Objective To investigate the effects of LBL-007, a novel fully human lymphocyte activation gene 3 (LAG-3) monoclonal antibody, in combination with programmed cell death protein 1 (PD-1) antibody, on the invasion, migration and proliferation of tumor cells, and to elucidate the underlying mechanisms. Methods Human lymphocyte cells Jurkat were co-cultured with A549 and MGC803 tumor cell lines and treated with the isotype control antibody human IgG, LBL-007, anti-PD-1 antibody BE0188, or tumor necrosis factor-alpha (TNF-α, the NF-κB signaling pathway agonist). Tumor cell proliferation was assessed using a colony formation assay; invasion was measured by Transwell^TM assay; migration was evaluated using a wound healing assay. Western blotting was employed to determine the expression levels of NF-κB pathway-related proteins: IκB inhibitor kinase alpha (Ikkα), phosphorylated Ikkα (p-IKKα), NF-κB subunit p65, phosphorylated p65 (p-p65), NF-κB Inhibitor Alpha (IκBα), phosphorylated IκBα (p-IκBα), matrix metalloproteinase 9 (MMP9), and MMP2. Results Compared with the control and IgG isotype groups, LBL-007 and BE0188 significantly reduced tumor cell proliferation, invasion, and migration. They also decreased the phosphorylation of p-IKKα, p-p65 and p-IκBα, and the expression of MMP9 and MMP2 of tumor cells in the co-culture system. The combined treatment of LBL-007 and BE0188 enhanced inhibitory effects. Treatment with the NF-κB signaling pathway agonist TNF-α reversed the suppressive effects of LBL-007 and BE0188 on tumor cell proliferation, invasion, migration, and NF-κB signaling. Conclusion LBL-007 and anti-PD-1 antibody synergistically inhibit the invasion, migration, and proliferation of A549 and MGC803 tumor cells by blocking the NF-κB signaling pathway.
Humans ; Cell Proliferation/drug effects* ; Cell Movement/drug effects* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Neoplasm Invasiveness ; Antibodies, Monoclonal/pharmacology* ; Programmed Cell Death 1 Receptor/antagonists & inhibitors* ; Cell Line, Tumor ; Antigens, CD/immunology* ; Lymphocyte Activation Gene 3 Protein ; A549 Cells ; I-kappa B Kinase/metabolism* ; Jurkat Cells ; Matrix Metalloproteinase 9/metabolism*

Background::Cerebrovascular disease (CVD) ranks among the foremost factors responsible for mortality on a global scale. The mortality patterns of CVDs and temporal trends in China need to be well-illustrated and updated.Methods::We collected mortality data on patients with CVD from Chinese Center for Disease Control and Prevention’s Disease Surveillance Points (CDC-DSP) system. The mortality of CVD in 2020 was described by age, sex, residence, and region. The temporal trend from 2013 to 2019 was evaluated using joinpoint regression, and estimated rates of decline were extrapolated until 2030 using time series models.Results::In 2019, the age-standardized mortality in China (ASMRC) per 100,000 individuals was 113.2. The ASMRC for males (137.7/10 5) and rural areas (123.0/10 5) were both higher when stratified by gender and urban/rural residence. The central region had the highest mortality (126.5/10 5), the western region had a slightly lower mortality (123.5/10 5), and the eastern region had the lowest mortality (97.3/10 5). The age-specific mortality showed an accelerated upward trend from aged 55-59 years, with maximum mortality observed in individuals over 85 years of age. The age-standardized mortality of CVD decreased by 2.43% (95% confidence interval, 1.02-3.81%) annually from 2013 to 2019. Notably, the age-specific mortality of CVD increased from 2013 to 2019 for the age group of over 85 years. In 2020, both the absolute number of CVD cases and the crude mortality of CVD have increased compared to their values in 2019. The estimated total deaths due to CVD were estimated to reach 2.3 million in 2025 and 2.4 million in 2030. Conclusion::The heightened focus on the burden of CVD among males, rural areas, the central and western of China, and individuals aged 75 years and above has emerged as a pivotal determinant in further decreasing mortalities, consequently presenting novel challenges to strategies for disease prevention and control.

