OBJECTIVE To study the effects of bergapten in the treatment of liver fibrosis and its mechanism based on serum metabolomics. METHODS Forty mice were divided into normal control group （0.5% carboxymethyl cellulose sodium solution）， model group （0.5% carboxymethyl cellulose sodium solution）， and BP low-dose and high-dose groups （50， 100 mg/kg）， with 10 mice in each group. Except for the normal control group， the other three groups were all treated with carbon tetrachloride to induce liver fibrosis model； they were given relevant medicine/solution intragastrically， once a day， for consecutive 8 weeks. After the last medication， the levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum were detected， and liver pathological changes were observed； the expressions of α-smooth muscle actin （α-SMA） and Collagen Ⅰ were detected in liver tissue； the serum of the mice was collected for metabolomics analysis. RESULTS Compared with the model group， serum levels of ALT and AST and protein expressions of α-SMA and Collagen Ⅰ in liver tissue were decreased significantly in BP high-dose and low-dose groups （P＜0.05）， while liver fibrosis was improved significantly. Meanwhile， metabolomics analyses showed that there were a total of 175 serum differential metabolites in the BP high-dose group and model group， of which 18 substances were upregulated and 157 substances were downregulated； the main metabolic pathways involved in bergapten intervention were pyrimidine metabolism， butanoate metabolism， fatty acid synthesis， tyrosine metabolism， β-alanine metabolism， nicotinic acid and nicotinamide metabolism， glutathione metabolism， etc. CONCLUSIONS BP is effective in the treatment of liver fibrosis by regulating pyrimidine metabolism， butanoate metabolism， glutathione metabolism and so on in rats with liver fibrosis.

BACKGROUND:Irreducible femoral neck fracture was difficult to obtain anatomic reduction.As a new type of internal fixation,the femoral neck system is still blank for the treatment of non-anatomical reduced femoral neck fractures. OBJECTIVE:To explore the biomechanical stability of femoral neck system internal fixation under nonanatomical reduction in the treatment of femoral neck fractures based on finite element analysis. METHODS:CT data of the hip joint of a healthy female adult were obtained.Anatomical reduction of femoral neck fracture models with Pauwels angles of 30°,50°,and 70° were established using Mimics 21.0,Geomagic Wrap 2021,and SolidWorks 2020.The fracture proximal ends of the three anatomical reduction models were shifted upward by 2 mm along the fracture line,and three positive buttress models with different Pauwels angles were obtained.In the same way,three negative buttress models were acquired by shifting downward by 2 mm.SolidWorks 2020 was used to make the femoral neck system internal fixation,and the nine femoral neck fracture models were assembled with the femoral neck system.Then Ansys 19.0 was used for finite element analysis.The displacement distribution and maximum displacement,stress distribution and maximum stress of the femur and femoral neck system were recorded under 2100 N stress. RESULTS AND CONCLUSION:(1)When Pauwels angles were 30°,50°,and 70°,the maximum stresses of the femoral neck system appeared to be concentrated at the junction of the sliding hip screw and anti-rotation screw.The maximum femur stresses appeared to be concentrated in the medial cortex of the femur.The maximum displacement was concentrated at the upper of the femoral head and femoral neck system.(2)When Pauwels angles were 30° and 50°,the maximum displacement and maximum stress of the femoral neck system and femur were:negative buttress>anatomical reduction>positive buttress.(3)When Pauwels angle was 70°,the maximum displacement and maximum stress of the femoral neck system were:negative buttress>anatomical reduction>positive buttress;the maximum displacement and maximum stress of the femur were:negative buttress>positive buttress>anatomical reduction.(4)With the increase of Pauwels angle,the biomechanical advantage of the positive buttress was weakening.However,it was better than a negative buttress.When Pauwels angle was 30°,positive buttress was more stable than anatomical reduction.When Pauwels angle was 50°,the biomechanical difference between positive buttress and anatomical reduction became smaller.When Pauwels angle was 70°,the stability of anatomical reduction was slightly better than positive buttress.(5)If it was difficult to achieve anatomical reduction of femoral neck fracture during operation,but the positive buttress had been displaced within 2 mm,the femoral neck system could be used to offer stable mechanical fixation.It is necessary to avoid negative buttress reduction.

