Objective To determine the prognostic biomarkers and new therapeutic targets of the lung adenocarcinoma (LUAD), based on which to establish a prediction model for the survival of LUAD patients. Methods An integrative analysis was conducted on gene expression and clinicopathologic data of LUAD, which were obtained from the UCSC database. Subsequently, various methods, including screening of differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA), were employed to analyze the data. Cox regression and least absolute shrinkage and selection operator (LASSO) regression were used to establish an assessment model. Based on this model, we constructed a nomogram to predict the probable survival of LUAD patients at different time points (1-year, 2-year, 3-year, 5-year, and 10-year). Finally, we evaluated the predictive ability of our model using Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves. The validation group further verified the prognostic value of the model. Results The different-grade pathological subtypes' DEGs were mainly enriched in biological processes such as metabolism of xenobiotics by cytochrome P450, natural killer cell-mediated cytotoxicity, antigen processing and presentation, and regulation of enzyme activity, which were closely related to tumor development. Through Cox regression and LASSO regression, we constructed a reliable prediction model consisting of a five-gene panel (MELTF, MAGEA1, FGF19, DKK4, C14ORF105). The model demonstrated excellent specificity and sensitivity in ROC curves, with an area under the curve (AUC) of 0.675. The time-dependent ROC analysis revealed AUC values of 0.893, 0.713, and 0.632 for 1-year, 3-year, and 5-year survival, respectively. The advantage of the model was also verified in the validation group. Additionally, we developed a nomogram that accurately predicted survival, as demonstrated by calibration curves and C-index. Conclusion We have developed a prognostic prediction model for LUAD consisting of five genes. This novel approach offers clinical practitioners a personalized tool for making informed decisions regarding the prognosis of their patients.

Objective To study the factors affecting hospital death in elderly patients with novel coronavirus infec-tion/disease 2019(COVID-19),and to build a risk prediction model.Methods According to the diagnostic criteria of Diagnosis and Treatment Protocol for COVID-19 Infection(Trial 10th Edition).Totally 775 elderly patients(≥60 years old)diagnosed as COVID-19 infection in the emergency department and fever clinic of the First Hospital of Changsha were selected as the research objects.General data and serum biomarkers of patients were collected.After treatment,the patients'data were divided into survival group and hospital death group.Binary Logistic regres-sion was used to screen the independent influencing factors of death,and ROC curve was used to analyze the pre-dictive value of related indicators on hospital death.Results After treatment,712 patients(91.9%)survived and 63 patients(8.3%)died in hospital.Binary Logistic regression analysis showed that:≥90 years old[OR=5.065,95%CI(1.427,17.974)],type 2 diabetes mellitus[OR= 3.757,95%CI(1.649,8.559)],COPD[OR= 5.625,95%CI(2.357,13.421)],monocyte ratio[OR=0.908,95%CI(0.857,0.963)],plasma fibringen[OR=1.376,95%CI(1.053,1.800)]and lactate dehydrogenase[OR=1.005,95%CI(1.001,o1.008)]were independent factors of in-hospital death(P＜0.05).The predictive value of diabetes mellitus+COPD+age+monocyte ratio+plasma fibrinogen+lactate dehydrogenase was proved in hospital death from COVID-19 infected patients:the area under the curve(AUC)was 0.883(95%CI:0.827,0.940,P＜0.001),the critical value≥0.710 suggested the risk of death in hospital,the specificity was 0.851,the sensitivity was 0.857.Conclusions The hospital mortality of the elderly after COVID-19 infection is higher and closely related to type 2 diabetes,COPD,monocyte ratio,plasma fibrinogen and lactate dehydrogenase.

OBJECTIVES: To investigate the inhibitory effect of GSK484, a PAD4 inhibitor, on H3Cit expression following sepsis and its effects for improving sepsis-induced endothelial dysfunction. METHODS: Eighteen C57BL/6 mice were randomized into sham-operated group, sepsis model group and GSK484 treatment group (n=6), and in the latter two groups, models of sepsis were established by cecal ligation and puncture (CLP). The mice in GSK484 treatment group were given an intraperitoneal injection of GSK484 (4 mg/kg) on the second day following the surgery. Twenty-four hours after the injection, the mice were euthanized for measurement of serum levels of VEGF, ESM-1, IL-6 and IL-1β using ELISA. Lung tissue pathology was observed with HE staining, and pulmonary expressions of F-actin, VE-cadherin, ZO-1 and H3Cit proteins were detected using immunofluorescence staining and Western blotting. In primary cultured of mouse lung microvascular endothelial cells, the effect of stimulation with LPS (10 μg/mL) for 24 h on tube formation, proliferation, apoptosis and expressions of VEGF, ESM-1, IL-6 and IL-1β were assessed using CCK-8 assay, flow cytometry and ELISA. RESULTS: Compared to the sham-operated mice, the septic mice exhibited significant lung tissue pathologies characterized by vascular congestion, alveolar rupture, edema, and neutrophil infiltration. Serum levels of IL-6, IL-1β, VEGF, and ESM-1 were elevated, pulmonary expressions of F-actin, VE-cadherin, and ZO-1 were decreased, and H3Cit expression was increased significantly in the septic mice. GSK484 treatment effectively mitigated these changes in the septic mice. The LPS-stimulated endothelial cells showed increased productions of IL-6, IL-1β, VEGF and ESM-1, which were significantly reduced after treatment with 2.5 μmol/L GSK484. CONCLUSIONS GSK484 treatment effectively suppresses H3Cit expression in septic mice to ameliorate sepsis-induced endothelial dysfunction.
Animals ; Sepsis/drug therapy* ; Mice ; Mice, Inbred C57BL ; Lung Injury/drug therapy* ; Endothelial Cells/drug effects* ; Interleukin-6/metabolism* ; Protein-Arginine Deiminase Type 4/metabolism* ; Lung/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Interleukin-1beta/metabolism* ; Disease Models, Animal ; Cadherins/metabolism* ; Apoptosis/drug effects* ; Imidazoles ; Antigens, CD

