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.

With the rapid aging of the global population posing a serious problem, frailty, a non-specific state that reflects physiological senescence rather than aging in time, has become more widely addressed by researchers in various medical fields. A high prevalence of frailty is found among kidney transplant (KT) candidates and recipients. Therefore, their frailty has become a research hotspot in the field of transplantation. However, current studies mainly focus on the cross-sectional survey of the incidence of frailty among KT candidates and recipients and the relationship between frailty and transplantation. Research on the pathogenesis and intervention is scattered, and relevant review literature is scarce. Exploring the pathogenesis of frailty in KT candidates and recipients and determining effective intervention measures may reduce waiting list mortality and improve the long-term quality of life of KT recipients. Therefore, this review explains the pathogenesis and intervention measures for frailty in KT candidates and recipients to provide a reference for the formulation of effective intervention strategies.
Humans ; Frailty/epidemiology* ; Risk Factors ; Quality of Life ; Kidney Failure, Chronic ; Kidney Transplantation/adverse effects* ; Cross-Sectional Studies ; Transplant Recipients

Objective:To investigate the clinical effect of free anterolateral thigh perforator flap(ALTPF) in reconstruction of temporal scalp defect after blood circulation reconstruction surgery for moyamoya disease.Methods:From May 2020 to July 2022, 7 patients with scalp defect after revascularisation of moyamoya disease were treated in Department of Hand and Foot Microsurgery, Henan Provincial People’s Hospital (People’s Hospital of Zhengzhou University). The patients were 4 males and 3 females, aged 33-59 years old, at 43 years old in average. There were 5 defects in left tempus and 2 in right tempus. The sizes of scalp defect were 4.5 cm × 5.5 cm-7.5 cm × 9.5 cm. Debridement and VSD management were primarily performed. After wounds were stabilised, ultrasound location of perforator vessels of ALTPFs was performed. Having confirmed that the perforator vessels were suitable for the surgical requirements, flap transfers were then performed. The descending branch of the lateral femoral circumflex artery was end-to-side anastomosed with the superficial temporal artery, and the descending branch of the lateral femoral circumflex vein was end-to-end anastomosed with the superficial temporal vein. Postoperative follow-up was conducted through outpatient clinic visits, telephone and WeChat reviews. Appearance, texture of ALTPFs and the flap donor sites were observed in follow-ups. Comparisons of the changes of nervous system before and after surgery were made. Cognitive function of the patients was assessed with the Mini Mental State Examination (MMSE), together with the Activities of Daily Living (ADL) .Results:All 7 flaps survived. One flap had vascular compromise 6 hours after surgery, and was rectified after surgical intervention. All the patients were included in the postoperative follow-up for 7-33 (average 19) months. All flaps had good appearance with soft texture. There was no obvious difference in colour comparing with the skin around the recipient region. The donor sites healed well without hypertrophic scar. Examinations of nervous system of the patients were found the same as that before surgery. Using Manual Muscle Testing (MMT), the average limb muscle strength of the patients was 4 before surgery and 4 after surgery, without change; Using the Ashworth assessment scale, the average preoperative and postoperative limb muscle tension in this group of patients was 1, without change; The Berg balance scale was used to evaluate the patient's balance function, with an average score of 42 before surgery and 42 after surgery, without any changes; There was no change in limb sensation before and after surgery; Using the MMSE, the average preoperative score and postoperative score of this group of patients were 25 points, without any change. Using the modified Barthel index scoring standard, the average preoperative score for this group of patients was 75 points, and the average postoperative score was 79 points, and the ADL of the patient had improved to various levels.Conclusion:Reconstruction of scalp defect with free ALTPF after revascularisation of moyamoya disease has obvious advantages, such as it closes the wound quickly, prevents infection and achieves a good appearance. This surgical procedure can produce a good clinical effect.

