Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective To explore the value of improved ResNet18 lightweight deep learning(DL)models for automatically detecting gouty arthritis(GA)based on ultrasonogram of the first metatarsophalangeal joint(MTP1).Methods A total of 2 401 ultrasonograms obtained from 260 patients with suspected gout who underwent MTP1 ultrasound examination were included and divided into training set(1 910 ultrasonograms from 209 cases)and test set(491 ultrasonograms from 51 cases)at the ratio of 4∶1.GA lesions on ultrasonograms were manually labeled.After preprocessing,ResNet18 lightweight network was used to construct DL models for identifying the ultrasonogram category was normal or abnormal(with any manifestation of GA).Five-fold cross-validation method was adopted to evaluate the efficacy of the DL models constructed with 2,3,4 or 6 residual blocks,i.e.model 1,2,3 and 4,respectively,and the computational cost and the amount of parameters of each model were recorded.The efficacy of the models were verified using test set,and the best DL model was screened.Results The computational cost of model 1,2,3 and 4 was 7 558.27,2 963.73,4 012.33 and 6 093.39 M,respectively,while the amount of parameters was 4.61,4.91,4.91 and 5.28 M,respectively.Model 2 had the least computational cost with parameters only slightly more than model 1.In test set,no significant difference of accuracy nor the area under the curve was found among 4 models(all P＞0.05).The sensitivity of model 2 was higher than that of model 3,while its specificity was lower only than that of model 3(both P＜0.05),hence model 2 was the best DL model.Conclusion Improved ResNet18 lightweight DL models could be used for automatically detecting GA based on ultrasonogram of MTP1,among which model 2 was the best one.

Objective To explore the value of improved ResNet18 lightweight deep learning(DL)models for automatically detecting gouty arthritis(GA)based on ultrasonogram of the first metatarsophalangeal joint(MTP1).Methods A total of 2 401 ultrasonograms obtained from 260 patients with suspected gout who underwent MTP1 ultrasound examination were included and divided into training set(1 910 ultrasonograms from 209 cases)and test set(491 ultrasonograms from 51 cases)at the ratio of 4∶1.GA lesions on ultrasonograms were manually labeled.After preprocessing,ResNet18 lightweight network was used to construct DL models for identifying the ultrasonogram category was normal or abnormal(with any manifestation of GA).Five-fold cross-validation method was adopted to evaluate the efficacy of the DL models constructed with 2,3,4 or 6 residual blocks,i.e.model 1,2,3 and 4,respectively,and the computational cost and the amount of parameters of each model were recorded.The efficacy of the models were verified using test set,and the best DL model was screened.Results The computational cost of model 1,2,3 and 4 was 7 558.27,2 963.73,4 012.33 and 6 093.39 M,respectively,while the amount of parameters was 4.61,4.91,4.91 and 5.28 M,respectively.Model 2 had the least computational cost with parameters only slightly more than model 1.In test set,no significant difference of accuracy nor the area under the curve was found among 4 models(all P＞0.05).The sensitivity of model 2 was higher than that of model 3,while its specificity was lower only than that of model 3(both P＜0.05),hence model 2 was the best DL model.Conclusion Improved ResNet18 lightweight DL models could be used for automatically detecting GA based on ultrasonogram of MTP1,among which model 2 was the best one.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective To observe the value of follicular thyroid imaging reporting and data system(F-TIRADS)for differentiating benign and malignant follicular thyroid lesions.Methods Totally 502 patients with follicular thyroid lesions were retrospectively enrolled,including 104 patients with single malignant lesion(malignant group,containing 77 follicular thyroid carcinomas[FTC]and 27 follicular variant of papillary thyroid carcinomas[FVPTC])and 398 patients with 416 benign lesions(benign group,containing 197 follicular thyroid adenomas[FTA]and 219 thyroid adenomatous hyperplasia).Ultrasonic features of lesions were recorded,and F-TIRADS scores were assigned by 1 junior and 1 senior ultrasound physicians.Taken histopathology results as gold standard,receiver operating characteristic curve was drawn,the area under the curve(AUC)was calculated to evaluate the efficacy for differentiating benign and malignant follicular thyroid lesions using F-TIRADS.Results Significant differences of composition,internal echo,boundary,calcification and trabecular structure of lesions were found between groups(all P＜0.001).Taken F-TIRADS score≥ 7 as the optimal cut-off value,the sensitivity,specificity,accuracy,positive predictive value and negative predictive value for differentiating benign and malignant follicular thyroid lesions by the junior physician was 76.92％,77.40％,77.31％,93.06％and 45.98％,while by the senior physician was 78.84％,81.25％,80.76％,93.89％and 51.25％,respectively.The efficacy of the latter was higher than of the former(AUC was 0.827 and 0.859,respectively,P＜0.05).Conclusion F-TIRADS could effectively identifying benign and malignant follicular thyroid lesions.

