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.

Standards are the technical support for economic activities and social development. The construction and standardization of the pathogenic microorganism preservation standard system is an important technical foundation for the high-quality development of preservation work. Establishing a pathogenic microorganism resource standard system is also important to the national biosafety standards. Through the standardization of pathogenic microbial resource preservation, we can ensure the effective management and sustainable utilization of pathogenic microbial resources, promote the transformation of resources, and serve as an important new element of new productivity to assist the innovative development of biosafety science and technology. This article elaborates and analyzes the establishment background, construction framework, standardization process, and application effects of the standard system for preserving pathogenic microbial resources, providing stronger support for further improving the standard system and promoting the standardization of pathogenic microbial resource preservation.

Humans ; SARS-CoV-2 ; COVID-19 ; Antibodies ; Antibodies, Viral/therapeutic use* ; Antibodies, Neutralizing/therapeutic use*

The pathogenic microorganism laboratory is the main workplace for the detection of pathogenic microorganisms, including bacterium and virus, or related samples, which plays an important supporting role in the prevention and control of infectious disease and the fight against biological terrorist attacks. Unified biosecurity standard and sound biosecurity standard system should be established for the laboratory experiment of pathogenic microorganisms.

Objective:To study the risk factors of adverse pregnancy outcomes for the diagnosis and treatment of pregnancy after cesarean section complicated with placenta previa.Methods:A national multicenter retrospective study was conducted to select a total of 747 pregnant women with the third trimester singleton pregnancy after cesarean section complicated with placenta previa from 12 tertiary hospitals in January 1st to December 31st, 2018. The risk factors of severe adverse outcomes [hysterectomy, intraoperative blood loss ≥1 000 ml, intraoperative diagnosis of placenta accreta spectrum disorders (PAS)] in pregnant women with second pregnancy complicated with placenta previa after cesarean section were investigated by logistic regression analysis. The roles of prenatal ultrasonography and magnetic resonance imaging (MRI) in the prediction of PAS and severe adverse outcomes were observed. According to whether vascular intervention was performed (uterine artery embolization or abdominal aortic balloon occlusion), the pregnant women were divided into the blocked group and the unblocked group, and the maternal and infant perinatal outcomes between the two groups were compared.Results:(1) General information: the hysterectomy rate of 747 pregnant women with second pregnancy complicated with placenta previa after cesarean section was 10.4% (78/747), the intraoperative blood loss ≥1 000 ml in 55.8% (417/747), and PAS was confirmed in 47.5% (355/747). The incidence of uterine rupture was 0.8% (6/747). (2) Analysis of risk factors for severe adverse outcomes: based on binary unconditioned logistic regression univariate and multivariate analysis, the risk factors for hysterectomy were the mode of vascular embolization and intraoperative blood loss. The probability of hysterectomy with uterine artery embolization was 5.319 times higher than that with abdominal aortic balloon occlusion (95% CI: 1.346-21.018). The risk factors of intraoperative blood loss ≥1 000 ml were the number of cesarean section delivery, ultrasonography indicated PAS and suspected PAS, intraoperative PAS and complete placenta previa. The risk factors for intraoperative PAS were uterine scar thickness, ultrasonography indicated PAS and suspected PAS, MRI indicated PAS and suspected PAS, and complete placenta previa. (3) The roles of ultrasonography and MRI in predicting PAS: the sensitivity and specificity of ultrasonography in predicting PAS were 47.5% and 88.4%; the kappa value was 0.279 ( P<0.001), with fair agreement. The sensitivity and specificity of MRI to predict PAS were 79.2% and 97.8%, respectively. The kappa value was 0.702 ( P<0.001), indicating a good agreement. The intraoperative blood loss and hysterectomy rate of pregnant women with PAS indicated by ultrasonography and MRI were significantly higher than those with PAS only by ultrasonography or MRI. (4) Influence of vascular occlusion on pregnancy outcome: there were no significant differences in intraoperative blood loss and incidence of intraoperative bleeding ≥1 000 ml between the blocked group and the unblocked group (all P>0.05). There was no significant difference in intraoperative blood loss between the pregnant women with abdominal aortic balloon occlusion, uterine artery embolization and those without occlusion ( P=0.409). The hysterectomy rate of pregnant women with uterine artery embolization was significantly higher than those with abdominal aortic balloon occlusion [39.3% (22/56) vs 10.0% (5/50), P=0.001]. Conclusions:In the third trimester of pregnancy with placenta previa after cesarean section, MRI examination has better consistency in predicting PAS than ultrasonography examination. Ultrasonography examination combined with MRI examination could effectively predict the hysterectomy rate and intraoperative blood loss. Vascular occlusion could not reduce the amount of intraoperative blood loss. The hysterectomy rate of pregnant women with uterine artery embolization is higher than those with abdominal aortic balloon occlusion.

