AIM To investigate the repair effects of tauroursodeoxycholic acid(TUDCA)combined with bone marrow mesenchymal stem cells(BMSCs)transplantation on spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the TUDCA group,the BMSCs transplantation group and the combination therapy of TUDCA and BMSCs transplantation group,with the SCI rat model established by Allen's method.The next day after modeling,the rats of TUDCA and combination therapy groups were given 200 mg/kg TUDCA by gavage.On the 3rd day after modeling,rats in BMSCs transplantation group and combination therapy group were injected with 1 mL tuned bone marrow BMSCs(the 3rd generation,1× 106/mL)via tail vein.Rats in the sham operation group and the model group were given gastric perfusion of normal saline and injection of 1 mL PBS through tail vein.On the 3rd,7th and 14th day after modeling,the rats had their motor function of hind limbs observed and BBB score determined.After the corresponding drug administration,the rats had their movement track of hind limbs recorded by footprint experiment;their the protein expressions of IL-6,IL-10,Arg-1,PI3K and Akt in spinal cord tissue detected by Western blot;their pathological changes of spinal cord tissue observed by HE staining and Nissl staining;and their expressions of MAP2,GAP43 and GFAP detected by immunofluorescence staining.RESULTS Compared with the model group,the groups intervened with TUDCA,or BMSCs transplantation,or combination therapy shared improved hind limb function and spinal cord histomorphology(P＜0.05);increased fluorescence intensity of MAP2 and GAP43,and protein expressions of IL-10,Arg-1,p-PI3K and p-Akt(P＜0.05);decreased fluorescence intensity of GFAP and IL-6 protein expressions(P＜0.05);among which the combination therapy group took the lead(P＜0.05).CONCLUSION The combination therapy of TUDCA and BMSCs transplantation may restore the function of the rat model of SCI by reducing inflammatory reaction,alleviating secondary injury,and promoting axon and myelin regeneration via PI3K/Akt signaling pathway.

AIM To investigate the promotional effects of esculin combined with bone marrow mesenchymal stem cells(BM-MSCs)transplantation on the repair of spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the esculin group for gavage of 20 mg/kg esculin,the BM-MSCs group for tail vein injection of 1 mL of 1×106/mL BM-MSCs,and the combinaiton treatment group.The SCI rat model was established using Allen's method,followed by the 14 days consecutive corresponding drug administration starting from the 2nd day after modeling.On days 3,7 and 14 of drug administration,the rats had their hind limbs motor function evaluated by the BBB scoring;and their footprint experiment conducted on the 14th day after modeling.After 14 days of administration,the rats had their morphological changes of spinal cord tissue observed with HE staining and Nissl staining;their activities of SOD and GSH,and level of MDA in spinal cord tissue detected by kits;their expressions of MAP2,GAP43 and GFAP in spinal cord tissue detected by immunofluorescence;and their expressions of NQO-1,Nrf-2,Bcl-2 and Bax proteins in spinal cord tissue detected by Western blot.RESULTS Compared with the model group,the groups interved with esculin,or BM-MSCs,or the combination treatment showed improvements in hind limb function and spinal cord tissue morphology(P＜0.05);decreased MDA levels(P＜0.05);increased SOD and GSH activities(P＜0.05);increased MAP2 and GAP43 fluorescence intensity(P＜0.05);decreased GFAP fluorescence intensity(P＜0.05);increased NQO-1,Nrf-2 and Bcl-2 protein expressions(P＜0.05);and decreased Bax protein expression(P＜0.05).And the combination treatment group was observed with an even better effects(P＜0.05).CONCLUSION The combination of esculin and BM-MSCs transplantation can effectively improve the spinal cord tissue damage and hind limb function in SCI rats.This effect may be achieved by activating the Nrf-2/NQO-1 signaling pathway to inhibit oxidative stress response,thereby reducing neuronal apoptosis,blocking glial scar formation,and promoting stem cell differentiation to rebuild neurons.

AIM To investigate the repair effects of tauroursodeoxycholic acid(TUDCA)combined with bone marrow mesenchymal stem cells(BMSCs)transplantation on spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the TUDCA group,the BMSCs transplantation group and the combination therapy of TUDCA and BMSCs transplantation group,with the SCI rat model established by Allen's method.The next day after modeling,the rats of TUDCA and combination therapy groups were given 200 mg/kg TUDCA by gavage.On the 3rd day after modeling,rats in BMSCs transplantation group and combination therapy group were injected with 1 mL tuned bone marrow BMSCs(the 3rd generation,1× 106/mL)via tail vein.Rats in the sham operation group and the model group were given gastric perfusion of normal saline and injection of 1 mL PBS through tail vein.On the 3rd,7th and 14th day after modeling,the rats had their motor function of hind limbs observed and BBB score determined.After the corresponding drug administration,the rats had their movement track of hind limbs recorded by footprint experiment;their the protein expressions of IL-6,IL-10,Arg-1,PI3K and Akt in spinal cord tissue detected by Western blot;their pathological changes of spinal cord tissue observed by HE staining and Nissl staining;and their expressions of MAP2,GAP43 and GFAP detected by immunofluorescence staining.RESULTS Compared with the model group,the groups intervened with TUDCA,or BMSCs transplantation,or combination therapy shared improved hind limb function and spinal cord histomorphology(P＜0.05);increased fluorescence intensity of MAP2 and GAP43,and protein expressions of IL-10,Arg-1,p-PI3K and p-Akt(P＜0.05);decreased fluorescence intensity of GFAP and IL-6 protein expressions(P＜0.05);among which the combination therapy group took the lead(P＜0.05).CONCLUSION The combination therapy of TUDCA and BMSCs transplantation may restore the function of the rat model of SCI by reducing inflammatory reaction,alleviating secondary injury,and promoting axon and myelin regeneration via PI3K/Akt signaling pathway.

