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 investigate the transfer and diffusion of berberine hydrochloride(BBH), the main active component of Coptis and Phellodenticum in the system of carboxymethyl chitosan(CMCS)-sodium alginate(SA). METHODS CMCS and SA were stirred in a certain proportion, and D-gluconolactone(GDL) was added to form polyelectrolyte hydrogel. Rheometer was used to study the rheological properties of CMCS-SA hydrogel, including the elastic modulus G′ and the viscous modulus G′′. A BBH diffusion model for CMCS-SA hydrogel was designed, and the relevant rules of BBH permeation through CMCS-SA polyelectrolyte hydrogel were observed by UV-VIS. RESULTS The elastic modulus G′ of the hydrogel was measured when the ratio of CMCS to SA was 3∶1, 2∶1, 1∶1, 1∶2, and 1∶3. When the ratio of CMCS to SA was 1∶1, G′ was the highest, and the crosslinking strength of the hydrogel was the highest. The cumulative amount of BBH transfer was measured by the BBH transfer model, and the diffusion of BBH in CMCS-SA hydrogel was fitted as the skeleton dissolution by Peppas equation, indicating that BBH dissociation and the transfer efficiency increased as the amino group of CMCS decreased or the carboxyl group of SA increased. The elastic modulus G′ of CMCS-SA hydrogel increased with the increase of GDL content. The reason was that the binding force between CMCS and SA molecules gradually increased with the decrease of pH, and the crosslinking degree of the hydrogel was enhanced. When ratio of fixed CMCS to SA was 1∶1 and the GDL content was 0.15 g·mL−1, the formability of CMCS-SA hydrogel was good. In addition, when BBH was transferred in hydrogel with different concentrations of GDL, the transfer efficiency increased with the increase of GDL content. When BBH was delivered in different thickness hydrogel, the delivery efficiency of CMCS-SA hydrogel increased with the decrease of thickness. CONCLUSION The CMCS-SA hydrogel system, as a potential drug carrier for traditional Chinese medicine extracts such as BBH, is expected to serve as a gel carrier for transdermal drug delivery.

【Objective】 To evaluate the screening efficacy and practical value of the portable microfluidic biochemical analyzer in the detection of blood donors before blood donation. 【Methods】 Blood donor samples, clinical blood samples and constant quality control products were collected. Referring to the documents of ISO15189 and National Health Industry Standard, the precision and accuracy of hemoglobin (Hb) and alanine aminotransferase (ALT) were verified and compared with other detection systems. 【Results】 The MS200 biochemistry instrument has an intra-batch precision of 1.40% to 1.46%, inter-batch precision of 1.91% to 1.94%, and correctness bias of -0.9% to -1.3% for Hb test, and an intra-batch precision of 3.77% to 4.86%, inter-batch precision of 4.92% to 6.02%, and correctness bias of -3.0% to -4.8% for ALT test, which were within the range of quality requirements of industry standard. Comparison of Hb test results between MS200 biochemistry and Hb201 analyser on 1 189 peripheral blood samples from donors showed no statistically significant difference (P>0.05). 65 samples showed positive correlation between MS200 biochemistry and XS-900i automated hematology analyzer on Hb test results (R²=0.986, P=0.000). Correlation analysis of all the results of ALT detection by MS200 biochemical analyzer and AU480 biochemical analyzer in 1 065 samples showed a positive correlation (R²=0.965, P=0.000). The elevated ALT samples did not affect the Hb test results, and the samples with abnormal Hb value did not affect the ALT test results, with no interference between the two items in the detection. 【Conclusion】 The MS200 biochemical analyzer based on microfluidic technology has reliable methodological performance and can meet the need of pre-donation testing.

Objective To report and analyze the clinical characteristics of kidney transplant recipients(KTRs)combined with novel coronavirus Omicron variant strain infection of novel coronavirus(SARS-CoV-2),and to investigate the possible factors affecting the serum creatinine change.Methods The patients under-going allogeneic kidney transplantation and complicating Omicron variant strain infection in this hospital from October 2022 to December 2023 were retrospectively observed.Their clinical data,basic complications and prognosis,etc.were collected and analyzed.The possible factors affecting the serum creatinine change were an-alyzed.Results Among the 114 cases of KTRs combined with Omicron variant strain infection included in this study,there were 90 cases(78.9％)in the home management group(group A),18 cases(15.8％)in the non-intensive isolation ward group(group B)and 6 cases(5.3％)in the ICU group(group C).The most common symptoms were in turn fever(90.4％),fatigue(65.8％)and cough(61.4％),the clinical manifesta-tions were mainly upper respiratory tract infection symptoms.The overall mortality rate was 2.6％(3/114),moreover the dead patients all were in the group C.The number of basic comorbidities in the group C was higher than that in the group B and group A(P＜0.05).The patients were re-divided into 33 cases(28.9％)in the creatinine increase group(group D),71 cases(62.3％)in the creatinine unchange group(group E)and 10 cases(8.8％)in the creatinine decrease group(group F).The patients in the F group were the patients with mild and moderate Omicron variant strain infection in the group A,and a larger proportions of the pa-tients in the group D and group F discontinued or reduced the calcineurin inhibitor(CNI)type drugs than in the group E.Conclusion The hazard of Omicron variant strains to KTRs has been greatly reduced compared with previous other variant strains.Realizing the immune balance between anti-infection and anti-rejection is the effective measure for preventing renal function damage in KTRs.

