The changes of[Ca~(2+)]and metabolism of lipid in human monocyte-macrophages as inter- acted with glycosylated LDL(glc-LDL)were observed.The intracellular[Ca~(2+)]was higher than that of LDL(P

Objective To investigate the influence of retinoic acid receptor (RAR-α,RAR-β and RAR-γ)-mediated all-trans retinoic acid (ATRA) on renal tissue cell proliferation and apoptosis in rats with diabetic nephropathy,and to analysze the possible mechanism. Methods Male SD rats were randomly divided into normal control group (group N,n=10) and diabetic model group (n=20).Diabetes was induced by streptozotocin(STZ) injection.After successful modeling,the model rats were randomly divided into diabetes group (group D,n=10) and ATRA treatment group (group T,n=10).Rats in group T received ATRA 10 mg·kg-1·d-1 by gavage from the 2nd day of successful modeling for 8 or 12 weeks,meanwhile group N and group D received same volume distilled water.In each group,5 rats were sacrificed respectively at the 8th week or the 12th week,then biochemical markers were measured and kidney pathology was examined.Apoptosis index(AI)of renal tissue cells of each group was tested by TUNEL.The expressions of RAR-α,RAR-β and RAR-γ in renal tissues were tested using indirect immunofluorescence.The expressions of type Ⅰ collagen and laminin as proliferation indicators,along with Smac and caspase-3 as the correlated factors of apoptosis in renal tissue of each group were tested by immunohistochemistry staining.The mRNA expressions of Smac and caspase-3 were tested using real-time fluorescence quantitative PCR. Results Compared with group N,24 h urine protein,serum creatinine,blood urea nitrogen,ratio of kidney weight/body weight increased significantly (P＜0.05,respectively) in group D,and further increased with observation time.Compared with the group D,24 h urine protein and ratio of kidney weight/body weight decreased in group T (P＜0.05,respectively).Compared with group D,the group T presented minor pathological changes.TUNEL assay indicated that compared with group N,the group D showed an obvious increase in renal cell apoptosis in time-dependent manner,and the group T showed a decrease compared with the group D (P＜0.01,respectively).Compared with group N,the expression of RAR-α and RAR-β positive cells number in group D were decreased (P＜0.01,respectively).Compared with group D,the expression of RAR-α and BAR-β positive cells number in group T increased (P＜0.01,respectively).Renal tissues of each group did not show expressions of RAR-γ.After 12 weeks,compared with group N,expressions of type-Ⅰ collagen,laminin,Smac and caspase-3 protein in the glomerular mesangial area and basement membrane of renal tissues in group D increased significantly (P＜0.01,respectively),and enhanced with time.Compared with the group D,expressions of type Ⅰ collagen,laminin,Smac and caspase-3 protein in group T decreased (P＜0.01,respectively).Compared with the group N,group D had an obvious increase in the mRNA expressions of Smac and caspase-3,and a significantly decrease in group T (P＜0.01,respectively). Conclusions ATRA may prevent the cell proliferation and apoptosis in diabetic renal tissue through its receptor-mediated pathway,and may protect rats against diabetic nephropathy.

ObjectiveTo study the reasons and mechanism of cardiomyocyte apoptosis in chronic heart failure by using Losartan and to provide a theoretical basis for the treatment of chronic heart failure. Methods The models of chronic heart failure were produced by injecting Adriamycin and Losartan as intervention agents, the expression of apoptotic protein Bax, Bcl-2 and channel protein ERK1, JNK1 and P38MAPK were detected by immunohistochemistry and RT-PCR.Cardiomyocyte apoptosis and myocardial ultrastructure are detected by transmission electron microscopy and TUNEL staining.Results Compared with the model group of heart failure, after Losartan treatment, the ultra structure of myocardial cells were significantly improved, Apoptosis index was decreased significantly (P <0.01), The level of Bax and JNK1 decreased (Bax χ~2=6.6149, P=0.0078; JNK1 q=22.0156,P<0.01). However, the expressions of ERK1 and Bcl-2 were significantly increased (ERK1 q=15.3514,P<0.01;Bcl-2 χ~2=6.81,P=0.0074).Conclusion The effect of Losartan on chronic heart failure is related closely with the pathway of ERK1 and JNK1, and no p38 MAPK pathway.

AIM:Toinvestigatewhetherautophagyisup-regulatedwhenresveratrol(Res)inducesapoptosis in chondrosarcoma , and to study the effects of autophagy inhibitor combined with Res on chondrosarcoma .METHODS:SW1353 cells were divided into 4 groups: control group, Res group, 3-methyladenine (3MA) group, and Res +3MA group.Electron microscopy was used to observe the autophagyosomes in control group and Res group .At the same time, the viability of the cells in the 4 groups was detected by CCK-8 assay.TUNEL staining and Western blotting (for determi-ning the levels of cleaved caspase-3, Bax and Bcl-2) were used to reflect levels of apoptosis in all groups .The expression of autophagy-related proteins Beclin 1, LC3-Ⅱ and p62 was detected by Western blotting .RESULTS: Exposure of the cells to Res resulted in a decrease in cell viability and an increase in the level of apoptosis ( P<0.05 ) .Compared with control group, the level of apoptosis was increased but the autophagy was decreased (P <0.05).Compared with Res group, the cell viability and the level of autophagy were decreased and the level of apoptosis was increased ( P<0.05 ) . CONCLUSION:Resveratrol induces apoptosis and autophagy , and inhibition of autophgay enhances resveratrol-induced apoptosis in chondrosarcoma .

