Lymphocyte-activation gene 3 (LAG-3), also known as CD223, is a 498-amino-acid type I transmembrane protein encoded by LAG-3 gene, which consists of extracellular, transmembrane and intracellular regions.LAG-3 negatively regulates T lymphocyte by binding extracellular domain to ligand, thus avoiding autoimmunitycaused by T cell over-activation. Like programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), LAG-3 is an important immune checkpoint in vivo and plays a balanced regulatory role in human immune system.Tumor cells escape the surveillance of the immune system by over-expressing LAG-3 ligand. With the development in research of immune checkpoints, LAG-3 has become a new generation of immunotherapy targets after PD-1 and CTLA-4. This article reviews the structure and function of LAG-3 and the application of its inhibitors in tumor immunotherapy, in order to provide reference for the further study of LAG-3.

Abstract: Objective To investigate the clinical distribution characteristics, drug resistance trends and the carrying of antiseptic resistance gene of Pseudomonas aeruginosa infection in children in Suzhou, in order to provide theoretical basis for the prevention and treatment of Pseudomonas aeruginosa infection in children. Methods The clinical distribution characteristics and drug resistance trends of Pseudomonas aeruginosa isolated from Children's Hospital of Soochow University from 2016 to 2021 were retrospectively analyzed. Forthermore, 101 strains of Pseudomonas aeruginosa were randomly selected to detect the expression of 9 antiseptic resistance genes (qacEΔ1-sul1, qacE, qacEΔ1, qacG, sugE(p), sugE©, emrE, ydgE, ydgF) by polymerase chain reaction. Results Pseudomonas aeruginosa in Soochow University Children's Hospital was mainly isolated from respiratory specimen (47.83%), pus (28.60%) and urine (11.72%); the main departments were intensive care unit(21.45%), general surgery department (15.71%) and respiratory department (12.31%). Patients were mainly aged from 1 month to 1 year old and older than 6 years old (34.31% and 25.38%). The top three drug resistance rates of Pseudomonas aeruginosa were imipenem (11.25%), aztreonam (9.26%) and meropenem (8.02%). Among the 853 strains of Pseudomonas aeruginosa, the drug-resistant strains were mainly from the intensive care unit (58/183), hematology department (33/91), neonatology department (31/96), and there were 57 strains of multi-drug-resistant strains with the detection rate of 6.68%. There were 98 strains (11.49%) of Carbapenem resistant Pseudomonas aeruginosa, and the annual detection rates were 22.06%, 8.40%, 3.60%, 5.67%, 9.85% and 17.20%, respectively. Among the 9 antiseptic resistance genes, the carrying rate of ydgF, sugE© and qacE was 98.02%, 94.06% and 0 respectively. Conclusion Pseudomonas aeruginosa has high resistance to some drugs, so attention should be paid to rational drug use. The carriage rates of of two antiseptic resistance genes exceeded 90%, indicating the need to strengthen research on the mechanism of antiseptic resistance research and rational use of disinfectants

Ribavirin is a broad-spectrum antiviral agent and glycyrrhizin has activities of anti-inflammation, immunoregulation and anti-viral infections. To enhance antiviral efficacy and weaken side-effects of ribavirin, antiviral effects of the combination of glycyrrhizin and ribavirin were studied in the present study. Firstly, a mouse model of viral pneumonia was established by inoculation of influenza H1N1 virus. Protective effects of glycyrrhizin and ribavirin used alone or in combination against H1N1 virus infection in mice were evaluated based on the survival rate, lung index and virus titer in lungs of mice. Results showed that the combination of glycyrrhizin and ribavirin significantly inhibited the lung consolidation with a 36% inhibition ratio on the lung swell of infected mice. The combination of the two drugs exhibited synergetic effects on survival of infected mice. The combination of 50 mg · kg(-1) · d(-1) glycyrrhizin and 40 mg · kg(-1) · d(-1) ribavirin resulted a 100% protection for infected mice with a synergetic value of 36, which was significantly higher than the control group and each drug alone. This combination also resulted a significant drop of lung virus titer (P < 0.01), as well as inhibition on the production of proinflammatory cytokines IL-6 (P < 0.01), TNF-α (P < 0.01) and IL-1β (P < 0.05) induced by virus infection compared to the control. The treatment of ribavirin plus glycyrrhizin was more effective in influenza A infection in mice than either compound used alone, which suggested a potential clinical value of the combination of the two agents.