Objective: To investigate the early diagnosis and treatment options for steroid-induced osteonecrosis of the femoral head (SONFH). Methods: Retrospective analysis was conducted in 73 patients with unilateral SONFH from January 2010 to June 2017. There were 27 males and 46 females, aged 34.26±10.35 years (range, 20-45 years). The following type of cases were included, 21 cases of ARCO I, 24 cases of IIa, 8 cases of IIb, 18 cases of IIc and 2 cases of IIIa. Patients with ARCO I were limited in weight and were treated with low molecular weight heparin sodium and ginkgo dharma drugs after excluding bleeding risk. Core decompression was performed in patients with ARCO IIa and IIb vascularized greater trochanter bone transfer was conducted in patients with IIc and IIIa. During the follow-up duration, when the ARCO I progressed to ARCO IIa and IIb, the core decompression was performed. When the ARCO IIa and IIb progressed to the ARCO IIc or IIIa, the vascularized greater trochanter bone transfer was conducted. Vascularized greater trochanter bone combined with the tantalum rod was implanted in ARCO IIIb. The femoral head reconstruction with the larger trochanter bone flap or joint replacement was performed in ARCO IIIc and above. The Harris hip score was used to evaluate the clinical outcomes. The femoral head survival curve of SONFH was drawn with the end of joint replacement. Results: All 73 patients were followed up for an average of 29 months (range, 18 to 48 months). After treatment of 21 patients with ARCO I, a total of 14 (67%) patients had no ARCO staging progress. After 6 months, three patients progressed to ARCO IIb and 4 patients progressed to ARCO IIc. All 32 patients with ARCO IIa and IIb were treated, of which 25 (78%) did not progress but 4 patients progressed to ARCO IIIa at 6 months. Only one patient progressed to ARCO IIIb at 6 months, and 2 patient progressed to ARCO IIIc at 12 months. There were 18 patients with ARCO IIc underwent treatment, of which 14 patients (78%) did not progress but 2 patients progressed to ARCO IIIa at 6 months and 2 patients progressed to ARCO IIIc at 24 months and to ARCO IV at 42 months, respectively. Two patients of ARCO IIIa, 1 patient did not progress and the other one progressed to ARCO IV at 36 months. The Harris hip score was 90.48±5.36 before treatment and 91.76±8.19 at the last follow-up. The difference was not statistically significant (t=1.231, P=0.402). The Harris hip score of patients with ARCO IIa and IIb in creased from 75.22±8.30 to 84.47±16.77 with statistically significant difference (t=5.624, P<0.001). The Harris hip score of patients with ARCO IIc and IIIa increased from 59.80±9.24 to 77.75±20.75 with statistically significant difference (t=12.033, P<0.001). Four patients eventually underwent arthroplasty. The femoral head survival rate was 98.6% at 2 years and 94.5% at 4 years. Conclusion The SONFH can be diagnosed early by screening, and is treated by different reserving hip methods according to severe stages. The short-term clinical effects are satisfied.

Objective To investigate the difference of blood supply in different areas of the normal femoral head in adults.Methods A retrospective study analyzed the DCE-MRI parameters data of 2 5 normal adults (25 right hips)in our hospital.The femoral head was assumed to be a sphere.On T1 WI of DCE-MRI,the right femoral head was divided into three parts equally in coronal,sagittal, and transverse plane respectively.Time to peak(TTP),maximum of enhancement at first past(fEmax),maximum of enhancement (Emax)were measured in three parts and compared in coronal,sagittal and transverse plane respectively.Results (1 )In coronal plane,there were no significant differences between the three parts in TTP,fEmax and Emax.(2 )In transverse plane,fEmax and Emax were lower in the transverse superior zone than that in the transverse central zone significantly (P＝0.024 and P＝0.001)and the transverse inferior zone(P＝0.005 and P＝0.018).TTP was higher in the transverse superior zone than that in the transverse central zone and the transverse inferior zone(P＝0.005 and P＝0.018).(3)In sagittal plane,fEmax and Emax were lower in the sagittal lateral zone than that in the sagittal centralzone (P＝0.019 and P＝0.041)and sagittal medial zone (P＝0.047 and P＝0.01 1).TTP was higher in the sagittal lateral zone than that in the sagittal central zone and the sagittal medial zone(P＝0.014 and P＝0.010).There were no significant differences between other paired zones of the any values.Conclusion DCE-MRI can show the microcirculation in the normal adult femoral head in a non-invasive way.According to DCE-MRI parameters,there are poor perfusions on the transversesuperior and sagittallateral zones of the normal femoral head in adults.