A large number of data show that the prevalence rate of alcoholic liver injury （ALI） is increasing year by year， and it has become one of the main causes of death due to chronic liver diseases such as liver cancer and liver cirrhosis. Quitting drinking is the main method for the prevention of ALI in modern medicine， and the main treatment methods include Western medicine with antioxidant and anti－fibrotic effects and nutritional support. However， Western medicine tends to have an unsatisfactory treatment effect and can only alleviate initial symptoms， and severe ALI still requires surgical treatment. Studies have shown that the monomers extracted from natural drugs and foods have obvious preventive and therapeutic effects on ALI， with high safety and easy access. Therefore， this article systematically summarizes the main natural drug and food monomers used for the prevention and treatment of ALI and proposes the idea of the combination of drug and food for the prevention and treatment of ALI from the perspective of paying attention to the whole process of health， in order to explore more effective prevention， health care， and treatment methods and provide ideas for research on the prevention and control of ALI.

Objective In order to obtain small molecule compounds with novel structure and good biological activity, the secondary metabolites of polar sponge-symbiotic Streptomyces sp. LHW11-07 were studied. Methods The fermentation product of Streptomyces sp. LHW11-07 was isolated and purified by gel column chromatography, silica gel column chromatography, reversed-phase medium pressure column chromatography and high performance liquid chromatography. The structures of the monomeric compound were identified by modern spectroscopic methods such as mass spectrometry, nuclear magnetic resonance and related literature reports. Results A total of nine compounds were isolated from the fermentation of this strain, which were cyclo-(L-Tyr-L-Trp) (1), cyclo-(L-Trp-L-Ser) (2), cyclo-(D-Tyr-D-Pro) (3), cyclo-(L-Tyr-L-Phe) (4), cyclo-(L-Tyr-L-Leu) (5), albaflavenol B (6), β-adenosine (7), N-formylantimyic acid methyl ester (8) and conglobatin A (9). Conclusion Compounds 1 and 2 were isolated from Streptomyces sp. for the first time.

Objective:To comprehensively evaluate the input and output efficiency of scientific research in hospital by bootstrap data envelopment analysis, to provide useful information for optimization of scientific performance appraisal and hospital discipline development strategy.Methods:37 disciplines were included as decision making unit, input variables include research expenditure and number of research personnel, and output variables include number of science and technology awards, research projects, patent transfer, paper, composition, and academic influence. The bootstrap-DEA method was used to evaluate the efficiency of all DMUs.Results:The main of overall efficiency and pure technical efficiency in basic DEA model are 0.858 and 0.909, but are 0.804 and 0.853 in Bootstrap DEA model, the differences between two models have statistically significant ( P<0.001). There are 11 DMUs with an overall efficiency in 0.9~1.0, 14 DMUs in 0.8~0.9, 7 DMUs in 0.6~0.8, 5 DMUs lower than 0.6. There are 3 DMUs are increasing return to scale, 16 DMUs are constant return to scale, 18 DMUs are decreasing return to scale. No statistically significance was observed between different types of DMUs( P>0.05). There are 4 DMUs reveal input slacks in number of research staffs and 10 DMUs reveal output slacks. Conclusions:The results of Bootstrap-DEA are more accurate than the basic methods for the evaluation of the input-output efficiency of hospital scientific research, so that it is worth popularizing and applying. According to the evaluation results, the hospital management department and disciplines could optimize their discipline development strategies and put forward targeted improvement measurements.

