Objective To study the improvement of hemorheology and prognosis of cervical spondylosis by Tongmai Dingxuan Decoction combined with Manipulation.MethodsA total of 106 patients with cervical spondylopathy in our hospital from November 2014 to November 2015 were randomly divided into observation group and control group,with 53 cases in each group.The control group were treated with manipulation,the observation group was treated with Tongmai Dingxuan Decoction combined with manipulation.The changes of hemorheology parameters such as high blood viscosity, whole blood low shear viscosity, plasma viscosity, whole blood reduction viscosity, hematocrit, erythrocyte aggregation index, fibrinogen were compared between the two groups before and after treatment.The two groups of patients were observed for a one-year follow-up, one year recurrence rate were compared.ResultsThe total effective rate was 92.45% in the observation group was significantly higher than that in the control group 77.36% (P<0.05).The whole blood low shear viscosity (7.01±1.52) mPa·s, the whole blood viscosity (1.18±0.28) mPa·s, fibrinogen (3.91±0.94) g/L were significantly lower than those in the control group (7.88±1.65) mPa·s, (1.47±0.34) mPa·s, (4.51±0.98) g/L (P<0.05).The recurrence rate in the observation group was 13.21%, which was significantly lower than that in the control group (30.19%) (P<0.05).ConclusionTongmai Dingxuan Tang combined with manipulation in the treatment with cervical spondylosis is significant, the whole blood viscosity is reduced, blood circulation function is improved, the recurrence rate after treatment is low, which is worthy of clinical application.

Hypoxia is a general characteristic of most solid malignancies and intimately related to cancer progression. Homeostatic response to hypoxia is primarily mediated by hypoxia inducible factor-1alpha (HIF-1alpha) that elicits transcriptional activity through recruitment P300 coactivator. Targeting the interaction of HIF- alpha and P300 would thus constitute a novel approach for cancer treatment by suppressing tumor angiogenesis and metastasis. Here, a screening assay was developed for inhibitors targeting the interaction between HIF-1alpha and P300. The nucleotide sequence of human HIF-1alpha and P300 were cloned into pBIND and pACT vectors, named pBIND-HIF1alpha and pACT-P300. The interaction of HIF-1alpha and P300 was identified in HEK293 cell using mammalian two-hybrid system. And compound chetomin decreased their interaction in this mammalian two-hybrid system. We further verified HIF-1 inhibition effect of chetomin in U251-HRE cells. Therefore, we established a screening assay combined HIF-1alpha and P300 mammalian two-hybrid system and U251-HRE reporter assay for HIF-1 selective inhibitors.

The aim of this study is to evaluate anti-tumor activities and mechanism of a novel kinase inhibitor ZLJ213 which targeted Aurora A and vascular endothelial growth factor receptor (VEGFR) in vitro and in vivo against human colon cancer. Results showed that ZLJ213 inhibited cell proliferation and induced cell cycle arrest and apoptosis of HCT1 16 and SW48 cell lines. In HCT116-derived xenograft, ZLJ213 dosed at 100 mg · kg(-1) inhibited tumor growth by 73.24%. The IC50 of ZLJ213 on the expression of p-Aurora A was 0.258 µmol · L(-1) analyzed by ELISA. Under the concentration of 0.08 µmol · L(-1), ZLJ213 could inhibit the activities of Aurora A, Histone H3 and VEGFR of HCT116 and SW48 cell lines. Simultaneously, ZLJ213 induced activation of Caspase 3 and PARP cleavage. Above data suggested that ZLJ213 had the ability to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo in colon cancer, and down-regulate the expression of p-Aurora A and p-VEGFR. ZLJ213 might be a potential therapeutic agent against colon cancer.

