To search for potent drugs against non-small-cell lung cancer(NSCLC),a series of hybrids(9a-9e, 10a-10e and 11a-11e﹚ from anilinopyrimidines and diazeniumdiolates were designed and synthesized.The MTT assay was employed to evaluate their antiproliferative activity against H1975 cells harboring epithelial growth factor receptor(EGFR)L858R/T790M mutation.The results showed that compounds 9a-9e displayed remarkable inhibitory activity on H1975 cells.Among these compounds, the most potent was compound 9b(IC50=0.65 μmol/L),which was superior to the positive control gefitinib.Additionally,molecular docking study indicated that 9b could bind with EGFR T790M by forming hydrogen bond, electrostatic interactions, et al, suggesting that compound 9b may be a potential anti-NSCLC agent for further investigation.

Objective:To evaluate the posterior fixation with inclined-long pedicle screws for the injured vertebra combined with two-level interbody fusion for thoracolumbar burst fractures with severe disc injury.Methods:A retrospective study was conducted to analyze the clinical data of 22 patients who had been treated for thoracolumbar burst fractures with severe disc injury at Department of Orthopaedic, General Hospital of Central Theater Command from June 2016 to June 2021. There were 15 males and 7 females, aged 43.50 (29.75, 52.25) years. By the AO classification, there were 12 cases of type B2, 10 cases of type C3. All the patients were treated by the posterior fixation with inclined-long pedicle screws for the injured vertebra combined with two-level interbody fusion. The visual analogue scale (VAS), Oswestry disability index (ODI), anterior vertebral height ratio (AVHR), kyphosis Cobb angle (KCA), vertebral wedge angle (VWA) and spinal canal encroachment rate (SCER) were compared between pre-surgery, 1 week post-surgery, 3 months post-surgery and the last follow-up. Their neurological function was graded according to the American Spinal Injury Association (ASIA) impairment scale and interbody fusion evaluated according to their 3D CT at the last follow-up.Results:All the 22 patients were followed up for (26.1±1.3) months. In all patients, the VAS and ODI were significantly lower at 1 week post-surgery than the pre-surgery ones ( P<0.05), and then decreased significantly at 3 months post-surgery and at the last follow-up compared with the values at 1 week post-surgery ( P<0.05). For all patients, there were significant improvements in AVHR, KCA, VWA and SCER at 1 week post-surgery, 3 months post-surgery and the last follow-up compared with the pre-surgery values ( P<0.05), and the SCER at the last follow-up was significantly decreased compared with that at 1 week post-surgery ( P<0.05). All patients experienced improved neurological function in different degrees at the last follow-up, and all intervertebral spaces achieved solid bony fusion. Conclusion:In the treatment of thoracolumbar burst fractures with severe disc injury, the posterior fixation with inclined-long pedicle screws for the injured vertebra combined with two-level interbody fusion can lead to satisfactory long-term therapeutic efficacy, because this strategy can effectively reduce spinal canal encroachment, restore the height of the injured vertebra, reconstruct the curvature of the fracture area and ensure reliable intervertebral fusion.

Objective:To investigate the complex Calculus Bovis-target-keratitis network and to explore the molecular mechanism of Calculus Bovis treating keratitis through network pharmacology. Methods:Genes related to keratitis were searched in the online DisGeNET database and the protein-protein interaction (PPI) network of keratitis-associated proteins was constructed.The components isolated and identified in Calculus Bovis were collected through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP, https: //tcmsp-e.com/tcmsp.php), Chemistry Database by Shanghai Institute of Organic Chemistry of CAS (http: //www.organchem.csdb.cn), and published literature.The canonical SMILES information of the collected components was exported, which were submitted to the SwissTargetPrediction platform to predict potential targets of the components.The active component-predicted target network of Calculus Bovis was constructed and merged with the PPI network of keratitis-associated proteins to build the active component-potential target network of Calculus Bovis and systemically investigate the potential targets and signal pathways of Calculus Bovis in treatment of keratitis.The component-target-pathway network was established to analyze the mechanism of Calculus Bovis treating keratitis. Results:Thirty-nine components isolated and identified in Calculus Bovis were searched and 65 target genes related to keratitis were screened.Of the 28 potential targets involved in Calculus Bovis treating keratitis, there were 7 direct targets, including tumor necrosis factor, caspase 1, Toll-like receptor 9, C-X-C motif chemokine ligand 8, interleukin-6, mitogen-activated protein kinase 8, neurotrophic receptor tyrosine kinase 1.The 28 potential targets were annotated to 12 entries for biological process, 18 for cellular components and 13 for molecular function.In the Kyoto encyclopedia of genes and genomes pathway enrichment analysis, 10 signal pathways were identified as enriched categories, which were mainly related to human cytomegalovirus infection, amoebiasis, antifolate resistance, PI3K-Akt signaling pathway, rheumatoid arthritis, apoptosis, cytokine-cytokine receptor interaction, malaria, non-alcoholic fatty liver disease, interleukin-17 signaling pathway. Conclusions:Calculus Bovis may play an adjuvant therapeutic effect on keratitis through anti-inflammatory, antibacterial, antiviral, immune regulation, inflammatory regulation and other functions.

