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 analyze the process of intercomparison of national personal dose monitoring, evaluate the ability of personal dose monitoring, and ensure the accuracy and reliability of monitoring results in our laboratory. Methods In accordance with the intercomparison protocol for 2019—2021, an energy-discriminant thermoluminescence dosimeter was used for measurement at different doses. The uncertainty of measurement was evaluated and compared with the reference value. Results H_p(10) was measured for intercomparison in 2019—2021. In 2019, the single group performance difference was −0.02 to 0.02 and the comprehensive performance was 0.02. These values were 0.02-0.10 and 0.05 in 2020, and −0.02 to 0.02 and 0.01 in 2021. The intercomparison results were rated as excellent in the three consecutive years. Conclusion The personal dose monitoring system in our laboratory was in good condition, and the monitoring results were accurate and reliable. Improving the knowledge of personnel and cultivating a serious working attitude are important for intercomparison and personal dose monitoring.

²¹⁰Po and ²¹⁰Pb exist widely in nature, and they have strong toxicity and strong ionization ability, which can cause continuous harm to human health. Therefore, it is of great significance to determine the activity concentrations of ²¹⁰Po and ²¹⁰Pb in environmental samples and to evaluate their harmful effects on human health. This article reviews the research progress in analytical methods and measurement techniques of ²¹⁰Po and ²¹⁰Pb in environmental samples.

Objective:To preliminarily evaluate the effect of tension stimulation on the biological activity of and expression of fibrosis marker genes in keloid fibroblasts (KD-Fbs) .Methods:Three patients who were diagnosed with keloids and received surgical treatment were collected from the Department of Dermatology, Tangdu Hospital, the Fourth Military Medical University from January to March 2017. Human KD-Fbs were isolated from resected keloid tissues, and subjected to primary culture. The third- to sixth-passage KD-Fbs were divided into tension group and control group to be cultured in the tension-based chamber and control chamber respectively, and subjected to tension stimulation and normal culture respectively. Cell counting kit-8 (CCK8) assay was performed to assess the proliferative activity of KD-Fbs after 1-, 2-, 3- and 4-day culture, and the scratch assay to evaluate the migratory ability of KD-Fbs after 1- and 2-day culture. After 48-hour treatment, real-time quantitative PCR and Western blot analysis were performed to determine the mRNA and protein expression of fibrosis markers type Ⅰ collagen, fibronectin and α-smooth muscle actin (α-SMA) in KD-Fbs respectively. Two-independent-sample t test was used for comparisons between 2 groups. Results:CCK8 assay showed that the proliferative activity of KD-Fbs was significantly higher in the tension group than in the control group after 1-, 2-, 3- and 4-day culture ( t=3.05, 7.00, 16.65, 15.19, respectively, all P< 0.05) . After 1- and 2-day culture, the scratch assay showed that the migration rate of KD-Fbs was significantly higher in the tension group (48.65%±3.96%, 100.00%, respectively) than in the control group (9.36%±1.14%, 50.35%±4.23%, t=16.53, 20.35, respectively, both P< 0.01) . Real-time quantitative PCR showed that the mRNA expression of type Ⅰ collagen, fibronectin and α-SMA was significantly higher in the tension group (3.04±0.20, 2.16±0.10, 3.76±0.24, respectively) than in the control group (1.00; t=17.57, 21.01, 20.25, respectively, all P< 0.01) . As Western blot analysis revealed, changes in the protein expression of the 3 fibrosis markers were consistent with their mRNA expression changes (all P< 0.05) . Conclusion:Tension may participate in the fibrosis in keloids by promoting the expression of fibrosis marker genes, and enhancing the proliferative and migratory ability of KD-Fbs.

