BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

Objective To investigate the changes of serum levels of soluble scavenger receptor 163 (sCD163),angiopoietin-like protein 3 (ANGPTL3) before and after intravenous thrombolysis in patients with acute cerebral infarction (ACI) and their correlation with prognosis. Methods A total of 60 ACI patients accepted by Cangzhou Central Hospital from June 2021 to June 2022 were collected as the ACI group,and another 60 healthy individuals were regarded as the control group. According to the National Institutes of Health Stroke Scale (NIHSS) score after admission,60 patients were divided into mild group (n=10),moderate group (n=38) and severe group (n=12).According to the scores on the modified Rankin scale 90 days after thrombolysis,patients were separated into a good prognosis group (n=42) and a poor prognosis group (n=18). The serum levels of sCD163 and ANGPTL3 were detected using enzyme linked immunosorbent assay (ELISA),and receiver operating characteristic (ROC) curve was applied to analyze the predictive value of serum sCD163 and ANGPTL3 levels for the prognosis of ACI patients after intravenous thrombolysis therapy. Results Compared with the control group,the levels of serum sCD163 (687.55±86.43 ng/ml vs 411.07±58.24 ng/ml) and ANGPTL3 (60.28±10.55 mg/L vs 25.34±5.93 mg/L) in ACI group were significantly increased,and the differences were significant (t=20.549,22.363,all P<0.05). The levels of serum sCD163 (551.65±69.66 ng/ml,668.92±81.12 ng/ml,859.79±117.24 ng/ml) and ANGPTL3 (44.52±8.12 mg/L,58.67±10.37 mg/L,75.34±13.12 mg/L) in mild,moderate and severe groups were gradually increased,and the differences were significant (F=36.011,23.007,all P<0.05). Compared with the good prognosis group,the proportion of time from onset to thrombolysis≥ 3 h,the proportion of NIHSS score>10 at admission,and the serum sCD163 and ANGPTL3 levels before and after thrombolysis were significantly increased in the poor prognosis group,and the differences were statistically significant (t/x2=5.644,4.775,8.982,10.866,10.293,9.702,all P<0.05). ROC results showed that the area under the curves(95％ confidence intervals)[AUC(95％CI)]of serum sCD163 and ANGPTL3 level alone in predicting the prognosis of ACI patients were 0.830 (0.711～0.915) and 0.783 (0.658～0.879),and their sensitivity and specificity were 72.22％ and 85.71％,77.78％ and 85.71％,respectively. The AUC(95％CI)of combined prediction of serum sCD163 and ANGPTL3 in predicting the prognosis of ACI patients[0.950(0.861～0.990)]was obviously greater than the AUC predicted by sCD163 and ANGPTL3 alone (Z=2.378,2.109,P=0.017,0.035). Conclusion sCD163 and ANGPTL3 levels are elevated in the serum of ACI patients,and are related to their severity and prognosis.

Objective To investigate the changes of serum levels of soluble scavenger receptor 163 (sCD163),angiopoietin-like protein 3 (ANGPTL3) before and after intravenous thrombolysis in patients with acute cerebral infarction (ACI) and their correlation with prognosis. Methods A total of 60 ACI patients accepted by Cangzhou Central Hospital from June 2021 to June 2022 were collected as the ACI group,and another 60 healthy individuals were regarded as the control group. According to the National Institutes of Health Stroke Scale (NIHSS) score after admission,60 patients were divided into mild group (n=10),moderate group (n=38) and severe group (n=12).According to the scores on the modified Rankin scale 90 days after thrombolysis,patients were separated into a good prognosis group (n=42) and a poor prognosis group (n=18). The serum levels of sCD163 and ANGPTL3 were detected using enzyme linked immunosorbent assay (ELISA),and receiver operating characteristic (ROC) curve was applied to analyze the predictive value of serum sCD163 and ANGPTL3 levels for the prognosis of ACI patients after intravenous thrombolysis therapy. Results Compared with the control group,the levels of serum sCD163 (687.55±86.43 ng/ml vs 411.07±58.24 ng/ml) and ANGPTL3 (60.28±10.55 mg/L vs 25.34±5.93 mg/L) in ACI group were significantly increased,and the differences were significant (t=20.549,22.363,all P<0.05). The levels of serum sCD163 (551.65±69.66 ng/ml,668.92±81.12 ng/ml,859.79±117.24 ng/ml) and ANGPTL3 (44.52±8.12 mg/L,58.67±10.37 mg/L,75.34±13.12 mg/L) in mild,moderate and severe groups were gradually increased,and the differences were significant (F=36.011,23.007,all P<0.05). Compared with the good prognosis group,the proportion of time from onset to thrombolysis≥ 3 h,the proportion of NIHSS score>10 at admission,and the serum sCD163 and ANGPTL3 levels before and after thrombolysis were significantly increased in the poor prognosis group,and the differences were statistically significant (t/x2=5.644,4.775,8.982,10.866,10.293,9.702,all P<0.05). ROC results showed that the area under the curves(95％ confidence intervals)[AUC(95％CI)]of serum sCD163 and ANGPTL3 level alone in predicting the prognosis of ACI patients were 0.830 (0.711～0.915) and 0.783 (0.658～0.879),and their sensitivity and specificity were 72.22％ and 85.71％,77.78％ and 85.71％,respectively. The AUC(95％CI)of combined prediction of serum sCD163 and ANGPTL3 in predicting the prognosis of ACI patients[0.950(0.861～0.990)]was obviously greater than the AUC predicted by sCD163 and ANGPTL3 alone (Z=2.378,2.109,P=0.017,0.035). Conclusion sCD163 and ANGPTL3 levels are elevated in the serum of ACI patients,and are related to their severity and prognosis.

