摘要：Type IV collagenase plays a pivotal role in invasion, metastasis and angiogenesis of tumor. Single domain antibodies are attractive as tumor-targeting vehicle because of their much smaller size com-pared with antibody molecules produced by conventional methods. Lidamycin (LDM) is a potent enediyne-containing antitumor antibiotic. In this study an engineered and energized fusion protein VL-LDP-AE composed of lidamycin and VL domain of mAb 3G11 directed against type IV collagenase was prepared using a novel two-step method. First a VL-LDP fusion protein was constructed by DNA recombination. Secondly VL-LDP-AE was obtained by molecular reconstitution. In MTT assay, VL-LDP-AE showed potent cytotoxicity to HT-1080 cells and KB cells with IC50 values of 8.55×10-12 and 1.70×10-11 mol/L, respectively. VL-LDP-AE showed antiangiogenic activity in chick chrorioallantoic membrane (CAM) assay and tube formation assay. In in vivo experiments, VL-LDP-AE was proved to be more effective than free LDM against the growth of subcutaneously transplanted hepatoma 22 in mice. Drugs were given intravenously on day 3 and 10 after tumor transplantation. Compared in terms of maximal tolerated doses, VL-LDP-AE at 0.25 mg/kg suppressed the tumor growth by 89.5%, LDM at 0.05 mg/kg by 69.9%, and mitomycin at 1 mg/kg by 35%. Having a molecular weight of 25.2 kDa, VL-LDP-AE was much smaller than other reported antibody-based drugs. The results suggested that VL-LDP-AE would be a promising candidate for tumor targeting therapy. And the 2-step approach could serve as a new technology platform for making a series of highly potent engineered antibody-based drugs for a variety of cancers.

摘要：The design and efficacy of surgery for horizontal idiopathic nystagmus （HIN） with abnormal head posture and strabismus were investigated. Different surgical procedures were selected according to the angle of head turn in 44 cases of HIN with abnormal head posture and strabismus. For patients with a head turn of 15° or less, the Anderson procedure was used; the yoke muscles were recessed upon slow-phase. For patients with a head turn between 15° and 25°, the surgery was designed as a Kestenbaum 5-4-4-5 procedure. For patients with a head turn of 25° or more, the surgery was designed as a Parks 5-8-6-7 procedure. The surgery to correct the abnormal head posture was performed on the fixating eye while that to correct the deviation was then performed on the non-fixating eye at the same time. The amount of surgery of the horizontal rectus muscles on the nonfixating eye was sum of the angle of head turn and the degree of deviation, which was calculated as follows： recession/resection amount of medial and lateral rectis/2×5=angle of head turn±degree of deviation. The results showed as follows： （1） Visual acuity： the visual acuity in the primary ocular position increased two lines or more in 35 patients, accounting for 79.55%. Nine patients had no or only one-line improvement, accounting for 20.45% of the entire study population; （2） The degree of deviation in the primary ocular position： 37 cases had a normal primary ocular position or the degree of deviation ≤8△ after surgery, accounting for 84.09%. Six patients had a residual degree of deviation of 8△―15△, accounting for 13.64%. One patient had a residual degree of deviation 〉20△, accounting for 2.27% of the patients examined; （3） Abnormal head posture： 34 patients had a normal head posture or a head turn of less than 5°, accounting for 72.27%. Eight patients had a residual head turn of 5°―15°, accounting for 18.18%. Two patients had a head turn of 15°― 25°, accounting for 4.55%. It was concluded that different surgical

摘要：The bioinert nature of polyether ether ketone(PEEK)material limits the widespread clinical application of PEEK *** the porous structure is considered to improve osseointegration of PEEK implants,it is hardly used due to its mechanical *** study investigated the combined influence of the porous structure and in vivo mechanical stimulation on implantation safety and bone growth based on finite element analysis of the biomechanical behavior of the implantation *** combined control of pore size and screw preloads allows the porous PEEK implant to achieve good osseointegration while maintaining a relatively high safety level.A pore size of 600μm and a preload of 0.05 N·m are the optimal combination for the long-term stability of the implant,with which the safety factor of the implant is>2,and the predicted percentage of effective bone growth area of the bone-implant interface reaches 97%.For further clinical application,PEEK implants were fabricated with fused filament fabrication(FFF)three-dimensional(3D)printing,and clinical outcomes demonstrated better bone repair efficacy and long-term stability of porous PEEK implants compared to solid PEEK ***,good osteointegration performance of 3D-printed porous PEEK implants was observed,with an average bone volume fraction>40%three months after *** conclusion,3D-printed porous PEEK implants have great potential for clinical application,with validated implantation safety and good osseointegration.