OBJECTIVE:To study anti-inflammatory,analgesic and anti-fatigue effects of polysaccharides from Acanthopanan trifoliatus (ATMP) in rats and mice. METHODS:In hot plate experiment,150 mice were randomly divided into normal control group (constant volume of normal saline),aspirin group [200 mg/(kg·d)],and ATMP high-dose,medium-dose and low-dose groups [400,200,100 mg(gross polysaccharide)/(kg·d)];the threshold of pain was determined,and analgesic effect of ATMP was investigated. 150 mice were included in exhaustive swimming test and then randomly divided into normal control group(con-stant volume of normal saline),Chongcao yangshen jijing group [400 mg/(kg·d)by total saponins],and ATMP high-dose,medi-um-dose and low-dose groups [200,100,50 mg(gross polysaccharide)/(kg·d)];the body weight and exhaustive swimming time of mice were determined,and biochemical process was used to determine the contents of hepatic glycogen and muscle glycogen, and serum levels of BUN,LDH and CK in mice. The anti-fatigue effect of ATMP was investigated. In carrageenan-induced paw swelling experiment,40 rats were divided into normal control group (constant volume of normal saline),dexamethasone acetate group [5 mg/(kg·d)],ATMP high-dose,medium-dose and low-dose groups [100,50,25 mg(gross polysaccharide)/(kg·d)];the degree of paw swelling was recorded,and anti-inflammatory of ATMP was investigated. RESULTS:Compared with normal control group,the threshold of pain in mice were increased in ATMP 400,200,100 mg(gross polysaccharide)/(kg·d)groups;the exhaus-tive swimming time of mice were prolonged significantly,and the contents of hepatic glycogen in mice were increased significant-ly,while serum contents of CK decreased in ATMP 200,100 mg(gross polysaccharide)/(kg·d)groups;the content of muscle gly-cogen in mice was increased significantly in ATMP 200 mg (gross polysaccharide)/(kg·d) group,while serum contents of BUN and LDH were decreased;the degree of paw swelling in rats was decreased in ATMP 100,50,25 mg(gross polysaccharide)/(kg·d) groups,with statistical significance (P<0.01 or P<0.05). There was no significant difference in body weight of mice before and after medication. CONCLUSIONS:ATMP has significant analgesic and anti-fatigue effects on mice and anti-inflammatory effect on rats.

BACKGROUND:Constant magnetic field of proper intensity can inhibit the proliferation of vascular smooth muscle cells,and it can be used to inhibit the restenosis following percutaneous coronary intervention.OBJECTIVE: To observe the effect of constant magnetic field of different intensities on the expression of osteopontin gene in rat aorta smooth muscle cells, so as to investigate whether magnetic field can be used to prevent and treat restenosis following percutaneous coronary intervention.DESIGN: A randomly grouping and controlled observation.SETTING: Department of Cardiology, Xijing Hospital of the Fourth Military Medical University of Chinese PLA.MATERIALS: The experiments were carried out in the laboratory of Department of Cardiology (Military Institute of Cardiovascular Disease), Xijing Hospital of the Fourth Military Medical University of Chinese PLA from February to December in 2006. Male pure SD rats of 200-250 g were used.METHODS : Rat aorta smooth muscle cells were cultured in vitro in DMEM medium containing fetal bovine serum (0.1 in volume serum), and then the cells were randomly divided into control group, constant magnetic field of 1, 5, 10 and 50 Gs groups, those in the control group were not treated with magnetic field, and those in the other groups were treated with magnetic field and cultured for another 48 hours. Reverse transcription-polymerase chain reaction and Western blotting were combined with absorbance (A) scanning analysis to observe the effect of constant magnetic field on the expressions of osteopontin and its mRNA in smooth muscle cells.MAIN OUTCOME MEASURES: Expressions of osteopontin and its mRNA in smooth muscle cells.RESULTS: The expressions of osteopontin and osteopontin genes in the constant magnetic field groups were significantly decreased as compared with that in the control group (P ＜ 0.05), there were also significant differences among the constant magnetic field groups of different intensities (P ＜ 0.05). It was indicated that the stimulation of constant magnetic field was in an intensity-dependent manner, and the expressions of osteopontin and osteopontin mRNA were enhanced as the intensity of magnetic field was increased.CONCLUSION: Constant magnetic field of proper intensity can inhibit the osteopontin expression in vascular smooth muscle cells on the gene level, and magnetic field may play a role in preventing and treating the restenosis following percutaneous coronary intervention.