Objective:In the research, the traditional mercury sphygmomanometer was used to press the puncture point to evaluate the hemostatic effect.Methods:Eighty patients with acute cerebral infarction diagnosed clinically in Xuanwu Hospital of Capital Medical University from June 2018 to December 2019 were examined by magnetic resonance perfusion examination. The serial number of the patient was randomly divided into the group by random digital table, and the puncture point was pressed by mercury sphygmomanometer after needle extraction in the auxiliary pressing group, and the individual systolic blood pressure intensity was set as the pressing intensity, while the control group adopted independent vertical pressing technique. After examination, the puncture points of the two groups were qualitatively evaluated, such as secondary bleeding, hematoma, ecchymosis, normal and so on.Results:In the auxiliary compression group, there were 3 cases of secondary hemorrhage, 1 case of hematoma, 0 cases of ecchymosis and 36 cases of normal, while in the control group, there were 4 cases of bleeding, 2 case of hematoma, 1 case of ecchymosis and 33 cases of normal ( χ2value was 4.372-34.225, P<0.05). Conclusion:Traditional mercury sphygmomanometer-assisted pressing puncture point can make personalized nursing hemostasis plan for patients with acute cerebral infarction, reduce the phenomenon of puncture point bleeding, ecchymosis, and even subcutaneous hematoma caused by unstable pressing and unequal force, and practice high-quality nursing service.

Objective:To study the risk factors of adverse pregnancy outcomes for induced abortion of cesarean scar pregnancy in midtrimester.Methods:A national multicenter retrospective study was conducted. A total of 154 singletons pregnant women with cesarean scar pregnancy during the second trimester induced abortion by various reasons in 12 tertiary A hospitals were selected, their pregnant outcomes were observed and the risk factors of serious adverse outcomes were analyzed with univariate and multivariate logstic regression; the role of ultrasound and MRI in predicting placenta accreta and severe adverse outcomes was evaluated, the effectiveness of uterine artery embolization (UAE) in preventing hemorrhage in pregnant women with and without placenta accreta was compared.Results:Among 154 subjects, the rate of placenta accreta was 42.2% (65/154), the rate of postpartum hemorrhage≥1 000 ml was 39.0% (60/154), the rate of hysterectomy was 14.9% (23/154), the rate of uterine rupture was 0.6% (1/154). The risk factor of postpartum hemorrhage≥1 000 ml and hysterectomy was placenta accreta ( P<0.01). For each increase in the number of parity, the risk of placenta accreta increased 2.385 times (95% CI: 1.046-5.439; P=0.039); and the risk of placenta accreta decreased with increasing ultrasound measurement of scar myometrium thickness ( OR=0.033, 95% CI: 0.001-0.762; P=0.033). The amount of postpartum hemorrhage and hysterectomy rate in the group with placenta accreta diagnosed by ultrasound combined with MRI were not significantly different from those in the group with placenta accreta diagnosed by ultrasound only or MRI only (all P>0.05). For pregnant women with placenta accreta, there were no significant difference in the amount of bleeding and hysterectomy rate between the UAE group [median: 1 300 ml; 34% (16/47)] and the non-embolization group (all P>0.05); in pregnant women without placenta accreta, the amount of bleeding in the UAE group was lower than that in the non-embolization group (median: 100 vs 600 ml; P<0.01), but there was no significant difference in hysterectomy rate [2% (1/56) vs 9% (3/33); P>0.05]. Conclusions:(1) Placenta accreta is the only risk factor of postpartum hemorrhage≥1 000 ml with hysterectomy for induced abortion of cesarean scar pregnancy in midtrimester; multi-parity and ultrasound measurement of scar myometrium thickness are risk factors for placenta accreta. (2) The technique of using ultrasound and MRI in predicting placenta accreta of cesarean scar pregnancy needs to be improved. (3) It is necessary to discuss of UAE in preventing postpartum hemorrhage for induced abortion of cesarean scar pregnancy in midtrimester.

