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The important function of the endplate is to transmit stress and supply nutrition. Endplate degeneration might induce or promote degeneration of the intervertebral disc, causing a series of spine diseases that seriously impair people’s health and life quality. Endplate chondrocytes can respond to mechanical stimulation, which is an important factor affecting endplate degeneration. Inappropriate mechanical stimulation will accelerate endplate degeneration. This review summarized the effects of mechanical stimulation on vertebral endplate chondrocyte apoptosis, synthesis inhibition, calcification, and extracellular matrix degradation. The endplate degeneration induced by mechanical stimulation is regulated by a complex network of signal pathways composed of various signal transduction factors. The signal pathways involved in this review included NF-κB, Wnt, Hedgehog, MAPK, RhoA/Rock-1, AKT/mTOR, TGF-β signaling pathway and miRNA related signals. The interconnection of these pathways was highlighted and summarized. Multiple signaling pathways work together to regulate endplate chondrocyte metabolism, which ultimately leads to the endplate degeneration. This review might shed light on early diagnosis and precise treatment of cartilage endplate degeneration.
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Chloroquine (CQ) and hydroxychloroquine (HCQ) have been used in treating COVID-19 patients recently. However, both drugs have some contradictions and rare but severe side effects, such as hypoglycemia, retina and cardiac toxicity. To further uncover the toxicity profile of CQ and HCQ in different tissues, we evaluated the cytotoxicity of them in 8 cell lines, and further adopted the physiologically-based pharmacokinetic models (PBPK) to predict the tissue risk respectively. Retina, myocardium, lung, liver, kidney, vascular endothelium and intestinal epithelium originated cells were included in the toxicity evaluation of CQ and HCQ respectively. The proliferation pattern was monitored in 0-72 hours by IncuCyte S3, which could perform long-term continuous image and video of cells upon CQ or HCQ treatment. CC50 and the ratio of tissue trough concentrations to CC50 (RTTCC) were brought into predicted toxicity profiles. The CC50 at 24 h, 48 h, 72 h of CQ and HCQ decreased in the time-dependent manner, which indicates the accumulative cytotoxic effect. HCQ was found to be less toxic in 7 cell types except cardiomyocytes H9C2 cells (CC50-48 h=29.55 M; CC50-72 h=15.26 M). In addition, RTTCC is significant higher in CQ treatment group compared to HCQ group, which indicates that relative safety of HCQ. Both CQ and HCQ have certain cytotoxicity in time dependent manner which indicates the necessity of short period administration clinically. HCQ has the less impact in 7 cell lines proliferation and less toxicity compared to CQ in heart, liver, kidney and lung.
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Chloroquine (CQ) phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019 (COVID-19). To develop a physiologically-based pharmacokinetic (PBPK) model for predicting tissue distribution of CQ and apply it to optimize dosage regimens, a PBPK model, with parameterization of drug distribution extrapolated from animal data, was developed to predict human tissue distribution of CQ. The physiological characteristics of time-dependent accumulation was mimicked through an active transport mechanism. Several dosing regimens were proposed based on PBPK simulation combined with known clinical exposure-response relationships. The model was also validated by clinical data from Chinese patients with COVID-19. The novel PBPK model allows in-depth description of the pharmacokinetics of CQ in several key organs (lung, heart, liver, and kidney), and was applied to design dosing strategies in patients with acute COVID-19 (Day 1: 750 mg BID, Days 2-5: 500 mg BID, CQ phosphate), patients with moderate COVID-19 (Day 1: 750 mg and 500 mg, Days 2-3: 500 mg BID, Days 4-5: 250 mg BID, CQ phosphate), and other vulnerable populations (.., renal and hepatic impairment and elderly patients, Days 1-5: 250 mg BID, CQ phosphate). A PBPK model of CQ was successfully developed to optimize dosage regimens for patients with COVID-19.