Objective To explore the relationship between microelement intake and metabolic syndrome (MS) in elderly males and females in Zhejiang province. Methods Non-parametric Kruskal-Wallis tests were used to compare the intake of microelements by sex among different groups according to the diagnostic criteria of MS in 780 people(404 male,376 female).Logistic regression was used to explore the association between microelements and MS and its components.Results The percentages of inadequate intake of Mn,Zn and Se were relatively high among elderly people of Zhejiang province(males:30.45%,72.52%,75.74%;females:47.34%,33.78%,80.59%,respectively).Microelement intake in males were higher than females(P<0.05).The intake of Fe and Se were higher in the abdominal obesity group than the non-abdominal obesity group among elderly males,the intakes of Fe,Zn,Se in hypertension group were lower, and Se intake was higher in hyperglycemia and hypertriglyceridemia groups. Furthermore, enough intake of Fe(odds ratio OR,0.41;95% confidence interval CI:0.19,0.87)and Se(OR,0.30;95% CI:0.14, 0.63)decreased the risk of hypertension,and high Cu(OR,2.35;95% CI:1.18,4.71)intake increased the risk of hyperglycemia.Among females,Zn intake in the MS group was lower than in the non-MS group;the intakes of Cu, Zn and Se in the hypertension group were lower; the intakes of Fe, Mn and Zn in the hyperglycemia group were lower as well;and Se intake was lower in the low HDL-C group.Again,the high intake of Zn (OR, 3.21; 95% CI: 1.36, 7.59) and Se (OR, 2.79; 95% CI: 1.24, 6.27) increased the risk of abdominal obesity, but moderate intake of Cu (OR, 0.37; 95% CI: 0.19, 0.72) had a protective effect on hypertension. Conclusions The percentages of inadequate microelement intake were relatively high in elderly people of Zhejiang province. There is a relationship between dietary microelements and MS or its components. It is necessary to guide elderly people to adopt reasonable diet by referring to the Chinese dietary reference intake and Dietay Guidelines in order to improve the situation of microelements intake and promote health.

Objective To explore the effects of mirror therapy on the lower-limb muscles of hemiplegic stroke survivors. Methods Sixty-two hemiplegic stroke survivors were divided by stratified random grouping into a mirror group and a control group, each of 31. Both groups accepted routine rehabilitation training, while the mirror group was additionally provided with mirror therapy to train the non-paretic limb for 30 min per day, 5 days a week, lasting 4 weeks. Before and after the 4 weeks of training, integrated electromyography was performed and the maximum voluntary contraction force (MVC) of the tibialis anterior, rectus femoris and biceps femoris of the paretic limb were recorded and compared. Results Compared with before the training, the average root mean square values of the electromyographs and the average MVCs of all three muscles had improved significantly in both groups after training. Compared with the control group, the improvements were significantly greater in the mirror group. Conclusion Mirror therapy can promote the activation and synchronization of motor units, as well as increase the number discharging and the total discharge, promoting the recovery of muscle strength.

Objective To explore the correlation between apolipoprotein E (ApoE) gene polymorphism and urine Alzheimer-associated neuronal thread protein (AD7c-NTP) level in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI).Methods The cognitive function of 30 AD patients (AD group),30 MCI patients (MCI group) and 30 normal controls (NC group) was evaluated by neuropsychological batteries like MMSE,the Cambridge Cognitive Examination-Chinese Version (CAMCOG-C),etc.ELISA was used to test the urine level of AD7c-NTP.The genotypes of ApoE were analyzed by the high-resolution melting assay in blood samples.Results Compared with the NC group (0.59 (0.40,0.66) ng/ml),the urine level of AD7c-NTP in the AD group (1.03(0.80,1.41) ng/ml) and the MCI group (0.69(0.53,0.91) ng/ml) was increased (Z =33.727,P ＜0.01).The urine level of AD7c-NTP in the AD group was higher than that in the MCI group (Z =8.232,P ＜ 0.05).The level of AD7c-NTP in urine was negatively correlated with MMSE and CAMCOG-C scores (rMMSE =-0.604,P ＜ 0.01;rCAMCOG-C =-0.486,P ＜ 0.01).According to receiver operating characteristic curve,the optimal cutoff point of AD7c-NTP in urine for diagnosis of patients including AD and MCI was 0.70 ng/ml,with sensitivity of 71.7％ and specificity of 83.3％,and area under the curve of 0.82 (95％ CI 0.73-0.90,P ＜0.05).There were four genotypes comprising ε2/3,ε3/3,ε3/4 and ε4/4 for ApoE gene.The frequencies of ε4 carriers were 46.7％ (14/30),23.3％ (7/30) and 23.3％ (7/30) in the AD,MCI and NC groups,respectively.There was a notable increase in urine AD7c-NTP and a significant decrease in CAMCOG-C scores in MCI patients who harbored the ApoE ε4 allele (ZAD7c-NTP =4.857,P ＜ 0.05;ZCAMCOG-C =4.284,P ＜0.05).Conclusions The urine level of AD7c-NTP was significantly increased in AD and MCI patients,the higher the level of AD7c-NTP,the more serious the cognitive impairment.The ε4 carriers exhibited higher urine level of AD7c-NTP,but worse cognitive function compared to ε4 non-carriers in the MCI group.