Background and objective Lung cancer is a common malignant tumor of the lung.To explore the molecular mechanism of the occurrence and development of lung cancer is a hot topic in current research.Cyclic RNA D1(CircCCND1)is highly expressed in lung cancer and may be a potential target for the treatment of lung cancer.The aim of this study was to investigate the effect of CircCCND1 on the malignant biological behaviors of lung cancer cells by regulat-ing the miR-340-5p/transforming growth factor β-induced factor homeobox 1(TGIF1)axis.Methods The expression of CircCCND1,miR-340-5p,and TGIF1 mRNA in human normal lung epithelial cells BEAS-2B and human lung cancer H446 cells were detected.H446 cells cultured in vitro were randomly divided into control group,CircCCND1 siRNA group,miR-340-5p mimics group,negative control group,and CircCCND1 siRNA+miR-340-5p inhibitor group.Cell proliferation,mito-chondrial membrane potential,apoptosis,migration,and invasion were detected,and the expressions of CircCCND1,miR-340-5p,TGIF1 mRNA,BCL2-associated X protein(Bax),cleaved Caspase-3,N-cadherin,E-cadherin,and TGIF1 proteins in each group were detected.The targeting relationship of miR-340-5p with CircCCND1 and TGIF1 was verified.Results Compared with BEAS-2B cells,CircCCND1 and TGIF1 mRNA were increased in H446 cells,and miR-340-5p expression was decreased(P＜0.05).Knocking down CircCCND1 or up-regulating the expression of miR-340-5p inhibited the proliferation,migration and invasion of H446 cells,decreased the expression of TGIF1 mRNA and TGIF 1 protein,and promoted cell apop-tosis.Down-regulation of miR-340-5p could antagonize the inhibitory effect of CircCCND1 knockdown on the malignant bio-logical behavior of H446 lung cancer cells.CircCCND1 may target the down-regulation of miR-340-5p,and miR-340-5p may target the down-regulation of TGIF 1.Conclusion Knocking down CircCCND1 can inhibit the malignant behaviors of lung cancer H446 cells,which may be achieved through the regulation of miR-340-5p/TGIF1 axis.

Objective:To evaluate the effect of down-regulating lncRNA LINC00263 targeting miR-4458 on the proliferation, migration, invasion and radiosensitivity of breast cancer SK-BR-3 cells.Methods:The expression differences of LINC00263 in breast cancer tissues, adjacent tissues, normal breast epithelial cells and breast cancer cells were determined by qRT-PCR. Transfection of LINC00263 shRNA in breast cancer SK-BR-3 cells down-regulated the expression of LINC00263, and the cloning experiment was used to detect the radiosensitivity. Breast cancer SK-BR-3 cells were treated with 6 Gy irradiation. CCK-8 assay was employed to detect cell proliferation. Flow cytometry was adopted to detect cell apoptosis. Transwell chamber test was performed to detect cell migration and invasion. Western blot was used to detect the expression levels of C-Caspase-3 and C-Caspase-9, MMP-2 and MMP-9 proteins. Bioinformatics software predicted that LINC00263 and miR-4458 had complementary binding sites, and the luciferase reporter system was utilized determine the targeting relationship between LINC00263 and miR-4458. LINC00263 shRNA and miR-4458 inhibitor were co-transfected into breast cancer SK-BR-3 cells, and 6 Gy irradiation was given to detect the changes in cell proliferation, apoptosis, invasion and migration.Results:The expression level of LINC00263 in breast cancer tissues was higher than that in adjacent tissues. The expression level of LINC00263 in breast cancer cells was higher compared with that in normal breast epithelial cells. The radiosensitivity of breast cancer SK-BR-3 cells was increased after transfection of LINC00263 shRNA. Transfection of LINC00263 shRNA and radiation exerted a synergistic effect, jointly inhibited breast cancer cell proliferation, migration and invasion, promoted cell apoptosis, up-regulated the expression levels of C-Caspase-3 and C-Caspase-9 proteins in cells, and down-regulated those of MMP-2 and MMP-9 proteins. Down-regulation of LINC00263 targetedly up-regulated miR-4458 expression. miR-4458 inhibitor reversed the inhibitory effect of LINC00263 shRNA combined with radiation on the proliferation, migration, invasion and apoptosis promotion of breast cancer SK-BR-3 cells.Conclusion:Down-regulating lncRNA LINC00263 targeting miR-4458 inhibits the proliferation, migration and invasion of breast cancer SK-BR-3 cells, and improves cell radiosensitivity.