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Objective@#To assess the effectiveness of acupuncture for hot flushes (HFs) in women with breast cancer (BC).@*Methods@#Ten databases (PubMed, Springer, Cochrane Central Register of Controlled Trials, EMBASE, PsycINFO, CINAHL, CNKI, VIP, CBM, and Wan Fang Database) were searched from their inceptions to autumn 2017 without language restrictions. The searching terms in English and Chinese literatures were"breast tumors/breast neoplasms/breast tumor/breast neoplasm/breast cancer/breast cancers/breast carcinoma/mammary cancer/mammary neoplasm/mammary neoplasms/mammary carcinoma" "hot flushes / hot flashes""acupuncture/ electro-acupuncture / needle/ acupoint". Finally, randomized controlled trials (RCTs) were aggregated to evaluate the therapeutic effect of acupuncture for HFs in women with BC.@*Results@#Eleven articles were systematically reviewed, and five trials (692 patients) were included in the Meta-analysis. Significant combined effects of acupuncture were observed in Hot Flash Related quality of life (d=-3.14; 95% CI, -4.93 to -1.34; P=0.000 6; I2 = 54%), however, no effect was evident for hot flash frequency. The articles included had low risk of bias. No serious adverse effects were reported in the included studies.@*Conclusions@#Acupuncture are associated with significant effects on HFs in women with BC. Large randomized controlled trials (RCTs) were recommended to carry out in China to verify the conclusion.
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Objective To assess the effectiveness of acupuncture for hot flushes (HFs) in women with breast cancer (BC). Methods Ten databases (PubMed, Springer, Cochrane Central Register of Controlled Trials, EMBASE, PsycINFO, CINAHL, CNKI, VIP, CBM, and Wan Fang Database) were searched from their inceptions to autumn 2017 without language restrictions. The searching terms in English and Chinese literatures were"breast tumors/breast neoplasms/breast tumor/breast neoplasm/breast cancer/breast cancers/breast carcinoma/mammary cancer/mammary neoplasm/mammary neoplasms/mammary carcinoma" "hot flushes/ hot flashes""acupuncture/ electro-acupuncture/ needle/ acupoint". Finally, randomized controlled trials (RCTs) were aggregated to evaluate the therapeutic effect of acupuncture for HFs in women with BC. Results Eleven articles were systematically reviewed, and five trials (692 patients) were included in the Meta-analysis. Significant combined effects of acupuncture were observed in Hot Flash Related quality of life ( d=-3.14; 95% CI ,-4.93 to-1.34; P=0.000 6; I2=54% ), however, no effect was evident for hot flash frequency. The articles included had low risk of bias. No serious adverse effects were reported in the included studies. Conclusions Acupuncture are associated with significant effects on HFs in women with BC. Large randomized controlled trials (RCTs) were recommended to carry out in China to verify the conclusion.
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Objective To investigate the role of vitamin D in the synthesis and degradation of aggrecan in rat articular chondrocytes at cellular level. Methods Rat articular chondrocytes were stimulated by IL-1α, IL-1β and TNF-α, respectively. Normal and inflammatory chondrocytes were treated with different doses of vitamin D, respectively. CCK8, Flow cytometry, real time-PCR and western blot analysis were used to examine the proliferation activity and apoptosis level of chondrocytes, and the expression of aggrecan, ADAMTS-4 and ADAMTS-5 at both mRNA and protein levels. Results IL-1α,IL-1β and TNF-α significantly decreased the proliferation activity and increased the apoptosis level of the chondrocytes. Furthermore, IL-1α, IL-1β and TNF-α significantly decreased the expression of aggrecan, and increased the expressions of ADAMTS-4 and ADAMTS-5 at both mRNA and protein levels in the chondrocytes. 1α,25 (OH)2D3supplementation significantly increased the proliferation activity and decreased the apoptosis level of chondrocytes stimulated by IL-1α, IL-1β and TNF-α in a dose-dependent manner, but not affected the normal chondrocytes. Meanwhile, 1α,25(OH)2D3also significantly increased the expression of aggrecan, and decreased the expressions of ADAMTS-4 and ADAMTS-5 at both mRNA and protein levels in the chondrocytes under inflammatory conditions. Conclusions Vitamin D may promote the anabolism of aggrecan and inhibit aggrecanase activity in chondrocytes under inflammatory conditions, which may impact overall protection for articular cartilage.
