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Objective To explore the value of ultrasound elastography in the non-invasive monitoring of liver elasticity of stable recipients at different stages after liver transplantation. Methods Clinical data of 73 stable recipients after liver transplantation were collected. According to the time after liver transplantation, all patients were divided into the early group (n=25) and medium-to-long group (n=48). In addition, 38 healthy subjects were assigned into the control group. The ultrasound indexes and liver function indexes were statistically compared among each group. The ultrasound elastography indexes of liver and spleen were analyzed, and their correlation with liver function indexes was analyzed. Results Compared with the control group, the ultrasound indexes, alanine aminotransferase (ALT), γ-glutamyl transferase (GGT) and alkaline phosphatase (ALP) levels were significantly increased in the early group (all P < 0.05), and the ultrasound indexes in the medium-to-long group were significantly increased, whereas the GGT level was significantly decreased (all P < 0.05). Compared with the early group, the right oblique diameter of liver, ALT, GGT and ALP levels were significantly decreased in the medium-to-long group (all P < 0.05). Compared with the control group, the sound touch elastography (STE) and sound touch quantify (STQ) values of liver and STE value of spleen in the early group and medium-to-long group were significantly increased (all P < 0.05). Compared with the early group, the ultrasound elastography indexes of liver and spleen in the medium-to-long group were remarkably decreased (all P < 0.05). The ultrasound elastography indexes of liver were weakly correlated with the ALT, aspartate aminotransferase (AST) and GGT levels, significantly correlated with ALP level. The STE value of spleen was weakly correlated with the ALP level. The STE value of liver was significantly correlated with the STQ value of liver. The STE and STQ values of liver were weakly correlated with the STE value of spleen. Conclusions The characteristics of liver elasticity in stable recipients after liver transplantation are various among different stages. Persistent monitoring of liver elasticity may provide a novelnon-invasive monitoring method during follow-up after liver transplantation.
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Objective To observe the effect of the method of warming kidney and dredging collaterals on the clinical effect and the content of urine C5b-9 in patients with idiopathic membranous nephropathy with spleen kidney yang deficiency and blood stasis. Methods A total of 60 idiopathic membranous nephropathy patients with spleen kidney yang deficiency and blood stasis type were randomly divided into the conventional western medicine treatment group (control group), Jingui-Shenqi pill and Taohong-Siwu decoction plus conventional western medicine treatment group (treatment group), 30 cases in each group. The Scr was detected by deproteinized alkaline picric acid method, and BUN was detected by rate method, and serum albumin (ALb) was detected by bromocresol green dye binding method, and 24 hours urinary protein was measured by pyrogallol red colorimetry, and the double antibody sandwich ELISA method was used for detection of urinary C5b-9. Results The Jingui-Shenqi pill combined with Taohong-Siwu decoction plus conventional western medicine treatment has obvious curative effect on patients. The total effective rate was 83.3 in the treatment group (25/30), and the control group was 60％ (18/30). After treatment, the Alb (33.5 ± 7.95 g/L vs. 28.8 ± 6.10 g/L, t=2.569) in the treatment groupwas significantly higher than that in the conventional treatment group (P<0.01). While the 24 h urine protein (2.40 ± 0.92 g/24 h vs.3.60 ± 2.3 g/24 h, t=2.653), the contents of C5b-9 in urine(42.5 ± 17.50 ng/mg vs.71 ± 25.2 ng/mg, t=5.088) in the treatment group were significantly lower than those in the conventional treatment group (P<0.01). Conclusions The method of warming kidney and dredging collaterals can improve the clinical symptoms, improve serum albumin level, reduce the 24 hour urine protein and urinary C5b-9 content of idiopathic membranous nephropathy of spleen and kidney yang deficiency and blood stasis type.
