Immunotherapy that targets checkpoints, especially programmed cell death protein 1 and programmed cell death ligand 1, has revolutionized cancer therapy regimens. The overall response rate to mono-immunotherapy, however, is limited, emphasizing the need to potentiate the efficacy of these regimens. The functions of immune cells are modulated by multiple stimulatory and inhibitory molecules, including lymphocyte activation gene 3 (LAG-3). LAG-3 is co-expressed together with other inhibitory checkpoints and plays key roles in immune suppression. Increasing evidence, particularly in the last 5 years, has shown the potential of LAG-3 blockade in anti-tumor immunity. This review provides an update on the biological properties and clinical applications of LAG-3 in cancers.

Objective:To investigate the ultrasound characteristics of benign and malignant endometrial lesions in postmenopausal women terminology.Methods:Patients with endometrial lesions who underwent transvaginal ultrasound examination in Beijing Tiantan Hospital affiliated to Capital Medical University from January 2019 to November 2021 were selected.Pathological diagnosis after surgery was used as the gold standard, and endometrial lesions were divided into a benign group(including endometrial hyperplasia and endometrial polyps)and a malignant group(endometrial cancer)according to surgical pathology results.Endometrial thickness and Doppler flow parameters were compared between the benign group and the malignant group.The chi-square test was used to compare the echogenicity, the presence or absence of cystic areas, the integrity of the endometrial-myometrial junction, the blood flow score, and the blood supply vessels between the benign and malignant groups.A prediction model was established according to the ultrasonic characteristics.Results:A total of 136 participants received surgery at our hospital with definitive pathological diagnoses, including 72 patients in the benign group and 64 patients in the malignant group.Peak systolic velocity(PSV) and end diastolic velocity(EDV) in malignant lesions were higher than those in benign lesions[(28.75±14.66)cm/s vs.(22.94±13.62)cm/s, (14.75±8.10)cm/s vs.(11.56±6.21)cm/s]. The thickness of malignant lesions was significantly greater than that of benign lesions[(19.31±8.97)mm vs.10.14±4.31)mm], and the blood flow resistance index was lower than that of benign lesions(14.75±8.10 vs.11.56±6.21). The differences were statistically significant( t=2.393, 2.597, 7.452, 2.028, all P<0.05). The prediction model was established based on the above ultrasonic characteristics.The area under the ROC curve for ultrasound physicians to diagnose benign and malignant endometrial lesions was 0.905( P<0.001), indicating that the prediction model had high diagnostic value. Conclusions:Both benign and malignant endometrial lesions in postmenopausal women have different ultrasonic characteristics.Malignant lesions tend to have a larger lesion thickness, an interrupted or irregular endometrial-myometrial junction, higher blood flow signal scores, and multiple blood supply patterns.The ultrasonic prediction model has high diagnostic value for benign and malignant endometrial lesions.

Objective:To investigate the value of contrast-enhanced ultrasound (CEUS) in the diagnosis of malignant endometrial lesions.Methods:A total of 142 patients with endometrial lesions who underwent contrast-enhanced ultrasound examination in Beijing Tiantan Hospital, Capital Medical University from January 2019 to September 2021 were selected. The endometrial lesions were divided into benign group (including endometrial hyperplasia and endometrial polyps) and malignant group (endometrial cancer) according to the pathological results of surgery, and the differences of contrast enhancement patterns between benign group and malignant group were compared. The sensitivity, specificity of CEUS in the diagnosis of endometrial cancer were calculated, and the Kappa value was calculated with the initial enhancement time earlier than or equal to the muscularity or the peak time earlier than the muscularity as the diagnostic index for the diagnosis of endometrial malignant lesions. The sensitivity, specificity, and Kappa value of CEUS in the diagnosis of endometrial cancer and endometrial cancer with thickness ≥10 mm were calculated.Results:A total of 108 patients underwent surgery with clear pathological results, including 66 patients in the benign lesion group and 42 patients in the malignant lesion group. The thickness of malignant lesions was significantly larger than that of benign lesions, and the difference was statistically significant( t=4.039, P<0.05), but there was no significant difference of hemodynamic parameters between the two groups ( P>0.05). The initial enhancement time, peak time and peak intensity of benign lesions were significantly different from those of malignant lesions(all P<0.05). The sensitivity, specificity, and Kappa value of CEUS in the diagnosis of endometrial cancer were 64.3%, 100% and 0.668, respectively. The sensitivity, specificity and Kappa value of CEUS in the diagnosis of endometrial carcinoma with lesion thickness ≥10 mm were 75.0%, 100% and 0.795, respectively. Conclusions:For the diagnosis of endometrial lesions, especially the malignant endometrial lesions with thickness and diameter greater than or equal to 10mm, there is a high diagnostic coincidence rate between CEUS and pathological diagnosis, and endometrial malignant lesions have more specific CEUS manifestations.

