1.Combined therapy of implants internal fixation and Halo-vest external fixation for the treatment of subaxial cervical fracture-dislocation
Guanfeng YAO ; Xinjia WANG ; Bin LUO ; Weidong WANG ; Jican ZENG
Chinese Journal of Tissue Engineering Research 2013;(35):6351-6356
BACKGROUND:There is controversial in choosing the treatment method for the treatment of traumatic subaxial cervical fracture-dislocation and spinal cord injury.
OBJECTIVE:To evaluate the clinical effect of implant internal fixation and Halo-vest external fixation on the stability after treatment of subaxial cervical fracture-dislocation.
METHODS:A retrospective analysis was conducted on 17 patients with subaxial cervical fracture-dislocation in the Department of Orthopedics, the Second Affiliated Hospital of Shantou University Medical Col ege between January 2009 to December 2011, including 13 male patients and 4 female patients, the age was ranged from 21-65 years, average 41.6 years. There were six cases of high fal ing injury, three cases of crush injury and eight cases of traffic accident injury. The hospitalization time after injury was 2 hours to 5 days, average 2.5 days. Al the patients received Halo-vest external fixation under local anesthesia, then distraction gradual y, and received anterior decompression graft and titanium screw fixation under reduction. The treatment effect was evaluated
through Frankel classification and imaging examination.
RESULTS AND CONCLUSION:Al the patients were fol owed-up for 12-24 months, average 15.4 months. Normal anteraposterior X-ray film showed fracture reduction, the cervical vertebra restored to the normal
sequence and physiological curvature;CT showed graft fusion without internal fixation fracture and loosing;
according to Frankel classification, marked effect (decreased for 2 grade) in five cases, effective (decreased for 1
grade) in 10 cases, and ineffective in two cases. Implant internal fixation combined with Halo-vest external fixation is safe and reliable in the instability fixation of subaxial cervical fracture-dislocation, and can better restore the spinal sagittal alignment.
2.Experimental Study on the Mechanism of ACSL4 Inhibition of Sevoflurane-induced Neuronal Iron Death through the AMPK/mTOR Pathway
Cheng LIU ; Juan ZHAO ; Qian JIA ; Shengchun XIE ; Bin LUO ; Guanfeng WEI
Journal of Modern Laboratory Medicine 2024;39(6):67-72
Objective To investigate the role and mechanism of acyl-CoA syntbetase long chain family member 4(ACSL4)in Sevoflurane(Sev)induced neuronal cell damage.Methods Human neuroblastoma SH-SY5Y cells were used as the research object,and control group(dimethyl sulfoxide,10 μmol/L),Sev group and Sev+iron death inhibitor Ferrostatin-1(Fer-1,10 μmol/L)group were set up.CCK-8 method was used to detect cell activity in each group.4.1%Sev exposed postoperative cognitive dysfunction model was constructed in vitro and divided into Ctrol group,Sev group,Sev+si-NC group,Sev+si-ACSL4 group,and Sev+si-ACSL4+compound C group according to the transfection category.The contents of Malonaldehyde(MDA),4-hydroxynonenal(4-HNE),Glutathione(GSH)and Fe2+in each group were detected by colorimetry.The level of reactive oxygen species was detected using a 2',7'-dichlorofluorescein diacetate(DCFH-DA)fluorescent probe.Real time fluorescence quantitative PCR(qRT-PCR)was used to detect the mRNA expression of ACSL4,glutathione peroxidase 4(GPX4),and solute carrier family 7 member 11(SLC7A11).Protein immunoblotting was used to detect the expression of ACSL4,GPX4,adenosine 5'-monophosphate activated protein kinase(AMPK),phosphorylated(p)-AMPK,mammalian target of rapamycin(mTOR)and p-mTOR proteins.Results CCK-8 results showed that the cell viability of Sev group(0.41±0.11)was significantly lower than that of control group(0.98±0.07),and the cell viability of Sev+Fer-1 group(0.83±0.09)was significantly higher than that of Sev group(0.41±0.11),and the differences were statistically significant(t=7.572,5.118,all P<0.01).The levels of Fe2+,MDA,4-HNE,ROS and p-AMPK/AMPK ratios,as well as the mRNA and protein expression of ACSL4 in the Sev group cells,were higher than those in the Ctrol group(t=5.900,7.421,4.795,13.517,10.825,9.945,11.334),the GSH conten,p-mTOR/mTOR ratio,and mRNA and protein expression of SLC7A11 and GPX4 were lower than those in the Ctrol