Objective To analyze the process of intercomparison of national personal dose monitoring, evaluate the ability of personal dose monitoring, and ensure the accuracy and reliability of monitoring results in our laboratory. Methods In accordance with the intercomparison protocol for 2019—2021, an energy-discriminant thermoluminescence dosimeter was used for measurement at different doses. The uncertainty of measurement was evaluated and compared with the reference value. Results H_p(10) was measured for intercomparison in 2019—2021. In 2019, the single group performance difference was −0.02 to 0.02 and the comprehensive performance was 0.02. These values were 0.02-0.10 and 0.05 in 2020, and −0.02 to 0.02 and 0.01 in 2021. The intercomparison results were rated as excellent in the three consecutive years. Conclusion The personal dose monitoring system in our laboratory was in good condition, and the monitoring results were accurate and reliable. Improving the knowledge of personnel and cultivating a serious working attitude are important for intercomparison and personal dose monitoring.

Objective:To investigate the safety and efficacy of Tubridge flow diverter for the treatment of recurrent internal carotid blood blister-like aneurysms after stent-assisted embolization.Methods:From June 2018 to April 2021, patients with recurrent internal carotid blood blister-like aneurysms treated with Tubridge flow diverter in the Department of Neurosurgery, Changhai Hospital, Naval Medical University were enrolled retrospectively. The perioperative safety, immediate postoperative and follow-up results were analyzed.Results:A total of 6 patients with recurrent internal carotid blood blister-like aneurysm after stent-assisted embolization were enrolled. The time interval from the first stent-assisted embolization to Tubridge placement was 14 to 90 d. Tubridge implantation alone was used in 4 patients, and Tubridge was implanted in the other 2 patients after the coils were packed. There were no complications during the perioperative period, and no rebleeding was observed after clinical follow-up for 5 to 36 months. Five patients were followed up by angiography for 1-3 months, and the aneurysms disappeared completely.Conclusion:Tubridge flow diverter for the treatment of recurrent internal carotid blood blister-like aneurysms is safe and effective.

Objective:To analyze and summarize the clinical characteristics of autoimmune pancreatitis (AIP) patients in China from 2009 to 2018.Methods:Studies published from January 2009 to December 2018 were searched in CNKI, Wanfang and VIP databases by using " autoimmune pancreatitis" , " immune pancreatitis" and " IgG related pancreatitis" as search items, respectively. One hundred and ten articles were finally included, and a total of 2 364 AIP patients were involved. The gender, age, clinical manifestations, laboratory tests, radiological examination, treatment and prognosis of these AIP patients were analyzed and summarized.Results:Among the 2 364 AIP patients, there were 1 777 males and 587 females, with an average age of 58 years. The main clinical manifestations were jaundice(61.31%), abdominal pain(52.45%), abdominal discomfort(34.78%) and body weight loss(22.62%). 50.13% of the patients suffered from extrapancreatic manifestations. Serological examination detected significantly increased levels of IgG4 (74.14%), CRP (73.68%), IgG (71.41%), erythrocyte sedimentation (67.34%), total bilirubin (62.44%), ALT/AST(50.83%), CA19-9(43.85%) and positive rheumatoid factor (42.04%). Pancreatic diffuse (46.87%) and regional enlargement (21.87%) was found in AIP patients by imaging examination. The pancreatic pathological manifestations mainly included lymphoplasmic cell infiltration, pancreatic acinar destruction and atrophy, fibrous tissue proliferation, and positive IgG4 deposition by immunohistochemistry. 282 patients (11.92%) were misdiagnosed, while 70.12% of AIP patients were attenuated by hormones therapies.Conclusions:AIP, which is more common in male in China, is often accompanied by extrapancreatic manifestations. Although imaging examinations were helpful for diagnosis, the misdiagnosis rate remains high. Clinicians need to raise awareness, enhance the ability to diagnose and treat AIP, thus reducing misdiagnosis.

In addition to causing high disability and high fatality rates, ruptured intracranial aneurysms can also cause cognitive impairment. Although preventive surgical treatment can avoid intracranial aneurysm rupture and bleeding, patients may still have a certain degree of cognitive impairment, even in patients with good clinical recovery after surgery. There is no systematic review on the effect of different surgical methods on cognitive function, and the best surgical method is still inconclusive. This article reviews the cognitive impairment in patients with intracranial aneurysm, hoping to provide a basis for clinical treatment decisions.

Minimizing the burden on study subjects and assessing the general dietary nutritional status as accurately as possible are the basis of a nutritional epidemiological cohort study in the general population. While introducing the main dietary nutrition assessment methods, this paper manly describes the basic contents and principles for the development of food frequency questionnaire, and briefly illustrates the problems and solutions for the development of area specific food frequency questionnaires by taking the example of Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort study. Finally, discusses preliminarily the necessity and possibility of developing a national food frequency questionnaire.