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 diagnostic value of endoscopic sign of light blue crest(LBC)capsuling papillary lesion(LCPL)for high-risk intestinal metaplasia(IM).Methods A total of 314 patients(352 biopsy specimens)who underwent endoscopic examination and biopsy in Department of Gastroenterology of Army Medical Center of PLA from January 2021 to June 2023 were recruited,and HE and HID-AB staining(the golden standard of high-risk IM)were apllied to detect the histological types and IM types.The samples were subsequently divided into chronic inflammation group,low-risk IM group,high-risk IM group,well-differentiated intestinal-type gastric cancer group,and poorly-differentiated intestinal-type gastric cancer group.The positive rate of LCPL in each group and its diagnostic efficacy were analyzed based on endoscopic images of the biopsy sites.Logistic regression analysis was used to investigate the relationship between LCPL sign and high-risk IM,as well as the clinical and pathological features associated with LCPL sign.Receiver operating characteristic(ROC)curve was plotted to evaluate the diagnostic efficacy of LCPL for high-risk IM,using indicators such as sensitivity,specificity,Youden index and area under the curve(AUC).Results The positive rate of the LCPL sign in high-risk IM group was 75.70%,significantly higher than that of the other groups(all P<0.001).Logistic regression analysis showed that LCPL sign was significantly correlated with high-risk IM(OR=30.286,95%CI:13.528～67.804,P<0.001).When the sign was employed in diagnosing high-risk IM,the sensitivity was 69.84%,the specificity was 93.75%,the Youden's index was 0.636,and the AUC value was 0.818(95%CI:0.773～0.857).Besides sensitivity,all above parameters of LCPL sign showed significantly better diagnostic efficacy than those of traditional LBC sign,which is used as a sign for diagnosing IM(P<0.001).Moreover,recognition of LCPL sign was not easily affected by age(OR=1.130,95%CI:0.709～1.800,P=0.607),lesion site(Angular incisure:OR=2.360,95%CI:0.732～7.613,P=0.151;Autrum:OR=2.257,95%CI:0.756～6.744,P=0.145),and presence of peptic ulcers(OR=1.085,95%CI:0.208～5.652,P=0.923).Significantly,94.12%of positive and 66.94%of negative LCPL signs could be rapidly recognized within 3 s(OR=4.536,95%CI:1.372～14.997,P=0.013).Conclusion LCPL sign shows high efficacy and potential clinical application value for high-risk IM in gastric mucosa of endoscopic diagnosis.

Objective To discuss the technical advantages of MRI image fusion technology in guiding percutaneous balloon compression(PBC)for trigeminal neuralgia(TN).Methods The clinical data of 13 patients with TN,who received MRI image fusion technology-guided PBC from November 2022 to July 2023,were retrospectively analyzed.The MRI images of the trigeminal nerve obtained one week before surgery were fused with the intraoperative DynaCT images of the skull base so as to simultaneously display the Meckel s cave and foramen ovale,and under the 3-D view the optimal puncture path was determined.The needle was positioned at the entry point of the skin,than the skin was cut open with a sharp surgical blade and the needle was inserted to the foramen ovale area to a predetermined depth.Lateral skull base fluoroscopy and DynaCT scan were used to check that the puncture needle tip was placed into the foramen ovale.Than the puncture needle was replaced by a fine guiding-needle and it was pushed into the Meckel's cave.Under the dual guidance of lateral fluoroscopy and fusion image,the balloon was push forward and was filled with iodine contrast media to compress the trigeminal ganglion within the Meckel's cave.After completion of the treatment,the balloon and puncture needle were removed and manual oppression was applied on the face to achieve hemostasis.Results Immediately after PBC,the pain was relieved in all patients.No permanent or serious complications occurred.One patient had a relapse 3 months after PBC and a second PBC procedure had to be carried out.No obvious pain recurrence was observed in the remaining patients during follow-up period.During the surgery,the mean number of foramen ovale puncturing was(1.31±0.46)times,the mean X-ray exposure time was(8.64±5.66)min,and the mean cumulative dose of X-ray was(570.29±257.15)mGy.After PBC,12 patients(92.31％)developed facial numbness and one patient(7.69％)developed facial pain,all of which were healed after treatment.Conclusion MRI image fusion technology can improve the visualization and accuracy of PBC procedure.It can also reduce the number of puncturing,decrease the radiation exposure dose,and improve the surgical ability of young doctors.Therefore,MRI image fusion technology should be further developed and applied in clinical practice.

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.

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.

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.