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 evaluate the clinical outcomes of combined complete preservation of chordal structure mitral valve replacement (C-MVR) with total anatomical arterial myocardial revascularization (TACR) in coronary patients with moderate-to-severe or severe ischemic mitral regurgitation (IMR).Methods:This is a retrospective multi-center case series study. Data were retrospectively collected from 127 patients with coronary artery disease with moderate to severe or severe IMR who received TACR with C-MVR from July 2015 to April 2024 in 13 hospitals in China. There were 90 males and 37 females, aged (56.5±10.7) years (range: 33 to 74 years). Perioperative data and follow-up data including left ventricular ejection fraction, left ventricular end-diastolic diameter, and patency rate of arterial grafts of patients were collected. Comparisons were made using paired sample t-test or χ2 test. Results:In this cohort of 127 patients, 67 underwent concurrent tricuspid valve repair. During surgery, 113 grafts of the left internal mammary artery (LIMA), 127 grafts of the left radial artery, 80 grafts of the right radial artery, and 110 grafts of the right internal mammary artery (RIMA) were harvested. The number of the distal anastomosis was 4.2±0.4 (range: 3 to 5). The aortic cross-clamp time and cardiopulmonary bypass time were (97.5±23.4) minutes (range: 90 to 161 minutes) and (145.4±19.2) minutes (range: 101 to 210 minutes), respectively. There was one operative death. Intraoperative placement of an intra-aortic balloon pump was performed in 21 patients to improve the left ventricular ejection. No sternal ischemic occurred. All patients completed follow-up, with a mean follow-up period of (64.3±7.5) months (range: 4 to 110 months). No major cerebrovascular events occurred during the follow-up period, and all patients survived. Left ventricular ejection fraction improved postoperatively (55.0%±5.3% vs. 41.0%±15.3%, t=17.23, P<0.01). The proportion of patients with New York Heart Association functional class ≤2 increased postoperatively (23.6% (30/127) vs. 87.3% (110/126), χ2=103.77, P<0.01). The proportion of patients with Canadian Cardiovascular Society Angina Classification ≤3 decreased postoperatively (4.8% (6/126) vs. 78.7% (100/127), χ2=142.19, P<0.01). The left ventricular end-diastolic diameter decreased postoperatively ((5.70±4.50) cm vs. (6.10±0.23) cm, t=12.15, P<0.01). Coronary multi-detector computed tomography angiography (MDCTA) follow-up was conducted for (60.5±11.7) months (range: 6 to 109 months) postoperatively. MDCTA confirmed the patency rates of the grafts: 96.4% (108/112) for the LIMA grafts, 88.9% (112/126) for the left radial artery grafts, 93.7% (74/79) for the right radial artery grafts, and 90.9% (100/110) for the free RIMA grafts. No significant differences in graft patency rates were observed between the arterial grafts ( χ2=5.24, P=0.155). Conclusion:The results of this multi-centre study demonstrate satisfactory mid-term results of C-MVR with TACR for the treatment of coronary artery disease with moderate to severe or severe IMR.

