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.

Purpose/Significance By integrating clinical and biological sample information,a big data research platform for biologi-cal sample information resources is built to provide one-stop data retrieval,integration and analysis services for researchers,and a data governance system is established,so as to improve the level of hospital clinical research infrastructure construction.Method/Process Common data model and data governance technology are adopted to integrate data sources from different vendors through extraction,trans-formation,loading and other steps to provide a unified data access portal.Result/Conclusion The big data research platform for biologi-cal sample information resources has the advantages of multi-dimensional data screening and rapid integrated analysis,which can pro-vide support for clinical research.

Objective To investigate the application value of type Ⅰ procollagen N-peptide front-end (PⅠNP) in growth and development in children.Methods The clinical data of 99 children visiting in the ped-iatric department of Guangdong Provincial Hospital of Traditional Chinese Medicine from March to August 2023 were analyzed retrospectively,including gender,age,height,weight,BMI,visiting season,Tanner stage,PⅠNP,β-collagen degradation product (β-CTx),N-terminal osteocalcin (N-MID).The general data of children with different sex and PⅠNP level were analyzed.The partial correlation between PⅠNP and growth rate was analyzed.Then the efficiency of PⅠNP for predicting the child growth rate slow was conducted by the receiver operating characteristic (ROC) curve.Results The children height standard deviation,Tanner stage,β-CTx,N-MID,height after blood drawing,growth rate after blood drawing,growth rate slowness had statistical difference among the children with different PⅠNP levels (P<0.05).In the partial correlation,PⅠNP has the correlation with β-CTx (r=0.671),N-MID (r=0.506),growth rate before blood drawing (r=0.551) and growth rate after blood drawing (r=0.474,P<0.05).In linear regression,PⅠNP was linearly correlated with children's height growth rate,and the greater the PⅠNP value was,the higher the children's height growth rate in the past or the next three months was likely to be (P<0.05).The ROC curve results showed that when PⅠNP<434.8 ng/mL,there was a risk of slow height growth rate in children (AUC was 0.819,95%CI:0.712-0.927,sensitivity was 80.0%,specificity was 78.6%).Conclusion The PⅠNP level could reflect the height growth rate of children in the past or the next three months in their daily life,and has certain predictive value for the slow growth rate of children.

The clinical data of a case of neonatal bacterial meningitis complicated with posterior fossa subdural empyema in the West China Second University Hospital in December 2019 were retrospectively analyzed.The 3-day-old male newborn was admitted for jaundice with decreased intake for 1 day.Examinations on admission showed increased C-reactive protein.The count of karyocytes in cerebrospinal fluid (CSF) significantly increased, which were mainly neutrophils, and pyocytes could be found.The protein content in CSF increased, while that of glucose decreased.Both CSF culture and blood culture detected the presence of Escherichia coli.Enhanced magnetic resonance imaging (MRI) of the head indicated large abnormal signals in bilateral occipital extra-cerebellar spaces.T1-weighted images presented mixed low and high signals, and T2-weighted images presented high signals, and marginal enhancement was observed after enhancement.After 6 weeks of antibiotic treatment using Meropenem combined with Ceftazidime, the CSF index of the newborn patient returned to normal, and the subdural empyema of the posterior fossae subsided.Bacterial meningitis complicated with subdural empyema of posterior fossa is a rare and critical disease of the central nervous system.It is easily misdiagnosed due to the atypical clinical manifestations and early imaging features.The disease requires an adequate course of anti-infective treatment.Surgical removal of the empyema should be performed if the anti-infective treatment is unresponsive.