Objective To investigate the effect and mechanism of all-trans retinoic acid (ATRA) on the cyclosporin (CsA)-induced proliferation and apoptosis of glomerular mesangial cells in rat models. Methods The glomerular mesangial cells induced by different doses of CsA were treated with different doses of ATRA. MTT assay was carried out to detect cell proliferation. Hoechst 33258 fluorescent staining was adopted to observe the morphology of the apoptotic cells. Flow cytometry was conducted to detect the cellular apoptosis rate. Immunofluorescent staining was employed to quantitatively measure the expression level of mitochondria-derived pro-apoptotic Smac protein. Results Compared with the control group, administration of CsA at a dose of 0.5 μg/mL and above could suppress cellular proliferation, and use of CsA at a dose of 1.0 μg/mL and above could induce cellular apoptosis. The expression level of Smac protein was significantly up-regulated by CsA administration with a dose and time dependence (all P<0.05).Compared with the CsA group, combined administration of CsA and ATRA exerted a more significant inhibitory effect on cellular proliferation. Supplement of ATRA could significantly inhibit glomerular mesangial cellular apoptosis induced by CsA and down-regulate the expression of Smac protein with a dose dependence (both P<0.05). Conclusions CsA can inhibit cellular proliferation, induce cellular apoptosis and up-regulate the expression of Smac protein of glomerular mesangial cells. ATRA is capable of suppressing glomerular mesangial cellular apoptosis induced by CsA, which is probably mediated by the Smac signaling pathway.

Objective:To propose a monosegment thoracic and lumbar fracture dislocation (mTLFD) classification, and to evaluate its reliability and clinical application.Methods:All of 298 cases of thoracic and lumbar fracture dislocation who received surgical management in our hospital from January 2014 to December 2019 were retrospectively analyzed. 123 cases were included in the study according to inclusion and exclusion criteria. mTLFD classification was proposed based on the imaging characteristics: type I (intervertebral disc injury mainly) and type II (vertebral burst fracture mainly). The type II was classified based on distribution of injury segment: type IIa (T 11 and above) and Ttype IIb (below T 11). Six spinal surgeons (3 residents, 3 associate chief physicians) were selected to classify the 123 cases according to preoperative imaging data, and to perform reliability test of each type. The repeatability and reliability of the classification were evaluated by ICC index. Different management strategies were performedf or each type: type I was managed with posterior decompression interbody fusion and internal fixation; type IIa underwent posterior decompression and fixation, subtotal vertebral resection and fusion was performed if bony compromise was still present through intra-operative exploration. Type IIb underwent posterior decompression, posterolateral fusion and internal fixation on the first stage, while anterior subtotal vertebral resection and reconstruction was performed on the second stage if the bony compromise was still present based on post-operative CT examination. The American Spinal Injury Association (ASIA) grading of all patients was recorded, and the visual analogue scale (VAS), Oswetry disability Iindex (ODI) and local Cobb angle of each type was compared between pre-operation and final follow-up. Results:The average follow-up time of all patients was 10.4±1.8 months. The average repeatability and reliability ICC index of mTLFD of 3 residents and 3 deputy chief physicians were 0.926 and 0.964, respectively, and 0.746 and 0.907, respectively. The reliability ICC index of type I, type IIa and type IIb was 0.918, 0.947 and 0.962, respectively, and the repeatability ICC index was 0.930, 0.940 and 0.966, respectively. The neurological function recovery was obtained in 56 patients. The preoperative VAS of type I, type IIa and type IIb were 8.5±1.0, 8.4±1.0 and 8.3±0.9, and 2.0±1.1, 1.8±1.0 and 1.8±0.9 at the final follow-up (all P<0.001). The ODI of type I, type IIa and type IIb were 97.0%±2.1%, 97.1%±1.9% and 97.3%±2.1% before surgery, and 29.5%±6.8%, 27.0%±6.0% and 29.0%±6.7% at the final follow-up (all P<0.001). The local Cobb angles of type I, type IIa and type IIb were 20.9°±7.1°, 29.0°±9.1° and 26.4°±6.9° before surgery, and 12.5°±5.4°, 18.0°±9.1° and 13.1°±5.1° at the final follow-up (all P<0.001). Conclusion:The mTLFD classification proposed in this study has strong repeatability and reliability, and management strategy of each type have achieved satisfactory clinical efficacy, indicating that the classification has certain significance for management of thoracic and lumbar spine fracture dislocation.