AIM To investigate the promotional effects of esculin combined with bone marrow mesenchymal stem cells(BM-MSCs)transplantation on the repair of spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the esculin group for gavage of 20 mg/kg esculin,the BM-MSCs group for tail vein injection of 1 mL of 1×106/mL BM-MSCs,and the combinaiton treatment group.The SCI rat model was established using Allen's method,followed by the 14 days consecutive corresponding drug administration starting from the 2nd day after modeling.On days 3,7 and 14 of drug administration,the rats had their hind limbs motor function evaluated by the BBB scoring;and their footprint experiment conducted on the 14th day after modeling.After 14 days of administration,the rats had their morphological changes of spinal cord tissue observed with HE staining and Nissl staining;their activities of SOD and GSH,and level of MDA in spinal cord tissue detected by kits;their expressions of MAP2,GAP43 and GFAP in spinal cord tissue detected by immunofluorescence;and their expressions of NQO-1,Nrf-2,Bcl-2 and Bax proteins in spinal cord tissue detected by Western blot.RESULTS Compared with the model group,the groups interved with esculin,or BM-MSCs,or the combination treatment showed improvements in hind limb function and spinal cord tissue morphology(P＜0.05);decreased MDA levels(P＜0.05);increased SOD and GSH activities(P＜0.05);increased MAP2 and GAP43 fluorescence intensity(P＜0.05);decreased GFAP fluorescence intensity(P＜0.05);increased NQO-1,Nrf-2 and Bcl-2 protein expressions(P＜0.05);and decreased Bax protein expression(P＜0.05).And the combination treatment group was observed with an even better effects(P＜0.05).CONCLUSION The combination of esculin and BM-MSCs transplantation can effectively improve the spinal cord tissue damage and hind limb function in SCI rats.This effect may be achieved by activating the Nrf-2/NQO-1 signaling pathway to inhibit oxidative stress response,thereby reducing neuronal apoptosis,blocking glial scar formation,and promoting stem cell differentiation to rebuild neurons.

OBJECTIVETo investigate the role of monocarboxylate transporter 1 (MCT1) in enhancing the sensitivity of breast cancer cells to 3-bromopyruvate (3-BrPA).

METHODSThe inhibitory effect of 3-BrPA on the proliferation of breast cancer cells was assessed with MTT assay, and brominated propidium bromide single staining flow cytometry was used for detecting the cell apoptosis. An ELISA kit was used to detect the intracellular levels of hexokinase II, lactate dehydrogenase, lactate, and adenosine triphosphate, and Western blotting was performed to detect the expression of MCT1. MDA-MB-231 cells were transiently transfected with MCT1 cDNA for over-expressing MCT1, and the effect of 3-BrPA on the cell proliferation and adenosine triphosphate level was deteced.

RESULTS3-BrPA did not produce significant effects on the proliferation and apoptosis of MDA-MB-231 cells, and the cells treated with 200 µmol/L 3-BrPA for 24 h showed an inhibition rate and an apoptosis rate of only 8.72% and 7.8%, respectively. The same treatment, however, produced an inhibition rate and an apoptosis rate of 84.6% and 82.3% in MCF-7 cells, respectively. In MDA-MB-231 cells with MCT1 overexpression, 200 µmol/L 3-BrPA resulted in an inhibition rate of 72.44%, significantly higher than that in the control cells (P<0.05); treatment of the cells with 25, 50, 100, and 200 µmol/L 3-BrPA for 6 h resulted in intracellular adenosine triphosphate levels of 96.98%, 88.44%, 43.3% and 27.56% relative to the control level respectively.

CONCLUSIONMCT1 can enhance the sensitivity of breast cancer cells to 3-BrPA possibly by transporting 3-BrPA into cells to inhibit cell glycolysis.

Traditional Chinese medicine (TCM) orthopedics formula is an important part of the prevention and treatment of orthopedics disease,which has curative effect and the advantages of the whole regulation,but it needs to strengthen its clinical development and reasonable application in clinical.In this paper,by reviewing the current clinical present situation and some problems of the research and development about the TCM orthopedics formula,research and development direction were put forward:the source of prescription,the change of disease spectrum,the clinical location,the apphcation of toxic drugs and animal materials,and the quality control of clinical trials should be paid attentions to,hoping to provide some thoughts for the research and development of TCM orthopedics formula.