group(t=20.438,3.551,11.460,12.211,6.845,8.287),and the differences were statistically significant(all P<0.05)repectively.The levels of Fe2+,MDA,4-HNE,ROS,and p-AMPK/AMPK ratios,as well as the mRNA and protein expression of ACSL4 in the Sev+si-ACSL4 group,were lower than those in the Sev+si-NC group(t=3.818,3.164,3.054,4.465,13.088,7.918,9.737),the cell viability,GSH content,p-mTOR/mTOR ratio,and protein expression of SLC7A11 and GPX4 were higher than those in the Sev+si-NC group(t=2.912,7.248,7.574,20.092,5.915),and the differences were statistically significant(all P<0.05),respectively.The cell viability,GSH content,SLC7A11,and GPX4 protein expression in the Sev+si-ACSL4+compound C group were lower than those in the Sev+si-ACSL4 group(t=4.435,8.521,4.522,8.767),while the levels of Fe2+,MDA,4-HNE,and ROS were higher than those in the Sev+si-ACSL4 group(t=10.046,4.004,2.957,3.752),and the differences were statistically significant(all P<0.05).Conclusion Inhibiting ACSL4 expression attenuates Sev-induced iron death in SH-SY5Y cells by activating the AMPK/mTOR signaling pathway.
3.Therapeutic mechanism of Shenbing Decoction Ⅲ for renal fibrosis in chronic kidney disease: a study with network pharmacology, molecular docking and validation in rats.
Guanfeng LUO ; Huaxi LIU ; Bei XIE ; Yijian DENG ; Penghui XIE ; Xiaoshan ZHAO ; Xiaomin SUN
Journal of Southern Medical University 2023;43(6):924-934
OBJECTIVE:
To observe the effect of Shenbing Decoction Ⅲ for improving renal function and pathology in rats with 5/6 nephrectomy and analyze its therapeutic mechanism for renal fibrosis in chronic kidney disease using network pharmacology combined with molecular docking.
METHODS:
Forty male SD rats were randomized into two groups to receive two-staged 5/6 nephrectomy (n=30) or sham operation (n=10), and 2 weeks after the final operation, serum creatinine level of the rats was measured. The rats with nephrectomy were further randomized into Shenbing Decoction Ⅲ group, losartan group and model group for daily treatment with the corresponding drugs via gavage starting at 1 week after 5/6 nephrectomy. After 16 weeks of treatment, serum creatinine and urea nitrogen levels of the rats were measured, and HE staining and Western blotting were used to examine the changes in renal pathology and fibrosis-related factors. Network pharmacology combined with molecular docking study was performed to explore the therapeutic mechanism Shenbing Decoction Ⅲ against renal fibrosis in chronic kidney disease, and Western blotting was used to verify the expressions of the core targets.
RESULTS:
Compared with those in the model group, the rats receiving 5/6 nephrectomy and Shenbing Decoction Ⅲ treatment showed significantly reduced serum creatinine and urea nitrogen levels, lessened renal pathologies, and improvement of the changes in epithelial mesenchymal transition-related proteins. Network pharmacological analysis showed that the main active ingredients of Shenbing Decoction Ⅲ were acacetin, apigenin, eupatilin, quercetin, kaempferol and luteolin, and the key targets included STAT3, SRC, CTNNB1, PIK3R1 and AKT1. Molecular docking study revealed that the active ingredients of Shenbing Decoction Ⅲ had good binding activity to the key targets. Western blotting showed that in rats with 5/6 nephrectomy, treatment with Shenbing Decoction Ⅲ obviously restored the protein expression of STAT3, PI3K, and AKT in renal tissue.
CONCLUSION
Shenbing Decoction Ⅲ can reduce renal injury induced by 5/6 nephrectomy in rats, and its therapeutic effects are mediated possibly by its main pharmacologically active ingredients that alleviate renal fibrosis via modulating multiple targets including STAT3, PIK3R1, and AKT1.
Male
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Animals
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Rats
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Rats, Sprague-Dawley
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Molecular Docking Simulation
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Network Pharmacology
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Creatinine
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Renal Insufficiency, Chronic/drug therapy*
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Fibrosis
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Urea