Objective:To explore the differences of functional small airway and pulmonary vascular parameters in chronic obstructive pulmonary disease (COPD) of different imaging phenotypes.Methods:One hundred and thirty COPD patients underwent biphasic CT scanning in Shanghai Changzheng Hospital from August 2018 to August 2020 were analyzed retrospectively. The patients were classified into three phenotypes based on the presence of emphysema and bronchial wall thickening on CT images. Phenotype A: no emphysema or mild emphysema, with or without bronchial wall thickening; Phenotype E: obvious emphysema without bronchial wall thickening; phenotype M: significant emphysema and bronchial wall thickening were present. Parametric response map (PRM) and pulmonary vascular parameters were quantitatively measured at the whole lung level. PRM parameters included the volume of emphysema (PRMV Emphysema), the volume of functional small airway (PRMV fSAD), the volume of normal pulmonary parenchyma (PRMV Normal) and its volume percentage (%). Pulmonary vascular parameters included the number of vessels (N) and cross-sectional area vessels<5 mm 2 (N -CSA<5) at 6, 9, 12, 15, 18 21, 24 mm distance from the pleura. ANOVA or Kruskal-Wallis H tests were used to compare the differences for PRM and pulmonary vascular parameters among the three phenotypes, and LSD or Bonferroni tests were used for multiple comparisons. Results:There were significant differences among the three phenotypes for PRMV fSAD, PRMV Emphysema, PRMV fSAD%, PRMV Emphysema%, and PRMV Normal% at the whole lung level ( P<0.05). PRMV Emphysema, PRMV Emphysema%, PRMV Fsad, PRMV fSAD% of phenotype A were lower than those of phenotype E and M ( P<0.001), while there was no significant difference for PRMV Emphysema, PRMV Emphysema%, PRMV fSAD, PRMV fSAD% between phenotype E and phenotype M ( P>0.05). There were significant differences in N and N -CSA<5 that 6 mm distance from the pleura among the three groups( P<0.05). Among them, N and N -CSA<5 that 6 mm distance from pleura in phenotype M were significantly lower than those in phenotype A( P<0.001,0.002); No significant differences was found in N between phenotype M and phenotype E( P>0.05), while there was significant differences in N -CSA<5 between phenotype M and phenotype E( P=0.034). Conclusion:Biphasic quantitative CT analysis can reflect the heterogeneity of the functional small airways and pulmonary vascular abnormality in COPD with different phenotypes, and provide objective evidence for individualized diagnosis and treatment.