Objective:To evaluate the clinical outcomes of combined complete preservation of chordal structure mitral valve replacement (C-MVR) with total anatomical arterial myocardial revascularization (TACR) in coronary patients with moderate-to-severe or severe ischemic mitral regurgitation (IMR).Methods:This is a retrospective multi-center case series study. Data were retrospectively collected from 127 patients with coronary artery disease with moderate to severe or severe IMR who received TACR with C-MVR from July 2015 to April 2024 in 13 hospitals in China. There were 90 males and 37 females, aged (56.5±10.7) years (range: 33 to 74 years). Perioperative data and follow-up data including left ventricular ejection fraction, left ventricular end-diastolic diameter, and patency rate of arterial grafts of patients were collected. Comparisons were made using paired sample t-test or χ2 test. Results:In this cohort of 127 patients, 67 underwent concurrent tricuspid valve repair. During surgery, 113 grafts of the left internal mammary artery (LIMA), 127 grafts of the left radial artery, 80 grafts of the right radial artery, and 110 grafts of the right internal mammary artery (RIMA) were harvested. The number of the distal anastomosis was 4.2±0.4 (range: 3 to 5). The aortic cross-clamp time and cardiopulmonary bypass time were (97.5±23.4) minutes (range: 90 to 161 minutes) and (145.4±19.2) minutes (range: 101 to 210 minutes), respectively. There was one operative death. Intraoperative placement of an intra-aortic balloon pump was performed in 21 patients to improve the left ventricular ejection. No sternal ischemic occurred. All patients completed follow-up, with a mean follow-up period of (64.3±7.5) months (range: 4 to 110 months). No major cerebrovascular events occurred during the follow-up period, and all patients survived. Left ventricular ejection fraction improved postoperatively (55.0%±5.3% vs. 41.0%±15.3%, t=17.23, P<0.01). The proportion of patients with New York Heart Association functional class ≤2 increased postoperatively (23.6% (30/127) vs. 87.3% (110/126), χ2=103.77, P<0.01). The proportion of patients with Canadian Cardiovascular Society Angina Classification ≤3 decreased postoperatively (4.8% (6/126) vs. 78.7% (100/127), χ2=142.19, P<0.01). The left ventricular end-diastolic diameter decreased postoperatively ((5.70±4.50) cm vs. (6.10±0.23) cm, t=12.15, P<0.01). Coronary multi-detector computed tomography angiography (MDCTA) follow-up was conducted for (60.5±11.7) months (range: 6 to 109 months) postoperatively. MDCTA confirmed the patency rates of the grafts: 96.4% (108/112) for the LIMA grafts, 88.9% (112/126) for the left radial artery grafts, 93.7% (74/79) for the right radial artery grafts, and 90.9% (100/110) for the free RIMA grafts. No significant differences in graft patency rates were observed between the arterial grafts ( χ2=5.24, P=0.155). Conclusion:The results of this multi-centre study demonstrate satisfactory mid-term results of C-MVR with TACR for the treatment of coronary artery disease with moderate to severe or severe IMR.

Objective Watch the proprioceptive neuromuscular facilitation(PNF)in the treatment of patients with shoulder-hand syndrome,and to explore its relevant therapeutic mechanisms.Methods Sixty patients with shoulder-hand syndrome were split into two groups at random:thirty cases each for observation and control.The control group received both standard medication and training in rehabilitation.Intradermal needles were inserted at the Jianjing,Jianyu,Binao,Qing Lengyuan,Shouwuli,and Quchi points and left in place for 48 hours for the treatment group.The PNF treatment was administered for thirty minutes every day,five times a week,whereas the control group underwent four weeks of traditional drug treatment and rehabilitation training.Before and after therapy,the following measures were used:the Disability of the Arm,Shoulder and Hand(DASH),the Activity of Daily Living Scale(ADL),the Simplified Fugl-Meyer Scale(FMA),and the Visual Analog Scale(VAS).In order to measure changes in endothelin-1(ET-1),nitric oxide(NO),and bradykinin(BK),serum was collected.Result Scale score:①Within-group comparison,compared with before treatment,VAS and DASH scores were significantly lower,FMA,a significant rise in ADL scores,differences were statistically significant(P<0.01).②Comparison between groups,compared with the control group,observation group of DASH score significantly lower after treatment(P<0.05),a significant rise in FMA and ADL scores(P<0.05),VAS score has no obvious difference(P>0.05).Laboratory index test:①Intra-group comparison:compared with before treatment,BK and ET-1 expression levels increased,NO and CGRP expression levels decreased,the differences were statistically significant(P<0.01).②Comparison between groups:Following treatment,the observation group showed increases in BK and ET-1 expression degrees as well as decreased NO and CGRP expression degrees.This difference was statistically significant(P<0.01).Conclusions Intradermal needle combined with PNF can promote shoulder pain symptoms,increase upper limb mobility,also improve quality of life in patients with shoulder-hand syndrome.One of the mechanisms may be to upregulate the expression level of BK and ET-1,and downregulate the expression level of NO and CGRP,so as to improve the microcirculation function and reduce the neurogenic inflammatory response.