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Objective To do a longitudinal study of nursing undergraduates′ humanistic care ability in different period of clinical practice, and analyze its trend, aiming to provide reference about how to intervene to enhance the nursing undergraduates' humanistic care ability. Methods A total of 67 nursing undergraduates were investigated about their humanistic care ability with the Care Ability Inventory (Caring Ability Inventory, CAI) at the beginning, middle and end of the internship. Results The scores of seniors′ humanistic care ability at the beginning, middle and end of the internship were 194.97±22.93, 192.18±26.87, 187.24±22.15, and there was a statistically significant difference among the three time points (F=3.234, P<0.05), there was significant difference of the dimension of courage in different periods (F=7.511, P<0.01). Conclusions There is a downtrend of nursing undergraduates′humanistic care ability in different stages of clinical practice, and we suggest that nursing educators and administrators should consider the characteristics of different periods in the clinical practice, and then do a targeted training to foster nursing students′humanistic care ability.
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Objective To observe the level of supportive care need and quality of life in patients postoperation for breast cancer and ac-cepting chemotherapy, and the relationship between them. Methods From September, 2015 to June, 2016, 235 patients with breast cancer af-ter surgery were conveniently sampled, and investigated with the general situation questionnaire, Supportive Care Need Survey Short-form (SCNS-SF34) and Functional Assessment of Cancer Therapy-Breast (FACT-B). Results A total of 230 patients were analyzed. Patients self-reported to need supportive care in all dimensions of SCNS-SF34, and the most frequency was in the health information (31.30%). The score of FACT-B was (93.25±23.53), that needed further improvement. The needs of supportive care in each dimension negatively correlat-ed with the scores of FACT-B in the dimensions (|r|>0.168, P<0.05) except society/family and function. Conclusion The patients with breast cancer need variety of supportive care, which may impact their quality of life.
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Objective To investigate demography of sensory tricks in cervical dystonia (CD),and to discuss the relationship between sensory tricks and the function of sensorimotor integration of cerebral cortex,meanwhile to explore potential worthiness using sensory tricks in the management of CD.Methods We recruited 75 patients (23 male,52 female,male female ratio:1:2.26;aged 19-72 years,mean (42.45 ± 13.09) years) admitted to the Dystonia Clinic Center of the First Affiliated Hospital of Dalian Medical University from March 2016 to April 2013.Standardized questionnaire on sensory tricks was used to investigate the sensory tricks first recognized in 75 patients retrospectively.Median nerve somatosensory evoked potential via multipoint recording was measured in 43 CD patients who manifested as simple rotation of neck.Bilateral amplitudes of P22/N30 derived from F (3,4) were compared.Results Frequency of sensory tricks in CD was 85.53% (64/75) in our research.As disease progressed,the type of sensory tricks used by patients may transform from one to another or even disappear.No statistically significant differences were found in ages among patients using classic sensory tricks,forcible tricks and patients without sensory tricks,whereas the complexity of the disease showed increased tendency among the three groups.Bilateral P22/N30 amplitudes of patients with classic sensory tricks showed no significant differences.P22/N30 amplitudes contralateral to the head turn were significantly higher than ipsilateral in patients using forcible tricks ((3.16 ± 1.71) μV vs (2.47 ± 1.28) μV,t =2.243,P=0.038) and patients without sensory tricks ((3.62 ±1.58) μV vs (2.73 ±1.14) μV,t=2.893,P=0.023).Tsui scores among patients using classic sensory tricks (9.36 ± 3.52) and forcible tricks (12.67 ± 5.00) or patients without sensory tricks (15.18 ± 4.07) had statistically significant differences (classic sensory tricks vs forcible tricks,t =-3.020,P =0.004;classic sensory tricks vs patients without sensory tricks,t =-4.452,P =0.000).Conclusions Types of sensory tricks used by patients are associated with severity of the disease.Different types of sensory tricks may reflect status of adaptive compensatory mechanism of the cerebral cortex.
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This study aimed at verifying a previous patented fraud detection method of propolis.In accordance with the patented process,the chromatographic separation was achieved on a Kromasil 100-5C18 column (250 mm × 4.6 mm,5 tm) as mobile phrase A was methanol and mobile phrase B was water (0.5% phosphoric acid) at the flow rate of 1 mL· min-1 for gradient elution.The detection wave length was 296 nm.Fraudpropolin A was taken as the reference,while the known sources of natural propolis were determined by HPLC.As a result,no fraudpropolin A was detected in the 134 sources of natural propolis at different types or from various origins.It was concluded that the patented process was sound in the fraud detection method of propolis.