摘要：The purpose of this study was to fabricate decelluarized valve scaffold modified with polyethylene glycol nanoparticles loaded with transforming growth factor-β1（TGF-β1）,by which to improve the extracellular matrix microenvironment for heart valve tissue engineering in *** glycol nanoparticles were obtained by an emulsion-crosslinking method,and their morphology was observed under a scanning electron *** valve scaffolds,prepared by using trypsinase and TritonX-100,were modified with nanoparticles by carbodiimide,and then TGF-β1 was loaded into them by *** TGF-β1 delivery of the fabricated scaffold was measured by asing enzyme-linked immunosorbent *** unseeded or reseeded with myofibroblast from rats,the morphologic,biochemical and biomechanical characteristics of hybrid scaffolds were tested and compared with decelluarized scaffolds under the same *** enzyme-linked immunosorbent assay revealed a typical delivery of *** morphologic observations and biological data analysis indicated that fabricated scaffolds possessed advantageous biocompatibility and biomechanical property beyond decelluarized *** this study proved that it was feasible to fabricate the hybrid scaffold and effective to improve extracellular matrix microenvironment,which is beneficial for an application in heart valve tissue engineering.

摘要：Tissue engineering is an interdisciplinary field promising new therapeutic means for replacing lost or severely damaged tissues or organs. However, the fabrication of complex engineered tissues has been hampered due to the lack of vascularization to provide sufficient blood supply after implantation. In this article, we propose using rapid prototyping technology to prefabricate a scaffold with an inside hollowed vascular system including an arterial end, a venous end and capillary networks between them. The scaffold will be ''printed'' layer by layer. When printing every layer, a ''low-melting point'' material will be used to form a blood vessel network and a tissue-specific material will be used outside it. Hereafter the ‘low-melting point’ material will be evacuated by vaporization to ensure a hollowed vessel network. Then the inside hollowed capillary network can be endothelialized by using autologous endothelial cells in a cycling bioreactor while the outside material can be embedded with tissue-special cells. In the end, the new vascularized autologous grafts could be transferred to the defect site by using microsurgical techniques to connect the grafts with the host artery and vein. The strategy would facilitate construction of complex tissue engineering if the hypothesis proved to be practical.

摘要：The aim of this study was to fabricate biomatrix/polymer hybrid scaffolds using an electrospinning technique. Then tissue engineered heart valves were engineered by seeding mesenchymal stromal cells （MSCs） onto the scaffolds. The effects of the hybrid scaffolds on the proliferation of seed cells, formation of extracellular matrix and mechanical properties of tissue engineered heart valves were investigated. MSCs were obtained from rats. Porcine aortic heart valves were decellularized, coated with poly（3-hydroxybutyrate-co-4-hydroxybutyrate） using an electrospinning technique, and reseeded and cultured over a time period of 14 days. In control group, the decellularized valve scaffolds were reseeded and cultured over an equivalent time period. Specimens of each group were examined histologically （hematoxylin-eosin [HE] staining, immunohistostaining, and scanning electron microscopy）, biochemically （DNA and 4-hydroxyproline） and mechanically. The results showed that recellularization was comparable to the specimens of hybrid scaffolds and controls. The specimens of hybrid scaffolds and controls revealed comparable amounts of cell mass and 4-hydroxyproline （P〉0.05）. However, the specimens of hybrid scaffolds showed a significant increase in mechanical strength, compared to the controls （P〈0.05）. This study demonstrated the superiority of the hybrid scaffolds to increase the mechanical strength of tissue engineered heart valves. And compared to the decellularized valve scaffolds, the hybrid scaffolds showed similar effects on the proliferation of MSCs and formation of extracellular matrix. It was believed that the hybrid scaffolds could be used for the construction of tissue engineered heart valves.

