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 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.

Background: The incidence density of metabolic dysfunction-associated fatty liver disease (MAFLD) and the effect of a healthy lifestyle on the risk of MAFLD remain unknown. We evaluated the prevalence and incidence density of MAFLD and investigated the association between healthy lifestyle and the risk of MAFLD. Methods: A cross-sectional analysis was conducted on 37,422 participants to explore the prevalence of MAFLD. A cohort analysis of 18,964 individuals was conducted to identify the incidence of MAFLD, as well as the association between healthy lifestyle and MAFLD. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) with adjustments for confounding factors. Results: The prevalence of MAFLD, non-alcoholic fatty liver disease, and their comorbidities were 30.38%, 28.09%, and 26.13%, respectively. After approximately 70 thousand person-years of follow-up, the incidence densities of the three conditions were 61.03, 55.49, and 51.64 per 1,000 person-years, respectively. Adherence to an overall healthy lifestyle was associated with a 19% decreased risk of MAFLD (HR, 0.81; 95% CI, 0.72 to 0.92), and the effects were modified by baseline age, sex, and body mass index (BMI). Subgroup analyses revealed that younger participants, men, and those with a lower BMI experienced more significant beneficial effects from healthy lifestyle. Conclusion Our results highlight the beneficial effect of adherence to a healthy lifestyle on the prevention of MAFLD. Health management for improving dietary intake, physical activity, and smoking and drinking habits are critical to improving MAFLD.

Inflammatory bowel disease (IBD) is a complex condition resulting from environmental, microbial, immunologic, and genetic factors. With the advancement of Mendelian randomization research in IBD, we have gained new insights into the relationship between these factors and IBD. Many animal models of IBD have been developed using different methods, but few studies have attempted to model IBD by combining environmental factors and microbial factors. In this review, we examine how environmental factors and microbial factors affect the development and progression of IBD, and how they interact with each other and with the intestinal microbiota. We also summarize the current methods for creating animal models of IBD and compare their advantages and disadvantages. Based on the latest findings from Mendelian randomization studies on the role of environmental factors in IBD, we discuss which environmental and microbial factors could be used to construct a more realistic and reliable IBD experimental model. We propose that animal models of IBD should consider both environmental and microbial factors to better mimic human IBD pathogenesis and to reveal the underlying mechanisms of IBD at the immune and genetic levels.We highlight the importance of environmental and microbial factors in IBD pathogenesis and offer new perspectives and suggestions for improving experimental animal modeling. Our goal is to create a model that closely resembles the clinical picture of IBD.

Objective:To explore the association between dietary patterns and the incidence of type 2 diabetes mellitus(T2DM), so as to provide insights for the prevention and management of T2DM.Methods:Participants were recruited from the " The Tianjin Chronic Inflammation and Health Cohort Study(TCLSIH)" cohort study from 2013 to 2018, who had completed the modified semiquantitative food frequency questionnaire(FFQ) and blood glucose testing( n=26 425), free of cardiovascular disease, cancer, or diabetes at baseline. The relevant information collected includes food frequency, blood glucose concentration, and other confounding factors. In this study, the correlation between dietary patterns and T2DM was tested using Cox proportional risk regression model, and the gender stratification analysis and body mass index stratification analysis of different gender groups were carried out. All statistical analysis was performed using SAS 9.3 software. Results:The age of all participants was (41.0±11.5)years, and the cumulative incidence was 3.84% for T2DM. The cumulative incidence of T2DM in male population was 5.29%, while that in female population was 2.16%. There were significant differences in the incidence of T2DM among different genders( P <0.001). The multivariable-adjusted hazard ratios( HR) and corresponding 95% CI of T2DM across the plant-based dietary pattern score were 1.09(95% CI 0.91-1.31), 0.80(95% CI 0.66-0.97), and 0.76(95% CI 0.62-0.94; Ptrend =0.010). Moreover, no statistically significant differences were observed between animal and traditional northern Chinese diets with the incidence of T2DM. Conclusions:The plant-based dietary patterns were associated with substantially lower risk of developing T2DM, and there were no significant association between animal and traditional northern Chinese dietary patterns with T2DM. Plant-based dietary patterns characterized by a variety of fruit, leeks, onions, seaweed may be beneficial to the prevention and control of T2DM.