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Objective To study the effect of once-weekly injection of recombinant human parathyroid hormone rhPTH(1-34) on the healing of bone fracture in rats.Methods Fifty male 3-month old SD rats were used in this study to produce unilateral tibial fracture and received internal fixation with a Kirschner needle.Based on the dose and frequency of rhPTH (1-34) injection, the rats were randomly divided into five groups (n=10 each) as follows: subcutaneous injec-tions of saline, and rhPTH in a dose of 10, 20, 10, and 20 μg/kg/d.After 4 weeks of treatment, the rats were euthana-tized and the fractured tibia were assessed by X-ray, dual energy X-ray absorptiometry ( DXA) ,micro-computed tomography ( microCT) and three-point bending test.Results The fracture healing in the 20μg/kg/w group was better than the saline group.The fracture healing in the 20μg/kg/w group was as well as the 10 μg/kg/dgroup.The BMD of 20μg/kg/w group was 26.2%higher than the saline group.The mineralized callus volume in the 20μg/kg/w group was 51.4%higher than the saline group.The total callus volume in the 20μg/kg/w group was 21.6%higher than the saline group.The ultimate load of the 20 μg/kg/w group was 29.3% higher than the saline group.There was no significant difference between the 20 μg/kg/w group and 10 μg/kg/d group in BMD, bone micro-architecture, and biomechanical strength ( P >0.05 ) . Conclusions Once weekly injection of rhPTH (1-34)can promote the bone fracture healing.
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Objective To investigate whether TG2 plays an important role in the osteoblast differentiation and mineralization.Methods TG2 mRNA of SaOS-2 cells was knocked down using a lentivirus stably expressing short-hairpin ( sh) RNA targeting TG2.Then the cells were cultured in osteo-inductive medium for 14 d to measure mineralization and for 7 d to measure the levels of osteoblastic differentiation markers including ALP activity and mRNA of collagen I, osteocalcin ( OCN) and BMP-2.The wild-type SaOS-2 cells and scrambled shRNA-transducted SaOS-2 cells served as the controls. Results The controls displayed an increasing trend of the level of ALP activity and mRNA of collagen I, osteocalcin and BMP-2,and notable mineralization at 14 d.When TG2 was knocked down, ALP activity, mRNA of collagen I, osteocalcin and BMP-2 at 7d,and mineralization at 14 d were all significantly lower in comparison with the corresponding values in the controls.Conclusion TG2 is involved in the differentiation and mineralization of osteoblasts in vitro.
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Objective To evaluate the effect of the collaboration care model on posttraumatic growth and resilience in patients with breast cancer.Methods 70 patients who were diagnosed with breast cancer in department of Breast Surgery of the First Affiliated Hospital of Dalian Medical University were assigned into two groups by random number table.32 patients who completed the research in the experimental group received collaboration care while 31 patients who completed the research in the control group received routine care both for there months.The patients were investigated with the Posttraumatic Growth Inventory (PTGI) and Connor-Davidson Resilience Scale (CD-RISC) before and after intervention.Results After the intervention,there were significant differences in scores of posttraumatic growth [(63.83±11.87) scores vs.(60.33±10.09) scores,t=2.384] and resilience [(66.52±15.23) scores vs.(61.33±10.09) scores,t=2.472] between the two groups (P<0.05).And also there were significant differences of posttraumatic growth scores before and after intervention in the experimental group [(56.24±10.01) scores vs.(63.83±11.87) scores,t=-3.988,P< 0.01] and the control group [(56.68±10.32) scores vs.(60.33±10.09) scores,t=-2.426,P<0.05].Differences of resilience also existed in the experimental group [(61.28±14.40) scores vs.(66.52±15.25) scores,t=-3.225,P<0.01] and the control group [(63.97±17.66) scores vs.(61.33±10.09) scores,t=-2.370,P<0.05].Conclusions Collaboration care model can significantly improve the level of patients' posttraumatic growth and resilience.