Objective:To investigate the improvement of the inhibition ability and brain activity characteristics in female methamphetamine addicts by rehabilitation exercise training. Method:Fifty-two females were methamphetamine addicts in abstinence were randomly divided into the inter-vention group and control group.All groups were completed the stop signal task and the desire for speed ques-tionnaire both before and after the intervention.Reaction times,the scores of the desire for speed question-naire and the amplitude of P3 were recorded and analyzed. Result:Compared with the control group,the stop signal response time was significantly decreased(P=0.003),the induced P3 amplitude was significantly increased(P=0.031),and the score of craving was signifi-cantly decreased in the intervention group(P=0.012)after rehabilitation exercise training. Conclusion:Rehabilitation exercise training for female methamphetamine addicts in the period of educational correction can effectively improve their inhibition ability and promote the reduction of amphetamine craving.

Gastric cancer is one of the most common malignant tumors worldwide,with its incidence and mortality rates ranking third among malignant tumors in China.Regulated cell death(RCD)is a type of cell death activated by signal transduction modules and closely connected to the progression and treatment of gastric cancer.Different types of RCD,comprising apoptosis,pyroptosis,ferroptosis,cuproptosis,and autophagy,not only aid in eliminating damaged cells,but also serve a crucial role in suppressing gastric cancer spread.This paper reviews different forms of RCD and their roles in the progression of gastric cancer,so as to provide reference for new diagnosis and treatment strategies of gastric cancer.

Objective To investigate the role of silencing regulatory protein 1(Sirt1)in the regulation of Vibrio vulnificus sepsis-induced macrophage apoptosis and the molecular mechanisms.Methods Mouse RAW264.7 macrophages which stably overexpressed Sirt1 were constructed and screened by genistein G418.CCK-8 analysis was used to detect the proliferation of cells in the control group and Sirt1-Flag group.The changes of expression levels of apoptosis-associated protein poly ADP-ribose polymerase(PARP),cleaved-PARP,caspase3,cleaved-caspase3 and acetylated p53 in different treatment groups were detected via Western blotting.A Vibrio vulnificus sepsis model in mice was established,and the expression levels of apoptosis-associated protein cleaved-caspase3 in the lung,spleen and liver of mice of different treatment groups were detected by immunohistochemistry.Results Overexpression of Sirt1 reduced VVC-induced RAW264.7 cell damage.Overexpression of Sirt1 as well as RSV pretreatment lowered the expression of apoptosis-associated protein cleaved-PARP,cleaved-caspase3 and acetylated p53 in VVC-stimulated RAW264.7 cells and mouse peritoneal macrophages.In the mouse model of Vibrio vulnificus sepsis,therapeutic administration of RSV reduced the expression of apoptosis-associated protein marker cleaved-caspase3 in lung,spleen and liver tissues.Conclusion Sirt1 can inhibit p53 acetylation and reduces apoptosis in mouse macrophages,which helps protect against Vibrio vulnificus sepsis.

Objective To evaluate the accuracy and clinical application value of the fluorescence quantitative PCR melting curve meth-od for detecting fungal nucleic acid.Methods 460 suspected or confirmed patients with respiratory fungal infections were enrolled in the study.The fluorescence quantitative PCR melting curve method was used as the test method,and the fungal 26S rRNA gene nucleic acid detection kit combined with Sanger sequencing was used as the reference method.Sputum samples from each study subject were collected and detected by the test method and reference method,respectively.The Kappa value of the two methods was calculated to evaluate the consistency of the results.Results Compared with the reference method,the overall conformity rate of the test method was 92.83%(427/460).Compared with the reference method,the positive conformity rates,negative conformity rates,and overall conformity rates of the test method for detecting 8 fungi,including Candida albicans,Candida glabrata,Candida krusei,Candida trop-icalis,Candida parapsilosis,Cryptococcus neoformans,Candida guilliermondii,and Aspergillus,were 97.34%(183/188),97.06%(264/272),and 97.17%(447/460),100.00%(33/33),99.77%(426/427),and 99.78%(459/460),100.00%(16/16),99.55%(442/444),and 99.57%(458/460),98.11%(52/53),99.75%(442/444),and 99.57%(458/460),95.08%(58/61),99.50%(397/399),and 98.91%(455/460),100.00%(9/9),99.56%(449/451),and 99.57%(458/460),85.00%(17/20),99.32%(437/440),and 98.70%(454/460),and 97.59%(81/83),97.88%(369/377),and 97.83%(450/460),respectively.The Kappa values for the consistency evaluation of the two methods'detection results were both greater than 0.8.Upon retesting the inconsistent re-sults of the two methods,it was found that 53.7%(22/41)of the detection results were consistent with the test method,and the others were consistent with the reference method.Conclusion The fluorescence quantitative PCR melting curve method can simultaneously detect 8 kinds of fungi,and the detection results are highly consistent with the reference method.It has unique advantages in fungal de-tection and important clinical application value.

