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 establish the content determination method of Zhihuoding granules(ZHDG)by the anti-inflammatory active ingredients and fingerprint.Methods The inflammatory model of BEAS-2B cells was established by LPS(10 μg·mL-1)stimulation for 24 h,and the level of TNF-α in the supernatant was detected by enzyme-linked immunosorbent assay(ELISA).Using the reverse high-performance liquid chromatography(RP-HPLC)of 7 batch ZHDG fingerprint;HPLC was used to determine the content of geniposide and baicalin in granules.Results Compared with LPS Group,ZHDG,prim-O-glucosylcimifugin,5-O-methylvisammioside,baicalin,geniposide,and total polysaccharide extract all significantly decreased TNF-αlevels in BEAS-2B cells induced by LPS(P＜0.05).Fingerprint spectra of 7 batches of ZHDG were established,with a similarity of 1.000 to the reference.A total of 15 peaks were calibrated,and 7 chromatographic peaks were identified.Gardenin and baicalin were selected as the index components of ZHDG for evaluation.The established method was rapid and accurate.Conclusion The method for the determination of baicalin and geniposide in ZHDG are exclusive,accurate,and effective,providing reference for the quality control and clinical application of ZHDG.

Objective:To analyze the real experience of elderly patients with chronic heart failure and type 2 diabetes in dealing with abdominal distension, and to provide a basis for medical staff to formulate targeted intervention strategies.Methods:Using the purpose sampling method, semi-structured interview was conducted on elderly patients with chronic heart failure and type 2 diabetes who were admitted to Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine from April 2024 to June 2024. Extract themes used Colaizzi 7-step analysis method.Results:There were 6 males and 8 femdes, aged 60-80 years old. A total of 4 themes and 10 sub-themes were extracted, namely somatic symptom distress (obvious related symptom clusters, aggravation of basic disease symptoms), emotional response differentiation (weakening of emotional control, positive psychological derivation), diversified coping strategies (negative coping included self-neglect and avoidance of medical treatment, positive coping included active medical treatment and self-adjustment), coping difficulties (lack of disease knowledge, contradiction of coping strategies, urgent need for optimization of TCM diagnosis and treatment, imperfect external support system).Conclusions:Medical staff should pay attention to the physical and mental feelings of elderly patients with chronic heart failure and type 2 diabetes in the process of abdominal distension coping, and provide targeted health guidance and comprehensive nursing, so as to reduce the physical symptoms of patients and promote their physical and mental health.

Objective To establish the content determination method of Zhihuoding granules(ZHDG)by the anti-inflammatory active ingredients and fingerprint.Methods The inflammatory model of BEAS-2B cells was established by LPS(10 μg·mL-1)stimulation for 24 h,and the level of TNF-α in the supernatant was detected by enzyme-linked immunosorbent assay(ELISA).Using the reverse high-performance liquid chromatography(RP-HPLC)of 7 batch ZHDG fingerprint;HPLC was used to determine the content of geniposide and baicalin in granules.Results Compared with LPS Group,ZHDG,prim-O-glucosylcimifugin,5-O-methylvisammioside,baicalin,geniposide,and total polysaccharide extract all significantly decreased TNF-αlevels in BEAS-2B cells induced by LPS(P＜0.05).Fingerprint spectra of 7 batches of ZHDG were established,with a similarity of 1.000 to the reference.A total of 15 peaks were calibrated,and 7 chromatographic peaks were identified.Gardenin and baicalin were selected as the index components of ZHDG for evaluation.The established method was rapid and accurate.Conclusion The method for the determination of baicalin and geniposide in ZHDG are exclusive,accurate,and effective,providing reference for the quality control and clinical application of ZHDG.

Objective:To analyze the real experience of elderly patients with chronic heart failure and type 2 diabetes in dealing with abdominal distension, and to provide a basis for medical staff to formulate targeted intervention strategies.Methods:Using the purpose sampling method, semi-structured interview was conducted on elderly patients with chronic heart failure and type 2 diabetes who were admitted to Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine from April 2024 to June 2024. Extract themes used Colaizzi 7-step analysis method.Results:There were 6 males and 8 femdes, aged 60-80 years old. A total of 4 themes and 10 sub-themes were extracted, namely somatic symptom distress (obvious related symptom clusters, aggravation of basic disease symptoms), emotional response differentiation (weakening of emotional control, positive psychological derivation), diversified coping strategies (negative coping included self-neglect and avoidance of medical treatment, positive coping included active medical treatment and self-adjustment), coping difficulties (lack of disease knowledge, contradiction of coping strategies, urgent need for optimization of TCM diagnosis and treatment, imperfect external support system).Conclusions:Medical staff should pay attention to the physical and mental feelings of elderly patients with chronic heart failure and type 2 diabetes in the process of abdominal distension coping, and provide targeted health guidance and comprehensive nursing, so as to reduce the physical symptoms of patients and promote their physical and mental health.