Objective:To explore the value of different levels of sonographers and International Ovarian Tumor Analysis (IOTA) simple rules in judging benign and malignant ovarian tumors.Methods:The ultrasound images of 182 patients treated in Beijing Tiantan Hospital, Capital Medical University from January 2017 to November 2020 with ovarian tumors were retrospectively analyzed. The ovarian tumors were diagnosed by two senior sonographers and two junior sonographers without knowing the pathological diagnosis. Another junior sonographer trained in IOTA terminology and simple rules applied IOTA simple rules to diagnose 182 ovarian tumors. The sensitivity, specificity, positive predictive value and negative predictive value of the diagnosis of ovarian tumors by senior sonographers, junior sonographers and IOTA simple rules were calculated using the postoperative pathological diagnosis as the gold standard. The Kappa value was calculated for the consistency between different levels of sonographers and the IOTA simple rules and pathological diagnosis.Results:Of the 182 cases, 61 cases were pathologically benign and 121 cases were pathologically malignant. The diagnostic sensitivity, specificity and accuracy of senior sonographers were 93.4%, 99.2%, 97.2%, respectively, Kappa value was 0.938. The diagnostic sensitivity, specificity, and accuracy of junior sonographers were 80.3%, 90.0%, 86.8%, respectively, Kappa value was 0.704. The diagnostic sensitivity, specificity and accuracy of IOTA simple rules(When an uncertain tumor was classified as malignant) were 95.0%, 73.5%, 80.7%, respectively, Kappa value was 0.614. The diagnostic sensitivity, specificity and accuracy of IOTA simple rules(when an uncertain tumor was excluded) were 94.2%, 90.9%, 92.0%, respectively, Kappa value was 0.834.Conclusions:IOTA simple rules is a very useful diagnostic tool for junior sonographers to judge benign and malignant ovarian tumors. When IOTA simple principle is judged as an uncertain case, it is recommended to refer to experienced senior sonographers for further diagnosis.

Objective:To find clues potentially valuable for fighting against infection with human respiratory syncytial virus (HRSV), the differentially expressed genes in HEp-2 cells infected with HRSV were analyzed.Methods:Gene expression profiles of HEp-2 cells infected with HRSV were collected from the public gene expression omnibus (GEO) database. The differentially expressed genes following HRSV infection at each time point of 4, 8, 12, and 15 hours were found using R language. The differentially expressed genes were analyzed by gene ontology (GO), KEGG pathway and protein-protein interaction network (PPI). Genes with relatively high protein interaction in PPI were randomly selected for quantitative reverse transcription-polymerase chain reaction (qRT-PCR) verification at the transcription level from HEp-2 cells after HRSV infection at 4 hours.Results:A total of 101 differentially expressed genes were determined, including 92 upregulated genes and 9 downregulated genes. Function enrichment analysis revealed that HRSV infection could cause significant changes in multiple signaling pathways such as immune response in HEp-2 cells. The results of qRT-PCR were consistent with the trend of transcriptome data.Conclusions:The differentially expressed genes and the change of signaling pathways in HRSV-infected HEp-2 cells is of great significance to the studies on pathogenic mechanism and prevention of HRSV infection.