The purpose of this study is to investigate the activity and mechanism of a new anti-tumor agent T03. MTT and colony formation assay were performed to determine anti-proliferation activity of T03 in vitro. Antitumor activity was observed by Renca xenograft model in vivo. The effect of T03 on cell cycle and apoptosis were measured by FCM analysis. Western blotting was performed to investigate the expression level of proteins in HepG2 cell lines treated with T03. T03 had anti-tumor activity by inhibiting tumor cell growth and colony formation in vitro, especially on hepatocellular carcinoma cells (HCC). At the concentration of 10 micromol x L(-1), T03 induced cell apoptosis and cell cycle arrest in HCC. Moreover, it proved that T03 reduced the tumor weight with the rate of 42.30% without any obviously side effect in Renca xenograft model. At the concentration of 2.0 micromol x L(-1), T03 was able to reduce the level of p-c-Raf (Ser259), and thus blocked Raf/MEK/ERK and AKT signaling in HepG2 cell lines. The result suggested that T03 has the potential to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo, particularly active against HCC, indicating T03 and its analogues may serve as a new anti-cancer drug against hepatocellular carcinoma.

Objective: To investigate the effects of terlipressin (TP) on blood pressure and survival in septic mice following trauma and its mechanism. Methods: ① Survival experiment: 120 male C57BL/6 mice aged 6-8 weeks were enrolled, the posttraumatic sepsis mice model was reproduced by traumatic hemorrhage (bilateral femoral fracture + 45% of total blood loss) followed by cecal ligation and puncture (CLP) after 8 hours. Intraperitoneal injection of TP was used for intervention. Sixty model mice were used to observe the effect of 0.05 μg/g TP at different intervention times (the drug was given immediately after traumatic hemorrhage + the administration was repeated after 6 hours, the drug was given immediately after traumatic hemorrhage + the administration was repeated every 6 hours until the end of the experiment, the drug was given at 4 hours after CLP + the administration was repeated every 6 hours until the end of the experiment) on 48-hour cumulative survival rate of mice with posttraumatic sepsis for finding the best intervention time of TP. The other 60 model mice were used to observe the effect of different TP intervention doses (0.01, 0.05, 0.25 μg/g) at the best intervention time on the 48-hour cumulative survival rate of mice with posttraumatic sepsis for finding the best intervention dose of TP. ② Intervention experiment: the other 45 mice were enrolled, and they were randomly divided into traumatic hemorrhage + sham group (TH+sham group, only laparotomy without CLP), TH+CLP group, and TH+CLP+TP group (the best intervention time and dose of TP shown by survival experiment were used), with 15 mice in each group. Mean arterial pressure (MAP) of mice was monitored continuously. The orbital whole blood was collected at 2 hours after successful reproduction of the model, and the lung tissues were harvested at 12 hours and 24 hours, respectively. The pathological changes in lung tissue were observed with light microscope. The contents of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in serum and lung tissue were determined by enzyme linked immunosorbent assay (ELISA). The expressions of IL-1β and TNF-α mRNA in lung tissue were determined by real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR). The expressions of nuclear factor-κB p65 (NF-κB p65) in the nucleus and cytoplasm of lung tissue were determined by Western Blot. Results: ① Survival experiment results showed that the 48-hour cumulative survival rate of mice was highest with TP intervention by 0.05 μg/g administration immediately after traumatic hemorrhage and repeated every 6 hours, which was the best intervention method of TP. ② Intervention experiment results showed that the pulmonary alveolar wall fracture accompanied by inflammatory cell infiltration was found at 12 hours after the successful reproduction of traumatic sepsis model, and the pathological damage was gradually increased with time prolongation. MAP was decreased sharply after traumatic hemorrhage, and it was continued to decrease after two-hit of CLP. The contents of IL-1β and TNF-α in serum and lung tissue, the expressions of IL-1β and TNF-α mRNA in lung tissue, and expressions of NF-κB p65 protein in cytoplasm and nucleus of TH+CLP group were significantly higher than those in TH+sham group. Compared with TH+CLP group, the pathological changes in lung tissue were improved significantly, and the MAP was decreased gently after TP intervention, the levels of inflammatory mediators in serum were significantly decreased [IL-1β (pg/L): 164.32±25.25 vs. 233.11±23.02, TNF-α (pg/L): 155.56±31.47 vs. 596.38±91.50, both P < 0.05], and their expressions in lung tissue [IL-1β content (ng/mg): 262.68±16.56 vs. 408.15±17.85, IL-1β mRNA (2^-ΔΔCt): 2.63±0.68 vs. 6.22±0.74; TNF-α content (ng/mg): 311.07±17.35 vs. 405.04±24.83, TNF-α mRNA (2^-ΔΔCt): 2.04±0.62 vs. 5.32±0.55, all P < 0.01], and NF-κB p65 protein expressions were significantly down-regulated (gray value: 0.47±0.01 vs. 1.28±0.05 in cytoplasm, 0.45±0.02 vs. 1.95±0.06 in nucleus, both P < 0.01]. Conclusions The continuous intervention with TP 0.05 μg/g administration immediately after traumatic hemorrhage and repeated every 6 hours could improve the MAP of mice with traumatic sepsis, and improve the prognosis. The mechanism may be related to alleviating the inflammatory response and inhibiting the activation of the NF-κB signaling pathway in the lung tissue.

