Adenovirus as gene transfer vector is characterized by high transfection efficiency,high titer,good stability in target cells and low pathogenicity,and has been widely used in gene therapy.Compared to first-and second-generation adenovirus vectors,the third-generation adenovirus vectors have unique advantages for gene therapy because of their low immunogenicity and high capacity.However,the clinical application of the third-generation adenovirus vectors is hampered by the existance of helper contamination and difficulties in their large-scale production.

Background and objective All the advanced NSCLC patients that received EGFR-TKI therapy will eventually relapse after a period of efficacy. The aim of this study is to investigate the serum biomarkers as potential predictive factors for the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeted therapy in advanced non-small cell lung cancer. Methods Twenty serf-paired serum samples were collected from 9 advanced NSCLC patients that evaluated as disease control (SD or PR) after gefinitib therapy, at the time points of before and after gefinitib treatment but 2 weeks before being evaluated as disease progress. AII samples were pre-separated by WCX microbeads, and then detected on the MALDI-TOF-MS platform of Bruker AutoflexTM. ClinProTools (Version: 2.1) was used to analyze the differentially expressed proteins. Results There were 7 protein peaks (m/z), 3 242.09, 8 690.36, 2 952.64, 3 224.04, 1 450.51, 1 887.8 and 3 935.73 found statistically differentially expressed between the self-paired samples. Three proteins (3 242.09, 2 952.64 and 3 224.04) were down-regulated and four proteins (8 690.36, 1 450.51, 1 887.8 and 3 935.73) up-regulated in gefinitib treated sera. Conclusion The data here suggest that several specific protein peaks might indicate gefinitib resistance, yet the identities of these proteins and the mechanisms underlying the responsiveness to gefinitib treatment need further investigation.

Objective:To discuss the clinical effect about the external locking compression plate(LCP) combined with lower abdominal conjoined flap for fixing the open fracture and covering the soft tissue defects on tibia.Methods:From August 2017 to December 2020, 18 patients with serve tibial open fracture were admitted into the trauma center, including 15 males and 3 females with a median age of 38 (ranged, 25-58) years old. The etiology involving: 9 cases by traffic accident, 3 by downfall, 6 by crushing, which classified as type III B( n=6) and III C( n=12) by the Anderson-Gustilo criterion. All wounds were taken radical debridement, fixed by the femur LCP and covered by the VSD during the emergency operation. The lower abdominal conjoined flap was dissected to cover the soft tissue defect, of which the dimension and pedicle length were tailored to the defect. Primary closure was performed on the donor site. Followed-up was conducted by telephone and WeChat. Results:One flap was changed to gastrocnemius myocutaneous flap because of the venous crisis. Seventeen flaps survived completely without significant complications. All the donor and recipient sites had primary healing. A mean follow-up of 15 (ranged, 12 to 18) months. The fracture healed without bone infection and bone nonunion. The aesthetic outcomes were satisfied without overgrown hairy and hyperpigmentation for all flaps. The concealed linear scar was left without hernia or other morbidity on the donor site. At the final follow-up, 12 cases were excellent and 6 cases were good evaluated by the Johner-Wruhs criteria.Conclusion:The external LCP can immobilise the knee and ankle joint with the preservation of the soft tissue, and the free lower abdominal conjoined flap was useful for covering extreme defects with concealed donor site, with enough tissue volume. The combination of both could lower the postoperative infection, reduce the operation time and shorten the hospital stay.

Objective:To compare the biomechanical properties of posterolateral distal humeral plate, inverted anterior proximal humerus internal locking system (PHILOS), and anterior reconstruction plate in the treatment of distal humeral shaft fractures by a finite element analysis.Methods:One healthy adult male volunteer, aged 27 years, with a height of 171 cm and a weight of 70 kg, was recruited for this study. The finite element method was used to establish a simulation model of distal humeral shaft fracture. The maximum displacement and maximum stress were compared between fixation with posterolateral distal humeral plate (group A), fixation with inverted anterior PHILOS (group B), and fixation with anterior reconstruction plate (group C).Results:In groups A, B, and C, respectively, the overall stress peak values were 409.07 MPa, 217.04 MPa, and 370.64 MPa; the peak stresses under torsional load were 234.55 MPa, 348.80 MPa and 458.17 MPa; the overall stress peaks under bending load were 250.22 MPa, 466.76 MPa, and 582.32 MPa. The smaller the stress, the smaller the risk of fatigue fracture. In groups A, B, and C, respectively, the overall displacement peak values were 5.18 mm, 3.04 mm and 3.75 mm; the peak displacements under torsional load were 1.20 mm, 1.02 mm and 2.05 mm; the peak displacements under bending load were 3.85 mm, 5.28 mm and 9.04 mm. The smaller the displacement, the better the fixation stability.Conclusions:In the treatment of distal humeral shaft fractures, fixation with inverted anterior PHILOS leads to the best mechanical stability under axial compression and torsional stress, while fixation with the posterolateral distal humeral plate leads to the best mechanical stability under bending stress.