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Objective To investigate the status of professional identity of nursing undergraduates in different grades and to search for their different professional identity level, so as to establish a pertinent method on nursing education for promoting nursing undergraduates′professional identity. Methods By stratified sampling, a total of 286 nursing undergraduates from four grades in Dalian Medical University were surveyed by general information questionnaire and the Professional Identification Scale for Nurses. Results The average total scores of the professional identity of nursing undergraduates were (107.29±15.01) points. There was significant difference in the total score and the five dimensions of professional identity,F=5.625, 5.258, 7.459, 4.182, 6.891, 7.299, P<0.01. Professional identity score was on the rise along with the grade growth, but the score of grade two was significant lower than the other three grades, and the score showed an increase in grade three; grade, whether profession was consistent with their own interests or not, the reasons of choosing the profession were the important factors affecting professional identity of nursing undergraduates. Conclusions The professional identity score of nursing undergraduates is in medium level and remains to be improved. It is suggested that nursing educators should take corresponding measures according to different grades, own interest and physical and mental characteristics of the students, so as to improve their professional identity and lay the foundation for stability and sustainable development of the nursing team in the future.
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@#Objective To explore the effect of postoperative progressive resistance training (PRT) on the upper limb function in breast cancer patients. Methods 66 breast cancer patients were randomly divided into intervention group (n=33) and control group (n=33). The in-tervention group accepted a 12-week PRT and the control group accepted the routine training since 4-6 weeks postoperative as they admitted to hospital for their first chemotherapy. All the patients received a same content of health education. Results The grip strength, range of mo-tion of abduction and flexion of shoulder were more in the intervention group than in the control group after intervention (P<0.01). Conclu-sion PRT can effectively improve the function of upper limbs in breast cancer patients.
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Local statins implant has been shown to promote bone healing, the underlying mechanisms are unclear. The purpose of this study was to test the effect of local simvastatin implant on bone defect healing; to evaluate the mobilization, migration, and homing of bone marrow-derived mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs) induced by simvastatin. We found that local simvastatin implant increased bone formation by 51.8% (week 6) and 64.8% (week 12) compared with polyglycolic acid controls (P < 0.01), as verified by X-ray, CT, and histology. Simvastatin increased migration capacity of BMSCs and EPCs in vitro (P < 0.05). Local simvastatin implant increased mobilization of EPCs to the peripheral blood by 127% revealed by FACS analysis (P < 0.01), and increased osteogenic BMSCs to the peripheral blood dramatically revealed by Alizarin Red-S staining for mineralized nodules formation. Pre-transplanted GFP-transfected BMSCs as a tracing cell and bioluminescence imaging revealed that local simvastatin implant recruited GFP-labeled BMSC. Also, local simvastatin implant induced the HIF-1α and BMP-2 expression. In conclusion, local simvastatin implantation promotes bone defect healing, where the underlying mechanism appears to involve the higher expression of HIF-1α and BMP-2, thus recruit autogenous osteogenic and angiogenetic stem cells to the bone defect area implanted with simvastatin.
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Implantes de Medicamentos/uso terapéutico , Hipolipemiantes/uso terapéutico , Simvastatina/uso terapéutico , Cráneo/efectos de los fármacos , Cráneo/lesiones , Células Madre/citología , Animales , Proteína Morfogenética Ósea 2/genética , Movimiento Celular/efectos de los fármacos , Células Cultivadas , Implantes de Medicamentos/farmacología , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Hipolipemiantes/farmacología , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Conejos , Simvastatina/farmacología , Células Madre/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacosRESUMEN
ObjectiveTo explore the bone anabolic effects after a single local injection of simvastatin into femoral cavities of osteoporotic rats.MethodsThirty-six female SD rats(3 months old,body weight 250-300 g) were ovariectomized(OVX) and low-calcium-diet fed for 3 months,OVX rats were randomized into 3 groups(n=12).Left femurs of group A,B and C were injected with 0,5 and 10 mg simvastatin,respectively.Half of the rats in each group were randomly euthanized separately 1 and 5 months after simvastatin injection.Left femurs were taken out for bone mineral density (BMD) assessment with dual energy X-ray absorptiometry,bone histomorphometic changes were analysized by Micro-CT,and two kinds of biomechanical tests were used to evaluate the osteogenic effects.ResultsOne and five months after injection,BMD in mid-diaphysis significantly increased in simvastatin-injected groups compared to the control group.For Micro-CT analysis,significant increase in total bone volume/total tissue volume,cortical wall thickness,trabecular thickness,trabecular number,and a significant decrease in trabecular spacing were observed in simvastatin-injected groups compared to the control group.For both biomechanics (the three-pointbreaking test of condyles and axial compressive testing of proximal femur),the values were significantly higher in simvastatin-injected groups than the control group.ConclusionLocal simvastatin treatment showed a positive effect on improving mechanical strength,structure of osteopenic femurs and BMD.Our findings may provide a new strategy for the prevention and treatment of osteoporosis,especially for osteoporotic fractures.