Objective To analyze the relevance between the consumption of various antimicrobials and antimicrobial re-sistance of Acinetobacter baumanni in a grade three hospital during 2007 -2010 .Methods A retrospective analysis was per-formed to count and sort the defined daily doses (DDDs) and the consumption of various antimicrobials in the hospital between 2007 and 2010 .Meanwhile the resistance rates of Acinetobacter baumanni to different antimicrobials were collected in the same period .Data was analyzed by SAS 8 .2 statistical software package using Spearman correlation method .Results The resistance rate of Acinetobacter baumanni to imipenem was significantly positively correlated with the consumption of carbapenems (r=0 .954 6 ,P<0 .01) ,it is positively correlated with the dosage of imipenem (r=0 .849 2 ,P<0 .05) ,it is also significantly posi-tively correlated with the consumption of meropenem (r=0 .999 2 ,P<0 .05) ,and the consumption of amoxicillin/clavulanate potassium ,respectively(r=0 .800 5 ,P<0 .05) .There was no correlation between the resistance rate of Acinetobacter bauman-ni and the dosage of aminoglycosides ,fluoroquinolones ,even β-lactamase inhibitors(P>0 .05) .Conclusion The use of car-bapenems should be correlated with their indications strictly ,only applying to severe infection of Acinetobacter baumanni .The aminoglycosides of amikacin and β-lactamase inhibitors of cefoperazone/sulbactam are the better options to treat A cinetobacter baumanni infection .

The objective of this work is to investigate how dilution rate and carbon-to-nitrogen (C/N) ratio affects lipid accumulation by Rhodosporidium toruloides AS 2.138 9 in continuous culture. Under steady-state conditions, the increase in dilution rate led to the decrease in lipid content and lipid yield. The highest lipid yield and lipid content at D = 0.02 h(-1) were 0.18 g lipid/g sugar and 57.1%, respectively, while the highest lipid productivity and biomass productivity were obtained at D = 0.14 h(-1). The increase in C/N ratio led to the increase in lipid content. The highest lipid content of 38% was obtained at C/N = 237. The highest lipid yield of 0.12 g lipid/g sugar was obtained at C/N = 92. However, the highest lipid productivity of 0.12 g/(L x h) was obtained at C/N = 32. No significant changes were observed in terms of fatty acid composition of the lipid produced under different C/N ratios, and these three fatty acids, palmitic acid, stearic acid and oleic acid, took over 85% in all samples.
Basidiomycota ; growth & development ; metabolism ; Batch Cell Culture Techniques ; Carbon ; metabolism ; Culture Media ; Fatty Acids ; metabolism ; Glucose ; metabolism ; Lipids ; biosynthesis ; Nitrogen ; metabolism ; Oleic Acid ; biosynthesis ; Palmitic Acid ; metabolism

Microbial lipid is a potential raw material for biofuel industry. In this review, we summarized recent progress in microbial lipid production by oleaginous fungi in terms of identifying cheap feedstock, developing robust lipid producer, establishing novel strategies and better culture modes for cellular lipid accumulation, as well as revealing the molecular mechanism of oleaginity. We discussed issues, solutions and directions for further development of microbial lipid technology.
Biofuels ; Cellulose ; metabolism ; Fatty Acids ; analysis ; Fermentation ; Fungi ; cytology ; growth & development ; metabolism ; Industrial Microbiology ; methods ; Lipids ; biosynthesis

To shorten the cultivation time and reduce the consumption of raw materials for microbial lipid production, oleaginous yeast Rhodosporidium toruloides AS 2.1389 was cultivated using a two-stage culture mode, in which the cell propagation and lipid accumulation were separated. The yeast cells recovered from the propagation culture were re-suspended in glucose solution for lipid accumulation, through which lipid content over 55% of the dry cell weight was achieved, the longer the propagation stage was, the higher the lipid content. Analysis of the lipid indicated that the long-chain fatty acids with 16 and 18 carbon atoms were major components, suggesting that the lipid can be an alternative feedstock for biodiesel production.
Basidiomycota ; growth & development ; metabolism ; Biofuels ; Cell Culture Techniques ; methods ; Fermentation ; Industrial Microbiology ; methods ; Lipids ; biosynthesis

Objective To explore the influence on cyclin and cyclin-dependent kinase inhibitor of cell cycle of Kasumi-1 cell-derived from t(8;21)/AML treated with histone deacetylase(HDAC)inhibitor valproic acid(VPA).Methods RT-PCR assay was applied to detect mRNA expression of regulation factor of cell cycle of Kasumi-1 cell with VPA at different concentration and different time. Results VPA could down-regulate mRNA expression of cyclinD1,cyclinE1 and cyclinB1,and up-regulate mRNA expression of p21 WAF1/CIP1 with no obvious variation of mRNA level of p27KIP1. Condusion VPA could regulate cell cycle through the regulation of cyclins and cyclin-dependent kinase,arresting Kasumi-1 cell at G0/G1 phase.