Objective:To analyze the clinical and pathological characteristics, treatment and prognosis of renal changes in patients with Kimura disease and improve the clinicians′ understanding on renal manifestations of Kimura disease.Methods:The clinical data of Kimura disease patients with definite diagnosis and detailed data in Peking Union Medical College Hospital from January 1980 to August 2020 were retrospectively analyzed. The patients were divided into renal impairment group and non-renal impairment group according to whether the kidney was involved or not and the related clinical data between the two groups were compared. The patients presenting with nephrotic syndrome were followed up.Results:There were 60 patients with Kimura disease confirmed by pathological diagnosis with 48 males. The median age was 33(3, 62) years old, and the median duration was 36(12, 111) months. There were 18 cases complicated with renal injury in 49 patients with complete routine urine and renal function examination and the main manifestations of renal injury were proteinuria and/or microscopic hematuria. There was no significant difference at age, sex and absolute value of eosinophils between the two groups (all P>0.05). Compared with the renal inpairment group, patients in non-renal inpairment group had longer course of disease, higher levels of hypersensitive C-reactive protein and erythrocyte sedimentation rate, and lower median values of total eosinophils and total IgE, but there was no statistically significant difference (all P>0.05). Among the patients with renal involvement, 6 patients met the diagnostic criteria for nephrotic syndrome, and 5 of them completed renal biopsies. The renal pathological diagnosis was membranous nephropathy in 2 cases and minimal change disease in 3 cases, and no interstitial eosinophil infiltration was found in renal biopsy tissues. These patients had a good response to glucocorticoids and/or immunosuppressive therapy, and achieved complete remission of nephrotic syndrome; at the same time, lymphadenopathy caused by Kimura disease could be well controlled. Conclusions:Kimura disease can combine with various renal lesions, and the pathology of nephrotic syndrome can be membranous nephropathy or minimal change nephropathy. After energetic treatment of glucocorticoids and/or immunosuppressive therapy, nephrotic syndrome can be completely relieved, and lymphadenopathy can be well controlled. The relationship between Kimura disease and renal disease needs further study.

