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 observe the influence of different energy windows of the medium-energy general-purpose(MEGP)collimator on image quality,so as to optimize the energy window of yttrium-90(90Y)bremsstrahlung SPECT imaging.Methods 90Y bremsstrahlung spectrum was acquired,and the sensitivity,percentage of the source counts in useful field of view(S/FOV%)and signal-to-background ratio(S/B)of 90Y bremsstrahlung SPECT imaging at MEGP under different energy windows were compared.Results The energy spectrum of 90Y bremsstrahlung was a continuous curve,with the peak of 76.2 keV with MEGP collimator.The images obtained with MEGP collimator were clear,and no significant differences of S/FOV%nor S/B was found between 10%and 20%window width groups(both P＞0.05),but the sensitivities of the latter was higher than the former(P＜0.05).The sensitivity of 70-90 keV images was relatively high,while the S/FOV%and S/B had decreased.The S/FOV%and S/B of images ranging from 40-60 keV were high,but the sensitivity was low.Images acquired with 100 keV±20%showed fairly high sensitivity,S/FOV%and S/B,which was 69.73%,0.62 and 1.64,respectively.Conclusion When performing 90Y bremsstrahlung SPECT with MEGP collimator,the image quality at 20%window width was better than at 10%window width,and 100 keV±20%showed fairly high sensitivity and not significantly decreased S/FOV%and S/B.

Objective To investigate the relationship between the expression of serum microRNA-326(miR-326)and microRNA-623(miR-623)in non-small cell lung cancer(NSCLC)patients and their clinical pathological characteristics and prognosis.Methods A total of 114 NSCLC patients diagnosed in our hospital from March 2019 to June 2020 were collected as study subjects as case group,123 healthy individuals who underwent physical examination were as the control group.According to the 3-year prognosis,patients were separated into a survival group of 71 cases and a death group of 43 cases.Patient related clinical data were collected,real-time fluorescence quantitative PCR method was applied to detect the expression levels of miR-326 and miR-623 in various serum samples;Kaplan-Meier method was applied to analyze the relationship between the expression levels of serum miR-326 and miR-623 in NSCLC patients and their 3-year prognosis;Cox proportional risk regression model was applied to analyze the influencing factors of 3-year prognosis in NSCLC patients.Results The expression levels of serum miR-326 in the case group and control group were 0.64±0.15 and 1.02±0.23,respectively,and the expression levels of miR-623 were 0.56±0.10 and 0.98±0.15,respectively.The difference between the two groups was statistically significant(P＜0.05).The proportions of patients with low expression of miR-326 and miR-623 in low differentiation,TNM stage Ⅲ+Ⅳ,and lymph node metastasis were higher than those in high differentiation,TNM stage Ⅰ and Ⅱ,and no lymph node metastasis(P＜0.05).The 3-year survival rates of patients with low expression of miR-326(20/55,36.36％)and miR-623(27/61,44.26％)in the serum of NSCLC patients were lower than those of patients with high expression of miR-326(51/59,86.44％)and miR-623(44/53,83.02％)(Log Rank x2=32.060,22.812,P＜0.05).Serum miR-326[(0.55±0.09)vs.(0.69±0.11)]and miR-623 levels[(0.48±0.08)vs.(0.61±0.10)]of patients in the death group were significantly lower than those in the survival group(P＜0.05).The area under the curve(AUC)for poor prognosis of serum miR-326 and miR-623 alone and in combination in patients diagnosed with NSCLC were 0.828(95％CI:0.754 to 0.901),0.763(95％CI:0.671 to 0.855),and 0.903(95％CI:0.849 to 0.958),respectively.The proportions of patients with TNM stage Ⅲ+Ⅳ,lymph node metastasis,low expression of miR-326 and low expression of miR-623in the death group were higher than those in the survival group(P＜0.05).MiR-326 and miR-623 were protective factors affecting 3-year mortality in NSCLC patients,while TNM staging and lymph node metastasis were independent risk factors affecting 3-year mortality in NSCLC patients(P＜0.05).Conclusion The low expression of miR-326 and miR-623 may be involved in the occurrence and development of lung cancer,which is closely related to the clinical pathological characteristics and poor prognosis of patients.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

Objective:To explore the application of Miller's pyramid theory combined with Bahrain's team activities in the standardized residency training (SRT) of burn surgeons.Methods:Seventy-four residents who were on the SRT program in the Department of Burns & Wound Care in The Second Affiliated Hospital of Zhejiang University were enrolled in the study. The students were divided into control group and observation group according to the teaching methods. Thirty-seven students in the control group were provided with conventional teaching, and 37 students in the observation group were provided with training based on Miller' pyramid theory combined with Bahrain's team activities. The two groups were evaluated for teaching effectiveness and doctor-patient communication skills. SPSS22.0 was used for the chi-square test and t test. Results:The evaluation outcome of teaching effectiveness in the observation group was better than that in the control group ( t=3.01, 3.47, 3.49, 3.32, and 2.54; P=0.004, 0.001, 0.001, 0.001, and 0.013). After the training, the scores of Set Elicit Give Understand End scale in the two groups increased, with significantly higher scores achieved in the observation group than in the control group ( t=3.23, 2.99, 2.07, 3.62, 3.00, and 7.89; P=0.002, 0.004, 0.042, 0.001, 0.004, and <0.001). Conclusion:The application of Miller's pyramid theory and Bahrain's team activities in the SRT of burn surgeons can improve students' evaluation of teaching effectiveness and improve their doctor-patient communication skills.

