Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Objective To investigate the correlation mechanism between miR-153-3p and Nrf2 expression in human nucleus pulposus cells and intervertebral disc degeneration(IDD).Methods The oxidative damage model of nucleus pulposus cells was duplicated induced by H2O2.MiR-153-3p inhibitor-NC,si-NRF2-NC,miR-153-3p inhibitor,and si-NRF2 were transfected into nucleus pulposus cells according to the grouping require.The transfection efficiency was detected by RT-qPCR and Western blot.The cell viability was determined by the CCK-8 assay,when the intracellular reactive oxygen species(ROS)levels and the ratio of mitochondrial membrane potential decline were measured by flow cytometry,RT-qPCR was used to detect the expression levels of Nrf2,MMP-3,Col II,PINK1,Parkin,P62,and p38 MAPK.And dual luciferase reporter assay was used to measure luciferase activity.Results(1)HNPCs treated with H2O2 showed a decrease in HNPCs cell viability,a reduction in mitochondrial membrane potential,an increase in ROS levels,and a decrease in Col II expression(P<0.05).And the expression of MMP-3,P62,and p38 MAPK increased,while the expression of PINK1 and Parkin decreased.There was no significant change in Nrf2(P>0.05).(2)Inhibition of miR-153-3p expression in nucleus pulposus cells treated with H2O2 led to increased cell viability,elevated mitochondrial membrane potential,reduced ROS levels,and enhanced Col-II expression,accompanied by decreased expression of MMP-3,P62,and p38 MAPK,while simultaneously increasing the expression of PINK1,Parkin,and Nrf2(P<0.05).(3)When miR-153-3p expression was inhibited and Nrf2 expression was silenced in nucleus pulposus cells treated with H2O2,a notable decline in cell viability and mitochondrial membrane potential was observed,along with a marked increase in ROS levels.Additionally,Col-II expression decreased,whereas the expression of MMP-3,P62,and p38 MAPK increased.However,the expression of Nrf2,PINK1,and Parkin decreased(P<0.05).(4)Dual-luciferase assay analysis revealed binding sites and a binding relationship between miR-153-3p and Nrf2,indicating a negative correlation between miR-153-3p and Nrf2(P<0.05).Conclusion Inhibition of miR-153-3p expression can alleviate H2O2 induced degeneration and fibrosis of nucleus pulposus cells,activate autophagy of damaged nucleus pulposus cells,and delay apoptosis of nucleus pulposus cells.This effect is related to the PINK1/Parkin pathway and p38 MAPK inflammatory response pathway regulated by Nrf2.

Objective To investigate the feasibility of defining the radiotherapy target of primary liver cancer using four-dimensional computed tomography (4DCT) and T2-weighted magnetic resonance (MR-T2) deformable image registration.Methods Ten patients with hepatocellular carcinoma (HCC) who first received radiotherapy were included in this study.The 4DCT in free breathing and MR-T2 in deep breathing were acquired sequentially.4DCT were sorted into ten series of CT images according to the respiratory phase.MIM software was used for deformable image registration.The accuracy of deformable image registration was assessed by the maximal displacements in three-dimensional directions of the portal vein and the celiac trunk and the degree of liver overlapping (P-LIVER).Gross tumor volume (GTV) was delineated on different series of CT images and the internal GTV (IGTV) was merged by ten GTVs on 4DCT images in each phase.The MR-T2 image was deformably registered to 4DCT images in each phase to acquire ten GTVDR.The IGTVDRwas obtained by merging the ten GTVDR.The differences between different target volumes were compared by paired t-test.Results The maximal displacements in three-dimensional directions of the portal vein were 0.3±0.8 mm along the x-axis, 0.8±1.8 mm along the y-axis, and 0.5±1.5 mm along the z-axis.The maximal displacements in three-dimensional directions of the celiac trunk were 0.1±1.0 mm along the x-axis, 0.7±1.2 mm along the y-axis, and 0.6±2.0 mm along the z-axis.Overlapping degree was 115.4±13.8%.The volumes of GTVs obtained from 4DCT images in each phase after DR increased by an average of 8.18%(P<0.05), and were consistent with those delineated on MR-T2 images.The IGTV after DR increased by an average of 9.67%(P<0.05).Conclusions MRI image can show more information and have a higher contrast than CT image.MRI images should be combined with 4DCT images for delineating the GTV.It can better determine the scope and trajectory of the target and improve the delineation accuracy of HCC target.

Objective To study the feasibility of defining the internal gross tumor volume (IGTV) of hepatocellular carcinoma applying the enhanced four-dimensional computed tomography (4DCT) images with deformable registration technology.Methods Ten HCC patients who accepted radiation therapy were selected in this study.The 4DCT in free breathing,non-enhanced 3DCT and arterial phase enhanced 3DCT in end inspiration breath holding associated with active breathing coordinator were acquired sequentially.4DCT were sorted into ten series CT images according to breath phase,and named CT00,CT10..…CT90.Gross tumor volume (GTV) were contoured on different CT series and the IGTV1 was merged by ten phases GTVs of 4DCT.The GTV of enhanced 3DCT was registered to different CT series of 4DCT and the IGTVDR was obtained by merging the GTVs after deformable registration.The target volumes differences were compared by paired t-test.Results The edge of tumor was difficult to define on 4DCT and non-enhanced 3DCT images.The enhanced 3DCT image showed clearer tumor edge,and the GTV increased by mean 37.99％ compared to GTV on 4DCT different series images and non-enhanced 3DCT image (P =0.002).The GTV after deformable registration on 4DCT different phase images increased by mean 36.34％ (P =0.011),which were similar to GTV on enhanced 3DCT image (P =0.632).The IGTVDR increased by 19.91％ (P =0.017),compared to IGTV1.Conclusions The contrast-enhanced 4DCT image which was obtained by combining enhanced 3DCT and 4DCT images with deformable registration technology could raise the position precision of the HCC IGTV effectively.

