OBJECTIVES: To explore the correlation of serum tryptophan level with 90-day mortality risk in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS: This retrospective study was conducted among 108 patients with HBV-ACLF, whose survival outcomes within 90 days after diagnosis were recorded. The correlation of baseline serum tryptophan levels measured by high-performance liquid chromatography with 90-day mortality of the patients was analyzed, and the predictive value of serum tryptophan for 90-day mortality was explored. RESULTS: Within 90 days after diagnosis, 53 (29.4%) of the patients died and 127 (70.6%) survived. The deceased patients had significantly lower baseline serum tryptophan levels than the survivors (7.31±3.73 pg/mL vs 13.32±7.15 pg/mL, P<0.001). Multivariate analysis suggested that serum tryptophan level was an independent factor correlated with mortality of HBV-ACLF after adjustment for confounding variables. The patients with serum tryptophan levels below the median level (10.14 pg/mL) at admission had significantly higher 90-day mortality risks than those with higher tryptophan levels (43.3% vs 15.6%, HR: 3.157, 95% CI: 1.713-5.817), and the complication by kidney dysfunction further increased the risk to 73.3% as compared with patients with higher serum tryptophan levels with normal kidney function (15.0%; HR: 7.558, 95% CI: 3.369-16.960). Serum tryptophan levels had an area under the receiver operating characteristic curve of 0.771 (95% CI: 0.699-0.844) for predicting 90-day mortality. CONCLUSIONS Serum tryptophan level is closely correlated with the survival outcomes of patients with HBV-ACLF, and a decreased tryptophan level indicates a high 90-day mortality risk, which can be further increased by the complication by kidney dysfunction.
Humans ; Tryptophan/blood* ; Retrospective Studies ; Acute-On-Chronic Liver Failure/virology* ; Male ; Female ; Middle Aged ; Adult ; Prognosis ; Hepatitis B/complications* ; Hepatitis B virus

OBJECTIVES: To explore the role of the cGAS-STING signaling pathway in the therapeutic mechanism of Liangxue Jiedu Huayu Formula (LXJDHYF) for acute-on-chronic liver failure (ACLF) in mice. METHODS: Thirty C57BL/6 mice were randomly divided into blank control group, model group, low- and high-dose LXJDHYF groups, and H151 (a specific cGAS-STING pathway inhibitor) group (n=6). In all but the control group, the mice were treated with CCl₄ to induce liver cirrhosis followed by intraperitoneal injections of lipopolysaccharide and D-amino galactose to establish mouse models of ACLF. After the treatments, the mouse livers were collected for HE and TUNEL staining, and serum levels of ALT, AST and TBil were determined. In bone marrow-derived macrophages (BMDMs) and liver tissues of ACLF mice, the expressions of cGAS-STING signaling pathway-related mRNAs including IFN‑β, ISG15, IL-6 and TNF-α were determined with RT-qPCR, and the phosphorylation levels of IRF3 and STING proteins were investigated using Western blotting. RESULTS: Compared with the mice in the model group, the LXJDHYF-treated mice exhibited milder hepatocyte necrosis and inflammatory cell infiltration in the liver with significantly reduced hepatocyte apoptosis. LXJDHYF treatment also significantly lowered serum levels of ALT, AST, TBil, IL-6 and TNF-α in ACLF mice and effectively suppressed the expressions of cGAS-STING signaling pathway-related mRNA in both the BMDMs and the liver tissues and the phosphorylation of IRF3 and STING proteins in the BMDMs. CONCLUSIONS LXJDHYF can significantly improve liver function and attenuate inflammation in ACLF mice possibly by inhibiting excessive activation of the cGAS-STING signaling pathway.
Animals ; Signal Transduction/drug effects* ; Mice ; Nucleotidyltransferases/metabolism* ; Mice, Inbred C57BL ; Acute-On-Chronic Liver Failure/etiology* ; Membrane Proteins/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Liver/metabolism* ; Disease Models, Animal ; Interferon Regulatory Factor-3/metabolism* ; Interleukin-6/metabolism* ; Male