Objective:To investigate the characteristics of digestive system symptoms and its relation with the time of nucleic acid continuous positive in population infected with severe acute respiratory syndrome coronavirus 2 Omicron variant, and to analyze the abdominal computed tomography (CT) features of patients infected with Omicron variant.Methods:From April 11 to May 23, 2022, a questionnaire survey was conducted in patients infected with Omicron variant admitted to the Shanghai National Convention and Exhibition Center Fangcang Hospital. The questionnaire included basic information, the start time of nucleic acid positive, respiratory symptoms, digestive system syptoms and outcomes, etc.Combined with the clinical data, the relation between digestive tract symptoms and the time of nucleic acid continuous positive were analyzed. Thoracic and abdominal CT were performed for patients with continuous positive nucleic acid results ≥10 d, and the relationship between the abdominal CT imaging characteristics and the time of nucleic acid continuous positive was analyzed. Independent sample t-test and multivariate logistic regression were used for statistical analysis. Results:A total of 4 360 valid questionnaires were collected, including 2 475 males and 1 885 females, with a hospital stay of (6.8±4.9) d. Among the 4 360 patients, 1 979 patients (45.4%) had gastrointestinal symptoms such as loss of appetite, abdominal discomfort or pain, constipation and diarrhea. The time of nucleic acid continuous positive in patients with gastrointestinal symptoms was (7.4±5.5) d, which was longer than that of patients without gastrointestinal symptoms (6.5±3.6) d, and the difference was statistically significant ( t=3.78, P<0.001). During the isolation period in the Fangcang Hospital, the time of nucleic acid continuous positive in patients with complete remission of digestive tract symptoms was shorter than that of patients with no remission of digestive tract symptoms ((7.3±5.2) d vs. (8.5±5.7) d), and the difference was statistically significant ( t=2.25, P=0.025). The results of multivariate logistic regression analysis showed that the combination of gastrointestinal symptoms was an independent risk factor for continuous positive nucleic acid result ≥10 d ( OR=1.316, 95% confidence interval 1.294 to 2.205, P=0.046). Among the 299 patients with continuous positive nucleic acid results≥10 d, 187 cases (62.5%) had gastrointestinal symptoms, and 146 cases (48.8%) had abdominal CT findings of thickening of the gastroduodenal wall, thickening of the small intestinal wall, indistinct mesenteric vessels of the small intestine, and dilatation and pneumatosis of the colon. In patients with continuous positive nucleic acid results ≥10 d, abdominal CT indicated that patients with gastrointestinal imaging changes had a longer time of nucleic acid continuous positive than those without gastrointestinal imaging changes ((16.0±2.8) d vs. (13.0±2.1) d), and the difference was statistically significant ( t=2.62, P=0.009). Conclusions:Digestive system symptoms are common in patients infected with Omicron variant. The time of nucleic acid continuous positive in patients with gastrointestinal symptoms is longer than those without gastrointestinal symptoms. Some patients may have gastrointestinal lesions on abdominal CT.

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 compare the clinical efficacy between robot-assisted and free-hand percutaneous cannulated screwing (PCS) in the treatment of femoral neck fractures in the middle-aged and young patients.Methods:A retrospective study was conducted to analyze the clinical data of 53 patients with femoral neck fracture who had been treated with PCS from May 2020 to May 2022 at Department of Traumatic Surgery, Maoming Hospital Affiliated to Southern Medical University. In the robot group of 25 patients subjected to robot-assisted PCS, there were 11 males and 14 females with an age of (48.2 ± 11.9) years; in the free-hand group of 28 patients subjected to free-hand PCS, there were 13 males and 15 females with an age of (48.5 ± 9.8) years. The 2 groups were compared in terms of operation time, intraoperative bleeding, intraoperative guide drills, intraoperative fluoroscopy frequency, fracture union time, Harris hip score at the last follow-up and postoperative complications. Postoperative imaging examination was performed to evaluate distribution accuracy of the cannulated screws in the femoral neck (deviation between the screws and the femoral neck axis, parallelism between the screws and distance between the screws and the neck cortex).Results:There was no statistically significant difference between the robot and free-hand groups in the general clinical data before operation, showing comparability ( P>0.05). The robot group showed significantly shorter operation time [(32.7 ± 4.8) min], significantly less intraoperative bleeding [(14.6 ± 4.8) mL], significantly less intraoperative guide drillings [(3.5 ± 0.7) times] and significantly less intraoperative fluoroscopy frequency [(7.9 ± 1.4) times] than the free-hand group [(56.9 ± 11.3) min, (27.0 ± 7.3) mL, (9.1 ± 1.8) times and (16.3 ± 6.0) times)] (all P<0.05). Postoperative imaging showed that the deviation between the screws and the femoral neck axis was 4.4° ± 1.1° on the anteroposterior X-ray film and 3.2° ± 0.8° on the lateral X-ray film, the parallelism between the screws 4.9° ± 0.8° on the anteroposterior X-ray film and 3.0° ± 0.7° on the lateral X-ray film, and the distance between the screws and the femoral neck cortex (10.4 ± 2.7) mm in the robot group, all significantly smaller than those in the free-hand group [10.5° ± 2.8°, 4.9° ± 1.1°, 12.1° ± 4.0°, 5.1° ± 1.3°, and (15.4 ± 3.2) mm] (all P<0.05). All the 53 patients were followed up for (22.2 ± 8.5) months. All fractures got united. The fracture union time in the robot group [(20.6 ± 4.6) weeks] was insignificantly shorter than that in the free-hand group [(23.7 ± 7.7) weeks] ( P>0.05). At the last follow-up, the Harris hip score in the robot group [(88.6 ± 5.6) points] was significantly higher than that in the free-hand group [(84.8 ± 6.3) points] ( P<0.05). Follow-ups revealed 2 cases of internal fixation loosening, 1 case of screw head cutting and 1 case of femoral head necrosis in the free-hand group but none of such complications in the robot group. Conclusion:In the treatment of femoral neck fractures in the middle-aged and young patients, compared with free-hand PCS, robot-assisted PCS shows advantages of shorter intraoperative time, less bleeding, less fluoroscopic radiation, higher accuracy of screw placement, a lower incidence of postoperative complications and better functional recovery of the hip joint.