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Objective To explore the molecular mechanism of Yishen Huoxue prescription in delaying the development of renal fibrosis by regulating the microRNA-126/vascular endothelial growth factor-Notch (miR-126/VEGF-Notch) signaling pathway. Methods Ninety male Sprague-Dawley (SD) rats were randomly divided into sham operation group (sham group), unilateral ureteral obstruction (UUO) model group, losartan group (50 mg·kg-1·d-1) and high, medium and low doses Yishen Huoxue prescription group (25.2, 12.6, 6.3 mL/kg). Each treatment group began to administer drugs by gavage on the day when UUO modeling was finished until the end of the experiment. Left renal tissues of rats were harvested after 7, 14 and 21 days postoperatively. The pathological changes of renal tissue were observed after hematoxylin and eosin (HE) and Masson staining under the microscope, and the renal fibrosis score was calculated. The mRNA expressions of renal tissues miR-126, VEGFA, vascular endothelial growth factor receptor-2 (VEGFR-2), Notch1 were detected by reverse transcription-polymerase chain reaction (RT-PCR). Results① Pathology results: the kidney tissue of sham group was normal. In UUO model group, renal tubules expanded and inflammatory cells in renal interstitium increased; renal tubulointerstitial fibrosis could be seen 7 days after operation, and the degree of fibrosis was gradually increased with time. The renal fibrosis score at each time point after operation in UUO model group was significantly higher than that in sham group. Compared with UUO model group, each treatment group were improved the degree of renal swelling and atrophy of renal parenchyma; the score of renal fibrosis were significantly decreased in the middle and high doses Yishen Huoxue prescription group and losartan group at the 7th day after operation (1.00±1.00, 0.91±0.58, 1.01±0.58 vs. 2.00±0.00,all P < 0.01); but there was no significant difference between low dose Yishen Huoxue prescription group and UUO model group. ② RT-PCR results: Compared with sham group, the mRNA expressions of miR-126, VEGFA, VEGFR-2 and Notch1 in renal tissues were significantly increased at each time point after operation in UUO model group. Compared with the UUO model group, the mRNA expressions of miR-126, VEGFA, VEGFR-2 and Notch1 in renal tissue of 7 days postoperatively in the middle and high doses Yishen Huoxue prescription group and the losartan group were significantly increased [miR-126(2-ΔΔCt):0.465±0.067, 0.639±0.092, 0.404±0.069 vs. 0.132±0.021; VEGFA(2-ΔΔCt): 0.024±0.005, 0.027±0.007, 0.023±0.006 vs. 0.014±0.006; VEGFR-2(2-ΔΔCt):0.021±0.007, 0.023±0.008, 0.019±0.007 vs. 0.012±0.004; Notch1(2-ΔΔCt):0.017±0.004, 0.020±0.005, 0.018±0.005 vs. 0.007±0.004; all P < 0.05]; compared with the losartan group, the mRNA expressions of each index in the middle and high doses Yishen Huoxue prescription group were increased at all the time points, but there was no significant difference between them (all P > 0.05). There was no significant difference in mRNA expression of each index between low dose Yishen Huoxue prescription group and UUO model group. Conclusions The medium and high doses of Yishen Huoxue prescription can effectively antagonize renal fibrosis. Yishen Huoxue prescription may use up-regulation the signaling pathways of miR-126/VEGF-Notch to mediate renal microvascular newly born, eventually to improve renal microvascular damage and delay the development of renal fibrosis progression.
