Objective: To verify the inhibitory effect of a carbon monoxide hemoglobin-based oxygen carrier (CO-HBOC) on the fibrotic process in mice with idiopathic pulmonary fibrosis (IPF), clarify its efficacy difference compared with hemoglobin-based oxygen carriers (HBOCs), and elucidate its mechanism of action via proteomic analysis. Methods: CO-HBOC was prepared using gas loading technology. An IPF mouse model was established and the mice were randomly divided into a normal saline control group, an HBOC treatment group, and a CO-HBOC treatment group. The fibrotic area percentage was analyzed using Micro-CT; the degree of inflammatory infiltration and fibrosis in lung tissue was assessed by pathological section staining (e.g., HE and Masson staining); and differentially expressed proteins in lung tissue of IPF mice after CO-HBOC treatment were screened using proteomic technology. Results: Micro-CT results showed that the mean fibrotic area percentage in the CO-HBOC treatment group on day 21 was (8.89±0.98)%, which was better than that of the HBOC group (16.5±1.732)% and the normal saline group (30.75±6.45)% (P<0.05). HE and Masson staining results showed that the CO-HBOC group had reduced inflammatory cell infiltration and significantly decreased collagen fiber deposition in lung tissue, with a mean pathological score of 3.33±0.58, which was lower than that of the normal saline control group (8.33±1.53)(P<0.05); the mean collagen-positive area percentage was (3.33±1.53)%, significantly lower than that of the normal saline control group (14.00±3.61)% (P<0.05). Proteomic analysis identified 330 differentially expressed proteins, which were mainly enriched in inflammatory response regulatory pathways (such as the complement and coagulation cascades), and the expression changes of complement proteins may be the core target of CO-HBOC's anti-fibrotic effects. Conclusion: CO-HBOC can inhibit inflammatory responses and regulate fibrosis-related signaling pathways, there-by effectively inhibiting the fibrotic process in IPF mice, with superior efficacy to HBOC. Its mechanism of action involves the regulation of complement cascade-related signaling pathways and complement protein expression, providing an experimental and theoretical basis for targeted therapy of IPF.

Objective·To explore the metabolic profiling and metabolic reprogramming patterns of lung cancer cells with acquired resistance to sotorasib,a specific inhibitor to KRAS.Methods·The H2122 and H358 lung cancer cell models with acquired resistance to sotorasib(H2122-SR and H358-SR cells)were established and validated by CCK-8 assay.Ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UPLC-QTOF/MS)was employed to acquire the metabolic profiling of the resistant lung cancer cells and their homologous parental cells.Untargeted metabolomics studies and metabolic characterizations were conducted with multi-dimensional methods,including principal component analysis(PCA)and partial least squares-discriminant analysis(PLS-DA),to identify differential metabolites associated with acquired resistance to sotorasib.Then these differential metabolites were subjected to pathway enrichment analysis.Heatmap analysis was used to compare the changes in metabolites in major differential metabolic pathways between the resistant and parental cells.Results·The cell models of H2122 and H358 with acquired resistance were successfully constructed,with half-maximal inhibitory concentrations(IC50)of sotorasib being 50 times higher than those of the parental cells.Besides,the metabolic profiling was significantly different between the resistant and parental cells.A total of 48 differential metabolites were identified between H2122-SR and H2122 cells.The top 10 differential metabolites,ranked by VIP values,were uridine,xanthylic acid,indole-3-carboxylic acid,nicotinic acid,xanthosine,xanthine,N-methylnicotinamide,hypoxanthine,trigonelline,and galactonic acid.Between H358-SR and H358 cells,a total of 79 differential metabolites were identified.The top 10 differential metabolites,ranked by VIP values,were glutathione,xanthosine,2-ketoglutaric acid,carboxyethyl lysine,thymidine,purine,riboflavin,3-indoleacrylic acid,indole-3-pyruvic acid,and dihydrouracil.The differential metabolites in the two lung cancer cell lines mainly participated in purine metabolism and glycolysis/gluconeogenesis,and purine metabolism was the most significantly altered metabolic pathway.Heatmap analysis showed that many metabolites in the purine metabolism were elevated in the sotorasib-resistant cells.Conclusion·The lung cancer cells with acquired resistance to sotorasib show enhanced purine metabolism.

