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 explore the risk factors of the stone-free rate after flexible ureteroscopy for lower pole calculi,develop a predictive model based on these identified factors,with subsequent validation and evalua-tion of the established model.Methods A retrospective analysis was conducted on 154 patients with lower pole renal calculi who underwent flexible ureteroscopy(FURS)at Guangdong Provincial Hospital of Traditional Chinese Medicine from 2020 to 2024.Based on postoperative stone clearance status,patients were categorized into a stone-free group and a residual stone group.Univariate analysis was performed to screen potential risk factors,while Pear-son correlation coefficients and variance inflation factor(VIF)were employed to assess multicollinearity,retaining the indicator with the highest area under the curve(AUC).Independent predictors were identified through multi-variate logistic regression analysis,and a nomogram model was constructed.Internal validation was conducd using the bootstrap resampling method.The predictive performance and clinical utility of the model were evaluated using receiver operating characteristic(ROC)curves and decision curve analysis(DCA).Results Univariate analysis demonstrated that largest stone diameter(LSD),cumulative stone diameter(CSD),stone volume(SV),stone surface area(SA),mean stone density(MSDE),and infundibular pelvic angle(IPA)were significantly associated with stone-free rate(SFR)following flexible ureteroscopy(FURS)for lower pole calculi(all P<0.05).After collinearity diagnostics,LSD(area under the curve[AUC]=0.724)was retained as the optimal stone burden parameter.Multivariate logistic regression analysis confirmed LSD,MSDE,and IPA as independent predictors of postoperative SFR.The nomogram model exhibited robust predictive performance with an AUC of 0.786(sensitivity:79.6%,specificity:71.0%).Internal validation via 1000 bootstrap resamples yielded an AUC of 0.792,and deci-sion curve analysis(DCA)confirmed clinical utility with net benefit across threshold probabilities of 4%—75%.Conclusions The nomogram model developed in this study,which incorporates both stone characteristics and renal anatomical parameters,demonstrates effective prediction of stone-free rate(SFR)following flexible ureteros-copy for lower pole calyceal stones.With stable predictive performance and high clinical applicability,this model provides a reliable tool for preoperative personalized decision-making in endourological management.

OBJECTIVE To explore the expressions of eosinophilic chemotactic factor 11(CCL11),leukotriene B4(LTB4),percentage of neutrophils(NEUT％)and C-reactive protein(CRP)in peripheral blood of the children with Mycoplasma pneumoniae(MP)infection complicated with plastic bronchitis and analyze the clinical signifi-cance.METHODS A total of 80 children with MP pneumonia complicated with plastic bronchitis who were trea-ted in the Second Hospital of Longyan City,Fujian Province from Jan.2020 to Dec.2023 were assigned as the study group,and 115 patients with MP pneumonia were chosen as the control group.The clinical data,manifesta-tions and Pediatric Risk of Mortality Ⅲ(PRISM Ⅲ)score were statistically analyzed.The levels of peripheral blood CCL11,LTB4,NEUT％and CRP were observed and compared between the two groups.Pearson analysis was performed for the associations of the levels of CCL11,LTB4,NEUT％and CRP with the PRISM Ⅲscore.The value of the joint detection of CCL11,LTB4,NEUT％and CRP in diagnosis of the MP pneumoni-a-induced plastic bronchitis was analyzed.RESULTS There were significant differences in reduction of bronchial breathing sound,pleural effusion and PRISM Ⅲ score between the two groups(P＜0.05).There were significant differences in the levels of peripheral blood CCL11,LTB4,NEUT％and CRP between the study group and the control group(P＜0.05);the CRP level of the study group was(29.42±8.14)mg/L,higher than that of the control group(t=10.138,P＜0.001).The levels of CCL11,LTB4,NEUT％and CRP were positively correlated with the PRISM Ⅲ score(r=0.723,0.710,0.771,0.754,respectively,all P＜0.001).The area under the curve(AUC)of the single detection of CCL11,LTB4,NEUT％and CRP was remarkably higher in diagnosis of MP pneumonia-induced plastic bronchitis than that of the joint detection of the four markers(P＜0.05).CONCLUSIONS The children with MP pneumonia complicated with plastic bronchitis show increased expressions of CCL11,LTB4,NEUT％and CRP.The four markers are positively correlated with the PRISM Ⅲ score.The four markers have high values in diagnosis of the MP pneumonia complicated with plastic bronchitis.

