OBJECTIVE To observe the clinical efficacy of donafenib combined with programmed death-1 （PD-1） inhibitors and vascular intervention therapy in the treatment of unresectable hepatocellular carcinoma （HCC）. METHODS This retrospective study included 165 patients with unresectable HCC who were treated at the Fourth and First Affiliated Hospitals of Soochow University between June 2022 and March 2023. Among them， 89 patients received PD-1 inhibitors （tislelizumab or sintilimab， similarly hereinafter） plus vascular intervention （control group） and 76 patients received donafenib in combination with PD-1 inhibitors and vascular intervention （observation group）. Short-term efficacy （3 months after treatment）， long-term efficacy （2 years after treatment）， the levels of liver function indexes [serum alanine amino-transferase （ALT）， aspartate transferase （AST）， and total bilirubin （TBil）] and tumor biomarkers [alpha fetoprotein （AFP）， carcinoembryonic antigen （CEA）， carbohydrate antigen 19-9 （CA19-9）， and des-gamma-carboxy prothrombin （DCP）] before treatment and after 3 months of treatment， as well as the occurrence of adverse drug reaction （ADR） during treatment， were compared between the two groups. In addition， overall response rate （ORR） stratified by PD-1 inhibitor type was analyzed. RESULTS After treatment， the ORR was significantly higher in the observation group than in the control group （P＜0.05）； although the disease control rate was higher in the observation group compared to the control group， the difference was not statistically significant （P＞0.05）. The median overall survival of patients in the observation group was 16.9 months [95% confidence interval （CI）： 14.2 to 19.1 months]， which was significantly longer than that in the control group （12.4 months， 95%CI： 10.1 to 15.3 months） （P＜0.05）. Subgroup analysis result indicated that therapeutic advantage was consistent across both sintilimab and tislelizumab subgroups， with no significant heterogeneity （P＞0.1， I 2＜0.001%）. Before treatment， there were no significant differences in liver function indexes or tumor marker levels between 2 groups （P＞0.05）. After treatment， both groups showed significant declines in these indicators compared with baseline （P＜0.05）， with greater reductions observed in the observation group （P＜0.05）. There were no statistically significant differences in overall incidence of ADR and grade ≥3 ADRs between the two groups （P＞0.05）. CONCLUSIONS For patients with unresectable HCC， the combination of donafenib， PD-1 inhibitors and vascular intervention therapy may achieve superior clinical outcomes without increasing the risk of treatment-related ADR.

Aging has always been a topic that has been widely concerned and discussed. The aging of lower eyelid starts to accelerate after the age of 40 years, which is an important indicator of people’s perceived age, mainly manifested as the emergence of tear trough, palpebromalar groove, eyelid bags, and skin aging. It is of great significance to evaluate the state of lower eyelid completely and objectively for the aging degree of lower eyelid, the formulation of individualized treatment plan and the evaluation of surgical effect. This article reviews the current status and progress of lower eyelid assessment method in recent years.

Aging has always been a topic that has been widely concerned and discussed. The aging of lower eyelid starts to accelerate after the age of 40 years, which is an important indicator of people’s perceived age, mainly manifested as the emergence of tear trough, palpebromalar groove, eyelid bags, and skin aging. It is of great significance to evaluate the state of lower eyelid completely and objectively for the aging degree of lower eyelid, the formulation of individualized treatment plan and the evaluation of surgical effect. This article reviews the current status and progress of lower eyelid assessment method in recent years.

To explore the ideal pretarsal shows and morphological characteristics of double eyelids in Chinese populations through a morphometric analysis.

To explore the ideal pretarsal shows and morphological characteristics of double eyelids in Chinese populations through a morphometric analysis.

Objective:To investigate the diagnostic performance of CT-derived fractional flow reserve (CT-FFR) derived from standard images (STD), images processed by first-generation (SSF1) and second-generation (SSF2) whole-heart motion correction algorithm, respectively.Methods:Patients who underwent both coronary CT angiography (CCTA) and invasive coronary angiography (ICA) with FFR examination within 3 months in Shanghai General Hospital, Shanghai Jiao Tong Univerisity School of Medicine from January 2020 to December 2022 were screened in this retrospective study. Totally of 121 patients (134 lesions) were finally included in the study. CCTA images were reconstructed using iterative reconstruction, iterative reconstruction plus SSF1 and SSF2 algorithms. All images were divided into three groups: STD group, SSF1 group, and SSF2 group. The image quality of the CCTA images was assessed using the Likert scale, and differences between the two groups were compared using the Mann-Whitney U and Kruskal-Wallis test. The correlation and consistency between CT-FFR and FFR were evaluated using Spearman correlation coefficient and Bland-Altman plots. The diagnostic performance of CCTA and CT-FFR from three groups was compared by receiver operating characteristic (ROC) curves. The area under the curve (AUC) was compared using the DeLong test. Results:Compared to the STD group and SSF1 group, the SSF2 group showed the best performance in image quality score (median=3.7). Best correlation ( r=0.652, P<0.001) and consistency (mean difference=0.03) between CT-FFR and FFR were observed in SSF2 group. ROC analysis results revealed that, at the per-lesion level, in the diagnosis of ischemic lesions, the diagnostic performance of CT-FFR in the SSF2 group was significantly better than that of the SSF1 group (AUC=0.88 vs. 0.76, P=0.003), while no significant difference was observed between STD group and SSF1 group ( P=0.125). At the per-patient level, the SSF2 group also demonstrated the highest diagnostic performance. Conclusion:The SSF2 algorithm significantly improved CCTA image quality and enhanced its diagnostic performance for evaluating stenosis severity and CT-FFR calculations.