Objective To evaluate the vulnerability of carotid arteriosclerosis plaque by ultrasound real-time tissue elastography in patients with SSS-TOAST1 style cerebral infarction, and discussing the value of the technique in assessment of the clinical course after cerebral infarction. Methods There were 113 patients of SSS-TOAST1 style cerebral infarction who had carotid arteriosclerosis plaque and 48 patients of contrast group who had carotid arteriosclerosis plaque selected by ultrasound in Department of Ultrasound, Beijing Tiantan Hospital, Capital University of Medical Sciences. The results between two groups were compared. The cerebral infarction group was divided into two sub-groups according to the clinical course of patients after cerebral infarction, and the difference between them was compared. Results The size had no significant difference between cerebral infarction group and contrast group as well as between aggravated group and non-aggravated group (t=15.61, 10.77, 4.52, P<0.05). The real-time tissue elastography of carotid arteriosclerosis plaques were red-green in most patients of cerebral infarction group. The real-time tissue elastography of carotid arteriosclerosis plaques were green-blue in most patients of in control group. The value of elasticity of plaque, vessel wall and stiffness of carotid arteriosclerosis plaque between cerebral infarction group and control group had significant differences (t=15.61, 10.77, 4.52, P<0.05). The value of real-time tissue elastography between aggravated group and non-aggravated group had significant difference (t=6.39, 2.30, 3.80, P<0.05). Conclusion Real-time tissue elastography could evaluate the stiffness of carotid arteriosclerosis plaque, which was related with the vulnerability of carotid arteriosclerosis plaque. The values of elasticity of plaque, vessel wall and stiffness of carotid arteriosclerosis plaque in patients with SSS-TOAST1 style cerebral infarction were lower, and the vulnerability of carotid arteriosclerosis plaque was higher. Real-time tissue elastography had some worth in evaluating the clinical course of patients after cerebral infarction.

Objective To investigate the alteration of peripheral tissue`s temperature of the coagulation zone of microwave ablation in brain tissue, and to provide experimental evidence for clinical application. Methods Twelve canines were treated by microwave ablation in brain tissue. Each was ablated for 180 s with microwave output power of 20 W, 30 W, and 40 W. During the operation the peripheral temperature at the distance of 0.5 cm, 1.0 cm, 1.5 cm and 2.0 cm from the ablation center was recorded respectively. The ultrasound was performed 1 hour after the operation, and then the animals were executed and the microscopic changes of the ablation lesion were observed. Results Eleven canines suffered well for the ablation, while 1 presented abnormal respiration during the operation and died 2 hours later. During the operation, the temperature of the area 0.5 cm from the center rose signiifcantly, with the maximum temperature was (96.40±1.46)℃at the power of 20 W, and 100℃at the power of 30 W and 40 W. The temperature of the area 1.0 cm from the center rose faster, with the maximum temperatures at different powers all above the 46℃. The temperature of the area 1.5 cm from the center rose slower, with the maximum temperature below 46℃at the power of 20 W and 30 W and above 46℃at the power of 40 W. The maximum temperatures of the area 2.0 cm from the center at different powers were all below 46℃. The difference of the maximum temperature at different distances (1.0 cm, 1.5 cm, and 2.0 cm from the center) was signiifcant (F=776.78, 2640.64 and 3025.53, all P<0.05). The length and width of the ablation lesion as well as the area of edema increased with the power. At the power of 20 W, 30 W, and 40 W, the length of the ablation lesion was (29.3±1.8) mm, (32.7±2.1) mm and (34.2±2.4) mm, the width was (22.5±1.5) mm, (23.7±1.7) mm and (27.1±2.0) mm, and the width of the edema zone was (2.3±0.4) mm, (2.6±0.4) mm and (2.7±0.5) mm. The differences of the length and width of the ablation lesion at different powers were signiifcant (F=11.46, 14.49, both P<0.01). The difference of the edema area at different powers was insigniifcant (F=1.94, P=0.169). Conclusions Microwave ablation is a safe therapeutic modality. However, the shorter distance from the ablation center and greater ablation power give rise to larger ablation lesion, higher maximum temperature, and faster temperature increase. Therefore, 2.0 cm from the ablation center is a safe area.