Objective:To understand the mental health status of pregnant women in the third trimester of pregnancy, and explore the influencing factors.Methods:The general demographic information and pregnancy information of 575 pregnant women in the Chinese Pregnant Women Cohort Study were collected. The mental health status of pregnant women in the third trimester was investigated by using Edinburgh Postpartum Depression Scale, Self-Rating Anxiety Scale and University of California at Los Angeles. Multivariate unconditional logistic regression was used to analyze the influencing factors for mental health of pregnant women.Results:In the third trimester of pregnancy, the incidence of depression was 16.52%, the incidence of anxiety was 11.13%, and the incidence of feeling loneliness was 26.26%. Logistic regression analysis showed that compared with those with education level of junior high school below, those with education level of college or bachelor's degree ( OR=0.418, 95% CI: 0.184-0.950) and master's degree or above ( OR=0.116, 95% CI: 0.027-0.503) were less likely to feel loneliness. Pregnant women with higher annual family income (10 000 RMB yuan) were less likely to suffer from depression (≥20 vs. <10: OR=0.527, 95% CI: 0.279-0.998), anxiety (10-20 vs. <10: OR=0.363, 95% CI: 0.180-0.731; ≥20 vs. <10: OR=0.271, 95% CI: 0.132-0.554) and feeling loneliness (≥20 vs. <10: OR=0.477, 95% CI: 0.276-0.826). Conclusions:The education level and family income have impacts on the mental health status of pregnant women in the third trimester. Medical staff should give targeted psychological advice to pregnant women to improve their mental health status.

Objective To understand the status of economic burden of maternal health care of pregnant women in China, and to discuss the equity and accessibility of maternal health care during pregnancy among different regions and populations. Methods A total of 9 193 women during early pregnancy were recruited from the Chinese Pregnant Women Cohort Study between July 25, 2017 and November 26, 2018. Information on general condition and economic burden of maternal health care was surveyed. SPSS 25.0 software was used for statistical analysis. Results The median direct medical cost of maternity check-ups for pregnant women was 400 CNY per visit, and the median cost of lost work was 360 CNY per visit. The analysis of the results showed that the median medical expense was highest in pre-pregnant women with BMI <18.5kg/m² (P=0.008). The median medical expense was higher in urban residents than rural residents (P<0.001). Families with fewer members had higher direct medical expenses (P<0.001, P_trend=0.003). The higher the socioeconomic status was, the higher the direct medical expense was (P<0.001, P_trend=0.003). The cost of lost work was lower in pregnant women with higher socioeconomic status (P=0.025, P_trend=0.017). In addition, the medical expense was highest in women living in the eastern part of China (P<0.001). The direct medical expenses (P=0.002) and lost-time expenses of pregnant women in the North were higher than those in the South (P=0.013). Conclusion The problem of equity and accessibility of maternal health care still existed. It is recommended that relevant departments further improve maternal health care services and build a diversified healthcare service system to ensure maternal and child health and promote eugenics.

Objective To analyze the prevalence of depression in early pregnancy, explore its possible influencing factors, and provide reference for mental health care during pregnancy. Methods A baseline survey of 9 193 early pregnant women recruited by the Chinese Pregnant Women Cohort Study (CPWCS) program was conducted. Edinburgh Postnatal Depression Scale was used to assess the depression symptoms in early pregnancy. The χ² test and multivariable logistic regression were used to analyze the influencing factors. Results The rate of depression in early pregnant women in CPWCS was 46.50%. Multivariate analysis showed that unplanned pregnancy (OR=1.23, 95%CI: 1.12~1.35, P<0.001), passive smoking (OR=1.28, 95%CI: 1.18~1.39, P<0.001), drinking (OR=1.35, 95%CI: 1.12~1.63, P=0.002) and consumption of carbonated or sugary beverages （OR=0.80, 95%CI: 0.73~0.88, P<0.001） were risk factors for depression during early pregnancy, while enough sleep (OR=0.71, 95%CI: 0.57~0.88, P=0.002), moderate-high level of physical activity (OR=0.87, 95%CI: 0.78~0.98, P=0.023), healthy intake of vegetables and fruits（OR=0.60, 95%CI: 0.51~0.70, P<0.001), animal foods（OR=0.82, 95%CI: 0.74~0.91, P<0.001） and milk and dairy products（OR=0.81, 95%CI: 0.72~0.90, P<0.001）were protective factors. Conclusion The rate of depression was high and it was affected by many factors. It is necessary to pay more attention to depression symptoms during early pregnancy and carry out targeted psychological health care during pregnancy.