BACKGROUND: The imaging methods of evaluating the volume of necrotic femoral head are based on Kerboul angle and necrosis index revealed on X-ray, as well as CT and MRI three-dimensional reconstruction, but the accuracy of each method is different, and none is widely accepted. Additionally, the association of the volum and degree of necrotic femoral head with the status of blood supply to the femoral head remain unclear. OBJECTIVE: To evaluate the accuracy of each imaing method for assessing different stages of femoral head necrosis, and to confirm a convenient method used for measuring the volum of necrotic femoral head. METHODS: This diagnostic in vivo animal trial was finished in the Affiliated Zhongshan Hospital of Dalian University, Liaoning Province, China. The canine models of steroid-induced necrosis of femoral head were prepared, and received CT and MRI examinations, followed by three-dimensional reconstruction combined with Micro-CT to make accuratediagnosis; the degree of necrotic femoral head and its association with the status of blood supply were evaluated throughangiography and histopathological examination. All above outcome measures were compared with the Association Research Circulation Osseous to testify the consistency of this precise method with traditional methods. The experiment follows the national guidelines for the Care and Use of Laboratory Animals, and Consensus author guidelines on animal ethics and welfare by the international Association for Veterinary Editors (IAVE). The article was prepared in accordance with the Animal Research: Reporting of In Vivo Experiments Guidelines (ARRIVE Guidelines). RESULTS AND CONCLUSION: The aim of the study is to obtain a accurate measurement method by detecting different stages of osteonecrosis using different imaging techniques, which enables surgeons make exact diagnosis and clinical stage of osteonecrosis, thus desiging standardized treatment program.

BACKGROUND:There are a variety of treatments for femoral head necrosis,but their efficacy is not confirmed and unified.How to improve the differentiation ability of osteoblasts in the femoral head and improve the biomechanical support after the repair of the femoral head is an urgent problem to be solved.OBJECTIVE:To explore the clinical outcome of stem cells combined with vascularized iliac bone flap and tantalum rod implantation for the treatment of osteonecrosis of the femoral head (ONFH).METHODS:Totally 28 cases (36 hips) of non-traumatic ONFH admitted at the Zhongshan Hospital of Dalian University from January 2010 to January 2011 were enrolled.Bone marrow samples were extracted from each patient to isolate bone marrow stromal stem cells which were cultured in vitro for 2 weeks.Tantalum rod implantation with vascularized iliac bone graft was conducted to restore the femoral head shape,and then,prepared stem cell suspension were injected into the iliac bone flap and into the subchondral space of the femoral head.RESULTS AND CONCLUSION:All the 28 cases (36 hips) were followed up for 6-20 months (average 12 months),and their Harris hip scores and visual analogue scale scores at postoperative 6 and 12 months were significantly higher than the baseline (P ＜ 0.05).The Harris hip score at postoperative 12 months was significantly higher than that at postoperative 6 months (P ＜ 0.05),but there was no significant difference in the visual analogue scale scores at 6 and 12 months postoperatively (P ＞ 0.05).At the end of 12-month follow-up,clinical outcomes were excellent in 13 hips,good in 15 hips,fair in 4 hips,and poor in 4 hips,with an excellent and good rate of 90％.These findings indicate that autologous bone marrow stromal stem cell transplantation with vascularized iliac bone flap and tantalum rob implantation is an effective method with high clinical success rate for the treatment of ONFH.

Objective To investigate the possibility of the domestic reticulated vitreous carbon as a kind of scaffold material for bone tissue engineering,the biocompatibility of domestic reticulated vitreous carbon was first successfully tested with bone marrow stromal cells (BMSCs) in vitro and for bone tissue repair in vivo.Methods From June,2013 to August,2014,the morphology and proliferation of BMSCs co-cultured with scaffold material in vitro was measured.Differences of measurement were compared with single factor analysis of variance to detect the cytotoxicity of reticulated vitreous carbon.In vivo reticulated vitreous carbon were implanted into the bone defect site and the groin.After 12 weeks,the biocompatibility of reticulated vitreous carbon was observed.Results MTT results showed that after 7d co-culture,the survival and proliferation of BMSCs had not been significantly inhibited (P ＞ 0.05).Inverted fluorescence microscope and scanning electron microscope found that newly developed three-dimensional domestic reticulated vitreous carbon could promote adhesion,aggregation and proliferation of BMSCs in vitro.Studies in vivo demonstrate that implanted reticulated vitreous carbon with a high porosity and host bone may produce a stable connection and integration.Conclusion Non-cytotoxic domestic reticulated vitreous carbon can promote the adhesion and proliferation of bone marrow mesenchymal stem cells in vitro and has good bone induction properties in vivo.

