This paper is to establish a three-dimensional finite element model (3D-FEM) of pelvic floor levator ani muscles in an old healthy women. We acquired the image data of the pelvic bones and pelvic floor muscles from CT and MRI scanning in a non-pregnant old healthy female volunteers. The 3-D reconstruction and mesh optimization of the whole pelvic bones and muscles with application of image processing software Mimics12.0 and Geomagic9.0 were obtained. Then we built the 3D-FEM of the musculoskeletal system of the pelvic bones and levator ani muscles with Ansys11.0 software. We obtained an accurate 3D-FEM of pelvic bones and levator ani muscles in the older healthy woman. The results showed that it was reliable to build 3D-FEM with CT and MRI scanning data and this model could vividly reflect the huge space anatomy of the real pelvic floor levator ani muscles. It avoids the defects to gain the model from the body of anatomical specimens in the past. The image data of model are closer to vivisection, and the model is more conducive to the latter finite element analysis.
Female ; Finite Element Analysis ; Humans ; Imaging, Three-Dimensional ; Magnetic Resonance Imaging ; Middle Aged ; Muscle, Skeletal ; anatomy & histology ; diagnostic imaging ; Pelvic Floor ; anatomy & histology ; diagnostic imaging ; Tomography, X-Ray Computed ; methods

Objective:To explore the effect of modified Simiao Yong'an Decoction combined with conventional western medicine on lower limb hemodynamics in patients with low-risk diabetes foot (DF).Methods:This retrospective cohort study included 70 patients with infectious diabetic foot, between January 2015 and May 2019, and they were divided into control group and study group, with 35 in each group. The control group was treated with conventional western medicine, while the study group was treated with modified Simiao Yong'an Decoction on the basis of the control group. Both groups were treated for 4 weeks and followed up for 1 year. The levels of basic fibroblast growth factor (bFGF) and VEGF were detected by ELISA, the levels of blood viscosity, fibrinogen and HbAlc were detected by automatic hemorheological analyzer, the dorsal artery of foot was detected by color Doppler ultrasound, the diameter and blood flow velocity of dorsal artery of foot were recorded, and the conduction velocity of sural nerve and common peroneal nerve were detected by electromyography for recurrence rate calculation. And the clinical response rates were evaluated.Results:The total clinical response rate was 94.3% (33/35) in the study group and 77.1% (27/35) in the control group, and there was significant difference between the two groups ( χ2=4.20, P=0.040). After treatment, the bFGF [(177.15±7.96)ng/L vs. (158.87±7.21)ng/L, t=10.00], VEGF[(53.77±4.15)ng/L vs. (45.44±4.92)ng/L, t=7.66] levels in the study group were significantly higher than those in the control group ( P<0.01). After treatment, the whole blood viscosity [(3.84±0.86)mPa?s vs. (4.56±0.99)mPa?s, t=3.25], fibrinogen [(3.59±0.78) g/L vs.(4.23±0.97)g/L, t=3.04]and HbAlc[(9.61±1.31)% vs. (10.85±1.82)%, t=3.27] levels in the study group were significantly lower than those in the control group ( P<0.01). After treatment, the sural nerve conduction velocity [(39.42±5.11)m/s vs. (34.22±4.52)m/s, t=4.51], common peroneal nerve conduction velocity [(40.94±4.22)m/s vs. (35.52±3.72)m/s, t=5.70], blood vessel diameter [(2.21±0.60)mm vs. (1.92±0.52)mm, t=2.16], while the blood flow velocity [(55.89±5.84)cm/s vs. (52.95±5.85)cm/s, t=2.10] in the study group were significantly higher than those in the control group ( P<0.05). During the follow-up, the recurrence rate was 21.21% (7/33) in the study group and 29.63% (8/27) in the control group. with out statistical significance between the two groups ( χ2=0.20, P=0.653). Conclusion:Modified Simiao Yong'an Decoction combined with conventional western medicine can improve lower limb blood circulation and nerve conduction velocity of low-risk DF patients, promote rehabilitation and reduce recurrence.

