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Polyphyllin Ⅰ(PPⅠ)and polyphyllin Ⅱ(PⅡ)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPⅠ and PⅡ exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepa-totoxicity of PPⅡ and PⅡwas associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the choles-terol synthesis,selected as the potential targets,were confirmed by the molecular docking,the over-expression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPⅠ could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPⅠ-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.
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Objective To observe the effect of Chinese herbal fumigation combined with CPM promote the function recovery after Postoperative Patellar Fracture. Methods Eighty patients with patellar fracture were randomly divided into treatment group (40 cases) and control group (40 cases). The control group was treated with CPM. The treatment group was treated with Chinese Herbal Fumigation and CPM. After 8th weeks, the clinical curative effect, knee range of motion and KSS knee score were observed and compared. Results The effect rate of the treatment group was 87.5% (35/40), and the control group was 65.0% (26/40). The difference was statistically significant (χ2=5.591, P<0.01). After treatment, the range of motion of knee joint (138.38°± 7.82°vs. 0.29°± 7.83°, t=10.338), KSS knee function score (88.38 ± 9.52 vs. 3.46 ± 9.36, t=2.330) of the treatment group were higher than those in the control group (P<0.01 or P<0.05). Conclusions The Chinese medicine fumigation combined with CPM functional exercise could accelerate the recovery of knee function and reduce the complications of fracture after patellar fracture.
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AIM To investigate the effects of Sanqi Huayu Oral Liquid (Notoginseng Radix et Rhizoma,Corydalis Rhizoma) on femoral shaft comminuted fracture caused by trauma in perioperative period of high-risk groups.METHODS One hundred and twenty patients meeting the inclusion criteria were randomly and equally divided into treatment group and control group.The control group was treated by low molecular weight heparin calcium injection,while the treatment group was additionally given Sanqi Huayu Oral Liquid.Two groups' levels of serum IL-6,TNF-α and D-D were detected on pre-operation and the 1 st,3rd,7th after operation,respectively.Additionally,the adverse drug reactions were also observed.RESULTS There were no statistically significant differences in the levels of serum IL-6,TNF-α and D-D between the two groups before operation.The first day after operation,the levels of serum IL-6,TNF-α and D-D between the two groups showed increasing trends,which had similar elevated levels without statistically significant differences.The third day after operation,the levels of serum IL-6,TNF-α and D-D between the two groups presented downward trends,but those in the treatment group were decreased more markedly with statistically significant differences.Furthermore,the seventh day after operation,the levels of serum IL-6,TNF-α and D-D between the two groups were lower than those before the operation,and these indices in the treatment group were lower than those in the control group with statistically significant differences.CONCLUSION Sanqi Huayu Oral Liquid can not only effectively reduce the levels of serum IL-6,TNF-α and D-D in perioperative period of high-risk groups,but also prevent the formation of deep vein thrombosis.
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Objective Evaluation of the effect of manual reduction with small external fixation on the treatment of elderly Barton fractures.Methods A total of 244 elderly patients with Barton fractures were divided into conservative group (n=126) and operation group (n=118) according to random number table. The conservative group was treated by with manual reduction with small external fixation, and the operation group was treated with open reduction and internal fixation. The complications of the patients, the time of fracture healing, hospitalization time and treatment cost were recorded.The wrist function was evaluated by PRWE wrist score system and Wrightington wrist function score system.The clinical efficacy was evaluated by Gartland-Werley Colles fracture evaluation method.Results The excellent and good effect rate was 91.3% (115/126) in the conservative group and 97.5% (115/118) in the operation group. There was no significant difference between the two groups(χ2=0.857,P=0.354). One year, 6 months, 3 months and 6 weeks after treatment, in the conservative group, the PRWE score (10.4 ± 7.9, 19.1 ± 8.0, 40.5 ± 7.8, 55.7 ± 8.1vs. 80.8 ± 8.2,F=113.665), wrightington score (8.2 ± 3.7, 13.2 ± 4.0, 21.4 ± 3.9, 26.3 ± 4.2vs. 30.1 ± 4.2,F=121.348) were significantly lower than those before treatment (P<0.01). And in the operation group, the PRWE score (10.2 ± 7.8, 15.0 ± 8.0, 26.5 ± 8.0, 44.7 ± 8.2vs. 79.6 ± 8.6,F=81.411), Wrightington score (8.1 ± 3.8, 12.1 ± 4.0, 16.5 ± 4.0, 20.6 ± 4.3vs. 29.8 ± 4.6,F=69.113) were significantly lower than those before treatment (P<0.01). But there was no significant difference in PRWE score and Wrightington scores between the two groups after treatment (t=0.149, 0.104,P=0.881, 0.917, respectively). In the conservative group, the hospitalization time (5.28 ± 2.10 dvs. 12.8 ± 2.21d,t=25.260) was significantly shorter than that of the control group (P<0.01), and the treatment cost (3.26 ± 0.93 thousandvs. 28.66 ± 1.04 thousand,t=200.369) was significantly lower than that in the control group (P<0.01). The overall incidence of complication was 8.7% (11/126) in the conservative group and 17.8% in the surgery group (21/118). There was significant difference between the two groups(χ2=4.396,P=0.036).Conclusions The manual reduction with small splint external fixation was simple, low cost, small trauma, short hospitalization time, and less complications.