Objective:To assess the effectiveness of a model created using clinical features and preoperative chest CT imaging features in predicting the chronic obstructive pulmonary disease (COPD) among patients diagnosed with lung cancer.Methods:A retrospective analysis was conducted on clinical (age, gender, smoking history, smoking index, etc.) and imaging (lesion size, location, density, lobulation sign, etc.) data from 444 lung cancer patients confirmed by pathology at the Second Affiliated Hospital of Naval Medical University between June 2014 and March 2021. These patients were randomly divided into a training set (310 patients) and an internal test set (134 patients) using a 7∶3 ratio through the random function in Python. Based on the results of pulmonary function tests, the patients were further categorized into two groups: lung cancer combined with COPD and lung cancer non-COPD. Initially, univariate analysis was performed to identify statistically significant differences in clinical characteristics between the two groups. The variables showing significance were then included in the logistic regression analysis to determine the independent factors predicting lung cancer combined with COPD, thereby constructing the clinical model. The image features underwent a filtering process using the minimum absolute value convergence and selection operator. The reliability of these features was assessed through leave-P groups-out cross-validation repeated five times. Subsequently, a radiological model was developed. Finally, a combined model was established by combining the radiological signature with the clinical features. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) curves were plotted to evaluate the predictive capability and clinical applicability of the model. The area under the curve (AUC) for each model in predicting lung cancer combined with COPD was compared using the DeLong test.Results:In the training set, there were 182 cases in the lung cancer combined with COPD group and 128 cases in the lung cancer non-COPD group. The combined model demonstrated an AUC of 0.89 for predicting lung cancer combined with COPD, while the clinical model achieved an AUC of 0.82 and the radiological model had an AUC of 0.85. In the test set, there were 78 cases in the lung cancer combined with COPD group and 56 cases in the lung cancer non-COPD group. The combined model yielded an AUC of 0.85 for predicting lung cancer combined with COPD, compared to 0.77 for the clinical model and 0.83 for the radiological model. The difference in AUC between the radiological model and the clinical model was not statistically significant ( Z=1.40, P=0.163). However, there were statistically significant differences in the AUC values between the combined model and the clinical model ( Z=-4.01, P=0.010), as well as between the combined model and the radiological model ( Z=-2.57, P<0.001). DCA showed the maximum net benifit of the combined model. Conclusion:The developed synthetic diagnostic combined model, incorporating both radiological signature and clinical features, demonstrates the ability to predict COPD in patients with lung cancer.

Objective:To explore the predictive value of random forest regression model for pulmonary function test.Methods:From August 2018 to December 2019, 615 subjects who underwent screening for three major chest diseases in Shanghai Changzheng Hospital were analyzed retrospectively. According to the ratio of forced expiratory volume in the first second to forced vital capacity (FEV 1/FVC) and the percentage of forced expiratory volume in the first second to the predicted value (FEV 1%), the subjects were divided into normal group, high risk group and chronic obstructive pulmonary disease (COPD) group. The CT quantitative parameter of small airway was parameter response mapping (PRM) parameters, including lung volume, the volume of functional small airways disease (PRMV fSAD), the volume of emphysema (PRMV Emph), the volume of normal lung tissue (PRMV Normal), the volume of uncategorized lung tissue (PRMV Uncategorized) and the percentage of the latter four volumes to the whole lung (%). ANOVA or Kruskal Wallis H was used to test the differences of basic clinical characteristics (age, sex, height, body mass), pulmonary function parameters and small airway CT quantitative parameters among the three groups; Spearman test was used to evaluate the correlation between PRM parameters and pulmonary function parameters. Finally, a random forest regression model based on PRM combined with four basic clinical characteristics was constructed to predict lung function. Results:There were significant differences in the parameters of whole lung PRM among the three groups ( P<0.001). Quantitative CT parameters PRMV Emph, PRMV Emph%, and PRMV Normal% showed a moderate correlation with FEV 1/FVC ( P<0.001). Whole lung volume, PRMV Normal,PRMV Uncategorized and PRMV Uncategorized% were strongly or moderately positively correlated with FVC ( P<0.001), other PRM parameters were weakly or very weakly correlated with pulmonary function parameters. Based on the above parameters, a random forest model for predicting FEV 1/FVC and a random forest model for predicting FEV 1% were established. The random forest model for predicting FEV 1/FVC predicted FEV 1/FVC and actual value was R 2=0.864 in the training set and R 2=0.749 in the validation set. The random forest model for predicting FEV 1% predicted FEV 1% and the actual value in the training set was R 2=0.888, and the validation set was R 2=0.792. The sensitivity, specificity and accuracy of predicting FEV 1% random forest model for the classification of normal group from high-risk group were 0.85(34/40), 0.90(65/72) and 0.88(99/112), respectively; and the sensitivity, specificity and accuracy of predicting FEV 1/FVC random forest model for differentiating non COPD group from COPD group were 0.89(8/9), 1.00 (112/112) and 0.99(120/121), respectively. While the accuracy of two models combination for subclassification of COPD [global initiative for chronic obstructive lung disease (GOLD) Ⅰ, GOLDⅡ and GOLD Ⅲ+Ⅳ] was only 0.44. Conclusions:Small airway CT quantitative parameter PRM can distinguish the normal population, high-risk and COPD population. The comprehensive regression prediction model combined with clinical characteristics based on PRM parameter show good performance differentiating normal group from high risk group, and differentiating non-COPD group from COPD group. Therefore, one-stop CT scan can evaluate the functional small airway and PFT simultaneously.