Objective:To investigate the regulatory effect of WNT1-inducible signaling pathway protein 2(WISP2)on macrophage polarization in palmitic acid(PA)and lipopolysaccharide(LPS)-induced inflammation.Methods:The macrophage cell line RAW264.7 was treated with different concentrations of WISP2 protein, and cell viability was determined by means of luminescence assay using Cell-Titer Glo to determine the concentration of WISP2.The cells were divided into control group, palmitic acid group, palmitic acid combined with different concentrations of WISP2 group(10 μg/L and 100 μg/L)and lipopolysaccharide group, lipopolysaccharide combined with different concentrations of WISP2 group(10 μg/L and 100 μg/L). mRNA expression of M1 and M2 macrophages phenotype of each group were detected by real-time quantitative polymerase chain reaction.The protein expression of important inflammatory factors, TNF-α and IL-6, were evaluated by ELISA.Results:Compared with the control group, both 10 μg/L and 100 μg/L WISP2 groups had no effect on the activity of RAW264.7 cells, but significantly up-regulated the expression of various inflammatory factors, including Tnfα(1.877±0.039, 2.202±0.034, F=309.7, P<0.001), Il6(1.418±0.056, 1.506±0.059, F=81.39, P<0.001), Mcp1(1.620±0.014, 1.982±0.125, F=71.45, P<0.001), Ccl3(1.892±0.118, 1.942±0.132, F=32.93, P<0.001), and iNos(1.691±0.201, 1.548±0.090, F=13.60, P<0.05). mRNA in macrophages, and significantly down-regulated the expression of anti-inflammatory factors, including Tgfβ(1.376±0.025, 2.152±0.107, F=1.846, P<0.05), CD206(2.123±0.031, 3.139±1.663, F=8.037, P<0.05), Il4(2.098±0.464, 2.494±0.141, F=48.68, P<0.01), and Il10(1.303±0.216, 1.574±0.274, F=5.774, P<0.05)mRNA, causing M1 type macrophage polarization.Compared with the control group, 100 μmol/L palmitic acid could mildly but significantly increase the expression of inflammatory factors such as TNF-α and IL-6 at the transcriptional and protein levels.Compared with palmitic acid stimulation alone, the combination of palmitic acid and WISP2 further promoted the protein expression of macrophage inflammatory factors TNF-α[(589.4±17.0)ng/L, (692.6±83.4)ng/L, F=56.38, P<0.05], IL-6[(15.13±1.14)ng/L, (13.33±1.22)ng/L, F=23.32, P<0.001]and the mRNA expression of chemokines Mcp1(160±9.796, 140±18.91, F=141.1, P<0.0001)and C cl3(17.76±1.92, 14.41±1.27, F=125.2, P<0.0001). Compared with the control group, 100 μg/L lipopolysaccharide strongly stimulated the expression of inflammatory factors such as TNF-α[(3444±423)ng/L, F=71.20, P<0.0001]and IL-6[(497.0±41.2)ng/L, F=63.50, P<0.0001]in macrophages at the protein level.Compared with lipopolysaccharide stimulation alone, the combination of lipopolysaccharide and WISP2 further significantly up-regulated the mRNA expression of chemokines Mcp1(106.8±8.7, 118.7±4.6, F=251.5, P<0.0001)and Ccl3(35.3±12.5, 116.4±4.5, F=160.1, P<0.0001). Conclusions:The adipokine WISP2 can promote M1 macrophage polarization in palmitic acid and lipopolysaccharide-induced inflammation, and it had distinct regulation in macrophage polarization under different inflammatory response conditions.

T cell immunoglobulin and ITIM domain (TIGIT) is a novel immune checkpoint that has been considered as a target in cancer immunotherapy. Current available bioassays for measuring the biological activity of therapeutic antibodies targeting TIGIT are restricted to mechanistic investigations because donor primary T cells are highly variable. Here, we designed a reporter gene assay comprising two cell lines, namely, CHO-CD112-CD3 scFv, which stably expresses CD112 (PVRL2, nectin-2) and a membrane-bound anti-CD3 single-chain fragment variable (scFv) as the target cell, and Jurkat-NFAT-TIGIT, which stably expresses TIGIT as well as the nuclear factor of activated T-cells (NFAT) response element-controlled luciferase gene, as the effector cell. The anti-CD3 scFv situated on the target cells activates Jurkat-NFAT-TIGIT cells through binding and crosslinking CD3 molecules of the effector cell, whereas interactions between CD112 and TIGIT prevent activation. The presence of anti-TIGIT mAbs disrupts their interaction, which in turn reverses the inactivation and luciferase expression. Optimization and validation studies have demonstrated that this assay is superior in terms of specificity, accuracy, linearity, and precision. In summary, this reliable and effective reporter gene assay may potentially be utilized in lot release control, stability assays, screening, and development of novel TIGIT-targeted therapeutic antibodies.