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.

OBJECTIVES: To explore the risk factors for malnutrition in patients with ulcerative colitis complicated with pyoderma gangrenosum and establish a nutritional risk prediction model for these patients. METHODS: A total of 277 patients with ulcerative colitis complicated with pyoderma gangrenosum treated from 2019 to 2024 were divided into malnutrition group (n=185) and normal nutrition group (n=92) according to whether malnutrition occurred. The data of 25 potential related factors pertaining to general demography, living and eating habits, and disease-related data were compared between the two groups. Lasso regression was used to screen the risk factors, and a nomogram model was established based on the screened factors and its prediction performance was assessed. RESULTS: The patients in the malnutrition group and normal nutrition group showed significant differences in 21 factors including gender, age, education level, BMI, place of residence, course of disease, and SAS language score (P<0.05). Lasso regression analysis identified 6 factors associated with malnutrition in these patients, namely the duration of ulcerative colitis, activity of ulcerative colitis, duration of pyoderma gangrenosum, number of chronic diseases, SAS score, and sleep quality. The nomogram prediction model established based on these 6 factors had an AUC of 0.992 (95% CI: 0.984-1.000) for predicting malnutrition in these patients, and its application in 14 clinical cases achieved an accuracy rate of 100%. CONCLUSIONS The duration of ulcerative colitis, activity of colitis, duration of pyoderma gangrenosum, number of chronic diseases, anxiety, and sleep quality are closely related with malnutrition in patients with ulcerative colitis complicated by pyoderma gangrenosum, and the nomogram prediction model based on these factors can provide assistance for predicting malnutrition in these patients.
Humans ; Colitis, Ulcerative/complications* ; Malnutrition/etiology* ; Risk Factors ; Pyoderma Gangrenosum/complications* ; Female ; Male ; Adult ; Nomograms ; Middle Aged ; Nutritional Status ; Regression Analysis

Using high-energy proton to image the region of interest can directly obtain the accurate estimation of the proton stopping power of the lesions,which is of great significance to reduce the range uncertainty in proton therapy.As a fundamental function of proton computed tomography(CT),radiographic imaging plays a crucial role in assisting clinical positioning.The study develops a compact proton CT detector based on an active array pixel CMOS chip in Monte-Carlo simulation toolkit Geant4,and evaluates the radiographic imaging capability of the system using 180 MeV protons.The angles of tracks are successfully reconstructed.CTP404,CTP528,and the CTP515 of specific materials are used for simulation,obtaining the spatial and density resolutions,and measuring the proton relative stopping power(RSP).The image signal-to-noise ratio is improved when using 2° proton scattering angle cut-off value.The spatial resolution is 3-4 lp/cm measured using CTP528 module.The density resolution is better than 0.05 g/cm3,and the RSP resolution is within 5%when CTP404 module is used.Through the imaging of CTP515 phantom of specific material,it is demonstrated that the system has potential for imaging common human tissues.

ObjectiveTo study the effect and mechanism of Yixintai on mitochondrial fission proteins in the rat model of chronic heart failure. MethodTen of 60 SD rats were randomly selected as the sham operation group， and the remaining 50 rats were subjected to ligation of the left anterior descending coronary artery for the modeling of heart failure post myocardial infarction. The successfully modeled rats were randomized into model， low-， medium-， and high-dose （1.4， 2.8， and 5.6 g·kg^-1， respectively） Yixintai， and trimetazidine （10 mg·kg^-1） groups. The rats were administrated with corresponding doses of drugs by gavage， and the rats in the model group and sham operation group were given an equal volume of normal saline by gavage for 28 consecutive days. Enzyme-linked immunosorbent assay （ELISA） was then employed to measure the levels of amino-terminal pro-B-type natriuretic peptide （NT-pro BNP）， B-type natriuretic peptide （BNP）， and adenosine triphosphate （ATP） in the serum. Color Doppler ultrasound imaging was conducted to examine the cardiac function indicators. Hematoxylin-eosin staining and Masson staining were conducted to observe the pathological changes in the heart， and Image J was used to calculate collagen volume fraction （CVF）. Transmission electron microscopy was employed to observe the ultrastructural changes of myocardial cells. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling （TUNEL） was employed to measure the apoptosis rate of myocardial cells. Western blot was employed to determine the protein levels of mitochondrial fission protein 1 （Fis1） and mitochondrial fission factor （Mff） in the outer mitochondrial membrane of the myocardial tissue. ResultCompared with the sham operation group， the model group showed elevated levels of NT-pro BNP and BNP in the serum， decreased ATP content， left ventricular ejection fraction （LVEF）， and left ventricular fraction shortening （LVFS）， increased left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs）， disarrangement of myocardial cells， inflammatory cell infiltration， increased collagen fibers and CVF， damaged myocardium and mitochondria， and increased apoptosis rate of myocardial cells， and up-regulated expression of Fis1 and Mff in the cardiac tissue （P<0.01）. Compared with the model group， different doses of Yixintai and trimetazidine lowered the serum levels of NT-pro BNP and BNP （P<0.05）， increased the ATP content （P<0.05）， increased LVEF and LVFS （P<0.01）， decreased LVIDd and LVIDs （P<0.01）. Moreover， the drugs alleviated the myocardial inflammatory damage and fibrosis， reduced CVF （P<0.01）， repaired the myocardial mitochondrial structure， and decreased the apoptosis rate of myocardial cells （P<0.01）. Medium- and high-dose Yixintai and trimetazidine down-regulated the expression of Fis1 and Mff in the myocardial tissue （P<0.05）. ConclusionYixintai can improve mitochondrial structure， reduce myocardial cell apoptosis， and improve cardiac function by inhibiting the expression of Fis1 and Mff in the myocardial tissue.