Objective:To investigate sleep quality in pregnant women during their first and second trimester and to identify risk factors.Methods:Data was from the Chinese Pregnant Women Cohort Study. A total of 3 618 pregnant women were included, with the exclusion 346 women who had missing information. Sociodemographic, health-related behavior, depression and sleep quality information were collected and analyzed. Logistic regression analysis were used to explore the influencing factors of sleep quality in pregnant women.Results:Among the 3 618 pregnant woman 28.2% had poor sleep quality in their first trimester and 28.7% in the second trimester. 15.2% pregnant women had progressively worse sleep and 13.0% had persistently poor sleep had pregnant women were generally suffered from poor sleep quality, difficulty falling asleep, sleep disorders and daily fatigue. Regular diet ( OR=0.75, 95% CI: 0.62-0.92) and work ( OR=0.84,95% CI: 0.71-0.99) in the first trimester were protective factors of sleep quality in pregnant women. Age ≥30 year old ( OR=1.19, 95% CI: 1.03-1.37), passive smoking ( OR=1.18, 95% CI: 1.02-1.36) and depression ( OR=2.25, 95% CI: 1.95-2.61) in the first trimester were risk factors. Conclusions:The rate of poor sleep quality are high among Chinese pregnant woman during their first and second trimester. The risk factors of sleep quality are multiple. Regular diet and work, reduction of tobacco exposure, alleviation of depression symptom may help improve sleep quality among pregnant women.

Objective:To investigate the effect of changes in physical activities on depressive symptoms in the second trimester of pregnancy.Methods:Data from the Chinese Pregnant Women Cohort Study, from July 25, 2017 to November 26, 2018, were used. Women who had effectively completed the survey of physical activity and depressive symptoms in the first and second trimesters of pregnancy, were recruited. Both International Physical Activity Questionnaire-short and Edinburgh Postnatal Depression Scale were used, respectively. Pregnant women who had completed two surveys were included in our study and were divided into two groups according to the depressive symptoms, measured at the baseline. Among the pregnant women without depressive symptoms at the baseline, logistic regression was used to analyze the effects of changes in physical activity on the prevention of depressive symptoms. Effect on the reduction of depressive symptoms was analyzed, using the same method.Results:The prevalence rates of depressive symptoms were 23.83 % and 20.57 % in the baseline and second trimester, respectively. After adjusting for age, education level, occupation, family annual income and pre-pregnancy BMI, data from the logistic regression showed that women without depressive symptoms and with increased and adequate physical activities in the baseline, were with lower risks to develop depressive symptoms in the second trimester ( OR=0.479, 95 %CI: 0.335-0.684; OR=0.566, 95 %CI: 0.394-0.815). Among women with depressive symptoms in the baseline survey, association between physical activity and depressive symptoms was not statistically significant ( P>0.05). Conclusions:Increased and adequate physical activities showed preventive effects on depressive symptoms during pregnancy, but the remission effect was not obvious in women with depressive symptoms. Pregnant women should be encouraged to increase their physical activities while screening programs should also be carried out to reduce the depressive symptoms during pregnancy.

Objective:To prospectively explore the associations between total and different types of physical activities and gestational diabetes mellitus (GDM) in the first trimester of pregnant women, in Beijing.Methods:Data of 909 participants from the Chinese Pregnant Women Cohort study were extracted and studied. Four types of physical activities, including household/care-giving, occupational, sports/exercise and outdoor ways of transportation (walking/cycling/E-biking) in early pregnancy were studied by using the pregnancy physical activity questionnaire (PPAQ). All the participants were followed up and related data on GDM collected. Logistic regressions were conducted for data analysis on the associations of interests.Results:A total of 206 pregnant women (22.7 %) were diagnosed with GDM. After adjusting for age, pre-pregnancy BMI, family history of diabetes and other types of physical activities, results from the logistic regression showed that women with moderate level of household/care-giving activities were with the lower odds on GDM ( OR=0.654, 95 %CI: 0.436-0.980). Women who had met the guideline of exercise were less likely to have GDM ( OR=0.518, 95 %CI: 0.287-0.934). There was no significant association appeared between total physical, occupational and outdoor ways of transportation (walking/cycling/E-biking) activities with GDM. Conclusions:Sports/exercise and household/care-giving activities in early pregnancy appeared important on GDM prevention. Pregnant women are encouraged to wisely arranging their sports/exercise activities and engaging in moderate household/care-giving activities in the first trimester of pregnancy, to prevent GDM.