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Objective To observe the effect of fluvastatin(Flu) on differentiation and induction of human promyelocytic leukemia HL-60 cells and provide the theoretical foundation for treatment of human promyelocytic leukemia.Methods The cultured HL-60 cells were treated with 20 ?mol?L-1 Flu,the morphological changes of the cell differentiation were examined.The NBT reduction capability was detected in HL-60 cells treated with Flu for 72 h.After HL-60 cells were treated with 20 ?mol?L-1 Flu for 5 d,they were stained with non-specific esterase and the percentage of differentiation cells was analyzed.Results The HL-60 cells treated with Flu showed smaller cell body,reducing proportion of nucleus to cytoplasm,the nucleus tortuosity,fold or sublobe.There were specific granules and vacuoles in cytoplasm,displaying that some cells had differentiated to relative mature cells.As compared with control group,the NBT reduction capability in HL-60 cells treated with Flu for 72 h was significantly higher than that in control cells(P
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Objective From the angle of electrophysiology, go further into the mechanism of action of acupuncture treatment to the insufficient blood-supply of vertebral basilar artery and at the same time, make a comparison of the effects between the acupuncture on cephalic meridian points and zonation cephalic acupuncture. Methods Through the contrast before and after adopting the self-acupuncture on the testees of 28 cases (including healthy persons of seven cases and TIA patients of 21 cases), observe the change of immediate effect of all waves latent period values of BAEP. Results The BAEP wave latent period of healthy persons (exclusive of I wave of auditory fainting region) assumes a relative delay within the physiological range and by comparison between points and region, the delay of V-wave Baihui point is evidently higher than that of auditory fainting region. However, the latent period of all waves of TIA patients is relatively moved up, especially there are evident differences before and after the I-wave acupuncture is carried out. Viewing from the comparison between points and region, there is no significant difference. Conclusion The function of acupuncture lies in the adjustment of antagonistic body state and it is most effective under the pathological state. Acupuncture will play the main role of excitation to the auditory nerve conduction of BAEP of TIA patients (from cochlea to midbrain) and the influence over the peripheral nerves is more sensitive than over the center ones. Although points and region have their own relative specificities, there is no significant difference between them.
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Objective: To observe the effect of simvastatin on osteoblastic cell differentiation of bone marrow stromal cells in vitro, and to elucidate the mechanisms of anabolic effect of simvastatin on bone formation. Methods: Bone marrow stromal cells from femur and tibia of adult female BALB C mice were cultured in vitro , after being treated with different concentrations of simvastatin for 72 h, changes of mRNA level of osteocalcin (OCN) were detected by RT PCR, change of OCN, and osteopontin (OPN) expression were examined by Western blot, and the changes of cellular alkaline phosphatase activity (ALP) were examined by histochemistry and enzymologic measurement. Results: After bone marrow stromal cells were treated with different concentration of simvastatin for 72 h, level of OCN mRNA increased, and expression of OCN and OPN also increased in a concentration dependent manner, and cellular ALP activity significantly increased in a concentration dependent manner. Conclusion: Simvastatin can stimulate osteoblastic differentiation,and improve cellular ALPase activity with high expression of osteocalcin and osteopontin in vitro. These may be parts of the mechanism of anabolic effect of simvastatin on bone formation.