摘要：Arrhythmogenic right ventricular cardiomyopathy(ARVC)is a progressive disease characterized by adipose and fibrous replacement of the *** elevated testosterone levels have been implicated in the pathological process of ARVC,its exact contribution to cardiac fibrosis in ARVC remains *** this study,we analyzed the potential contribution of gender-based differences on the distribution of the low-voltage area in an ARVC cohort undergoing an electrophysiological study,which was indicated by feature ***,we established engineered cardiac spheroid models in vitro using patient-specific induced pluripotent stem cell(iPSC)-derived cardiomyocytes(iPSC-CMs)and iPSC-derived cardiac fibroblasts(icFBs).We elucidated the pathogenicity of abnormal splicing in the plakophilin-2(PKP2)gene caused by an intronic ***,pathogenic validation of the desmoglein-2(DSG2)point mutation further confirms the reliability of the ***,testosterone exacerbated the DNA damage in the mutated cardiomyocytes and further activated myofibroblasts in a chain *** conclusion,we designed and constructed an in vitro three-dimensionally-engineered cardiac spheroid model of ARVC based on clinical findings and provided direct evidence of the fibrotic role of testosterone in ARVC.

摘要：Lumbar degeneration leads to changes in geometry and density distribution of vertebrae,which could further influence the mechanical property and *** study aimed to quantitatively describe the variations in shape and density distribution for degenerated vertebrae by statistical models,and utilized the specific statistical shape model(SSM)/statistical appearance model(SAM)modes to assess compressive strength and fracture *** detailed SSM and SAM were developed based on the 75 L1 vertebrae of elderly men,and their variations in shape and density distribution were quantified with principal component(PC)*** vertebrae were classified into mild(n=22),moderate(n=29),and severe(n=24)groups according to the overall degree of *** computed tomography-based finite element analysis was used to calculate compressive strength for each L1 vertebra,and the associations between compressive strength and PC modes were evaluated by multivariable linear regression(MLR).Moreover,the distributions of equivalent plastic strain(PEEQ)for the vertebrae assigned with the first modes of SSM and SAM at mean±3SD were *** Leave-One-Out analysis showed that our SSM and SAM had good performance,with mean absolute errors of 0.335±0.084 mm and 64.610±26.620 mg/cm3,respectively.A reasonable accuracy of bone strength prediction was achieved by using four PC modes(SSM 1,SAM 1,SAM 4,and SAM 5)to construct the MLR ***,the PEEQ values were more sensitive to degeneration-related variations of density distribution than those of *** density variations may change the deformity type(compression deformity or wedge deformity),which further affects the fracture *** models can identify the morphology and density variations in degenerative vertebrae,and the SSM/SAM modes could be used to assess compressive strength and fracture *** above findings have implications for assisting clinicians in pathological dia

摘要：Fast electron-hole recombination issues during titanium dioxide(TiO_(2))photocatalysis limit its application in preventing bacterial infection during bone defect *** this study,TiO_(2)@reduced graphene oxide(rGO)composites were synthesized using a hydrothermal method in which rGO,which possesses very high electrical conductivity,promotes the separation of photoelectron-hole pairs of TiO_(2),thus improving the efficiency of photocatalytic production of reactive oxygen species(ROS).Subsequently,TiO_(2)@rGO composites were introduced into poly-L-lactic acid(PLLA)to prepare bone scaffolds with photocatalytic antibacterial function via selective laser *** results showed that TiO_(2)grew on the surface of rGO and formed a covalent bond connection(Ti-O-C)with rGO.A decreased electrochemical impedance of TiO_(2)@rGO composites was observed,and the transient photocurrent intensity increased from 0.05 to 0.5μA/cm^(2).Analysis of electron spin resonance found that the photocatalytic products of TiO_(2)were·OH and·O^(2-),two kinds of ROS capable of killing bacteria via disrupting the structure of the bacterial membrane in *** experiments showed that the PLLA/TiO_(2)@rGO scaffolds had good antibacterial properties against Escherichia coli and Staphylococcus ***,we report that these scaffolds exhibited both enhanced mechanical properties due to the addition of TiO_(2)@rGO as a reinforcement material and good biocompatibility during cell proliferation.

摘要：As surgical procedures transition from conventional resection to advanced tissue-regeneration technologies,human disease therapy has witnessed a great leap *** particular,three-dimensional(3D)bioprinting stands as a landmark in this setting,by promising the precise integration of biomaterials,cells,and bioactive molecules,thus opening up a novel avenue for tissue/organ *** by the editorial board of Bio-Design and Manufacturing,this review brings together a cohort of leading young scientists in China to dissect the core functionalities and evolutionary trajectory of 3D bioprinting,by elucidating the intricate challenges encountered in the manufacturing of transplantable *** further delve into the translational pathway from scientific research to clinical application,emphasizing the imperativeness of establishing a regulatory framework and rigorously enforcing quality-control ***,this review outlines the strategic landscape and innovative achievements of China in this field and provides a comprehensive roadmap for researchers worldwide to propel this field collectively to even greater heights.