Carcinoma, Non-Small-Cell Lung ; classification ; therapy ; China ; Humans ; Lung Neoplasms ; classification ; therapy ; Practice Guidelines as Topic ; Receptor Protein-Tyrosine Kinases ; metabolism

OBJECTIVE To investigate the mechanism of Mayuan tongbian zhitong decoction on improving slow-transmission constipation（STC）in rats by regulating AMP activated protein kinase （AMPK）/endothelial nitric oxide synthase （eNOS）signaling pathway. METHODS The rats were randomly divided into blank group ，model group ，Mayuan tongbian zhitong decoction low-dose，medium-dose and high-dose groups （6，12，18 mg/kg），with 10 rats in each group. Except for blank group ，other groups were given Compound diphenoxylate suspension to induce STC model. After modeling ，blank group and model group were given normal saline intragastrically ，and Mayuan tongbian zhitong decoction groups were given relevant medicine intragastrically ， once a day ，for consecutive 2 weeks. The number of feces and water content of feces in each group were observed before and after treatment；the carbon powder propulsion rate of rats in each group was calculated ；the pathological structure of colon in each group was observed ；the levels of nitric oxide （NO）and nitric oxide synthase （NOS）in colon tissues of rats in each group were detected；the expressions of AMPK ，eNOS，mammalian target of rapamycin （mTOR），tuberous sclerosis complex 1（Tsc-1）， Tsc-2 and eukaryotic promoter 4E binding protein （4ebp）were also detected. The active ingredients of Cannabis sativa ，Citrus aurantium and Rehmannia glutinosa were screened from Mayuan tongbian zhitong decoction. The active ingredients with high Degree value were docked with AMPK and eNOS ，to verify the interaction. RESULTS Compared with before treatment ，the number and water content of feces were increased significantly in Mayuan tongbian zhitong decoction groups （P＜0.05）. Compared with blank group ，carbon powder propulsion rate of model group was decreased significantly （P＜0.05）； colonic structure was disordered ，and a large number of inflammatory cells were seen in submucosa ；the levels of NO and NOS in colon tissue as well as the protein expressions of AMPK ，eNOS，mTOR，Tsc-1，Tsc-2 and 4ebp were increased significantly （P＜0.05）. Compared with model group ，above indexes of Mayuan tongbian zhitong decoction groups （except for NOS in low-dose group ）were reserved significantly （P＜0.05）. In the molecular docking experiment ，the active components with the highest Degree values in C. sativa ，C. aurantium and R. glutinosa were（Z）-3-（4-hydroxy-3-methoxy-phenyl）-N-[2-（4-hydroxyphenyl）ethyl] acrylamide，nobiletin and stigmasterol. The binding energies of AMPK with these three components were －5.15，－4.61 and －4.83 kJ/mol，the binding energies of eNOS with these three components were －6.11，－5.40 and －5.91 kJ/mol. The conformations of these three compounds with AMPK and eNOS were stable and their binding activities were high. CONCLUSIONS Mayuan tongbian zhitong decoction can improve the constipation symptoms and intestinal function in STC model rats ，and its specific mechanism may be related to the inhibition of AMPK/eNOS signaling pathway.

Gut microbiota plays an important role in development of diabetes with frailty. Therefore, it is of great significance to study the structural and functional characteristics of gut microbiota in Chinese with frailty. Totally 30 middle-aged and the aged participants in communities with diabetes were enrolled in this study, and their feces were collected. At the same time, we developed a metagenome analysis to explore the different of the structural and functional characteristics between diabetes with frailty and diabetes without frailty. The results showed the alpha diversity of intestinal microbiota in diabetes with frailty was lower.
Aged ; Diabetes Mellitus ; Epstein-Barr Virus Infections ; Frailty ; Gastrointestinal Microbiome ; Herpesvirus 4, Human ; Humans ; Middle Aged

BACKGROUND: The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex. METHODS: The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases. RESULTS: WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group. CONCLUSIONS This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.
Animals ; Mice ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Liver Neoplasms/genetics*