Objective:To analyze the data of clinical characteristics, hospitalization actual cost and hospital stay of inpatients with lymphoma, and to provide references for local epidemiological research, hospital optimization management, and appropriate resource allocation.Methods:The quadratic programming was performed based on hospital information management system and case system, as well as the information from inpatients with lymphoma in Shandong Tai'an Central Hospital between January 1, 2004 and November 30, 2019, and then they were derived and collected into the SQL server database. The gender, onset age, age distribution, and hospital stay of all inpatients with lymphoma were retrospectively analyzed. The patients were divided into the young group (< 45 years old), middle-aged group (≥45 years old and < 60 years old) and elderly group (≥ 60 years old) according to the age. The hospitalization cost and hospital stay of these inpatients in different age groups were collected and compared.Results:The number of admissions for inpatients with lymphoma between January 1, 2004 and November 30, 2019 was 3 866, accounting for 0.38% (3 866/1 011 627) of the total inpatient admissions. There were 817 newly-diagnosed lymphoma inpatients, including 499 males and 318 females (male to female ratio was 1.57:1). The median onset age of the newly-diagnosed lymphoma inpatients was 58 years old (7 months to 86 years old). Among the newly-diagnosed lymphoma patients, the proportion of them with age ≥ 45 years old was increased, and peaked at 60-65 years old, and decreased after 75 years old. There were 180, 270 and 367 cases in the young group, middle-aged group and elderly group respectively; the median hospital stay was 13.5 d, 13.0 d and 14.0 d, respectively (χ 2 = 0.419, P = 0.811). The median total cost of hospitalization was 9 846.39 yuan, 12 232.16 yuan and 14 022.36 yuan, respectively (χ 2 = 9.443, P = 0.009); and the median drug cost was 3 423.37 yuan, 3 523.62 yuan and 3 654.54 yuan, respectively (χ 2 = 2.202, P = 0.333); the ratio of median drug cost to the total cost was 44.80%, 40.49% and 34.58%, respectively (χ 2 = 6.512, P = 0.039). Conclusions:The number of lymphoma inpatients in Shandong Tai'an Central Hospital is on the rise. The incidence of inpatients with lymphoma is increased annually with older onset age. The total cost of inpatients was increased with the aging, but it has no obvious relevance with hospital stay. Middle-aged and elderly people are the target populations for disease control and prevention. Measures including screening, early diagnosis and early treatment should be enhanced.

Objective:To investigate the surgical method and clinical effect of one-stage repair of soft tissue defects of dorsum of hand and multiple fingers by using the polyfoliate conjoined anterolateral thigh perforator flap (ALTP) .Methods:From November, 2015 to September, 2019, 9 cases of soft tissue defects of dorsum of hand and multiple fingers were treated, including 8 males and 1 female. The average age was 32 years old. Causes of injury: 4 cases of thermal injury, 3 cases of strangulation injury, and 2 cases of traffic accident injury. Location of injury: 7 cases of right hand, 2 cases of left hand. Three cases of dorsum of hand with 1st-4th fingers, 3 cases with 2nd-5th fingers, 2 cases with 2nd-4th fingers, and 1 case with 3rd-5th fingers; All with bone, joint and tendon exposure. There were 6 cases with fracture or joint dislocation. All of them had no obvious defect of bone and joint. VSD was used to cover them after debridement. According to the shape and size of the wound, all flaps were designed to repair the soft tissue defect as the polyfoliate conjoined ALTP. The flap size was 7 cm×13 cm-12 cm×17 cm. Regular outpatient, telephone and Wechat follow-up were carried out to evaluate the flap survival, appearance, color elasticity, donor scar, sensory recovery, finger function recovery and patient satisfaction.Results:Nine cases of flap survived well. The average followed-up time was 12 (6-18) months. The postoperative followed-up revealed satisfactory shapes of the flaps, protective touch and recovery of functions. The donor site had good healing and no effect on function. In the last followed-up, according to the trial criteria for function evaluation of upper limbs by Chinese Society of Hand Surgery, 5 cases were excellent, 3 cases were good, and 1 case was fair. The hand function recovered well and returned to work and daily life on average 6 weeks after operation.Conclusion:The polyfoliate conjoined ALTP can repair the soft tissue defect of hand dorsum with multiple fingers at one stage, and the flap is in good shape. There is no need to divide the fingers. It is one of the ideal methods to repair the soft tissue defect of hand dorsum.