Objective:To investigate the clinical application of carbon nanoparticles mapping lymph nodes in curative resection for colorectal carcinoma.Methods:Patients diagnosed with colorectal cancer before operation and undergoing radical surgery with intact postoperative pathological data in the Sixth Affiliated Hospital, Sun Yat-sen University from March 2016 to March 2018 were included in this retrospective case-control study. Those who were diagnosed with ileus, recurrent carcinoma or underwent emergency operation were excluded. A total of 1421 cases were included, with 156 cases in the carbon nanoparticles mapping group and 1265 cases in the control group. Using 1∶3 case control matching based on gender, weight, TNM staging and neoadjuvant chemotherapy, 145 and 435 cases were finally recruited in the carbon nanoparticles mapping group and control group, respectively. Patients in the carbon nanoparticles mapping group underwent preoperative colonoscopy with carbon nanoparticles submucosal injection 2.4 (1.0 - 14.0) days before operation. Carbon nanoparticles of 0.25 ml was injected at 4 points (3, 6, 9 and 12 o'clock each) 0.5-1.0 cm around the tumor. The number of eliminated lymph node, number of positive lymph node and positive rate between the two groups were compared, and the number of eliminated lymph node in different subgroups of T stage, N stage, TNM stage and neoadjuvant chemotherapy was analyzed and compared.Results:After case control matching, total number of eliminated lymph nodes in the carbon nanoparticles mapping group was significantly higher than that in the control group (22.2±11.2 vs. 19.0±9.5, t=3.025, P=0.003). However, no statistically significant differences were found in the number of positive lymph node and lymph node positive rate between two groups (all P>0.05). Subgroup analysis showed that as compared to the control group, total number of eliminated lymph nodes in the carbon nanoparticles mapping group was significantly higher in T3 stage subgroup (median: 22 vs. 18, Z=2.435, P=0.015), N0 stage subgroup (median: 20.5 vs. 17.5, Z=2.772, P=0.006), TNM II stage subgroup (median: 23.5 vs. 19.0, Z=2.654, P=0.008) and neoadjuvant chemotherapy (median: 22.5 vs. 13.0, Z=3.287, P=0.001), while compared to the control group, the number of positive lymph node (median: 4.0 vs. 6.5, Z=-2.530, P=0.011) and the lymph node metastasis degree (median: 16% vs. 31%, Z=-2.862, P=0.004) were lower in the carbon nanoparticles mapping group in N2 subgroup. Conclusion:Carbon nanoparticles mapping lymph nodes can effectively enhance the number of eliminated lymph nodes in curative resection for colorectal cancer.

Objective:To investigate the clinical application of carbon nanoparticles mapping lymph nodes in curative resection for colorectal carcinoma.Methods:Patients diagnosed with colorectal cancer before operation and undergoing radical surgery with intact postoperative pathological data in the Sixth Affiliated Hospital, Sun Yat-sen University from March 2016 to March 2018 were included in this retrospective case-control study. Those who were diagnosed with ileus, recurrent carcinoma or underwent emergency operation were excluded. A total of 1421 cases were included, with 156 cases in the carbon nanoparticles mapping group and 1265 cases in the control group. Using 1∶3 case control matching based on gender, weight, TNM staging and neoadjuvant chemotherapy, 145 and 435 cases were finally recruited in the carbon nanoparticles mapping group and control group, respectively. Patients in the carbon nanoparticles mapping group underwent preoperative colonoscopy with carbon nanoparticles submucosal injection 2.4 (1.0 - 14.0) days before operation. Carbon nanoparticles of 0.25 ml was injected at 4 points (3, 6, 9 and 12 o'clock each) 0.5-1.0 cm around the tumor. The number of eliminated lymph node, number of positive lymph node and positive rate between the two groups were compared, and the number of eliminated lymph node in different subgroups of T stage, N stage, TNM stage and neoadjuvant chemotherapy was analyzed and compared.Results:After case control matching, total number of eliminated lymph nodes in the carbon nanoparticles mapping group was significantly higher than that in the control group (22.2±11.2 vs. 19.0±9.5, t=3.025, P=0.003). However, no statistically significant differences were found in the number of positive lymph node and lymph node positive rate between two groups (all P>0.05). Subgroup analysis showed that as compared to the control group, total number of eliminated lymph nodes in the carbon nanoparticles mapping group was significantly higher in T3 stage subgroup (median: 22 vs. 18, Z=2.435, P=0.015), N0 stage subgroup (median: 20.5 vs. 17.5, Z=2.772, P=0.006), TNM II stage subgroup (median: 23.5 vs. 19.0, Z=2.654, P=0.008) and neoadjuvant chemotherapy (median: 22.5 vs. 13.0, Z=3.287, P=0.001), while compared to the control group, the number of positive lymph node (median: 4.0 vs. 6.5, Z=-2.530, P=0.011) and the lymph node metastasis degree (median: 16% vs. 31%, Z=-2.862, P=0.004) were lower in the carbon nanoparticles mapping group in N2 subgroup. Conclusion:Carbon nanoparticles mapping lymph nodes can effectively enhance the number of eliminated lymph nodes in curative resection for colorectal cancer.