Objective The fully automatic segmentation of glioma and its subregions is fundamental for computer-aided clinical diagnosis of tumors.In the segmentation process of brain magnetic resonance imaging(MRI),convolutional neural networks with small convolutional kernels can only capture local features and are ineffective at integrating global features,which narrows the receptive field and leads to insufficient segmentation accuracy.This study aims to use dilated convolution to address the problem of inadequate global feature extraction in 3D-UNet.Methods 1)Algorithm construction:A 3D-UNet model with three pathways for more global contextual feature extraction,or 3DGE-UNet,was proposed in the paper.By using publicly available datasets from the Brain Tumor Segmentation Challenge(BraTS)of 2019(335 patient cases),a global contextual feature extraction(GE)module was designed.This module was integrated at the first,second,and third skip connections of the 3D UNet network.The module was utilized to fully extract global features at different scales from the images.The global features thus extracted were then overlaid with the upsampled feature maps to expand the model's receptive field and achieve deep fusion of features at different scales,thereby facilitating end-to-end automatic segmentation of brain tumors.2)Algorithm validation:The image data were sourced from the BraTs 2019 dataset,which included the preoperative MRI images of 335 patients across four modalities(T1,T1ce,T2,and FLAIR)and a tumor image with annotations made by physicians.The dataset was divided into the training,the validation,and the testing sets at an 8∶1∶1 ratio.Physician-labelled tumor images were used as the gold standard.Then,the algorithm's segmentation performance on the whole tumor(WT),tumor core(TC),and enhancing tumor(ET)was evaluated in the test set using the Dice coefficient(for overall effectiveness evaluation),sensitivity(detection rate of lesion areas),and 95%Hausdorff distance(segmentation accuracy of tumor boundaries).The performance was tested using both the 3D-UNet model without the GE module and the 3DGE-UNet model with the GE module to internally validate the effectiveness of the GE module setup.Additionally,the performance indicators were evaluated using the 3DGE-UNet model,ResUNet,UNet++,nnUNet,and UNETR,and the convergence of these five algorithm models was compared to externally validate the effectiveness of the 3DGE-UNet model.Results 1)In internal validation,the enhanced 3DGE-UNet model achieved Dice mean values of 91.47%,87.14%,and 83.35%for segmenting the WT,TC,and ET regions in the test set,respectively,producing the optimal values for comprehensive evaluation.These scores were superior to the corresponding scores of the traditional 3D-UNet model,which were 89.79%,85.13%,and 80.90%,indicating a significant improvement in segmentation accuracy across all three regions(P＜0.05).Compared with the 3D-UNet model,the 3DGE-UNet model demonstrated higher sensitivity for ET(86.46%vs.80.77%)(P＜0.05),demonstrating better performance in the detection of all the lesion areas.When dealing with lesion areas,the 3DGE-UNet model tended to correctly identify and capture the positive areas in a more comprehensive way,thereby effectively reducing the likelihood of missed diagnoses.The 3DGE-UNet model also exhibited exceptional performance in segmenting the edges of WT,producing a mean 95%Hausdorff distance superior to that of the 3D-UNet model(8.17 mm vs.13.61 mm,P＜0.05).However,its performance for TC(8.73 mm vs.7.47 mm)and ET(6.21 mm vs.5.45 mm)was similar to that of the 3D-UNet model.2)In the external validation,the other four algorithms outperformed the 3DGE-UNet model only in the mean Dice for TC(87.25%),the mean sensitivity for WT(94.59%),the mean sensitivity for TC(86.98%),and the mean 95%Hausdorff distance for ET(5.37 mm).Nonetheless,these differences were not statistically significant(P＞0.05).The 3DGE-UNet model demonstrated rapid convergence during the training phase,outpacing the other external models.Conclusion The 3DGE-UNet model can effectively extract and fuse feature information on different scales,improving the accuracy of brain tumor segmentation.