Objective To explore the influence of processing depth of verb comprehension on the pro-cess of sensorimotor simulation of verbs and its automatization characteristics.Methods Thirty-six com-mon college students were selected,and required to complete verb semantic judgment tasks of Experi-ment 1 and non-semantic judgment tasks of Experiment 2.The changes in hand and foot action out-puts were also observed.Results In Experiment 1,in semantic judgment tasks,the reaction time of leg-related verbs was significantly shorter than for hand-related verbs(P=0.001),with no significant differences in true-false word judgment tasks.Moreover,in Experiment 2,no significant interaction ef-fect was found between verb types and action execution(P=0.199).Conclusion The sensorimotor simula-tion triggered by verb comprehension is modulated by processing of different depths,and individuals are more inclined to utilize sensorimotor simulation of verbs at higher levels of processing depth,non-automatically.

Objective:To establish a new strategy for rapid correction of the interference of chyle blood on hemoglobin (HGB) and related indexes by reticulocyte (RET) channel research parameters (HGB-O, MCHC-O) from automatic hematological analyzer.Methods:With the diagnostic experimental design, a total of 90 impatient samples were sequential picked from Fuwai Hospital, which had routine blood testing from June 1 to July 31, 2021. The selected samples were free of hemolysis, jaundice, chylo. The age of the patients was (49.2±5.7) years, with 47 males and 43 females. Three different contents(25, 50, 75 μl) of fat emulsion injection were used to replace plasma in equal amounts to prepare chyle blood samples with mild, medium and heavy degrees of average red blood cell hemoglobin concentration (MCHC). The research parameters (HGB-O, MCHC-O) obtained by the RET channel detection of the automatic blood analyzer were used as the corrected HGB and its related index values (RET method), and the original values (the detection values before adding fat emulsion) and the formula correction values were paired with t-test or Wilcoxon signed rank test, single factor analysis of variance or Kruskal-Wallis rank-sum test, Bland-Altman and correlation analysis to evaluate the correction effect of RET method.Results:There was no significant difference ( H=0.035, P=0.983; H=0.097, P=0.953; H=0.112, P=0.945) between the RET correction values of HGB (g/L) [104.0(83.8, 132.8), 109.0(87.78, 128.25), 104.0(87.8, 131.8)] and the original values [104.0(83.0, 133.0), 107.5(86.75, 129.25), 103.5(85.8, 131.3)] and the formula correction values [104.0(84.0, 133.8), 106.0(86.75, 131.25), 102.5(86.8, 131.3)] in the samples of chythemia with varying degrees of MCHC (g/L) elevation; meanwhile, the RET correction values [366.5(325.8, 341.5), 333.5(323.8, 340.0), 333.5(327.0, 341.25)] and the original values [336.0(324.8, 342.0), 333.0(323.5, 342.3), 332.0(326.75, 340.5)] and the formula correction values [333.5(323.5, 343.3), 331.0(321.0, 338.3), 329.5(325.25, 337.25)] were also not statistically significant ( H=0.049, P=0.976; H=3.149, P=0.207; H=0.883, P=0.643). The detection values of HGB and related indexes corrected by RET method were in good agreement with the original values [96.7% (29/30) of the points were within the 95% consistency limit], and the two were positively correlated (the correlation coefficients were all higher than 0.919, P<0.01). Conclusion:The RET method based on the research parameters of RET channel of automatic hematological analyzer can serve as a new strategy to correct the interference of chyle blood on the detection of HGB and related indexes.