Objective To analyze retrospectively the clinical efficacy that the application with vascularized greater trochanter to reconstruct the collapse of femoral head necrosis.Methods Followed-up the data of 21 patients who underwent reconstruction of the femoral head from January,2008 to December,2012,by this we made the clinical and radiological assess,Harris hip scoring system was used to evaluate the situation of hip function.All patients were followed up regularly for X-ray film (after 3 months,6 months and then be reviewed once a year),by the film we assessed the bone healing and repair of the femoral head,and determined whether had the progress in phases.The clinical survival was decided by receiving or not the arthroplasty.Results All 21 patients were followed up for 24-72 months,with an average of 47 months.The postoperative Harris hip score was 82.8 ± 7.1 points,compared with the preoperative,the score improved significantly (average 52.4 ± 4.3 points for preoperative),the difference was statistically significant (P ＜ 0.05).Based on Ficat stage for osteonecrosis,8 patients in this group had progress after 24 to 48 months (mean 33 months),whose femoral heads got collapse worsened.The radiographic success rate was 61.9％.Six cases received arthroplasty in 18 to 48 months (mean 34 months) due to progressive collapse of the femoral head or severe hip pain,or both.FicatⅢ contained 25％ (4 hips),and Ⅳ had 40％ (2 hips),the clinical survival rate was 71.4％.Conclusion The application with vascularized greate.r trochanter transfer coverage to rebuild the collapse of the femoral head in patients with osteonecrosis is a good way.It' s worthy to be applied.

Objective To investigate the clinical effect of the iliac periosteal flap with ascending branch of lateral femoral circumflex artery for the treatment of Legg-Calvé-Perthes disease.Methods Followed-up 18 patients with Legg-Calvé-Perthes disease who had undergone the treatment of iliac periosteal flap with ascending branch of lateral femoral circumflex artery from January,2008 to May,2012 in our hospital.Minimum follow-up time was from 24 to 60 months,and the average time was 38 months.The followed-up period ended in May,2014.Assessed the effect of surgery by X-ray,clinical examination and Harris scoring system.Results Sixteen patients had good healing with iliac periosteal flap according to X-ray show.Their epiphyseal height recovered and the femoral head rounded gradually.Two cases became flat and collapse.The result of excellent and good rate was 88.9％ by Mose method combined with the results of X-ray.The average Harris hip score improved from 72.3 ± 4.9 points preoperatively to 91.3 ± 2.4 points postoperatively.The difference of the result was statistically significant (P ＜ 0.05).Conclusion The transfer of iliac periosteal flap with ascending branch of lateral femoral circumflex artery is an effective treatment for Legg-Calvé-Perthes disease.

Objective To explore the clinical outcome of vascularized iliac bone flap combined with tantalum rod implantation for the treatment of osteonecrosis of the femoral head (ONFH).Methods Totally 28 cases (36 hips) of non traumatic avascular necrosis of the femoral head patients from January 2010 to January 2011,which were 15 males and 13 females; a mean age of 40 years (ranged,18-53years),according to ARCO stages:eight hips of stage Ⅱ a,ten hips of stage Ⅱ b,nine hips of stage Ⅲ a,nine hips of stage Ⅲ b,adopt to vascularized iliac grafting combined with tantalum rod Implantation for osteonecrosis of the femoral head.The Harris hip score and VAS score of pre-and post-operation was recorded to evaluate the clinical outcome,and to compare observe and analyze the change of postoperative of patients by used three-dimensional gait.Results All 28 cases (36 hips) were followed up 6 ～20 months,averaged 12 months.The results of Harris hip score and VAS score of the 6 months postoperatively and last follow-up were significantly higher than preoperative ones (P ＜0.05).And the Harris hip score of the last follow-up was also significantly higher than the one of 6 months postoperatively (P ＜ 0.05).However,there was no significant different in that of VAS score (P ＞0.05).There were 13 cases in excellent,fourteen in good and 4 in fair with an excellent and good rate of 89.8％,which shows that the extension of time and changes in patients gait tends to normal by three-dimensional gait analysis.Conclusion Vascularized iliac bone flap transplantation combined with tantalum screw was an effective method with high clinical success rate for treatment of younger patients with early-mid stage ONFH.It provided good blood supply and enough mechanical support to reduce the progress of femoral head collapse.