.Nursing salary satisfaction was significantly and positively correlated with job performance(r= 0.594,P＜0.01)and work engagement(r= 0.600,P＜0.01).The standardized path coefficient of nursing staff's salary satisfaction on job performance was 0.637(P= 0.002).Conclusion:Pay satisfaction for caregivers has a significant positive impact on job outcomes,and job engagement serves as a mediator between reward satisfaction and job outcomes.It is suggested to improve the salary satisfaction and job involvement of nursing staff in order to promote the improvement of job performance.

Objective:To understand the current situation of nursing staff's salary satisfaction and job performance in Henan Province,and to explore the mechanism of salary satisfaction's influence on job performance.Methods:Electronic questionnaire was used to investigate the salary satisfaction,job performance and job involvement of nursing staff in sample public hospitals in Henan Province,and structural equation model was used to analyze the influence path of salary satisfaction on job performance.Results:The scores of nurses'salary satisfaction,job performance and job involvement were(68.59±19.99),(48.95±6.53)and(82.27±18.22)respectively.Nursing salary satisfaction was significantly and positively correlated with job performance(r= 0.594,P＜0.01)and work engagement(r= 0.600,P＜0.01).The standardized path coefficient of nursing staff's salary satisfaction on job performance was 0.637(P= 0.002).Conclusion:Pay satisfaction for caregivers has a significant positive impact on job outcomes,and job engagement serves as a mediator between reward satisfaction and job outcomes.It is suggested to improve the salary satisfaction and job involvement of nursing staff in order to promote the improvement of job performance.

Objective:To understand the current situation of nursing staff's salary satisfaction and job performance in Henan Province,and to explore the mechanism of salary satisfaction's influence on job performance.Methods:Electronic questionnaire was used to investigate the salary satisfaction,job performance and job involvement of nursing staff in sample public hospitals in Henan Province,and structural equation model was used to analyze the influence path of salary satisfaction on job performance.Results:The scores of nurses'salary satisfaction,job performance and job involvement were(68.59±19.99),(48.95±6.53)and(82.27±18.22)respectively.Nursing salary satisfaction was significantly and positively correlated with job performance(r= 0.594,P＜0.01)and work engagement(r= 0.600,P＜0.01).The standardized path coefficient of nursing staff's salary satisfaction on job performance was 0.637(P= 0.002).Conclusion:Pay satisfaction for caregivers has a significant positive impact on job outcomes,and job engagement serves as a mediator between reward satisfaction and job outcomes.It is suggested to improve the salary satisfaction and job involvement of nursing staff in order to promote the improvement of job performance.