Objective: To compare the clinicopathological characteristics of second primary lung cancer following breast cancer and lung metastases from breast cancer, and then to analyze the risk factors in breast cancer patients with second primary lung tumor. Methods: Clinical data of 55 breast cancer patients with second primary lung tumor and 205 breast cancer patients with solitary pulmonary metastasis in Shandong Cancer Hospital from January 2006 to January 2017 were retrospectively analyzed. The risk factors of primary lung cancer following breast cancer were analyzed using logistic regression model. Results: Second primary lung cancer in patients with first breast cancer accounted for approximately 21.2%(55/260) of pulmonary malignant solitary nodules, and 0.84%(55/6 580) of all breast cancer patients. The median intervals between the diagnosis of second primary lung cancer or lung metastasis and first breast cancer were 52 months and 42 months, respectively. These two groups showed significant difference between age, time interval between diagnoses, breast tumor size, axillary lymph node metastasis, estrogen receptor, molecular subtype (luminal B and triple-negative) and history of radiotherapy (P<0.05 for all). A multivariate logistic regression model confirmed that age (OR=1.088, P<0.001), breast tumor size(OR=0.480, P<0.001), and radiotherapy history (OR=3.460, P=0.004) were all independent factors for second primary lung cancer. Conclusions For isolated pulmonary nodules in patients with breast cancer, especially for those with elder age, larger tumor size and radiotherapy history, we should distinguish the second primary lung cancer from pulmonary metastasis. The treatment regimen for lung metastasis and primary lung cancer in patients with breast cancer are entirely distinct. The timely histopathology examinations for pulmonary nodes in patients with breast cancer are recommended.

Objective Metabolites produced by metabolic imbalance such as free fatty acids and lipopolysaccharides can result in a state of chronic low-grade inflammation, or metabolic inflammation, which plays an important role in the pathogenesis of atherosclerosis, type 2 diabetes, non-alcoholic fatty liver disease, and obesity. The above metabolic disorders are closely related with the metabolic inflammation, which always coexist. Therefore, we proposed the concept ofmetabolic inflammatory syndrome ( MIS). According to our study, patients with two or more metabolic disorders above could be diagnosed as MIS. The current research is aimed to investigate the prevalence of MIS and its components, and to compare the clinical values of MIS and metabolic syndrome ( MS) . Methods 2 001 in patients with type 2 diabetes from 6 hospitals in Shanghai were recruited in the current multi-center cross-sectional study. The diagnostic rates of MIS and MS and their components of both syndromes were compared. Results In the patients with type 2 diabetes, the detective rate of MIS was 96. 2%, which was higher than that of MS (71. 3%). Among 4 components of MIS, atherosclerosis showed the highest detective rate (75.6%). MIS[OR=2.252(95%CI1.026-4.942),P=0.043],atherosclerosis[OR=2.726(95% CI1.953-3. 804),P<0. 001], and MS[OR=1. 915 (95%CI 1. 444-2. 540),P<0. 01] were the risk factors of coronary heart disease. Conclusion With atherosclerosis, type 2 diabetes mellitus, non-alcoholic fatty liver disease, and obesity as its 4 components, MIS has a high detective rate in patients with metabolic disorders, and seems to be more sensitive than MS to distinguish inflammation-related metabolic diseases. The concept of MIS will promote the screening and prevention of atherosclerosis in its early stage.

Objective To investigate the effect of combined administration of autophagy inhibitor 3?methyladenine/bafilomycin A1 and EGFR inhibitor gefitinib on triple?negative breast cancer MDA?MB?468, MDA?MB?231 cells and estrogen receptor?positive MCF?7 cells. Methods All the cells were treated with 3?methyladenine/bafilomycin A1 and/or gefitinib. The effect of autophagy inhibitor and gefitinib on the cell growth was evaluated by MTT assay. Cell apoptosis was detected by flow cytometry. Western blot analysis was used to determine the alteration of autophagy?related protein ( such as LC3) and apoptosis?related proteins ( such as caspase?3 and caspase?9) . Results MTT assay showed that the IC50 in the GE+3?MA and GE+BAF groups were (4.1±0.2) μmol/L and (3.8±0.3) μmol/L, significantly lower than that of the gefitinib alone group [(7.0±0.2) μmol/L] in MDA?MB?468 cells (P<0.05). Similarly, the IC50 in the GE+3?MA and GE+BAF groups were (9.7±0.1) μmol/L and (7.7±0.2) μmol/L, significantly lower than that of the gefitinib alone group [(14.7±0.1) μmol/L]in MDA?MB231 cells (P<0.05). The flow cytometry assay revealed that the apoptosis rates of MDA?MB?468 cells in GE, GE+3?MA and GE+BAF groups were (12.43± 3.18)%, (23.37±2.71)% and (18.71±2.81)%, respectively. The apoptosis rates of MDA?MB?231 cells of the GE, GE+3?MA and GE+BAF groups were (12.15±1.82)%, (16.94±2.19)% and (33.83±5.92) %, significantly higher than that of the gefitinib alone group (All P<0.05). The apoptosis rates of the MCF?7 cells were not changed significantly among the three groups (P>0.05). Western blot data showed that the expression levels of LC3 and p?Akt were decreased in the combined groups than that of the gefitinib alone group, while the p?PTEN, caspase?3 and caspase?9 were increased. Conclusions Autophagy inhibitor may enhance the sensitivity to gefitinib in MDA?MB?468 and MDA?MB?231 cells by activation of the PTEN/P13K/Akt pathway. Apoptosis in MDA?MB?468 and MDA?MB?231 cells might be enhanced by the combination treatment through caspase cascade.