BACKGROUND:For thoracolumbar spine fractures with developmental stenosis of the vertebral arch,accurate nail placement is difficult using traditional fluoroscopy-assisted techniques.O-arm navigation assistance systems offer higher precision in general vertebral arch nail placement,but there is scarce literature on the application of O-arm navigation-assisted nail placement in thoracolumbar spine fractures with developmental stenosis of the vertebral arch both domestically and abroad. OBJECTIVE:To explore the accuracy of percutaneous vertebral arch nail placement assisted by O-arm navigation in patients with thoracolumbar spine fractures complicated by developmental stenosis of the vertebral arch. METHODS:A retrospective analysis was conducted on 53 patients who underwent percutaneous vertebral arch screw fixation surgery at Department of Orthopedics,General Hospital of Central Theater Command of PLA for thoracolumbar spine fractures complicated by developmental stenosis of the vertebral arch from January 2021 to March 2023.Totally 208 cases of vertebral arch developmental stenosis were found(cases with multiple vertebral arch developmental stenosis were counted separately).Based on the surgical approach,the patients were divided into two groups:O-arm navigation group(n=98)and C-arm fluoroscopy group(n=110).Postoperative imaging data were compared between the two groups,including anatomical perforation score,functional perforation score,actual vs.expected nail trajectory in the horizontal plane,and sagittal plane angle differences. RESULTS AND CONCLUSION:(1)There was no significant difference in the narrowest width of the pedicle isthmus(pow)between the two groups of patients(P>0.05).The proportions of different degrees of narrowing(mild:6 mm≤pow<7 mm,moderate:5 mm≤pow<6 mm,severe:pow<5 mm)were also not significantly different between the two groups(P>0.05).(2)The overall grade and scores of anatomical perforation and functional perforation were lower in the O-arm group compared to the C-arm group,and these differences were statistically significant(P<0.001).In terms of the angular deviation between the actual and planned screw trajectories,the O-arm group had smaller deviations,and these differences were statistically significant(P<0.05).(3)In the mild and moderate narrowing groups,the O-arm group showed significant advantages in anatomical perforation,functional perforation,and angular deviation between actual and planned screw trajectories,and these differences were statistically significant(P<0.001).(4)The O-arm group demonstrated better performance in anatomical perforation and functional perforation,especially in the T12-L2 segment,with more significant advantages.Additionally,the O-arm group had better angular deviations in actual and planned screw trajectories in all segments compared to the C-arm group.(5)Therefore,the use of O-arm navigation-assisted percutaneous screw placement for the treatment of thoracolumbar fractures with developmental pedicle isthmal narrowing provides higher accuracy and safer surgery.

ObjectiveTo investigate the effects of Asari Radix et Rhizoma-Zingiberis Rhizoma herb pair （XGHP） on lung and liver lipid metabolism in rats with chronic obstructive pulmonary disease （COPD）. MethodForty SD male rats were divided into a normal group （10 rats） and a model group （30 rats）. The method of cigarette smoke + tracheal injection of lipopolysaccharide（LPS） + cold stimulation was used to replicate COPD model with the syndrome of cold phlegm obstruction in lung. A COPD group， a XGHP group （5.4 g·kg^-1·d^-1）， and an aminophylline group （0.5 g·kg^-1·d^-1） were established after successfully inducing the model， with 10 rats in each group. After treatment， the serum triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） levels of rats in each group were measured. Gas chromatography-mass spectrometer （GC-MS） was used to detect the differential metabolites in the lung and liver tissues of rats in each group， and the relevant targets of the differential metabolites were predicted by network pharmacology. Molecular docking was used to verify the binding ability of key components in XGHP to the relevant targets in network pharmacology. The mRNA and protein expression levels of peroxisome proliferator-activated receptor α （PPARα） and fatty acid binding protein 4 （FABP4） in lung and liver tissues of rats in each group were detected by real-time polymerase chain reaction （PCR） and Western blot. ResultXGHP significantly increased the levels of TG， TC， and LDL-C in serum （P<0.05）， and decreased the level of HDL-C （P<0.05） in rats with COPD. GC-MS results showed that there were 8 lung differential metabolites and 17 liver differential metabolites in the COPD group and XGHP group. Network pharmacology predicted 59 common targets for the two differential metabolites， mainly enriched in the PPAR signaling pathway. Molecular docking results showed that the main components in XGHP were well combined with both PPARα and FABP4. Real-time PCR showed that XGHP effectively up-regulated the expression levels of PPARα and FABP4 mRNA （P<0.05）， and Western blot showed that XGHP effectively up-regulated the expression levels of PPARα and FABP4 proteins （P<0.05） in lung and liver tissues of rats with COPD. ConclusionXGHP effectively improves the blood lipid levels of rats with COPD， which may be related to the increase of the expression levels of PPARα and FABP4 mRNA and proteins in the PPAR signaling pathway， thus regulating lung and liver lipid metabolism.