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 investigate the influencing factors of antibiotic-associated diarrhea(AAD)following congenital heart disease(CHD)surgery in pediatric patients,develop a nomogram-based predictive model,and validate its efficacy.Methods A retrospective analysis was conducted on the clinical data of pediatric patients who underwent CHD surgery in the Pediatric Intensive Care Unit(PICU)of a tertiary hospital in Guang-dong Province from July 2022 to July 2024.Patients were categorized into an AAD group and a non-AAD group.Univariate and multivariate logistic regression analyses were performed to identify risk factors for AAD occurrence following CHD surgery.A risk prediction model was developed,and a nomogram was constructed.The predictive performance of the model was evaluated using the Receiver Operating Characteristic(ROC)curve to calculate the area under the curve(AUC),the Hosmer-Lemeshow goodness-of-fit test,calibration curves,and clinical decision curve analysis.External validation of the model was conducted using data from patients in the Surgical Intensive Care Unit(SICU).Results The incidence of AAD following CHD surgery was 48.52%(229 out of 472 cases).Risk factors for AAD included the combined use of antibiotics,mechanical ventilation,elevated C-reactive protein levels,prolonged surgical duration,and extended antibiotic usage time(all with OR>1,P<0.05).Conversely,probiotic administration was identified as a protective factor(OR<1,P<0.05).The predictive model demon-strated excellent discrimination,as evidenced by the ROC curve areas:0.922(95%CI:0.894～0.951)in the modeling group,0.886(95%CI:0.838～0.915)in the internal validation group,and 0.862(95%CI:0.784～0.941)in the external validation group.Additionally,the model exhibited satisfactory calibration,as indicated by the Hosmer-Lemeshow test results:χ2=7.96,P=0.538 in the modeling group;χ2=4.24,P=0.895 in the inter-nal validation group;and χ2=9.923,P=0.270 in the external validation group.Furthermore,the model provided significant clinical utility.Conclusions Combined antibiotic use,duration of antibiotic therapy,mechanical ventilation,surgical duration,C-reactive protein(CRP)levels,and probiotic administration are key factors influ-encing the occurrence of AAD.The risk prediction model developed based on these variables demonstrates robust predictive performance and can serve as a valuable reference for the development and implementation of preventive and therapeutic strategies in clinical practice.

Objective To investigate the influencing factors of antibiotic-associated diarrhea(AAD)following congenital heart disease(CHD)surgery in pediatric patients,develop a nomogram-based predictive model,and validate its efficacy.Methods A retrospective analysis was conducted on the clinical data of pediatric patients who underwent CHD surgery in the Pediatric Intensive Care Unit(PICU)of a tertiary hospital in Guang-dong Province from July 2022 to July 2024.Patients were categorized into an AAD group and a non-AAD group.Univariate and multivariate logistic regression analyses were performed to identify risk factors for AAD occurrence following CHD surgery.A risk prediction model was developed,and a nomogram was constructed.The predictive performance of the model was evaluated using the Receiver Operating Characteristic(ROC)curve to calculate the area under the curve(AUC),the Hosmer-Lemeshow goodness-of-fit test,calibration curves,and clinical decision curve analysis.External validation of the model was conducted using data from patients in the Surgical Intensive Care Unit(SICU).Results The incidence of AAD following CHD surgery was 48.52%(229 out of 472 cases).Risk factors for AAD included the combined use of antibiotics,mechanical ventilation,elevated C-reactive protein levels,prolonged surgical duration,and extended antibiotic usage time(all with OR>1,P<0.05).Conversely,probiotic administration was identified as a protective factor(OR<1,P<0.05).The predictive model demon-strated excellent discrimination,as evidenced by the ROC curve areas:0.922(95%CI:0.894～0.951)in the modeling group,0.886(95%CI:0.838～0.915)in the internal validation group,and 0.862(95%CI:0.784～0.941)in the external validation group.Additionally,the model exhibited satisfactory calibration,as indicated by the Hosmer-Lemeshow test results:χ2=7.96,P=0.538 in the modeling group;χ2=4.24,P=0.895 in the inter-nal validation group;and χ2=9.923,P=0.270 in the external validation group.Furthermore,the model provided significant clinical utility.Conclusions Combined antibiotic use,duration of antibiotic therapy,mechanical ventilation,surgical duration,C-reactive protein(CRP)levels,and probiotic administration are key factors influ-encing the occurrence of AAD.The risk prediction model developed based on these variables demonstrates robust predictive performance and can serve as a valuable reference for the development and implementation of preventive and therapeutic strategies in clinical practice.

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.

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 analyze and compare the changes in local functional activity of the brain under different recovery times after a 90-day,-6° head down bed rest(HDBR)experiment,clarify the mechanism of brain function remodeling during gravity adaptation,and provide imaging basis and guidance for the model construction and health assessment.Methods 36 healthy male volunteers underwent resting-state functional magnetic resonance imaging(rs-fMRI)scans before HDBR(PRE),3 days after 90-day HDBR(R+3),and 26-28 days after 90-day HDBR(R+26-28),and calculated regional homogeneity(ReHo)and low-frequency amplitude(ALFF)and perform statistical analysis between different time points.Results Compared with PRE-status,ReHo value in the left inferior parietal gyrus and ALFF value in the right posterior cingulate gyrus decreased significantly in R+3 status,while ReHo value in the left calcarine,right lingual gyrus and ALFF value in the precuneus,left paracentral lobule,and right postcentral gyrus increased significantly.At R+26-28 status,more brain areas showed significant changes.Conclusion 90 days of long-term HDBR and subsequent recovery will lead to changes in the neural functional activities of the brain's default network,sensorimotor network and visual network,and obvious adaptive remodeling will occur after a longer period of gravity re-adaptation and recovery.

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.

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 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 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.