Objective To observe the value of follicular thyroid imaging reporting and data system(F-TIRADS)for differentiating benign and malignant follicular thyroid lesions.Methods Totally 502 patients with follicular thyroid lesions were retrospectively enrolled,including 104 patients with single malignant lesion(malignant group,containing 77 follicular thyroid carcinomas[FTC]and 27 follicular variant of papillary thyroid carcinomas[FVPTC])and 398 patients with 416 benign lesions(benign group,containing 197 follicular thyroid adenomas[FTA]and 219 thyroid adenomatous hyperplasia).Ultrasonic features of lesions were recorded,and F-TIRADS scores were assigned by 1 junior and 1 senior ultrasound physicians.Taken histopathology results as gold standard,receiver operating characteristic curve was drawn,the area under the curve(AUC)was calculated to evaluate the efficacy for differentiating benign and malignant follicular thyroid lesions using F-TIRADS.Results Significant differences of composition,internal echo,boundary,calcification and trabecular structure of lesions were found between groups(all P＜0.001).Taken F-TIRADS score≥ 7 as the optimal cut-off value,the sensitivity,specificity,accuracy,positive predictive value and negative predictive value for differentiating benign and malignant follicular thyroid lesions by the junior physician was 76.92％,77.40％,77.31％,93.06％and 45.98％,while by the senior physician was 78.84％,81.25％,80.76％,93.89％and 51.25％,respectively.The efficacy of the latter was higher than of the former(AUC was 0.827 and 0.859,respectively,P＜0.05).Conclusion F-TIRADS could effectively identifying benign and malignant follicular thyroid lesions.

Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.
Animals ; Neurons/physiology* ; Mice ; Brain/physiology* ; Mice, Inbred C57BL ; Somatosensory Cortex/physiology* ; Neural Pathways/physiology* ; Hippocampus/physiology* ; Mice, Transgenic ; Male ; Brain Mapping ; Nerve Net/physiology* ; Substantia Nigra/physiology* ; Tomography, Optical/methods*

Objective To construct a prediction model for postoperative healthcare-associated infection(HAI)in elderly patients with hip fracture,analyze the economic burden,provide a reference and basis for the development of clinical prevention and control programs.Methods 627 elderly patients who underwent hip fracture surgery in a hospital from January 1,2017 to May 31,2023 were selected as the study subjects.Patients were randomly divided into a modeling group and a validation group at a 7:3 ratio.A logistic regression prediction model was constructed based on data from the modeling group,the discriminant and consistency of the model were evaluated by receiver ope-rating characteristic(ROC)curve and Hosmer-Lemeshow test,and the direct economic burden of postoperative HAI in patients was analyzed with 1∶1 propensity score matching(PSM).Results The incidence of postoperative HAI in elderly patients with hip fracture surgery was 12.1％,with pulmonary infection being the most common(52.6％).Logistic regression analysis showed that male,old age,perioperative disturbance of consciousness,gradeⅣ of American Society of Anesthesiologists(ASA)classification,low albumin level,and intensive care unit(ICU)admission were all independent risk factors for postoperative HAI in patients(all P＜0.05).There was good model discrimination and consistency between the training and validation groups in predicting the risk of postoperative HAI.The direct economic burden of postoperative HAI in patients was 7 927.4 Yuan,of which the burden of wes-tern medicine was the largest(3 139.7 Yuan).HAI prolonged patients hospitalization time by 3.6 days.Conclusion Postoperative HAI increases the economic burden of patients,the nomogram model constructed in this study can effectively predict the risk of postoperative HAI in patients,which can provide a basis for the early identification,as well as the implementation of targeted preventive and diagnostic measures for high-risk patients in the clinic.