Objective:To explore the value of fast susceptibility weighted imaging (SWI) generated by a deep learning model in assessment of acute ischemic stroke (AIS).Methods:From January 2019 to January 2021, 118 AIS patients [75 males and 43 females, aged 23-100 (66±14) years] who underwent MR examination and SWI sequence scanning within 24 h of symptom onset in the First Medical Center of PLA General Hospital were retrospectively analyzed. MATLAB ′s randperm function was used to divide 118 patients into a training set of 96 cases and a test set of 22 cases at a ratio of 8∶2. Fourty-seven AIS patients [38 males and 9 females, aged 16-75 (58±12) years] from one center of a multicenter study were selected to build the external validation set. SWI image and filtered phase image were combined into complex value image as full sampling reference image. Undersampled SWI images were obtained by retrospective undersampling of reference fully sampled images, and the undersampling multiple was five times which could save 80% of the scanning time, then the complex-valued convolutional neural network (ComplexNet) was used to develop reconstruct fast SWI. Interclass correlation coefficient (ICC) or Kappa tests were used to compare the consistency of image quality and the diagnostic consistency for the presence of susceptibility vessel sign (SVS), cerebral microbleeds and asymmetry of cerebral deep medullary veins (DMVs) in AIS patient on fully sampled SWI and fast SWI based on ComplexNet.Results:In test set, score of image quality was 4.5±0.6 for fully sampled SWI image and 4.6±0.7 for fast SWI based on ComplexNet, and coefficient was excellent (ICC=0.86, P<0.05). Full sampling SWI had good agreement with fast SWI based on ComplexNet in detecting SVS (Kappa=0.79, P<0.05), microbleeds (Kappa=0.86, P<0.05), and DMVs asymmetry (Kappa=0.82, P<0.05) in AIS patients. In the external validation set, score of image quality was 4.1±1.0 for fully sampled SWI image and 4.0±0.9 for fast SWI based on ComplexNet, and coefficient was excellent (ICC=0.97, P<0.05). Full sampling SWI had good agreement with fast SWI based on ComplexNet in detecting SVS (Kappa=0.74, P<0.05), microbleeds (Kappa=0.83, P<0.05), and DMVs asymmetry (Kappa=0.74, P<0.05) in AIS patients. Conclusions:Deep learning techniques can significantly accelerate the speed of SWI, and the consistency of image quality and detected AIS signs between fast SWI based on ComplexNet and fully sampled SWI is good. The fast SWI based on ComplexNet can be applied to the radiographic assessment of clinical AIS patients

Objective     To summarize the perioperative and long-term outcomes of ground-glass opacity (GGO) dominant early stage lung cancer patients treated by anatomic segmentectomy. Methods     We collected clinical data of 756 patients from Western China Lung Cancer Database, who underwent intentional anatomic segmentectomy [tumor size (T) ≤ 2 cm, GGO ≥ 50%] in the Department of Thoracic Surgery, West China Hospital, Sichuan University from 2009 to 2018. There were 233 males and 523 females at a median age of 53 (25-83) years including 290 (38.4%) patients of simple segmentectomy and 466 (61.6%) patients of complex segmentectomy. All patients were diagnosed as adenocarcinoma, including 338 (44.7%) patients of minimally invasive adenocarcinoma and 418 (55.3%) patients of invasive adenocarcinoma. Results     The median operative time was 115 (38-300) min, the median blood loss was 20 (5-800) mL, 58 (7.7%) patients had postoperative complications and the postoperative stay was 4 (2-24) days. The median follow-up period was 43.0 (30.1-167.9) months. Five-year overall survival rate was 99.5% [95%CI (98.8%, 100.0%)], 5-year recurrence-free survival rate was 98.8% [95%CI (97.5%, 100.0%)], and 5-year lung cancer-specific survival rate was 100.0%. Conclusion    Anatomic segmentectomy has favorable perioperative outcomes and excellent prognosis in GGO dominant early stage lung cancer patients.