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 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.

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.