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 explore the value of spectral CT in the preoperative evaluation of solid lung adenocarcinoma with different pathological grades based on the 2011 and 2020 version of the pathological grading system.Methods:A total of 76 cases of solid lung adenocarcinoma confirmed by surgery in Renji Hospital, School of Medicine, Shanghai Jiao Tong University, from January 2019 to September 2021 were analyzed retrospectively. All cases were divided into groups according to the grading system for invasive adenocarcinoma proposed by the International Association for the Study of Lung Cancer (IASLC) in 2011 and 2020 (G low group included G1 and G2 adenocarcinoma, G high group included G3 adenocarcinoma). The tumors with stage Ⅰ and Ⅱ were non-advanced and the tumors with stage Ⅲ and Ⅳ were advanced. The clinical manifestations (gender, age, smoking history and stage), routine CT parameters (tumor size, morphological characteristics, plain CT value and enhancement degree) and spectral parameters [iodine concentration, effective atomic number, enhanced monochromatic CT attenuation values of 40-200 keV (CT 40 keV-CT 200 keV), and the slope of spectral curve (k value)] were compared between G low group and G high group using independent sample t-test or Mann-Whitney U test. And the efficacy of each parameter for indicating G high adenocarcinoma was analyzed using receiver operating characteristic curve analysis and area under the curve (AUC), and the Z test was used to compare the AUC. Results:Seventy-six cases were included (59 cases of G low group and 17 cases of G high group in 2011 version; 46 cases of G low group and 30 cases of G high group in 2020 version). Among the 76 cases, 62 cases were non-advanced stage (50 cases of G low group and 12 cases of G high group in 2011 version; 37 cases of G low group and 25 cases of G high group in 2020 version) and 14 cases were advanced stage (9 cases of G low group and 5 cases in G high group in both 2011 and 2020 version). Among the non-advanced adenocarcinomas, the CT parameters of enhancement degree, k value and CT 40 keV-CT 60 keV in arterial phase and enhancement degree, k value and CT 40 keV-CT 70 keV in venous phase of G high group in 2011 grading system were significantly lower than those of G low group ( P<0.05), while other parameters were similar between G low and G high group in 2011 grading system ( P>0.05); and the CT parameters of CT 60 keV in arterial phase and CT 50 keV-CT 70 keV in venous phase of G high group in 2020 grading system were significantly lower than those of G low group ( P<0.05). Among the advanced adenocarcinomas, all of the clinical and CT parameters were similar between G low and G high group in both 2020 and 2011 grading systems ( P>0.05). For the non-advanced adenocarcinomas, there was medium to good efficacy of the CT parameters of enhancement degree, k value and CT 40 keV-CT 60 keV in arterial phase and enhancement degree, k value and CT 40 keV-CT 70 keV in venous phase for diagnosing 2011 grading system G high adenocarcinoma (AUC=0.700-0.853), with CT 50 keV in venous phase as the best; while the diagnosis efficacy of CT parameters of CT 60 keV in arterial phase and CT 50 keV-CT 70 keV in venous phase was poor for 2020 grading system G high adenocarcinoma (AUC=0.652-0.688), with CT 60 keV in venous phase as the best. After combining smoking history and CT 60 keV in venous phase, the diagnosis efficacy for 2020 grading system G high adenocarcinoma was slightly improved (AUC=0.772), but the difference had no significance ( Z=0.93, P=0.176). Conclusion:The spectral parameters are useful for distinguishing the pathological grades of solid lung adenocarcinoma. And the detecting efficacy for G high adenocarcinoma of IASLC 2011 version is slightly better than that of 2020 version.

To present the clinical characteristics and the misdiagnosis rate of acute coronary syndrome manifested primarily as throat discomfort, we conducted a multicentric and retrospective study in the cardiology and otorhinolaryngology departments. Records of patients with primary complaint of throat discomfort, absence of chest pain at onset, and an ultimate diagnosis of acute coronary syndrome, as well as patients with pharyngitis (as controls) were collected from May 2015 to April 2016. The patients' main manifestations were compared. Logistic regression results showed that chest tightness, dyspnea, perspiring, and exertional throat symptoms were significantly associated with acute coronary syndrome, with odds ratios of 8.3 (95% CI 2.2-31.5), 10.9 (95% CI 1.8-66.9), 25.4 (95% CI 3.6-179.9), and 81.2 (95% CI 13.0-506.7). A total of 25 (56.82%) out of 44 acute coronary syndrome patients, who were first admitted to the otorhinolaryngology department, were misdiagnosed, with a 12% (3/25) mortality rate. Throat discomfort can be the principal manifestation of acute coronary syndrome. Such patients exhibit high misdiagnosis and mortality rates. Exertional throat symptoms, chest tightness, perspiring, and dyspnea were important indicators of acute coronary syndrome in patients whose main complaint was throat discomfort. The awareness of this condition will result in prompt diagnosis and reduce morbidity and mortality.
Acute Coronary Syndrome/etiology* ; Dyspnea/etiology* ; Humans ; Pharyngitis/diagnosis* ; Pharynx ; Retrospective Studies