Objective To explore the association of arsenic with unexplained recurrent spontaneous abortion (URSA). Methods A case?control study was conducted to select URSA patients who were admitted to the Beijing Maternal and Child Health Care Hospital affiliated to Capital Medical University from April to October 2018 as a case group. Women who had a normal pregnancy in the Family Planning Department of the hospital but volunteered to have an abortion were selected as a control group. The case and control group were paired in a 1:1 ratio. The inclusion criteria of the case group were patients with newly diagnosed recurrent spontaneous abortion who had clinically confirmed more than 2 spontaneous abortions and had 20 weeks prior to pregnancy, excluding patients with recurrent spontaneous abortion caused by abnormal blood coagulation (anti?phospholipid antibody positive), abnormal physiological anatomy (B?ultrasound), abnormal immune factors (anti?nuclear antibody positive, anti?cardiolipin antibody, etc.), genetic chromosomal abnormalities (karyotype analysis) and pathogenic microbial infection. The control group was matched according to the age of the case group (±3 years old) and the gestational age (±2 weeks) to exclude adverse pregnancy outcomes such as stillbirth, congenital malformation, premature delivery and low birth weight infants. A total of 192 subjects were included. Questionnaires were used to collect information of all subjects, and 12 ml of peripheral venous blood was collected to detect blood arsenic levels. Blood arsenic levels were divided into low concentration group (<1.00 μg/L), medium concentration group (1.00-1.50 μg/L) and high concentration group (>1.50 μg/L). The multivariate conditional logistic regression was performed to analyze the relationship between blood arsenic exposure and URSA and explore the influencing factors of blood Arsenic. Results The geometric mean values of blood arsenic level in the cases group and control group were 1.68 (1.50-1.86) μg/L and 1.26 (1.17-1.37) μg/L, respectively. The blood arsenic level in the case group was significantly higher than that in the control group (P<0.05). The results of multivariate conditional logistic regression analysis showed that after adjusting for tobacco exposure during pregnancy, pre?pregnancy body mass index and the effects of residential decoration in past five years, the risk of URSA was higher in the high?concentration group compared with the low?concentration group ( OR=2.56, 95%CI :1.06-6.24). Conclusion Blood arsenic may increase the risk of URSA in women of childbearing age.

Objective To explore the association of arsenic with unexplained recurrent spontaneous abortion (URSA). Methods A case?control study was conducted to select URSA patients who were admitted to the Beijing Maternal and Child Health Care Hospital affiliated to Capital Medical University from April to October 2018 as a case group. Women who had a normal pregnancy in the Family Planning Department of the hospital but volunteered to have an abortion were selected as a control group. The case and control group were paired in a 1:1 ratio. The inclusion criteria of the case group were patients with newly diagnosed recurrent spontaneous abortion who had clinically confirmed more than 2 spontaneous abortions and had 20 weeks prior to pregnancy, excluding patients with recurrent spontaneous abortion caused by abnormal blood coagulation (anti?phospholipid antibody positive), abnormal physiological anatomy (B?ultrasound), abnormal immune factors (anti?nuclear antibody positive, anti?cardiolipin antibody, etc.), genetic chromosomal abnormalities (karyotype analysis) and pathogenic microbial infection. The control group was matched according to the age of the case group (±3 years old) and the gestational age (±2 weeks) to exclude adverse pregnancy outcomes such as stillbirth, congenital malformation, premature delivery and low birth weight infants. A total of 192 subjects were included. Questionnaires were used to collect information of all subjects, and 12 ml of peripheral venous blood was collected to detect blood arsenic levels. Blood arsenic levels were divided into low concentration group (<1.00 μg/L), medium concentration group (1.00-1.50 μg/L) and high concentration group (>1.50 μg/L). The multivariate conditional logistic regression was performed to analyze the relationship between blood arsenic exposure and URSA and explore the influencing factors of blood Arsenic. Results The geometric mean values of blood arsenic level in the cases group and control group were 1.68 (1.50-1.86) μg/L and 1.26 (1.17-1.37) μg/L, respectively. The blood arsenic level in the case group was significantly higher than that in the control group (P<0.05). The results of multivariate conditional logistic regression analysis showed that after adjusting for tobacco exposure during pregnancy, pre?pregnancy body mass index and the effects of residential decoration in past five years, the risk of URSA was higher in the high?concentration group compared with the low?concentration group ( OR=2.56, 95%CI :1.06-6.24). Conclusion Blood arsenic may increase the risk of URSA in women of childbearing age.