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.

Protein neddylation is catalyzed by a three-enzyme cascade, namely an E1 NEDD8-activating enzyme (NAE), one of two E2 NEDD8 conjugation enzymes and one of several E3 NEDD8 ligases. The physiological substrates of neddylation are the family members of cullin, the scaffold component of cullin RING ligases (CRLs). Currently, a potent E1 inhibitor, MLN4924, also known as pevonedistat, is in several clinical trials for anti-cancer therapy. Here we report the discovery, through virtual screening and structural modifications, of a small molecule compound HA-1141 that directly binds to NAE in both

Background: Esophageal mucosal injury induced by gastroesophageal reflux is a key link to the development of Barrett's esophagus-associated adenocarcinoma. However, the molecular mechanism is still not elucidated. Aims: To investigate the role of differentially expressed genes (DEGs) after stimulating esophageal cells with acid and bile acid in the development of esophageal adenocarcinoma (EAC). Methods: The DEGs were obtained through bioinformatics methods after stimulating esophageal cells with low pH and deoxycholic acid, and GO, KEGG enrichment analysis were performed. Protein-protein interaction (PPI) network was performed to screen the hub genes, and their relationships with prognosis and tumor stage of EAC patients were analyzed. The role of co-expressed genes of GADD45B in EAC was also analyzed. Results: Thirty-one overlapping DEGs were obtained after stimulating esophageal cells with low pH and deoxycholic acid, which mainly enriched in the cytokine-cytokine receptor interaction, transcription factors activity, and regulation of cell proliferation and apoptotic process. High expression of GADD45B was correlated with the survival prognosis and tumor stage of EAC patients. GADD45B and its co-expressed genes were involved in the production of tumor necrosis factor. Conclusions: The high expression of GADD45B induced by acid and bile acid is correlated with the prognosis and tumor stage of EAC patients, and is a potential diagnosis and treatment target for Barrett's esophagus-associated adenocarcinoma.

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 the efficacy of percutaneous ablative therapy for malignant liver lesions under real-time virtual guidance. Methods Percutaneous ablations were applied to 76 patients with 125 malignant liver lesions under the guidance of a real time virtual system (RVS). 64. 8% (81/ 125) lesions were undetectable on conventional ultrasound (US). The time spent on image fusion and the local treatment response were studied. Results The average time taken to synchronize the ultrasound and CT images was (19. 2±12. 8) min (range 5～55 min). Complete ablations were achieved in 86. 4% (38/44) of distinctly visualized lesions and in 91. 6% (74/81) of poorly visualized lesions on US. No treatment associated complications were found. Conclusion Ablation assisted by RVS and CT was safe and efficacious, especially for lesions undetectable by conventional ultrasound.