Objective:To investigate the changes of sphenoid sinus and related risk factors of sphenoid sinusitis after microscopic transsphenoidal pituitary adenoma resection.Methods:The clinical and imaging data of 106 patients with large pituitary adenoma in 900 Hospital of the PLA Joint Logistics Team between August 2012 and March 2015 were continually collected. The changes of accumulated blood and fluid, inflammation, mucocele, mucosa remodeling in sphenoid sinus cavity at preoperative and postoperative different time points were observed through the analysis of magnetic resonance imaging (MRI). Binary logistic multiple factors regression model was used to analyze the independent risk factors for postoperative sphenoid sinusitis.Results:MRI results showed that the blood and fluid accumulated in sphenoid sinus cavity were absorbed and dissipated 3 months after the surgery, and the saddle bone windows were covered by new mucous membrane at this time, but they were not complete; the remaining tumors in the saddle all sank into the saddle to different degrees. The reconstruction of sphenoid sinus mucosa was basically complete 6 months after the surgery. There were 7 (6.6%) cases of mucocele in sphenoid sinus and 26 (24.5%) cases of sphenoid sinusitis 3 months after the surgery among 106 patients. The results of multivariate analysis showed that growth hormone adenoma ( OR = 2.981, 95% CI 1.480-26.207, P = 0.014), preoperative sphenoid sinusitis ( OR = 12.392, 95% CI 2.927-52.462, P = 0.001), frequency of multiple transsphenoidal surgery ( OR = 14.758, 95% CI 2.431-89.584, P = 0.003) and perioperative cerebrospinal fluid leakage ( OR = 11.644, 95% CI 2.175-62.344, P = 0.004) were independent risk factors for postoperative sphenoid sinusitis. Conclusions:The evolution of sphenoid sinus cavity contents has its own rules after microscopic transsphenoidal pituitary adenoma resection. Patients with growth-hormone pituitary adenoma, sinusitis before surgery, multiple transsphenoidal surgery and cerebrospinal fluid leakage during the surgery should receive enhanced anti-infection treatment and nasal care in perioperative period to reduce the possibility of sphenoid sinusitis after surgery. The staged time of reoperation for pituitary adenoma resection by transsphenoidal approach should be about 3 months after the previous operation.

Objective:To summarize the clinical characteristics, common images, pathogens, and gene mutation types of chronic granulomatosis disease (CGD) in 19 children.Methods:The clinical manifestations, laboratory findings, treatment, and prognosis of 19 patients diagnosed with CGD in Hong Kong University-Shenzhen Hospital from December 2012 to December 2018 were analyzed.Results:The 19 patients were all males and confirmed as CGD by the dihydrorhodamine test and gene sequencing.The age of the first infection was mostly 1 month after birth(13 cases), and the age of clinical diagnosis ranged from 2 months to 10 years.Sixteen mothers were carriers.The patients presented with pulmonary fungal infection (19/19 cases), Bacillus Calmette Guerin (BCG)-osis (14/19 cases), lymphadenitis (14/19 cases), perianal abscess (9/19 cases), skin abscess (5/19 cases) and ulcerative colitis (2/19 cases). There were 59 positive cultures.Pathogens included fungi (9 cases), Klebsiella pneumonia (8 cases), mycobacteria (7 cases), Streptococcus Viridans (5 cases), Escherichia coli (3 cases), gram-positive bacteria (3 cases), Staphylococcus aureus (3 cases), and Burkholderia cenocepacia (2 cases). Gene mutations were found in all 19 patients, including 17 cases of CYBB, 1 case of CYBA and 1 case of NCF2.The type of mutations included nonsense mutations (6 cases), deletion mutations (5 cases, including 2 large fragment deletions), splice mutations (3 cases) and missense mutations (5 cases). Five mutations were novel.Splice mutations in 3 cases often led to skin abscess, perianal abscess and lymphadenitis.Two patients with large deletion mutations had more serious infection than other patients. Conclusions:In China, CGD is characterized with pulmonary infection and disseminated BCG-osis.Mycobacteria are common pathogens of CGD, and fungi are dominant pathogens of CGD.The most common infection is respiratory infection. Klebsiella pneumonia and Escherichia coli often lead to perianal abscess.The relationship between gene mutation types and clinical phenotypes requires further verification by big data.