Objective·To explore the metabolic profiling and metabolic reprogramming patterns of lung cancer cells with acquired resistance to sotorasib,a specific inhibitor to KRAS.Methods·The H2122 and H358 lung cancer cell models with acquired resistance to sotorasib(H2122-SR and H358-SR cells)were established and validated by CCK-8 assay.Ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UPLC-QTOF/MS)was employed to acquire the metabolic profiling of the resistant lung cancer cells and their homologous parental cells.Untargeted metabolomics studies and metabolic characterizations were conducted with multi-dimensional methods,including principal component analysis(PCA)and partial least squares-discriminant analysis(PLS-DA),to identify differential metabolites associated with acquired resistance to sotorasib.Then these differential metabolites were subjected to pathway enrichment analysis.Heatmap analysis was used to compare the changes in metabolites in major differential metabolic pathways between the resistant and parental cells.Results·The cell models of H2122 and H358 with acquired resistance were successfully constructed,with half-maximal inhibitory concentrations(IC50)of sotorasib being 50 times higher than those of the parental cells.Besides,the metabolic profiling was significantly different between the resistant and parental cells.A total of 48 differential metabolites were identified between H2122-SR and H2122 cells.The top 10 differential metabolites,ranked by VIP values,were uridine,xanthylic acid,indole-3-carboxylic acid,nicotinic acid,xanthosine,xanthine,N-methylnicotinamide,hypoxanthine,trigonelline,and galactonic acid.Between H358-SR and H358 cells,a total of 79 differential metabolites were identified.The top 10 differential metabolites,ranked by VIP values,were glutathione,xanthosine,2-ketoglutaric acid,carboxyethyl lysine,thymidine,purine,riboflavin,3-indoleacrylic acid,indole-3-pyruvic acid,and dihydrouracil.The differential metabolites in the two lung cancer cell lines mainly participated in purine metabolism and glycolysis/gluconeogenesis,and purine metabolism was the most significantly altered metabolic pathway.Heatmap analysis showed that many metabolites in the purine metabolism were elevated in the sotorasib-resistant cells.Conclusion·The lung cancer cells with acquired resistance to sotorasib show enhanced purine metabolism.

Nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important transcription factor that regulates redox, lipid metabolism and protein dynamic balance, and plays an important role in protecting the body from oxidative stress damage. Recently, more and more studies have shown that Nrf2 is activated in ovarian cancer by various mechanisms to induce increased antioxidant enzymes, change sex hormone metabolism and induce downstream targets. Further studying the mechanism of Nrf2 in promoting the development of ovarian cancer, exploring its role in drug resistance and seeking new therapeutic targets can provide new ideas for the treatment of drug-resistant ovarian cancer.

Objective To analyze the effect of limited internal fixation contrasting micro -external fixator in the treatment of fractures around the hand.Methods Sixty patients with fractures around the hand treated in the First People′s Hospital of Huizhou from May 2015 to May 2017 were selected and randomly divided into the internal fixation group and the external fixation group,and then were treated with effective internal fixation and mini external fixator respectively.The curative effect,operation condition,postoperative recovery and complications of the two groups were compared.Results The treatment effect(excellent and good rate was 96.67%(29/30)),fracture recovery time((6.37 ± 1.25)weeks),hospitalization time((4.32 ±1.23)d)and postoperative complication rate(10.0%(3/30))in the external fixation group were superior to those in the internal fixation group(76.67%(23/30),(8.87 ± 2.12)weeks,(7.29 ± 2.15)d,33.3%(10/30)),the differences were statistically significant(P=0.032;t=15.459,P=0.005;t=17.788,P =0.001;P=0.012).However,there were no significant differences between the external fixation group and internal fixation group in the operation time and the blood loss during operation((28.41±2.87)min vs.(27.67±1.42)min;(16.87 ± 3.71)ml vs.(16.43 ± 2.89)ml)(t=2.459,P=0.423;t=1.788,P =0.619). Conclusion Compared with limited internal fixation,the mini external fixator is reliable and effective,with less complications,and is more conducive to the early activity and functional recovery of the patients with hand fractures.

Objective To study antimicrobial resistance of clinically isolated Escherichia coli (E.coli),the preva-lence of integrons in E.coli,and relation of integron with antimicrobial resistance of E.coli.Methods E.coli isola-ted from three hospitals of Guangdong Province from 2010 to 2012 were collected,and antimicrobial susceptibility testing was performed by Kirby-Bauer method;integrons were detected by polymerase chain reaction (PCR),and gene cassette was analyzed by sequencing.Results A total of 156 E.coli isolates were collected,antimicrobial sus-ceptibility testing showed that resistance rate of E.coli to most penicillins,cephalosporins,fluoroquinolones,amin-oglycosides and sulfonamides were over 50%;the resistance rate to antimicrobials < 10% included cefoperazone/sulbactam(0),imipenem(3.85%),cefotetan(4.35%),ertapenem(7.69%)and piperacillin /tazobactam (8.97%);The positive rate of class I integron was 57.69%(90/156);the positive rate of class I integron in multidrug-resist-ant and non-multidrug-resistant E.coli was 66.00% (66/100)and 64.71 % (22/34)respectively,the difference was not statistically different (P >0.05),but compared with sensitive E.coli (9.09%,2/22),the difference was statisti-cally different (P<0.01 ).There were nine types of integron-drug resistant gene cassettes in the variable regions, most of which contained aadA and dfrA.Conclusion Antimicrobial resistance of E.coli is serious;high incidence of class I integrons are widely found in E.coli,and is closely related with drug resistance of E.coli,class I integrons mainly mediated aminoglycosides,sulfonamides and beta-lactams resistance.