Objective To analyze the application of three-dimensional visualization in interventional treatment of Budd-Chiari syndrome (BCS) with the hepatic vein occlusion type.Methods A retrospective study was conducted on 15 patients with BCS of the hepatic vein occlusion type who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2017 to June 2018.The study included 8 males and 7 females with a mean age of (36.7±14.4) years.All patients were examined with MRI enhanced scanning and the original MRI data of the DICOM format were extracted.The digital data were then extracted and reconstructed by the Mimics software to obtain a three-dimensional visualization model.The hepatic vein was recanalized under the guidance of the three-dimensional visualization model.Results The three-dimensional visualization model was successfully constructed.Of all the 15 three-dimensional visualization models,right hepatic vein ostial stenosis occurred in 4 patients and occlusion in 11 patients.The middle hepatic vein and the left hepatic vein formed a common trunk in 15 patients,and ostial stenosis and occlusion of the common trunk occurred in 3 and 12 patients,respectively.Communicating branches between the right and middle hepatic veins occurred in 6 patients.Accessory hepatic veins occurred in 3 of 15 patients,and the accessory hepatic vein ostium was stenosed in 3 patients.Communicating branches between the accessory hepatic vein and the right hepatic vein occurred in 2 patients,and communicating branches between the accessory hepatic vein and the middle hepatic vein occurred in 1 patient.All patients were treated successfully with interventional treatment without any complications.One,2,and 3 hepatic veins were recanalized in 7,5 and 3 patients,respectively.Conclusion The three-dimensional visualization was valuable in displaying the location,pattern and collateral vessels of the hepatic veins in BCS patients with the hepatic vein occlusion type.It was helpful for accurate preoperative assessment and to make individualized interventional treatment plans.

Objective: To evaluate the predictive value of 3 different risk stratification models including the risk adjustment in congenital heart surgery-1 (RACHS-1), Aristotle basic complexity (ABC), and Society of Thoracic Surgeons-European Association for cardiothoracic surgery congenital heart surgery mortality score (STAT) risk scoring system for death and major complications in patients after congenital heart surgeries. Methods: A total of 3 578 patients (age<18 years old) received surgery for congenital heart diseases from January to December 2015 in Fuwai hospital were enrolled, and the clinical data were retrospectively analyzed. The congenital heart disease patients were 1.7 (0.8, 4.5) years old, and the male accounted for 54.3% (1 943 cases).Death after surgery and major complications including use of extracorporeal membrane oxygenation, bedside thoracotomy, peritoneal dialysis for renal failure, bedside hemofiltration for renal failure, tracheotomy, reoperation for mediastinum infection, reoperation for heart in hospital were observed. The area under the receiver operating characteristic (ROC) curve was calculated to evaluate the predictive value for mortality after surgery and major complications with RACHS-1, ABC, and STAT risk scoring systems. Results: The mortality after surgery was 0.4% (14/3 578) , and the rate of major complications was 3.2% (113/3 578) . For mortality after surgery, areas under the ROC curve were 0.682 (95%CI 0.570-0.795, P=0.002), 0.722 (95%CI 0.612-0.832, P<0.001), and 0.753 (95%CI 0.659-0.847, P<0.001) with RACHS-1, ABC and STAT risk scoring systems, respectively. For major complications, areas under the ROC curve were 0.709 (95%CI 0.667-0.751, P<0.001), 0.743 (95%CI 0.702-0.784, P<0.001), and 0.731 (95%CI 0.693-0.770, P<0.001) with RACHS-1, ABC and STAT risk scoring systems, respectively. Conclusion STAT risk scoring system is superior to RACHS-1 and ABC risk scoring systems on predicting death after surgery, and ABC risk scoring system is superior to RACHS-1 and STAT risk scoring systems on predicting major complications in Chinese patients with congenital heart disease in the single center.