Objective:To compare the clinical efficacy of endoscopic resection and laparoscopic surgery in the treatment of gastric gastrointestinal stromal tumor (GIST) with a maximum diameter of 2 to 5 cm, and to analyze the influence of factors such as tumor surface, growth pattern and lesion origin on the choice of resection method, so as to provide a safer and more effective treatment for patients with gastric GIST.Methods:From January 2012 to November 2019, at the First Affiliated Hospital of Zhengzhou University, the clinical data of 301 patients with gastric GIST who underwent endoscopic resection (137 cases in the endoscopic resection group) or laparoscopic surgery (164 cases in the laparoscopic surgery group) were retrospectively analyzed, including age, gender, whether there was depression on the tumor surface (the local subsidence depth of the mucosa on the tumor surface was >5 mm), whether the tumor surface was irregular (non-hemispherical or non-elliptical tumor surface), whether there was combined ulcer, location, shape, origin of the lesion, growth pattern (intralumina growth or combined intraluminal and extraluminal growth), risk classification (very low risk, low risk, medium risk, high risk), whether the tumor was en bloc resection, operation time, whether bleeding or not, fasting time, indwelling time of gastric tube, time of hospitalization, time of postoperative hospital stay, postoperative complications and follow-up. Independent sample t test, chi-square test or Fisher′s exact test and Wilcoxon rank sum test were used for statistical analysis. Results:Among the 137 patients with gastric GIST in the endoscopic resection group, 85 cases (62.0%) underwent endoscopic submucosal dissection, 9 cases (6.6%) underwent endoscopic submucosal excavation, 42 cases (30.7%) underwent endoscopic full-thickness resection, and 1 case (0.7%) underwent submucosal tunnel endoscopic resection. There were no significant differences in gender, age, lesion location, tumor size, and risk classification between the endoscopic resection group and the laparoscopic surgery group (all P>0.05). The tumor surface was depressed, with ulcer or irregular in 1, 49, 26, and 2 cases of patients with gastric GIST of very low risk, low risk, medium risk and high risk, respectively. There was statistically significant difference in the proportion of depression, irregularity and ulcer on the tumor surface at different risk levels ( Z=-2.55, P=0.011). The complete tumor resection rate of the endoscopic resection group was lower than that of the laparoscopic surgery group (86.1%, 118/137 vs. 100.0%, 164/164), and the difference was statistically significant ( χ2=24.28, P<0.001). However the operation time, fasting time, the indwelling time of gastric tube, time of hospitalization, and the time of postoperative hospital stay of the endoscopic resection group were shorter than those of the laparoscopic surgery group, and the total hospitalization cost was lower than that of the laparoscopic surgery group (90.0 min (62.5 min, 150.0 min) vs. 119.5 min, (80.0 min, 154.2 min); 3 d (3 d, 4 d) vs. 5 d (4 d, 7 d); 3 d (2 d, 4 d) vs. 4 d (2 d, 6 d); 11 d (10 d, 14 d) vs. 16 d (12 d, 20 d); 7 d (6 d, 9 d) vs. 9 d (7 d, 11 d); (38 211.6±10 221.0) yuan vs. (59 926.1±17 786.1) yuan), and the differences were statistically significant ( Z=-2.46, -7.12, -4.44, -6.89 and -5.92, t=-13.24; all P<0.05). The incidence of postoperative abdominal pain and other severe postoperative complications (including shock, respiratory failure, pulmonary embolism, gastroparesis, etc.) of the endoscopic resection group were all lower than those of the laparoscopic surgery group (16.8%, 23/137 vs. 27.4%, 45/164; 0.7%, 1/137 vs. 4.9%, 8/164), and the differences were statistically significant ( χ2=4.84, Fisher′s exact test, P=0.028 and 0.043). There were no significant differences in the incidence of intraoperative bleeding, postoperative bleeding, fever and perforation between the two groups (all P>0.05). The incidence of operation-related complications of lesions with intraluminal growth and originating from muscularis propria in the endoscopic resection group were lower than those of the laparoscopic surgery group (19.5%, 25/128 vs. 32.6%, 45/138; 12.6%, 12/95 vs. 31.4%, 37/118), and the differences were statistically significant ( χ2=5.86 and 10.42, P=0.016 and 0.001). There was no significant difference in the postoperative tumor recurrent rate between the endoscopic resection group and the laparoscopic surgery group (0, 0/137 vs. 2.4%, 4/164; Fisher’s exact test, P=0.129). Conclusions:Endoscopic treatment is safe and effective for gastric GIST with a maximum diameter of 2 to 5 cm, which is superior to laparoscopic surgery. However, laparoscopic surgery is recommended for tumor with depressed, ulcerative, or irregular surface and combined intraluminal and extraluminal growth.

Objective:To analyze the clinical characteristics of adult Chinese patients with syncope.Methods:This is a cross-sectional survey study. Patients with preliminary diagnosis of syncope in the Emergency Department, Geriatrics and Cardiology Outpatient Department, or Syncope Unit of 37 hospitals in 19 provinces, autonomous regions and the Hong Kong Special Administrative Region from June 2018 to March 2021 were included in this study. The clinical features of these patients with syncope were analyzed.Results:A total of 4 950 consecutive patients with syncope were included in this study. The age was (56.3±16.8)years, and 2 604 cases (52.6%) were male. The most common type of syncope was neurally mediated syncope (2 345 (47.4%)), followed by cardiac syncope (1 085 (21.9%)), orthostatic hypotensive syncope (311 (6.3%)), and unexplained syncope accounted for nearly one third (1 155 (23.3%)). Predisposing syncope was more common in patients under 65 years of age(2 066(72.4%) vs. 786(27.6%),χ 2=136.5, P<0.001). Presyncope was more common in patients with neurally mediated syncope (1 972(79.0%) vs.1 908(73.9%), χ 2=17.756, P<0.001). Premonitory symptoms were more common in women(1 837(80.0%) vs. 1 863(73.0%),χ 2=33.432, P<0.001). Presyncope syndrome was more common in patients under 65 years of age (2 482(77.8%) vs. 1 218(73.4%),χ 2=17.523, P=0.001). Cyanosis was more common in ≥65 years old patients (271(18.2%) vs. 369(12.7%), χ 2=23.235, P<0.001). Urinary incontinence was more common in old patients aged ≥65 years(252(15.2%) vs. 345(10.8%), χ 2=19.313, P<0.001). Family history was more common in patients with cardiogenic syncope compared with other types of syncope (264(24.3%) vs. 754(19.5%), χ 2=11.899, P=0.001). Hypertention(1 480(30.5%)), coronary heart disease(1 057(21.4%)), atrial flutter and atrial fibrillation(359(7.2%)), second degree atrioventricular block(236(4.8%)) were common complications of syncope. The proportion of patients with coronary heart disease was significantly higher in cardiac syncope than that of other types of syncope(417(38.4%) vs. 640(16.6%), χ 2=241.376, P<0.001). Other common complications included cerebrovascular diseases (551 (11.1%)) and diabetes mellitus (632(12.8%)). Conclusions:Neurally mediated syncope is the most common syncope in adult Chinese population. Patients with predisposing conditions and premonitory conditions are younger. Presyncope is more common in women. The proportion of family history and coronary heart disease is higher in patients with cardiogenic syncope.