Objective:To investigate the awareness of digestive system injury caused by coronavirus disease 2019 (COVID-19) in gastroenterologists.Methods:From February 21 to 23 in 2020, the electronic questionnaire was used to learn about the condition of the basic knowledge of COVID-19 and awareness of digestive system injury caused by COVID-19 among the gastroenterologists across the country. Chi-square test was used for statistical analysis.Results:A total of 2 216 gastroenterologists from 31 provinces, autonomous regions and municipalities nationwide completed the survey. 99.7% (2 209/2 216) of gastroenterologists stated that they had read the COVID-19 diagnosis and treatment guidelines. The percentages of physicians who knew clearly about the diagnostic criteria of suspected and confirmed cases of COVID-19 was 34.9% (774/2 216) and 39.4% (874/2 216), respectively. The percentages of physician who gave the right answers of COVID-19 detectable methods and pulmonary imaging was 68.4% (1 516/2 216) and 71.6% (1 586/2 216), respectively. The percentages of correct answers of digestive system injury caused by COVID-19 were physicians and chief physicians was 30.9% (134/433) in residents, 33.9% (234/691) attending physicians, 32.4% (213/657) associated chief physicians and 34.9% (152/435) chief physicians, respectively, however there were no statistically significant differences among physicians with different professional titles ( χ2=6.60, P> 0.05). 95.6% (2 119/2 216) of gastroenterologists believed that probiotics could effectively improve bowel function, and 94.0% (2 082/2 216) of gastroenterologists considered that enteral nutrition support could improve patients’ prognosis. Conclusions:The knowledge and dynamic progress of the digestive system injury caused by COVID-19 are still insufficiently grasped by gastroenterologists in China. So it is necessary to carry out systematic and pertinent training programmes for them.

Objective: To investigate awareness of digestive system injury caused by corona virus disease 2019 (COVID-19) in gastroenterologists. Methods: From February 21 to 23 in 2020, the electronic questionnaire was sent out to explore the condition of the basic knowledge of COVID-19 and knowledge of digestive system injury caused by COVID-19 grasped by gastroenterologists. Chi-square test was used for statistical analysis. Results: A total of 2 216 gastroenterologists from 31 provinces, autonomous regions and municipalities nationwide completed the survey. 99.7% (2 209/2 216) of gastroenterologists stated that they had read the COVID-19 diagnosis and treatment guidelines. The percentage of physicians who well knew the diagnostic criteria of suspected and confirmed cases of COVID-19 was 34.9% (774/2 216) and 39.4% (874/2 216), respectively. The percentage of physician who gave the right answer of COVID-19 detectable methods and lung imaging was 68.4% (1 516/2 216) and 71.6% (1 586/2 216), respectively. The percentage of correct answer of digestive system injury caused by COVID-19 in residents, attending physicians, associate chief physicians and chief physicians was 30.9% (134/433), 33.9% (234/691), 32.4% (213/657) and 34.9% (152/435), respectively, however there were no statistically significant differences among physicians of different level (χ²=6.60, P> 0.05). 95.6% (2 119/2 216) of gastroenterologists believed that probiotics could effectively improve bowel function, and 94.0% (2 082/2 216) of gastroenterologists considered that enteral nutrition support could improve patients’ prognosis. Conclusions The knowledge and dynamic progress of the digestive system injury caused of COVID-19 are still insufficiently grasped by gastroenterologists in China. So it is necessary to carry out systematic and pertinent training for them.

Objective To discuss the feasibility,the advantages and disadvantages,the clinical efficacy and the indications of minimally invasive transforaminal endoscopic debridement combined with allograft and posterial percutaneous internal fixation for thoracolumbar spinal tuberculosis.Methods All of 22 patients with thoracolumbar tuberculosis treated in our department from January 2012 to December 2013 were retrospectively reviewed.There are 11 male and female cases separately,with an average age of 54.1 ±10.2 years and with an average disease duration of 5.3 ± 1.9 months.Endoscopic lesion removal and allograft bone grafting combined with posterial percutaneous immobilization were performed on all these cases.The data of these patients were complete,and all patients had been followed up for more than 36 months.The clinical and radiographic results were recorded and analyzed.Results In this group,22 patients were followed-up for 41.9±2.5 months(36-48 months).The spinal kyphosis was not improved 3 months after surgery (t=0.3546,P=0.7029),but the amount of blood loss (30.5±7.9 ml) was less in the operation,the amount of postoperative analgesics(0.3±0.1 g) was low and the bed time(1.5±0.3 days) was short.No recurrence and no internal fixation failure was found after long term follow-up.Good clinical outcomes were achieved with the fusion rate reached above grade 2 in all patients(95.5％) except one.The neuralgia was relieved,and the spinal cord injury was recovered to ASIA E.The VAS score and SF-36 score which were recorded 1 month and 3 months after operative were all improved significantly compared with those before operation,and patients' life quality in the early period after operation was excellent.The incidence of complications was low(9.0％),and the patients were satisfied with the treatment process.Conclusion It may be a potential way to treat spinal tuberculosis with minimally invasive transforaminal endoscopic debridement combined with allograft and percutaneous internal fixation,which could be a powerful supplement to other therapeutic measures,and is worthy of further research and development.