Objective:To investigate the effect of embedded guidance technique assisted transconjunctival lower eyelid blepharoplasty.Methods:A retrospective study was conducted to include 88 patients who underwent transconjunctival blepharoplasty and tear trough deformity correction with orbital septum fat release and fixation (referred to as transconjunctival lower eyelid blepharoplasty) at the Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, from October 2021 to August 2022. There were 9 male patients (10.23%) and 79 female patients (88.77%), aged 22 to 51 years, with an average age of (34.42±6.17) years. The internal fixation of septum fat flap was assisted with embedded guidance technique, and the Barton grades system was used to evaluate the surgical effect, while the patient satisfaction and complications were collected.Results:The followed-up period is 6-16 months. Before operation, 35 eyes (19.89%) were classified as Barton Ⅰ, 86 eyes (48.86%) were classified as Barton Ⅱ, and 55 eyes (31.25%) were classified as Barton Ⅲ. After transconjunctival lower eyelid blepharoplasty, 151 eyes (85.80%) recovered to Barton grade 0, 22 eyes (12.50%) recovered to grade Ⅰ, 3 eyes (1.70%) recovered to grade Ⅱ, and no case was grade Barton Ⅲ. The patient satisfaction score was (9.14±1.22) points, and 78 patients (88.64%) were very satisfied. Only 6 patients (6.82%) showed mild complications, mainly including postoperative bilateral lower eyelid asymmetry (3 cases), mild bilateral orbital area ecchymosis (2 cases) and mild surface depression at internal fixation position (1 case).Conclusions:The transconjunctival lower eyelid blepharoplasty assisted by the embedded guidance technique achieves favorable results with high patient satisfaction and few complications.

Objective: To investigate the incidence of microvascular myocardial ischemia in diabetic patients without obstructive coronary artery disease (CAD) and its relationship with angina. Materials and Methods: Diabetic patients and an intermediate-to-high pretest probability of CAD were prospectively enrolled. Non-diabetic patients but with an intermediate-to-high pretest probability of CAD were retrospectively included as controls. The patients underwent dynamic computed tomography-myocardial perfusion imaging (CT-MPI) and coronary computed tomography angiography (CCTA) to quantify coronary stenosis, myocardial blood flow (MBF), and extracellular volume (ECV). The proportion of patients with microvascular myocardial ischemia, defined as any myocardial segment with a mean MBF ≤ of 100 mL/min/100 mL, in patients without obstructive CAD (Coronary Artery Disease–Reporting and Data System [CAD-RADS] grade 0–2 on CCTA) was determined. Various quantitative parameters of the patients with and without diabetes without obstructive CAD were compared. Multivariable analysis was used to determine the association between microvascular myocardial ischemia and angina symptoms in diabetic patients without obstructive CAD. Results: One hundred and fifty-two diabetic patients (mean age: 59.7 ± 10.7; 77 males) and 266 non-diabetic patients (62.0 ± 12.3; 167 males) were enrolled; CCTA revealed 113 and 155 patients without obstructive CAD, respectively. For patients without obstructive CAD, the mean global MBF was significantly lower for those with diabetes than for those without (152.8 mL/min/100 mL vs. 170.4 mL/min/100 mL, P < 0.001). The mean ECV was significantly higher for diabetic patients (27.2% vs. 25.8%, P = 0.009). Among the patients without obstructive CAD, the incidence of microvascular myocardial ischemia (36.3% [41/113] vs. 10.3% [16/155], P < 0.001) and interstitial fibrosis (69.9% [79/113] vs. 33.3% [8/24], P = 0.001) were significantly higher in diabetic patients than in the controls. The presence of microvascular myocardial ischemia was independently associated with angina symptoms (adjusted odds ratio = 3.439, P = 0.037) in diabetic patients but without obstructive CAD. Conclusion Dynamic CT-MPI + CCTA revealed a high incidence of microvascular myocardial ischemia in diabetic patients without obstructive CAD. Microvascular myocardial ischemia is strongly associated with angina.

Objective:To investigate the changes in adaptive phenotypes of Yersinia pestis ( Yp) during successive passages in macrophages. Methods:A Yp strain of 201-MI was induced by 50 successive passages of Yp 201 strain in Raw264.7 cells. Phenotypic characteristics of 201 and 201-MI strains were compared by analyzing their survival rates in macrophages, growth curves, biofilm formation abilities, acid and hydrogen peroxide-stress tolerance, and virulence to mammal cells (Raw264.7 and HeLa cells) and mice. Results:Comparing with 201 strain, 201-MI strain showed various phenotypic changes, including higher survival rate in Raw264.7 cells, faster growth in iron-deficient medium, higher tolerance to acid and hydrogen peroxide, decreased biofilm formation ability, and less damages to Raw264.7 and HeLa cells. More-over, 201-MI strain showed decreased virulence to mice in both subcutaneous and intraperitoneal challenges. Preliminary comparative genomics analysis revealed some indel and nonsense mutations in 201-MI strain, which might account for its phenotype changes.Conclusions:After successive passages in macrophages, Yp showed some phenotypic changes, which might reflect its adaptive evolution under the pressure of macrophages. Detailed multi-omics analysis would be of great help to understand the underlying genetic mechanisms of these changes, and the related Yp-macrophage interaction processes as well.