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Objective To observe the influence of Yishen Huoxue prescription on expressions of vascular endothelial growth factor-2 (VEGF-2) and Notch4 in rats with unilateral ureter obstruction (UUO).Methods Ninety-six male Sprague-Dawley (SD) rats were randomly divided into sham operation group, UUO model group, losartan group, and Yishen Huoxue group, with 24 rats in each group. The rat models of renal fibrosis were reproduced by using UUO method, and they were treated by Yishen Huoxue herb prescription or losartan intra-gastric administration respectively for therapeutic interference. In the sham operation group, simply the unilateral ureter was separated from the near-by tissues and then the abdomen incision was stitched. The blood was collected on 7, 14 and 21 days after operation for determination of blood urea nitrogen (BUN) and serum creatinine (SCr). Kidney tissues specimens were harvested, and microvessed desity (MVD), the protein expression levels of VEGF-2 and Notch4 in the kidney were detected. Results Compared with UUO model group, BUN and SCr in both treatment groups were significantly decreased with significant difference (allP 0.05). The expression levels of VEGF-2 and Notch4 in sham operation group at each time point were in normal range; with the time extension, the expressions of VEGF-2 and Notch 4 protein were slightly increased, and the descent degree of MVD in kidney was aggravated gradually in UUO model group. The VEGF-2 and Notch4 protein expressions in kidney tissues of the two treatment groups were significantly increased compared with those in model group, the expression of VEGF-2 (A value) reached the highest level on the 14th day after operation (VEGF-2 levels in sham operation, model, Yishen Huoxue Herb prescription and losartan groups were 0.18±0.09, 4.73±0.72, 7.27±1.35, 8.11±1.64 on the 14th day, and they were 0.19±0.07, 4.05±0.88, 7.10±1.12,7.79±1.53 on 21th day, respectively), later representing a tendency of slight decrease, and Notch4 protein expression (A value) peaked on the 21st day (0.62±0.35, 9.08±1.52, 14.48±3.14, 15.54±3.38 in above four groups, allP < 0.05). The degrees of decrease in renal MVD (microvessel/mm2) in the both treament groups was significantly less than that in model group (45.20±6.25, 25.34±4.67, 30.23±4.20, 32.26±4.36 on the 7th day, 46.07±6.22, 20.06±3.98, 26.88±4.36, 26.95±4.11 on the 14th day, 45.18±6.10, 17.79±3.72, 21.71±4.25, 21.68±4.41 on the 21st day in above four groups,P < 0.05 orP < 0.01). There were no statistically significant differences in the above values between Yishen Huoxue herb group and losartan group.Conclusion Traditional Chinese medicine benefiting qi for activating blood circulation therapy (Yishen Huoxue herb prescription) has obvious improving effect on the microvascular injury in the process of renal fibrosis that possibly is related closely to the drug regulation on VEGF/Notch signaling cascade.
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<p><b>OBJECTIVE</b>To compare the differences of the efficacy and adverse reaction of Oxaliplatin (L-OHP) treatment to oral squamous cell carcinoma (OSCC) at four different daily time points, and to analyze the characteristics of circadian rhythms.</p><p><b>METHODS</b>Seventy-five nude mice were placed under 12h light and 12h dark cycles. Human OSCC cell line BcaCD885 was inoculated on the cheek of nude mice to establish a nude mice model of OSCC. After 3 weeks, mice were divided into 5 groups (4 experimental groups and 1 control group), with 15 in each group. L-OHP (17 mg x kg(-1)) was injected intravenously at 4 different time points during a period of 24 h, including 4 hours after lights on JHALO), 10 HALO, 16 HALO and 22 HALO for 4 experimental groups. The control group received normal saline of the same volume as that of L-OHP. The efficacy (tumor inhibition rate and survival time) and adverse reaction (body weight, white blood cell and perianal swelling) were observed after administration. The circadian rhythms of the efficacy and adverse reaction were examined by cosine analysis.</p><p><b>RESULTS</b>L-OHP injected at 4, 16 and 22 HALO had great tumor inhibition rates, however, only 16 and 22 HALO groups significantly prolonged survival time of mice. The adverse reactions at 4 and 10 HALO were significantly severer than that of 16 and 22 HALO. Cosine analysis showed survival time, body weight and white blood cell counts had significant circadian rhythms. Mice received L-OHP at 14.88 HALO had the longest survival time.</p><p><b>CONCLUSION</b>The time factor should be considered in L-OHP chronchemotherapy of patients with OSCC in order to increase the efficacy, decrease the adverse reaction of the drug and to improve the life quality of patients with OSCC.</p>