Objective: To explore the possible mechanism of statins improving endothelial function via observing the effect of a high single dose atorvastatin on endothelial dysfunction and peripheral blood leucocyte Rho kinase activity in patients with unstable angina (UA). Methods: A total of 78 consecutive UA patients admitted in our hospital from 2012-08 to 2014-02 were enrolled. The patients received a single dose of atorvastatin 80 mg on the day of admission. Flow-mediated vasodilation (FMD) of brachial artery was examined by high-resolution ultrasound at before and 12 hours after medication. Protein expression of phospho-speciifc Thr853-MYPT1 (p-MYPT1Thr853) and MYPT1 was measured by Western blot analysis; peripheral blood leukocyte Rho kinase activity was assayed by the proportion of phospho-Thr853 in myosin binding subunit of light chain phosphatase (MYPT1). Results: Compared to prior medication, with atorvastatin 80 mg for 12 hours, FMD was increased 28.15% as (6.50 ±1.68) % vs (8.33 ± 1.93) %,P<0.001 and peripheral blood leucocyte Rho kinase activity was decreased 32.78% as (58.91 ± 5.22) % vs (39.6 ± 3.85 ) %,P=0.002. Conclusion: High dose atorvastatin could rapidly improve vascular endothelial dysfunction in UA patients. inhibiting of RhoA/Rho kinase pathway may involve in the effect of statins improving endothelial function.

Objective To evaluate the implementation feasibility of the nurse performance appraisal and allocation plan based on the holistic nursing mode, and the clinical effect in mobilizing nursing staff's work enthusiasm and ensuring the quality of nursing service. Methods The nurse performance appraisal and allocation plan were further improved based on the previous research of this index system construction. The model were implemented in 32 clinical departments of Yidu Center Hospital of Weifang City. Four aspects data were collected for analysis six months later to evaluate the effect. They were nurses on merit pay distribution satisfaction, patients′satisfaction, doctors′satisfaction with nursing job, different clinical departments′nursing quality scores. Results Six months later, four factor scores of nurses to the satisfaction of merit pay distribution were significantly improved. The scores of fairness and impartiality evaluation of the merit pay distribution, incentive effect evaluation, pay and return on equity evaluation and performance pay gap rationality evaluation were higher than before [(3.39 ±0.64) points vs. (1.88 ±0.33) points, (3.28 ±0.74) points vs. (1.84 ±0.49) points , (3.28 ±0.71) points vs. (1.88 ±0.42) points and (3.38 ±0.67) points vs. (2.01±0.53) points, t=19.28, 16.22, 18.08, 16.79, all P<0.05]. Patients′satisfaction, doctors′satisfaction with nursing job and different clinical department' nursing quality scores were significantly increased as well [(99.14±0.82) points vs. (96.78±0.84) points, (96.59±0.91) points vs. (93.59±1.27) points and(97.67±0.41) points vs. (95.70±1.13) points]. Difference had statistical significance (t=11.79, 11.63, 9.60, P<0.05). Conclusions The performance salary allocation plan can effectively improve the hospital nurses on performance salary allocation satisfaction, patients′satisfaction, doctor′s satisfaction with nursing work and the quality of nursing department, and has good incentive in arousing the work enthusiasm of nursing staff and in ensuring the quality of nursing service.

A DNA fragment encoding human interleukin 4 was obtained by PCR from pORF-hIL4 plasmid. The amplified fragment was inserted into prokaryotic expression vector PQE60 and recombinant protein was expressed in E. Coli M15 by adding isopropyl-beta-D-thiogalactoside (IPTG). The hIL-4 protein was present as insoluble inclusion bodies in the bacterial extract. After denaturation of inclusion bodies with 5 mol/L guanidine hydrochloride, the supernate was diluted to get renaturized. Then dialysis and Ni chelating chromatography were used for purification. TF-1 proliferation assay of recombinant human interleukin 4 was performed, and then rhIL-4 was fit to be used for proliferation of human dendritic cells from monocyte in vitro.
Escherichia coli ; genetics ; metabolism ; Genetic Vectors ; Humans ; Inclusion Bodies ; metabolism ; Interleukin-4 ; biosynthesis ; genetics ; Protein Folding ; Recombinant Proteins ; biosynthesis ; genetics ; isolation & purification