Objective:To analyze the characteristics of immune status in patients with different types of oral lichen planus(OLP). Methods:197 cases of OLP,61 with reticular OLP(ROLP)and 136 with hyperaemia erosion OLP(HEOLP)were included.The im-mune status of the patients were investigated by flow cytometry (FCM)for the expression of CD3 +,CD4 +,CD8 +,CD19 +,CD16 ++56 +and CD4 +/CD8 +cells,and nephelometry for the measurements of IgG,IgA,IgM,C3 and CH50 in peripheral blood.The la-brotary norm was used as the reference and the characteristics of immune status in patients with different clinical characters of OLP were analyzed by SPSS 16.0.Results:CD3 +,CD4 +,IgA and C3 decreased,CD19 +cells,IgG,IgMand CH50 increased in patients with OLP.CD16 ++56 +,CD4 +/CD8 +cells decreased in the cases with ROLP(P<0.05);CD8 +cells decreased in the cases with HE-OLP.CD3 +,CD8 +cells were fewer in HEOLP patients than that in ROLP,CD4 +/CD8 +cells were more in HEOLP than that in ROLP(P<0.05).Conclusion:There are defects of cellular immune function and increase of humoral immune in patients with OLP. The patients with different clinical types of OLP may have different immune fuction changes.

ObjectiveTo study the feasibility of RapidArc (RA) associated with active breath coordinator (ABC)for hepatocelluar carcinoma (HCC)radiotherapy comparing of three-dimensional conformal radiotherapy (3DCRT),intensity modulated radiotherapy (IMRT),RA treatment plans in different breath status.Methods12 HCC cases were selected.Three series CT scanning were completed in Free Breathing (FB),End Inspiration Hold (EIH) and End Expiration Hold (EEH) associated with ABC device.3DCRT,IMRT and RA (three 135° arcs) treatment plans were respectively designed on planning target volume (PTV) in different breath status.The dosimetric differences among 3 DCRT,IMRT and RA,among RA plans under different breath status were compared.ResultsThe PTV in FB was larger than in EEHand EIH (160.8 cm3,89.5 cm3,83.1 cm3,F=6.63,P=0.004). The conformity index and homogeneity index of RA plans were better than IMRT and 3DCRT ( 0.92,0.90,0.77,F =72.55,P =0.000 ;0.90,0.89,0.84,F =125.49,P =0.000 ) ;the V20,V30,V40 of normal liver in 3DCRT were higher than IMRT and RA (24％,20％,19％,F=3.56,P =0.032;13％,10％,10％,F=5.74,P =0.004;8％,5％,6％,F =3.72,P =0.027).The normal liver mean dose,V10,V20,V30,V40 of RA plans in FB were higher than in EEH and EIH ( 13.46 Gy,10.25 Gy,9.48 Gy,F =3.627,P =0.038 ;46％,35％,32％,F =2.96,P=0.066;24％,16％,16％,F=3.69,P=0.036;13％,8％,8％,F=4.28,P=0.022;8％,5％,5％,F =2.39,P =0.108 ).The duodenum D5 cm3 of RA in EEH was lower than in FB and EIH (8.78 Gy,19.35 Gy and 11.67 Gy,F =1.56,P =0.224 ).The mean monitor units for 3 DCRT,IMRT,RA was 254.06 MU,626.33 MU and 550.28 MU ( F =147.35,P =0.000 ),while the mean treatment time was 135 s,540 s and 130 s respectively (F =62.83,P =0.000).ConclusionsThe RapidArc applying three 135°arcs with ABC in HCC radiotherapy can achieve better PTV coverage than IMRT with fewer monitor units,shorter treatment time and sparing more normal liver.

Objective To research the feasibility of using three-dimensional CT (3DCT) associated with active breathing control (ABC) in determination of the individual internal tumor volume (ITV) for hepatocellular carcinoma (HCC) comparing the four-dimensional CT (4DCT).Methods After 4DCT scans of 15 HCC patients who had accepted TACE,completed the 3DCT scans associated with ABC in three ways of breathing:free breathing ( FB),end inspiration hold ( EIH),end expiration hold (EEH).4DCT images were sorted into 10 phases and the maximum intensity projection (MIP) images were constructed.The GTVs were manually contoured on 4DCT and 3DCT images (labeled as GTV0,GTV10.….GTV90,GTVMIP,,GTVFB,GTVEIH and GTVEEH).GTV0…GTV90,GTV0 and GTV50,GTV0,GTV20 and GTV50,GTVEIH and GTVEEH were respectively merged into IGTV1,IGTV2,IGTV3,IGTV4.The volume and geometry displacement of GTVs and IGTVs were compared.Results All patients were compatible with the ABC technique and completed the CT scans in two ways.The motion of diaphragm measured between 4DCT and 3DCT images was not significantly different ( 1.39 cm and 1.39 cm,t =-0.02,P =0.983 ),it was similar to the volume difference among GTV0,GTV20,GTV50,GTVEIH,GTVEEH and GTVFB (56.4,54.6,55.5,55.6,55.2,59.7 cm3,F =0.01,P =1.000 ).The comparison result of volume difference among IGTV1,IGTV2,IGTV3,IGTV4 and GTVMIP (77.9,71.4,73.4,72.3 and 66.3 cm3,F =0.02,P =1.000)were similar to the differences of geometry displacement in x,y and z axial among them (F =0.48,0.04,0.02,P =0.750,0.997,0.999,respectively).Conclusion The application of 3DCT associated with ABC in determination of the individual IGTV for HCC is feasible and safe comparing to 4DCT.