Objective Watch the proprioceptive neuromuscular facilitation(PNF)in the treatment of patients with shoulder-hand syndrome,and to explore its relevant therapeutic mechanisms.Methods Sixty patients with shoulder-hand syndrome were split into two groups at random:thirty cases each for observation and control.The control group received both standard medication and training in rehabilitation.Intradermal needles were inserted at the Jianjing,Jianyu,Binao,Qing Lengyuan,Shouwuli,and Quchi points and left in place for 48 hours for the treatment group.The PNF treatment was administered for thirty minutes every day,five times a week,whereas the control group underwent four weeks of traditional drug treatment and rehabilitation training.Before and after therapy,the following measures were used:the Disability of the Arm,Shoulder and Hand(DASH),the Activity of Daily Living Scale(ADL),the Simplified Fugl-Meyer Scale(FMA),and the Visual Analog Scale(VAS).In order to measure changes in endothelin-1(ET-1),nitric oxide(NO),and bradykinin(BK),serum was collected.Result Scale score:①Within-group comparison,compared with before treatment,VAS and DASH scores were significantly lower,FMA,a significant rise in ADL scores,differences were statistically significant(P<0.01).②Comparison between groups,compared with the control group,observation group of DASH score significantly lower after treatment(P<0.05),a significant rise in FMA and ADL scores(P<0.05),VAS score has no obvious difference(P>0.05).Laboratory index test:①Intra-group comparison:compared with before treatment,BK and ET-1 expression levels increased,NO and CGRP expression levels decreased,the differences were statistically significant(P<0.01).②Comparison between groups:Following treatment,the observation group showed increases in BK and ET-1 expression degrees as well as decreased NO and CGRP expression degrees.This difference was statistically significant(P<0.01).Conclusions Intradermal needle combined with PNF can promote shoulder pain symptoms,increase upper limb mobility,also improve quality of life in patients with shoulder-hand syndrome.One of the mechanisms may be to upregulate the expression level of BK and ET-1,and downregulate the expression level of NO and CGRP,so as to improve the microcirculation function and reduce the neurogenic inflammatory response.

Gene Ontology(GO)has been widely used to annotate functions of genes and gene prod-ucts.Here,we proposed a new method,TripletGO,to deduce GO terms of protein-coding and non-coding genes,through the integration of four complementary pipelines built on transcript expression profile,genetic sequence alignment,protein sequence alignment,and naive probability.TripletGO was tested on a large set of 5754 genes from 8 species(human,mouse,Arabidopsis,rat,fly,budding yeast,fission yeast,and nematoda)and 2433 proteins with available expression data from the third Critical Assessment of Protein Function Annotation challenge(CAFA3).Experimental results show that TripletGO achieves function annotation accuracy significantly beyond the current state-of-the-art approaches.Detailed analyses show that the major advantage of TripletGO lies in the coupling of a new triplet network-based profiling method with the feature space mapping technique,which can accurately recognize function patterns from transcript expression profiles.Meanwhile,the combination of multiple complementary models,especially those from transcript expression and protein-level alignments,improves the coverage and accuracy of the final GO anno-tation results.The standalone package and an online server of TripletGO are freely available at https://zhanggroup.org/TripletGO/.

Objective To develop a convolution neural network (CNN) model to classify multi?sequence MR images of the prostate. Methods ResNet18 convolution neural network (CNN) model was developed to classify multi?sequence MR images of the prostate. A deep residual network was used to improve training accuracy and test accuracy. The dataset used in this experiment included 19 146 7?sequence prostate MR images (transverse T1WI, transverse T2WI, coronal T2WI, sagittal T2WI, transverse DWI, transverse ADC, transverse PWI), from which a total of 2 800 7?sequence MR images was selected as a training set. Three hundred and eighty eight 7?sequence MR images were selected as test sets. Accuracy was used to evaluate the effectiveness of ResNet18 CNN model. Results The classification accuracy of the model for transverse DWI, sagittal T2WI, transverse ADC, transverse T1WI, and transverse T2WI was as high as 100.0% (44/44,52/52), and the accuracy for transverse PWI was also as high as 96.7% (116/120). The accuracy for coronal T2WI was 77.5% (31/40). 0.8% (1/120) of transverse PWI was incorrectly assigned to transverse T2WI, and 2.5% (3/120) incorrectly assigned to sagittal T2WI. 15.0% (6/40) of coronal T2WI was incorrectly assigned to transverse T2WI, and 7.5% (3/40) to sagittal T2WI. Conclusion The experimental results show the effectiveness of our deep learning method regarding accuracy in the prostate multi?sequence MR images detection.