Knee osteoarthritis (KOA) is a clinical common and frequent ly-occurring disease,traditional Chinese medicine (TCM) and Chinese medicine have certain advantages for patients in the treatment of early-middle period KOA.In this paper,by reviewingthe clinical feature,evaluation methods and present status of treatment of KOA,the evaluation of traditional Chinese medicine of KOA was proposed.the disease characteristics and clinical localization and clinical characteristics of TCM should be paid attention to,so as to select the evaluation method that can reflect the treatment of characteristics.

Knee osteoarthritis(KOA) is a clinical common and frequently -occurring disease,traditional Chinese medicine (TCM) and Chinese medicine has a certain advantage for patients in the treatment of early-middle period.In this paper,review the clinical feature,evaluation methods and present status of treatment of KOA,offer the evaluation of traditional Chinese medicine of KOA,should pay attention to the disease characteristics and clinical localization and clinical characteristics of TCM,select the evaluation method that it can reflect the treatment of characteristics.

Vertebral artery type cervical spondylosis is a common type of cervical spondylosis, also known as cervical vertigo. In recent years, with the increase of people's life pace and the number of office staff, the incidence rate has been rising year by year, with a trend of younger age. Because traditional Chinese medicine has unique advantages in treating cervical vertigo, it is necessary to study the regularity of the Chinese medicine for cervical vertigo. But at present, the research is mainly based on the statistics for frequency and proportion of herbs. In addition, in the process of diagnosis and treatment of Chinese medicine, personal experience also caused differences in prescription compatibility and drug dosage, which makes difficult guarantee for the safety and effectiveness of drug treatment. So, this paper is based on literatures about the traditional Chinese medicine in treatment of cervical vertigo in the past 5 years, by using association rules algorithm, complex system entropy clustering and other non supervised data mining methods. Analysis was made for the use of various drugs in the frequency, the association rules, the core drug combination and the new prescriptions. The traditional Chinese medicine inheritance support system(TCMISS) was utilized to analyze 154 drugs from the 101 prescriptions, determine the use frequency of drugs, analyze the characteristics and the compatibility of core drugs, and dig out 14 core drug combinations and 7 new prescription combinations. The prescription and medication regularities illustrates the drugs for treatment of cervical vertigo, including those for flating liver and suppressing yang, invigorating the circulation of blood to remove blood stasis, reducing water and permeating dampness, increasing qi and activating blood, and nourishing the liver and kidney mainly. Treatment rules are nourishing liver and kidney, invigorating the circulation of blood stasis Tongqiao, reducing phlegm and dampness, flating liver and suppressing yan, dredging collaterals, supplementing qi and nourishing blood. This study aims to summarize frequently used single herbs for vertebral artery type cervical spondylosis, combinations of frequently used herbs and dosage of frequently used herbs with significant efficacy, define the current prescription and medication regularities for treating cervical vertigo and give guidances for clinical mediation.

BACKGROUNDPostoperative knee soft tissue irritation is a common complication after retrograde nail fixation of femoral fractures. Distal locking screw prominence is one of the causes for soft tissue irritation. This study aimed to determine whether the use of the femoral condyles tangential views improve the diagnostic accuracy compared with anteroposterior (A-P) view in detecting distal locking screw penetrations during retrograde femoral nailing.

METHODSThe angle between the sagittal plane and lateral aspect of the condyle and the angle between the sagittal plane and medial aspect of condyle were measured on computed tomography (CT) images. After the angles were measured and recorded, cadaveric femurs were used in a simulated surgical procedure. The retrograde femoral nail was inserted into the femur and placed distal locking screws, which were left 2, 4, and 6 mm proud of the medial and lateral condyles for each femur. A-P view, lateral condyle tangential view and medial condyle tangential view were obtained. All fluoroscopic images were recorded and sent to three observers blinded to the experimental procedure to determine whether screws penetrated the condyle cortex or not.

RESULTSAccording to the results of CT scan, the lateral condyle view was 20.88 ± 0.98° and the medial condyle view was 40.46 ± 3.14°. In the A-P view, we detected 0% at 2 mm penetration, 16.7% (lateral condyle screw) and 25.0% (medial condyle screw) at 4 mm, and 41.7% (lateral condyle screw) and 58.3% (medial condyle screw) at 6 mm. In the lateral tangential view, we detected 91.7% at 2 mm penetration of the lateral condyle and 100% at 4 mm and 6 mm. In the medial tangential view, we detected 66.7% at 2 mm penetration of the medial condyle and 100% at 4 mm and 6 mm. The femoral condyle tangential views provided significant improvement in detecting screw penetrations at all lengths (2, 4, and 6 mm) compared with the A-P view (P < 0.05).

CONCLUSIONSThe femoral condyles tangential views increased the accuracy of detecting screw penetrations on the medial and lateral condyles. Routine clinical use of the femoral condyles tangential views has the potential to increase accuracy in detecting distal locking screw penetration during retrograde femoral nailing.