Objective:To assess the consistency of ultrasound and dual-energy computed tomography (DECT) in the diagnosis of gouty arthritis(GA), reasons of the differences were further analyzed.Methods:The ultrasound and DECT images of 150 knee joints from 147 patients diagnosed with gout at the Gout Specialty Clinic of Qingdao University Affiliated Hospital from February 2022 to October 2023 were retrospectively analyzed. According to anatomy, the knee joint was anatomically segmented into five regions: intra-articular, anterior, posterior, medial, and lateral.Location of monosodium urate (MSU) deposition was meticulously recorded. The Kappa consistency test was employed to assess the consistency of the two examination results in different regions of the knee joint. The McNemar chi-square test was utilized to conduct a differential analysis between DECT and ultrasound results.Results:Double contour sign(DCS) (81.2%, 92/112) was the most common intra-articular ultrasound sign in knee joints with GA. In the extra-articular region, MSU was commonly deposited in and around the popliteal tendon (ultrasound: 51.6%, 66/128; DECT: 54.7%, 70/128). Corresponding MSU deposits on DECT were found in 9 of 92 joints with DCS and in 9 of 49 joints with aggregates detected on ultrasound.In the assessment of MSU deposits, ultrasound showed an overall higher positive rate than DECT (87.3% vs. 72.3%, P=0.001), with poor consistency between the two examinations (Kappa=0.153). In distinct anatomical regions, ultrasound and DECT showed high consistency in the medial (Kappa=0.697) and lateral (Kappa=0.718) sides and the difference was not statistically significant ( P>0.05). Intra-articular (Kappa=0.289) and anterior (Kappa=0.303) regions exhibited only fair consistency, with statistically significant diagnostic differences ( P<0.05). When exclusively assessing cases with tophus, ultrasound and DECT demonstrated high consistency in the medial and lateral aspects(Kappa=0.685, 0.748) without statistical difference ( P>0.05). In the anterior region, the consistency between the two examinations was moderate (Kappa=0.256), while in the intra-articular region, the consistency of the two methods was lower (Kappa=0.147), and the differences was statistically significant ( P<0.001). Conclusions:Both ultrasound and DECT exhibit good diagnostic capabilities for gouty knee arthritis.However, the consistency between the two techniques varies in different anatomical locations. Clinical assessment should be tailored based on the specific anatomical position. DECT has an advantage in evaluating intra-articular MSU deposits, while ultrasound is more sensitive to detect early and scattered MSU deposits.

Objective:To assess the discriminatory value of the Thyroid Follicular Tumor Ultrasound Risk Stratification System (F-TIRADS) in differentiating follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA), and to compare its performance with other risk stratification systems(RSS).Methods:A retrospective analysis was conducted on 325 patients (327 thyroid nodules) diagnosed postoperatively as FTC or FTA at Affiliated Hospital of Qingdao University from January 2016 to December 2023. The cases were divided into FTC group (81 nodules) and FTA group (246 nodules). The nodules were classified based on F-TIRADS, the 2020 Chinese Thyroid Imaging Reporting and Data System (C-TIRADS), the 2015 American Thyroid Association guidelines (ATA guidelines), and the 2017 European Thyroid Association Thyroid Imaging Reporting and Data System (EU-TIRADS) by two ultrasound physicians. Multivariate Logistic regression analysis was used to identify independent predictors associated with FTC. Diagnostic performance of the 4 RSS was compared using postoperative pathological results as the gold standard.Results:Multivariate Logistic regression analysis showed maximum diameter, solid composition, hypoechogenicity, unclear or angular margins, marginal or ring calcifications, trabecular structure, and central blood flow were independent predictors of FTC( OR=1.914, 3.427, 9.926, 9.163, 45.918, 3.191, 8.936, respectively; all P<0.05). Within each RSS, the actual malignancy rate increased with higher risk categories, aligning closely with the recommended malignancy rates (except for ATA guidelines). The optimal cut-off values for distinguishing FTC from FTA were FTC risk 50%-90% in F-TIRADS, C-TIRADS 4B, moderately suspicious nodules in ATA guidelines, and EU-TIRADS 4, with areas under the curve of 0.916, 0.808, 0.827, and 0.836, respectively. F-TIRADS demonstrated the best overall performance (sensitivity: 82.72%, specificity: 82.93%), with significant differences compared with C-TIRADS, ATA guidelines, and EU-TIRADS (all P<0.05). Conclusions:F-TIRADS is highly effective in distinguishing FTA from FTC, outperforming C-TIRADS, ATA Guidelines, and EU-TIRADS. Clinicians should pay close attention to solid hypoechoic nodules with unclear or angular margins, marginal or ring calcifications, central blood flow, or a trabecular structure.