ObjectiveTo explore the rehabilitation outcome of personalized pulmonary rehabilitation therapy in pneumoconiosis patients in the rehabilitation station. Methods A total of 42 pneumoconiosis patients were selected as the study subjects from seven pneumoconiosis rehabilitation stations in Xinjiang Uygur Autonomous Region using the judgment sampling method. Patients were treated with personalized rehabilitation therapy for three months, and the outcome was analyzed. Results The six-minute walking test distance, maximum inspiratory pressure, maximum expiratory pressure, forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), and FEV₁/FVC ratio of the pneumoconiosis patients were higher after rehabilitation therapy than those before therapy (all P<0.05). The score of Chronic Obstructive Pulmonary Disease Assessment Test of patients after therapy was lower than that in pre-treatment (P<0.05). There was no significant difference in respiratory difficulty, Borg scale, balance ability, depression symptoms, anxiety symptoms, nutritional status scores, body mass index, blood oxygen saturation, and heart rate before and after rehabilitation therapy (all P>0.05). Conclusion The individualized pulmonary rehabilitation therapy of pneumoconiosis patients at pneumoconiosis rehabilitation station can improve the respiratory muscle strength and lung function of patients, and improve their quality of life.

Objective:To explore the application process, efficacy and safety of MR-guided radiotherapy based on MR-linac in esophageal cancer.Methods:The clinical data of patients with esophageal cancer treated with MR-linac at Shandong Cancer Hospital and Institute from September 2021 to July 2022 were retrospectively analyzed, to investigate the treatment process of esophageal cancer with MR-linac, and to analyze the efficacy and safety of patients. All patients received MR-guided radiotherapy, underwent CT and MR localization, target area delineation, and design of the Monaco treatment planning system plan. Adaptation-to-position adjustment was conducted during the pre-treatment evaluation. The median number of fractions was 25, the median single dose of planning target volume was 1.8 Gy, and the median total dose was 50.2 Gy. Median follow-up was 16 months.Results:Among the 12 patients in the whole group, there were 1 case of cervical esophageal cancer, 3 cases of upper thoracic esophageal cancer, 4 cases of middle thoracic esophageal cancer and 4 cases of lower thoracic esophageal cancer, including 3 cases of neoadjuvant radiotherapy and 9 cases of radical radiotherapy. All patients had a smooth treatment process. The median treatment time was 33 min, and the patients had good compliance. For patients with radical radiotherapy, one month after radiotherapy, the number of objective remission cases was 3, and the number of disease-control cases was 9; six months after radiotherapy, the number of objective remission cases was 3, and the number of disease-control cases was 6. All patients treated with neoadjuvant radiotherapy underwent surgery within 2 months, and one patient achieved pathological complete remission. The most common acute adverse reactions were radiation esophagitis (7 cases) and leukopenia in bone marrow suppression (8 cases), with late-stage adverse reactions being radiation pneumonia (1 case). The adverse reactions to radiotherapy were slight, and no grade 4 or above adverse reactions were observed.Conclusion:The clinical treatment process for esophageal cancer under MR-guided radiotherapy based on MR-linac is feasible, with good curative effects and mild adverse reactions.

Heart failure is a group of complex clinical syndromes in the middle and late stages of cardiovascular diseases.Mitochondrial homeostasis imbalance is one of the pathological mechanisms in the occurrence and development of heart failure.This article revolved around the"yin-yang theory"in TCM and explained the pathological mechanism of heart failure through mitochondrial homeostasis.Heart failure is the syndrome of deficiency in nature and excess in superficiality fundamental.Its basic pathogenesis is"yang deficiency and yin excess".Based on the deficiency of heart yang qi and the stagnation of yin pathogens,the combination of deficiency and excess runs through the entire disease.Mitochondrial homeostasis imbalance is a manifestation of yin-yang imbalance at the cellular micro level,mainly manifested as inhibition of mitochondrial biosynthesis,mitochondrial dynamics imbalance,mitophagy disorder,etc.,which affects mitochondrial structure and function and leads to abnormal myocardial energy metabolism.Therefore,based on the"yin-yang theory",the basic treatment method is to"tonify deficiency and damage excess"to regulate mitochondrial biosynthesis,mitochondrial dynamics,and mitophagy,thereby maintaining mitochondrial homeostasis and improving myocardial energy metabolism,which is of great significance for the prevention and treatment of heart failure.

In recent years, biological agents have played a positive role in the treatment of psoriasis, especially severe, refractory and special subtypes of psoriasis. However, their safety has attracted increasing attention, especially the risk of tuberculosis infection. This review summarizes the effect of biological agents with different targets on tuberculosis infection and relevant mechanisms, aiming to provide a theoretical basis for psoriasis patients to choose appropriate biotherapy.