Objective To investigate the role and primary mechanism of a novel fusion gene RELCH-RET in driving the malignant transformation of normal human bronchial epithelial(HBE)cells.Methods Based on retrospective clinical data from 456 non-small cell lung cancer(NSCLC)patients admitted in the Second Affiliated Hospital of Army Medical University from January 2019 to June 2022,a fusion gene,RELCH-RET,was identified as a research target.Three cell models were established:negative control(HBE VC,transfected with empty lentiviral vector),RET control(HBE RET,transfected with lentiviral overexpression vector of Flag-RET),and experimental group(HBE RELCH-RET,transfected with lentiviral overexpression vector of Flag-RELCH-RET).MTS assay and Transwell assay were used to detect cell proliferation and migratory and invasive abilities.In vivo tumorigenicity of the 3 cell models was assessed in 15 female non-obese diabetic/severe combined immunodeficiency(NOD/SCID)mice(SPF grade,4 weeks old,weighing 15.1±0.4 g)via subcutaneous xenograft experiments,with 5 animals in each group.Western blotting was employed to detect the autophosphorylation of RET(Y905)and the phosphorylation of downstream signaling proteins ERK1/2,EGFR(Y845)and STAT3(Y705).Dimerization and multimerization status of RELCH-RET were analyzed by chemical cross-linking(DTME treatment)in combination with Western blotting,with the reversibility being confirmed through de-cross-linking experiments.Results There were 3 cases carrying RELCH-RET fusion gene screened out from the 469 NSCLC patients.Compared with the HBE VC and HBE RET groups,the HBE RELCH-RET group exhibited significantly enhanced cell proliferation(P<0.01),and acquired migratory and invasive abilities(P<0.01),while the control groups did not demonstrate the abilities.In the mouse xenograft tumor model,HBE cells stably expressing RELCH-RET developed significant tumor nodules(P<0.001),whereas the control groups(empty vector and wild-type RET)failed to exhibit detectable tumor growth.Western blotting revealed that RELCH-RET could induce the autophosphorylation of the RET tyrosine residue(Y905)and significantly up-regulate the phosphorylation levels of ERK1/2,EGFR(Y845),and STAT3(Y705)proteins.Chemical cross-linking combined with Western blot analysis demonstrated that RELCH-RET formed a dimer(～170 kDa)in HBE cells,which is reversibly dissociated into monomers upon decross-linking treatment.Conclusion The novel fusion gene RELCH-RET,promotes ligand-independent dimerization/oligomerization,thereby mediating RET autophosphorylation,subsequently activates the downstream typical RET signaling pathway and ultimately drives the malignant transformation of normal HBE cells.

Objective To elucidate the effects of miR-616 on the malignant biological processes of osteosarcoma and to preliminarily explore its potential mechanisms.Methods In situ hybridization(ISH)was employed to analyze miR-616 expression in 11 paraffin-embedded osteosarcoma specimens collected in our department during January 2018 to December 2019.Quantitative real-time PCR(qRT-PCR)was used to compare the mRNA expression level of miR-616 in the osteoblast cell line hFOB1.19 and osteosarcoma cell lines 143B and HOS.Stable cell lines with miR-616 knockdown or overexpression were established via lentiviral transfection in 143B and HOS cells.Cell proliferation and apoptosis were detected by flow cytometry,while cell invasion and migration were assessed using Transwell and colony formation assays,respectively.To evaluate the effect of miR-616 on tumor growth in vivo,10 female nude mice(4 weeks old,weighing 18～20 g)were randomized into a control group and a miR-616 overexpression group.After the xenograft tumor model was constructed,the growth of subcutaneous tumors was monitored.Finally,next-generation sequencing and a dual-luciferase reporter assay were performed to identify the target genes of miR-616.Results ISH results showed that miR-616 expression was up-regulated in osteosarcoma tissues than adjacent tissues,and primarily localized in the cytoplasm.qRT-PCR confirmed that miR-616 level was significantly higher in 143B and HOS cells than hFOB1.19 cells(P<0.05).In vitro experiments revealed that miR-616 overexpression enhanced the proliferation,migration and invasion,while suppressing apoptosis in 143B and HOS cells(P<0.01).Conversely,miR-616 knockdown weakened these malignant phenotypes(P<0.05),with miR-616-3p showing a stronger effect on apoptosis than miR-616-5p.Animal experiments demonstrated that the tumor weight in the miR-616 overexpression group was significantly greater than that of the control group(98.00±17.22 vs 33.60±8.08 mg,P<0.01).Furthermore,KLF2 was identified and confirmed as a direct target of miR-616.Conclusion MiR-616 promotes malignant biological behaviors in osteosarcoma,and its expression level indicates that it may serve as a potential therapeutic target.