Objective:To evaluate modified Lanza score (MLS) of gastric mucosa for predicting the prognosis of geriatric patients with sepsis.Methods:Data of 50 patients with sepsis, who were over 60 years old and underwent gastroscopy for suspected gastrointestinal bleeding in the Department of Geriatric Critical Care Medicine of Guangdong Provincial People's Hospital from January 2019 to April 2022, were retrospectively analyzed. Patients were divided into the death group ( n=32) and the survival group ( n=18) according to their regression within 28 days after gastroscopy. Their gastric mucosa was scored by using MLS system, and the mortality of patients with MLS≥1 was calculated, then the patients were further divided into 2 groups, MLS=0-2 ( n=23, less than 2 regions of lesions ) and MLS=3-5 ( n=27, two or more regions of lesions). The relationship between MLS and acute physiology and chronic health status evaluation (APACHE) Ⅱ score, risk factor of death and mortality in each group were compared. The correlation between MLS and mortality was analyzed. The influence of geriatric sepsis risk factors affecting the prognosis of patients within 28 days were analyzed by using logistic regression. Results:Among the 50 geriatric patients with sepsis, those with gastric mucosal lesions, i.e., MLS ≥1, accounted for 68.00% (34/50), including 84.38% (27/32) patients with MLS≥1 in the death group, which was significantly higher than the 38.89% (7/18) patients with MLS≥1 in the survival group ( χ 2=10.593, P<0.001). Patients with MLS=3-5 had significantly higher APACHE Ⅱ scores (26.09±6.47 VS 18.57±7.66, t=3.527, P=0.001) and higher mortality [85.19% (23/27) VS 39.13% (9/23), χ 2=11.434, P=0.001] compared with MLS=0-2. Correlation analysis showed a significant correlation between MLS and mortality ( r=0.886, P=0.019). Multivariate logistic regression analysis showed that MLS=4-5 was an independent risk factor for death in geriatric patients with sepsis ( OR=17.055, 95% CI: 1.387-209.744, P=0.027). Conclusion:MLS presents high sensitivity in predicting 28-day outcomes for geriatric patients with sepsis. Two or more than 2 regions of gastric mucosal lesions can significantly increase the risk of death in geriatric patients with sepsis.

Objective:To preliminarily evaluate the effect of tension stimulation on the biological activity of and expression of fibrosis marker genes in keloid fibroblasts (KD-Fbs) .Methods:Three patients who were diagnosed with keloids and received surgical treatment were collected from the Department of Dermatology, Tangdu Hospital, the Fourth Military Medical University from January to March 2017. Human KD-Fbs were isolated from resected keloid tissues, and subjected to primary culture. The third- to sixth-passage KD-Fbs were divided into tension group and control group to be cultured in the tension-based chamber and control chamber respectively, and subjected to tension stimulation and normal culture respectively. Cell counting kit-8 (CCK8) assay was performed to assess the proliferative activity of KD-Fbs after 1-, 2-, 3- and 4-day culture, and the scratch assay to evaluate the migratory ability of KD-Fbs after 1- and 2-day culture. After 48-hour treatment, real-time quantitative PCR and Western blot analysis were performed to determine the mRNA and protein expression of fibrosis markers type Ⅰ collagen, fibronectin and α-smooth muscle actin (α-SMA) in KD-Fbs respectively. Two-independent-sample t test was used for comparisons between 2 groups. Results:CCK8 assay showed that the proliferative activity of KD-Fbs was significantly higher in the tension group than in the control group after 1-, 2-, 3- and 4-day culture ( t=3.05, 7.00, 16.65, 15.19, respectively, all P< 0.05) . After 1- and 2-day culture, the scratch assay showed that the migration rate of KD-Fbs was significantly higher in the tension group (48.65%±3.96%, 100.00%, respectively) than in the control group (9.36%±1.14%, 50.35%±4.23%, t=16.53, 20.35, respectively, both P< 0.01) . Real-time quantitative PCR showed that the mRNA expression of type Ⅰ collagen, fibronectin and α-SMA was significantly higher in the tension group (3.04±0.20, 2.16±0.10, 3.76±0.24, respectively) than in the control group (1.00; t=17.57, 21.01, 20.25, respectively, all P< 0.01) . As Western blot analysis revealed, changes in the protein expression of the 3 fibrosis markers were consistent with their mRNA expression changes (all P< 0.05) . Conclusion:Tension may participate in the fibrosis in keloids by promoting the expression of fibrosis marker genes, and enhancing the proliferative and migratory ability of KD-Fbs.