OBJECTIVE To explore the expressions of eosinophilic chemotactic factor 11(CCL11),leukotriene B4(LTB4),percentage of neutrophils(NEUT％)and C-reactive protein(CRP)in peripheral blood of the children with Mycoplasma pneumoniae(MP)infection complicated with plastic bronchitis and analyze the clinical signifi-cance.METHODS A total of 80 children with MP pneumonia complicated with plastic bronchitis who were trea-ted in the Second Hospital of Longyan City,Fujian Province from Jan.2020 to Dec.2023 were assigned as the study group,and 115 patients with MP pneumonia were chosen as the control group.The clinical data,manifesta-tions and Pediatric Risk of Mortality Ⅲ(PRISM Ⅲ)score were statistically analyzed.The levels of peripheral blood CCL11,LTB4,NEUT％and CRP were observed and compared between the two groups.Pearson analysis was performed for the associations of the levels of CCL11,LTB4,NEUT％and CRP with the PRISM Ⅲscore.The value of the joint detection of CCL11,LTB4,NEUT％and CRP in diagnosis of the MP pneumoni-a-induced plastic bronchitis was analyzed.RESULTS There were significant differences in reduction of bronchial breathing sound,pleural effusion and PRISM Ⅲ score between the two groups(P＜0.05).There were significant differences in the levels of peripheral blood CCL11,LTB4,NEUT％and CRP between the study group and the control group(P＜0.05);the CRP level of the study group was(29.42±8.14)mg/L,higher than that of the control group(t=10.138,P＜0.001).The levels of CCL11,LTB4,NEUT％and CRP were positively correlated with the PRISM Ⅲ score(r=0.723,0.710,0.771,0.754,respectively,all P＜0.001).The area under the curve(AUC)of the single detection of CCL11,LTB4,NEUT％and CRP was remarkably higher in diagnosis of MP pneumonia-induced plastic bronchitis than that of the joint detection of the four markers(P＜0.05).CONCLUSIONS The children with MP pneumonia complicated with plastic bronchitis show increased expressions of CCL11,LTB4,NEUT％and CRP.The four markers are positively correlated with the PRISM Ⅲ score.The four markers have high values in diagnosis of the MP pneumonia complicated with plastic bronchitis.

Objective To explore the risk factors of the stone-free rate after flexible ureteroscopy for lower pole calculi,develop a predictive model based on these identified factors,with subsequent validation and evalua-tion of the established model.Methods A retrospective analysis was conducted on 154 patients with lower pole renal calculi who underwent flexible ureteroscopy(FURS)at Guangdong Provincial Hospital of Traditional Chinese Medicine from 2020 to 2024.Based on postoperative stone clearance status,patients were categorized into a stone-free group and a residual stone group.Univariate analysis was performed to screen potential risk factors,while Pear-son correlation coefficients and variance inflation factor(VIF)were employed to assess multicollinearity,retaining the indicator with the highest area under the curve(AUC).Independent predictors were identified through multi-variate logistic regression analysis,and a nomogram model was constructed.Internal validation was conducd using the bootstrap resampling method.The predictive performance and clinical utility of the model were evaluated using receiver operating characteristic(ROC)curves and decision curve analysis(DCA).Results Univariate analysis demonstrated that largest stone diameter(LSD),cumulative stone diameter(CSD),stone volume(SV),stone surface area(SA),mean stone density(MSDE),and infundibular pelvic angle(IPA)were significantly associated with stone-free rate(SFR)following flexible ureteroscopy(FURS)for lower pole calculi(all P<0.05).After collinearity diagnostics,LSD(area under the curve[AUC]=0.724)was retained as the optimal stone burden parameter.Multivariate logistic regression analysis confirmed LSD,MSDE,and IPA as independent predictors of postoperative SFR.The nomogram model exhibited robust predictive performance with an AUC of 0.786(sensitivity:79.6%,specificity:71.0%).Internal validation via 1000 bootstrap resamples yielded an AUC of 0.792,and deci-sion curve analysis(DCA)confirmed clinical utility with net benefit across threshold probabilities of 4%—75%.Conclusions The nomogram model developed in this study,which incorporates both stone characteristics and renal anatomical parameters,demonstrates effective prediction of stone-free rate(SFR)following flexible ureteros-copy for lower pole calyceal stones.With stable predictive performance and high clinical applicability,this model provides a reliable tool for preoperative personalized decision-making in endourological management.

Objective To discuss The Clinical Significance of Eosinophil (EOS) in urosepsis. Methods A total of 99 patients of urosepsis in Department of Urology,Guangdong Provincial TCM Hospital from Mar. 2013 to Jul. 2016 were selected as research objects by retrospective analysis. The patients were classified into groupEOS= 0 andgroup EOS > 0,group PCT(procalcitonin)≥ 2 ng/mL andgroup PCT < 2 ng/mL,the differences of PCT concentration and percentage of EOS in two groups were analyzed comparatively. 99 patients of urosepsiswere also compared the difference of the percentage of EOS with another group including 100 patients of urinary tract infection (UTI) without Sepsis. Results The percentage of EOS was significantly decreased in 86.9%(86/99)of patients of urosepsis. The paired student t test show the percentage of EOS in two days after treatment,four days after treatment, before hospital discharge were higher than that before the treatment, the difference wassignificant (P < 0.05). The Independent-Sample Test show that the PCTconcentration in EOS = 0 group were higher than EOS > 0 group,the percentage of EOS in PCT≥2 ng/mL groupwere lower than PCT<2 ng/mL group,difference were significant(P<0.05). And The Independent-Sample Testalso showed that the percentage of EOS of the Urosepsis group was definitely lower than the UTI group without Sepsis. Difference was statistically significant. Concusions The percentage of EOS could be applied to assess the severity of urosepsis, monitor the disease progression and evaluate the infection control. The cost was lower than PCT in therapeuticprocess ofurosepsis.