Objective To investigate the effect of combined administration of autophagy inhibitor 3?methyladenine/bafilomycin A1 and EGFR inhibitor gefitinib on triple?negative breast cancer MDA?MB?468, MDA?MB?231 cells and estrogen receptor?positive MCF?7 cells. Methods All the cells were treated with 3?methyladenine/bafilomycin A1 and/or gefitinib. The effect of autophagy inhibitor and gefitinib on the cell growth was evaluated by MTT assay. Cell apoptosis was detected by flow cytometry. Western blot analysis was used to determine the alteration of autophagy?related protein ( such as LC3) and apoptosis?related proteins ( such as caspase?3 and caspase?9) . Results MTT assay showed that the IC50 in the GE+3?MA and GE+BAF groups were (4.1±0.2) μmol/L and (3.8±0.3) μmol/L, significantly lower than that of the gefitinib alone group [(7.0±0.2) μmol/L] in MDA?MB?468 cells (P<0.05). Similarly, the IC50 in the GE+3?MA and GE+BAF groups were (9.7±0.1) μmol/L and (7.7±0.2) μmol/L, significantly lower than that of the gefitinib alone group [(14.7±0.1) μmol/L]in MDA?MB231 cells (P<0.05). The flow cytometry assay revealed that the apoptosis rates of MDA?MB?468 cells in GE, GE+3?MA and GE+BAF groups were (12.43± 3.18)%, (23.37±2.71)% and (18.71±2.81)%, respectively. The apoptosis rates of MDA?MB?231 cells of the GE, GE+3?MA and GE+BAF groups were (12.15±1.82)%, (16.94±2.19)% and (33.83±5.92) %, significantly higher than that of the gefitinib alone group (All P<0.05). The apoptosis rates of the MCF?7 cells were not changed significantly among the three groups (P>0.05). Western blot data showed that the expression levels of LC3 and p?Akt were decreased in the combined groups than that of the gefitinib alone group, while the p?PTEN, caspase?3 and caspase?9 were increased. Conclusions Autophagy inhibitor may enhance the sensitivity to gefitinib in MDA?MB?468 and MDA?MB?231 cells by activation of the PTEN/P13K/Akt pathway. Apoptosis in MDA?MB?468 and MDA?MB?231 cells might be enhanced by the combination treatment through caspase cascade.

Objective To discuss pathogens findings in children with severe pneumonia.Methods Bacteria was detected by using sputum culture and blood culture in sterile culture media.Viruses and atypical pathogenic antibodies were detected by using indirect immunofluorescence.Influenza A (H1N1) virus RNA were tested using RT-PCR.According to the results of bacterial culture and drug sensitive test,we can guide the use of antibiotics,and individualize treatment was carried out,including anti-inflammatory,organ function support.Results Bacteria was found in 69 children by using sputum culture.Gram negative bacteria accounted for 57.47％.Gram positive bacteria accounted for 42.53％.Escherichia coli(14.94％),Haemophilus influenzae (20.96％) and klebsiella pneumoniae(13.79％) were the main strains of Gram negative bacteria,Staphylococcus aureus (21.84％)and Streptococcus pneumonia(16.1％)were the main strains of Gram positive bacteria.Bacteria was found in 7 (8.00％) children by using blood culture.Virus were identified in 11 out of 123 patients,including 2 cases of respiratory syncytial virus antibody positive,2 cases of adenovirus antibodies positive,4 cases of influenza B virus antibody positive,2 cases of parainfluenza virus antibody positive and influenza A(H1N1) virus from only one case,Mycoplasma pneumonia agents were identified in 8 patients.Eighty-nine children (72.36％) complicated with sepsis,85 children (69.11％) with respiratory failure,48 children (39.02％) with gastrointestinal dysfunction,32 children (26.02％) with heart failure,18 children(14.63％) with septic shock,13 cases (10.57％) with toxic encephalopathy,5 children (4.07％) with disseminated intravascular coagulation.Among them,17 children (13.82％) complicated with multiple organ dysfunction syndrome.In the 123 children with severe pneumonia,46 cases (37.4％) were cured,73 cases (59.35％) improved,and 4 cases died (3.25％) with critical multiple organ dysfunction syndrome.Conclusion The detection rate of pathogen is high in this study.We should pay more attention to individualize therapy for complication,so that the cure rate could be increased.