Objective To explore the value of contrast-enhanced ultrasound (CEUS) in classifying lesions,measuring the range of lesions,and the ability of manifesting the boundary and the severity of lesions after traumatic brain injury.Methods 83 patients with traumatic brain injury underwent the emergency surgery operations were enrolled in this study.Intraoperative ultrasound was applied in detecting the echo characteristics of lesions and classifying.Traumatic brain injuries which were classified indefinitely by conventional ultrasound were examined by CEUS to observe enhanced features of trauma lesions and the surrounding tissue,confirm the types of lesions,identify the border of lesions,measure the range of lesions,and compare with conventional ultrasound,preoperative CT and operative results.The severity of lesions was judged according to the parameter of time intensity curve (TIC).The results which would help the operators to adjust the method of treatment timely was informed.Results 148 lesions were detected by intraoperative ultrasound among 83 patients in this study.Thirty-two lesions which were classified indefinitely by conventional ultrasound were examined by CEUS.The results of classifying were confirmed by CT and operations,the diagnostic accuracy rate was 100％.The absolute peak intensity was changed with the injury severity,the more serious of the tissue,the lower absolute peak intensity was displayed.The boundary of lesions was manifested clearly after CEUS.Compare to the conventional ultrasonography,the range of lesions was larger.The difference between them was meaningful significally(P =0.01).Based on the results of CEUS,the way of operation was adjusted in 21 lesions.Conclusions Using the contrastenhanced ultrasound and intraoperative ultrasound,various traumatic brain injuries can be diagnosed accurately.By CEUS,the perfusion of lesions would be displayed,which would hint the severity of the brain tissue and help the operators adjust the methods of treatment timely,and provide the reliable evidence for the operation precisely.

Objective To study the effect of Perfadex and Wisconsin Unviersity solution on the function of pulmonary artery endothelium.Methods Small lobe pulmonary arteries were dissected from nine porcine lungs.The artery from each lung was cut into six rings in 2mm.Two of them were randomly incubated in Krebs,Perfadex or Wisconsin Unviersity solution (UW solution) at 4℃ for 4 hours.Endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation (percentage of-7.5 logM U46619 precontraction) induced by bradykinin or calcium ionophone A23187 in the present of indomethacin,L-NNA and oxyhemoglobin were measured at 37 ℃ in the organ chambers.Results Vasoconstriction induced by U46619 is no significant difference among three groups (P＞ 0.05).Compared with Krebs group,the relaxation induced by bradykinin or A23187 was significantly decreased in Perfadex group (P＜0.01),while there is no significant difference in UW group (P＞0.05).Conclusion Endothelium-derived hyperpolarizing factor (EDHF) plays an important role in endothelium-mediated relaxation of porcine pulmonary artery.EDHF-mediated relaxation is impaired when the lung preserved with Wisconsin Unviersity solution,wheras its function is not affected by Perfadex solution.

Objective To study the effect of nicorandil on the function of coronary artery endothelium during hypoxiareoxygenation.Methods Forty-five fresh porcine left anterior descending coronary artery rings in 2mm long were randomly divided into five groups.Control group ( n =9):incubation in Krebs-Henseleit (KH) at 37℃ for 90 minutes with a constant supply of oxygen ; Group A ( n =9):30-minute hypoxia ( PO2 ＜ 15 mm Hg) followed by 30 minutes reoxygenation in KH at 37℃ ; Group B ( n =9):60-minute hypoxia followed by 30 minutes reoxygenation in KH at 37 ℃ ; Group C ( n =9):60-minute hypoxia followed by 30 minutes reoxygenation in KH added nicorandil ( 0.2 μmol/L) at 37 ℃ ; Group D ( n =9 ):60-minute hypoxia followed by 30 minutes reoxygenation in KH added nicorandil (0.2 μmol/L) and 5-hydroxydecanoate ( 10μmol/L) at 37 ℃.The endothelium-derived hyperpolarizing factor (EDHF) -mediated relaxation ( U46619 precontraction) induced by bradykinin in the present of indomethacin (7 μmol/L),LNNA (300 μmol/L) and oxyhemoglobin (20 μmol/L)were measured in the organ chambers.Results Compared with control group,the relaxation was significantly decreased in group A,B and D ( P ＜ 0.001 ),while there is no significant difference in group C ( P ＞ 0.05 ).Compared with group A,the relaxation was significantly reduced in group B and D (P ＜0.001 ).Conclusion Hypoxia-reoxygenation impairs EDHF mediated relaxation in coronary artery with more injury during prolonged hypoxia.This function can be restored by preconditioning with nicorandil The mechanism is mainly related to the mitochondrial ATP-sensitive K + channels.