Objective To investigate the change patterns of functional brain networks and their relations with cognitive function in patients with end-stage renal disease (ESRD).Methods Sixty-two patients with ESRD (ESRD group),admitted to our hospital from July 2018 to June 2019,and 36 age-,gender-,and education level-matched healthy controls (HC group) were enrolled.Mini-mental State Examination (MMSE),Montreal Cognitive Assessment (MoCA),Trail Making Test A (TMT-A),TMT-B and Symbol Digit Modalities Test (SDMT) were used to evaluate the cognitive function for all subjects.Resting-state functional magnetic resonance imaging data were acquired;after data preprocessing,the brain functional networks were constructed and the topological parameters were calculated.Statistical methods were used to compare the differences of cognitive function scores and topological parameters between the two groups,and to analyze the correlations between these topological parameters and cognitive function scores in the ESRD group.Results The MMSE,MoCA and SDMT scores of the ESRD group were significantly lower than those of the HC group (P＜0.05),and the ESRD group took significantly longer time to complete TMT-A and TMT-B than the HC group (P＜0.05).The ESRD group had significantly lower normalized clustering coefficient (γ),small-worldness (σ) and local efficiency (Elocal) values than the HC group (P＜0.05).Patients in the ESRD group exhibited significantly decreased nodal efficiency in the paralimbic-limbic network (including the bilateral insula,median cingulate and paracingulate gyri,hippocampus,parahippocampal gyrus,amygdala,temporal pole:superior temporal gyrus,and temporal pole:middle temporal gyrus),right heschl gyrus and left superior temporal gyrus,and exhibited significantly increased nodal efficiency in the visual network (including the right distal-shaped gyrus,bilateral wedge,and left superior and middle occipital gyrus) as compared with the HC group (P＜0.05).In the ESRD group,the area under the curve (AUC) ofγ and σ was positively correlated with MoCA scores (r=0.698,P=0.000;r=0.661,P=0.000),and the AUC of Elocal showed positive correlation with MMSE scores (r=0.407,P=0.003).Conclusion Abnormal topological organization of the functional brain networks is revealed in patients with ESRD,which affects the cognitive function of these patients.

Objective To explore the value of dual-source CT spectrum energy curve and iodine quantification in determining the degree of differentiation of clear cell renal carcinoma(ccRCC).Methods The radiographic data of 38 cases with pathologically confirmed ccRCC were analyzed retrospectively.All patients underwent dual-source CT,cortical phase and nephrographic phase dual energy scan,including 22 well-moderated differentiated(gradeⅠ,gradeⅡ)and 16 poorly differentiated neoplasms(gradeⅢ,gradeⅣ).The slope of spectrum energy curve (40-70 keV,70-100 keV,100-140 keV)and the normalized iodine concentration (NIC)between the two grades were compared. Results In the spectrum energy curve 40-70 keV and 70-100 keV segment interval,the slope of spectrum of well-moderated differentiated group was higher than that of poorly differentiated group,the difference was statistically significant(P<0.05).In the 100-140 keV segment interval,the slope of spectrum of well-moderated differentiated group was higher than that of poorly differentiated group, but the difference was insignificant(P>0.05).The NIC of well-moderated differentiated group was significantly higher than that of poorly differentiated group(P<0.05).Conclusion The slope of spectrum energy curve and NIC are correlated with the differentiation degree of ccRCC.The slope of spectrum energy curve and iodine quantification of dual-source CT could be used as new methods for preoperative grading of ccRCC.