Objective: To develop a convolution neural network (CNN) model to classify multi-sequence MR images of the prostate. Methods: ResNet18 convolution neural network (CNN) model was developed to classify multi-sequence MR images of the prostate. A deep residual network was used to improve training accuracy and test accuracy. The dataset used in this experiment included 19 146 7-sequence prostate MR images (transverse T₁WI, transverse T₂WI, coronal T₂WI, sagittal T₂WI, transverse DWI, transverse ADC, transverse PWI), from which a total of 2 800 7-sequence MR images was selected as a training set. Three hundred and eighty eight 7-sequence MR images were selected as test sets. Accuracy was used to evaluate the effectiveness of ResNet18 CNN model. Results: The classification accuracy of the model for transverse DWI, sagittal T₂WI, transverse ADC, transverse T₁WI, and transverse T₂WI was as high as 100.0% (44/44,52/52), and the accuracy for transverse PWI was also as high as 96.7% (116/120). The accuracy for coronal T₂WI was 77.5% (31/40). 0.8% (1/120) of transverse PWI was incorrectly assigned to transverse T₂WI, and 2.5% (3/120) incorrectly assigned to sagittal T₂WI. 15.0% (6/40) of coronal T₂WI was incorrectly assigned to transverse T₂WI, and 7.5% (3/40) to sagittal T₂WI. Conclusion The experimental results show the effectiveness of our deep learning method regarding accuracy in the prostate multi-sequence MR images detection.

Objective: To evaluate combined robotic and endoscopic surgery in the third space for gastric submucosal tumors(SMTs). Methods: Combined surgery in 4 patients were compared with 19 patients who underwent laparoscopic wedge resection between Aug 2017 and Feb 2018. Results: R₀ resection was achieved in all combined surgery patients. The operation time was longer (112±29 )min vs. (93±11 ) min (t=2.338, P<0.05), but less blood loss, (11±6)ml vs.(59±6)ml (t=15.102, P<0.01). In combined surgery group, there was a larger tumor over resected tissue percentage, 65.4%±28.2% vs.22.8%±19.6% ( t=3.680, P<0.05). Combined surgery group patients were with earlier first breaking wind (3±1.4) d vs.(4.1±0.9) d (t=2.026, P>0.05), and shorter hospital stay (6.5±1.3) d vs.( 8.5±0.6) d (t=4.902, P<0.01), but a little higher hospitalization costs(57 651±10 097)rmb vs.(42 620±5 086)rmb (t=4.508, P<0.01). There were no major postoperative complications occurred in neither groups, nor tumor recurrences after 3-month follow-up. Conclusion Combined robotic and endoscopic surgery in the third space for submucosal gastric tumors is a novel operation with short operation time, less blood loss and good result.

OBJECTIVE： To mine and analyze the formulation rules of Chinese patent medicine for cold， and to provide reference for clinical dialectical medication and R&D of new medicine for cold. METHODS： The name， dosage form， formulation， function of curing of Chinese patent medicines for cold were collected from 2015 edition of Chinese Pharmacopeia （part Ⅰ） and then input into TCM Inheritance Assistant Platform V 2.5； use frequency of TCM were counted. Apriori algorithm and association rules were used to analyze the core medicinal material combination （10％ support and 0.65 confidence）. New formulation combinations were extracted by unsupervised entropy hierarchical clustering method. RESULTS： A total of 130 kinds of Chinese patent medicine （196 Chinese patent medicine with the same prescription and different dosage forms） for treating cold were collected， including granules （47）， pills （32）， tablets （31）， mixtures （31）， etc. 264 medicinal materials were involved. The cold syndromes contained wind-heat syndrome， wind-cold syndrome， summer-dampness syndrome and Qi deficiency syndrome. Top 3 medicinal materials in the list of use frequency were Glycyrrhiza uralensis （45.38％）， Scutellaria baicalensis （32.31％） and Platycodon grandiflorus （31.54％）. There were 28 core medicinal material combinations， among which the top 3 were               G. uralensis-P. grandiflorus，  Mentha haplocalyx-P. grandiflorus and S. baicalensis-Forsythia suspensa. New combinations were excavated， including Nepeta cataria-P. grandiflorus-M. haplocalyx-Citrus reticulate-Folium Perillae-Citrus aurantium- Poria cocos， F. suspense-S. baicalensis-Lonicera japonica- Arctium lappa-Fermented soybean. CONCLUSIONS： This study analyzed the formulation rules of Chinese patent medicine for treating cold by using the TCM inheritance assistant platform V2.5， which can provide reference for clinical dialectical medication and R&D of new medicines for cold.