Both raw and vinegar products of the rhizome of Curcuma phaeocaulis are common drugs for promoting blood circulation and removing blood stasis in traditional Chinese medicine,which could be reflected in the inhibition of tail thrombosis in mice. As the traditional processing theory instructs,vinegar tastes sour and bitter,but can activate blood circulation and remove stasis after being infiltrated into the rhizome of C. phaeocaulis as an excipient. In this study,under the help of the ultrafast liquid chromatography-quadrupole time-offlight mass spectrometry( UFLC-Q-TOF-MS),the spectrum-effect relationship between the inhibition of tail thrombosis in mice and the rhizome of C. phaeocaulis both before and after the vinegar processing,were established to explore the functional changes of blood circulation and stasis after vinegar process. Based on the peak area from the fingerprint of UFLC-Q-TOF-MS of the alcohol extracts from the raw and vinegar-processed rhizome of C. phaeocaulis and their efficacy for inhibiting tail thrombosis,the correlation between the chromatography of UFLC-Q-TOF-MS and the inhibition of tail thrombosis in mice were analyzed by orthogonal partial least squares discriminant analysis( OPLS-DA) method. The results,produced by Simca-P software,showed that effective components consisted of eight peaks 16,24( aromadendrene oxide),3,11,22( dehydro-α-curcumene),19[( R)-(-)-α-curcumene],23 and 10 from the fingerprint,making great contribution to distinguish C. phaeocaulis raw products and the corresponding vinegar processed products. Therefore,from the perspective of inhibiting the formation of tail thrombosis in mice,the marker components could be found through the spectrum-effect relationship to distinguish C.phaeocaulis raw and vinegar products. This study provided new basis to explain the difference between the raw and the processed products of traditional Chinese medicine in the functional change of promoting blood circulation and removing blood stasis.
Acetic Acid ; Animals ; Chromatography, High Pressure Liquid ; Curcuma ; chemistry ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Mass Spectrometry ; Mice ; Rhizome ; chemistry ; Thrombosis ; drug therapy

Objective? To explore the attitude towards patients for patient safety and health literacy among patients with coronary artery bypass graft (CABG) and to analyze the correlation between them. Methods? From September 2017 to May 2018, a total of 210 CABG patients were investigated with the general information questionnaire, Patients for Patient Safety Questionnaire and Health Literacy Management Scale (HeLMS) by convenience sampling to evaluate the attitude towards patient participation as well as patient safety and health literacy. Pearson correlation analysis was used to explore the correlation between them. Results? A total of 209 valid questionaires were collected. Among 209 CABG patients, the average item scores of attitude towards patients for patient safety and health literacy were (3.68±0.20) and (4.14±0.23) respectively. Pearson correlation analysis showed that attitude towards patients for patient safety had a positive correlation with health literacy (r=0.422, P＜0.01). Conclusions? CABG patients are with the low level of attitude towards patients for patient safety and good level of health literacy. Corresponding measures should be taken in clinical work to improve the level of health literacy, attitude towards patients for patient safety safety and the safety of medical care.

Objective To observe the clinical,pathological features and prognosis of IgA nephropathy in children with crescent formation.Methods A total of 38 cases of children with IgA nephropathy diagnosed by renal biopsy at Qilu Hospital of Shandong University were retrospectively analyzed.According to whether there were crescent formation,they were divided into crescents formation group (crescent formation≥10％,n=18) and control group consisting of children with complete clinical data and matching age,gender and course of disease (no crescent formation,n=20).The clinical,pathological features and prognosis of the two groups were compared.Results Fourteen cases (77.78％) of crescents formation group were associated with nausea hematuria,and 12 cases (66.67％) had hypertension,8 patients in control group (40％) had gross hematuria,and 6 cases (30％)had high blood pressure.The differences were statistically significant (P ＜ 0.05).In crescents formation group,Alb and eGFR were significantly lower than those of control group.24 h urine protein and Scr were significantly higher than those of control group and there were significant statistically differences between two groups (P ＜ 0.05).Nephropathological changes in crescent formation group were mainly in grade Ⅱ and grade Ⅲ and were usually combined with tubular interstitial damages.In addition to IgA immunoglobulin deposition,they often accompanied by IgG and IgM immunoglobulin deposition.In control group,nephropathological changes were mainly in grade Ⅰ and grade Ⅱ and tubular interstitial damages were rare.IgA was the main form of deposition in control group.After 12 weeks steroid treatment and (or) immunosuppressive therapy,urinary protein turned negative in 7 cases in crescent formation group,24 h urinary protein level declined by half than before in 7 cases and no obvious change in 4 cases.In control group,urinary protein turned negative in 12 cases,6 cases showed a more than 50％ decline in urinary protein level and 2 cases had no obvious change.During the 1-3 years of follow-up,renal function of 14 cases and 19 cases was normal in the crescent formation group and control group respectively,serum creatinine of 3 cases and 1 case increased mildly in the crescent formation group and control group respectively,1 case needed dialysis treatment in the crescent formation group and the one in the control group who had slightly increasement of Scr did not reach the standard of dialysis treatment.Conclusions The clinical and pathological manifestations of children with IgA nephropathy with crescent formation are more severe and more likely to manifest renal insufficiency,suggesting that crescent formation is one of the indicators of poor prognosis.