Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Objective To study the effect of the reinforcing and reducing method of acupuncture reported in first Chapter the Nine Needles and Twelve Yuan of the Miraculous Pivot on interstitial fluid pressure (IFP) in subcutaneous tissue of minipig, and to investigate its biomechanical mechanism of regulating the interstitial fluid. Methods Nine healthy minipigs were randomly selected for reinforcing method (pull or press) and reducing method (wave a big pinhole), and tested on soft skin tissues of the abdomen. The IFP in the normal state (NS), the low volume (LV) state (by extracting interstitial fluid) and the high volume (HV) state (by injecting saline solution) was measured before and after acupuncture. Results In the normal state, pulling and pressing the needle could obviously increase IFP, while reducing method could significantly decrease IFP, leading to a rapid decrease in 5 min after acupuncture. In the LV state, pulling and pressing the needle could increase IFP. However, in 10 min after acupuncture, the descend rates of IFP were relatively slower. In the HV state, the reducing method could significantly decrease IFP, and the changing trend in 5 min after acupuncture was different from that of the control group. Conclusions The reinforcing and reducing method of acupuncture could increase or decrease IFP, which proved that the acupuncture method could regulate IFP in the opposite direction. The research findings provide a new scientific basis for using reinforcing and reducing method of acupuncture in clinic.

Objective To study the clinical efficacy of free anterolateral femoral skin flap on the repair of skin and subcutaneous soft tissue defects caused by excision of oversized malignant tumour in the skin. Methods A retrospective review was performed of free anterolateral femoral skin flap reconstructions for oversized malignant tumor cut on body surface since April 2007 to November 2010. There were 6 patients with head and limb squamous cell carcinoma because of bum scar and 3 patients with recurrence of dermatofibrosarcoma protuberans in wall of belly. The area of soft tissue defects ranged from 19 cm × 15 cm to 24 cm × 21 cm, and skin flaps was 20 cm × 16 cm to 25 cm × 22 cm in size. Three cases received radio therapy after operation. Results Nine flaps survived perfectly, one flap survived with partial necrosis and healed after changing dressings. No complications were observed in the donor site, including wound dehiscence, hernia and weakness. Follow-up survey of 12-24 months after the operation showed that the appearance and function in the repaired sites were normal, and norecurrence of the tumors. Conclusion Free transplantation of anterolateral femoral skin flap is relatively an ideal operative type for the repair of soft tissue defects caused by excision of oversized malignant tumour in the skin.

0 05).CD 34 , CD 31 and F VIII of the average counts of microvessels were (69 5?15 7), (65 3?14 5) and(58 3?16 3) respectively in the NSCLC with metastasis and (44 3?14 3), (40 5?12 6) and (36 5?15 8) respectively in those without metastasis,there was a significant difference (P