China has a heavy burden of hepatocellular carcinoma, which is a serious threat to people′s life and health. However, the available drugs for advanced hepatocellular carcinoma in the past are limited and the efficacy is not satisfactory. In recent years, immunotherapy has a significant effects in some tumors. The authors introduce the efficacy of restart immunotherapy on an advanced hepatocellular carcinoma patient undergoing interruption of treatment due to corona virus disease 2019, in order to provide references for the diagnosis and treatment of this kind of patients.

Objective To investigate the accuracy and application value of optical surface monitoring system in intensity modulated radiotherapy for thoracic tumors patients.Methods Twenty-eight patients with thoracic tumors were included.During each treatment fraction,the patients were immobilized with body surface markers and laser lamps.The surface images obtained by the optical surface monitoring system were registered with the reference images and recorded during the CBCT scan.The translation and rotation errors of x (left-right),y (craniocaudal) and z (anterior-posterior) axes were recorded.After scanning,the CBCT images were registered with the planned CT images and the translation and rotation errors of x,y and z axes were recorded.The setup errors of these two image systems were analyzed and corrected before each treatment.The correlation between the two sets of setup errors were analyzed with Pearson test,and systematic error (∑) and random error (σy) were also calculated.The consistency of the two image systems was evaluated with the Bland-Altman method and the 95％ limits of agreement were calculated.Results There was a good correlation between these two groups,and the correlation coefficients were 0.79,0.62,and 0.53 in x,y and z axes,respectively.The ∑/σr of the optical surface monitoring system were 0.7 mm/1.5 mm,0.9 mm/1.8 mm and 0.9 mm/1.5 mm in x,y and z axes,respectively.The ∑/σ of CBCT were 0.8 mm/1.6 mm,1.3 mm/1.9 mm and 0.7 mm/1.5 mm in x,y and z axes,respectively.The 95％ limits of agreement of translations direction were (-2.0-2.3),(-3.4-3.6) and (-3.3-2.4) mm,and the 95％ limits of agreement of rotation direction were (-2.0 to 1.6)°,(-2.0 to 1.4)° and (-1.6 to 1.6)° inx,y and z axes,respectively.Conclusions The optical surface monitoring system is an effective image guide tool,which can quickly and accurately verify the patient's position and improve the position accuracy.It can be applied for positioning in the intensity modulated radiation treatments for the thoracic tumor patients.

According the features of mine sweeping mission and the requirements of the armaments,the compound structure to reflect,absorb,block and attenuate the blast waves and to give dynamic protection against diffracted waves is designed,which is based on the theories of biomedical engineering,explosive mechanics and material mechanics.The calculation through3D nonlinear dynamic finite element and simultaneous tests are used in the de-velopment of the structure.These theories above-mentioned applied to the experiments and medical science com-bined with mechanical engineering,a series of technical problems in the protection against the injuries to human bodies by blast waves,detonations and mine fragments are solved.Through practical application,the outfit has been granted and finalized by Finalization Board of Armaments and given the name GGF110mine sweeping protective outfit.It has been equipped with the army and pointed for the first time to be used by the UN peacekeeping troops.

A new method of using photoactivable ester with azido group was described to immobilize urease on polyether sulfone(PES) film surface. The effects of photoactive enzyme concentration, temperature, pH, irradiation time on the activity of immobilized urease were investigated. Reused times and storage stability were also studied. The results showed that the surface concentration of urease immobilized on PES surface was about 0.33 mg/cm2. When the irradiation time was 5 minutes, the relative activity of immobilized urease was the highest and the activity increased with the increase of the concentration of photoactive urease solution. The optimum pH and temperature of immobilized urease were 7 and 50 degrees C respectively. The relative activity of immobilized urease was stable (50%) after 12 times reused at 50 degrees C.
Enzyme Stability ; Enzymes, Immobilized ; metabolism ; radiation effects ; Membranes, Artificial ; Photochemistry ; Polymers ; Sulfones ; Urease ; metabolism ; radiation effects

Objective To investigate the change of eNOS,the spermatogenic cell proliferation,apoptosis in mouse testis exerted by alcohol. Methods The immunohistochemical staining method for detecting of eNOS,PCNA,TUNEL method for detecting of apoptotic cells and the satistics analysis were used in the present study. Results With the increase of alcohol concentration,the structure of seminiferous tubule changed,the diameter of seminiferous tubule decreased,the surface density of postive eNOS cells increased gradually,and the number of positve PCNA cells and apoptosis cells also increased.There were significant difference in 15% alcohol concentration group compared with the other groups(P