BACKGROUND:Scaffold materials serve as platforms that provide space and structure,playing a crucial role in the regeneration of cartilage tissue.Scholars from around the world are exploring different approaches to fabricate more ideal scaffold materials. OBJECTIVE:To review the design principles and preparation methods of cartilage scaffolds,and to further explore the advantages and limitations of various preparation methods. METHODS:Literature searches were conducted on the databases of CNKI,WanFang Data,PubMed,and FMRS from 1998 to 2023.The search terms were"cartilage repair,cartilage tissue engineering,cartilage scaffold materials,preparation"in Chinese and English.A total of 57 articles were ultimately reviewed. RESULTS AND CONCLUSION:(1)The articular cartilage has a unique structure and limited self-repair capacity after injury.Even if self-repair occurs,the newly formed cartilage is typically fibrocartilage,which is far inferior to normal articular cartilage in terms of structure and mechanical properties.It is difficult to maintain normal function and often leads to degenerative changes.Currently,the design and fabrication of scaffold materials for cartilage repair need to consider the following aspects:biocompatibility and biodegradability,suitable pore structure and porosity,appropriate mechanical properties,and bioactivity.(2)Research on the preparation of cartilage scaffolds has made significant progress,continuously introducing new preparation methods and optimization strategies.These methods have their advantages and disadvantages,providing more possibilities for customized preparation and functional design of cartilage scaffolds according to specific requirements.

BACKGROUND:Bone formation is the process by which osteoblasts synthesize and secrete osteoid and promote its mineralization,which generally involves mechanical signal transduction.Osteoblasts are primarily regulated by mechanical factors such as gravity,compressive stress,tensile stress,fluid shear stress,and hydrostatic pressure in vivo,and different mechanical stimuli modulate the proliferation,differentiation,and apoptosis of osteoblasts through various mechanisms,including hormones,cytoskeletal proteins,and microRNAs.By clarifying the effects of biomechanical forces on osteoblasts,it provides ideas and a reference basis for the treatment of osteometabolic diseases involving osteoblasts. OBJECTIVE:To review the effects of different biomechanical forces on the biological characteristics of osteoblasts. METHODS:We conducted a literature search using PubMed,Web of Science,FMRS,CNKI,and WanFang databases for relevant publications published from 2000 to 2023,covering basic research and tissue engineering studies related to the effects of biomechanical forces on osteoblasts.Ultimately,a total of 70 articles were reviewed. RESULTS AND CONCLUSION:Different biomechanical forces have an impact on the biological characteristics of osteoblasts,including proliferation,differentiation,and apoptosis,and these effects are dependent on the intensity and duration of the applied force.Specifically,the effects are as follows:(1)Under microgravity conditions,osteoblast proliferation and differentiation are inhibited,resulting in a decrease in bone density and the development of osteoporosis.(2)Compared to microgravity,hypergravity has a promoting effect on osteoblast proliferation.(3)The effects of compressive stress on osteoblasts are dependent on the loading intensity and time.Appropriate compressive stress can promote osteoblast proliferation and differentiation,which is beneficial for bone tissue formation and repair,while excessive compressive stress can cause osteoblast apoptosis and bone tissue destruction.(4)The biological effects of different types of tensile stress on osteoblasts differ.Studies have shown that a strain rate within the range of 0-12%has a promoting effect on osteoblast proliferation.(5)Fluid shear stress can promote osteoblast proliferation and differentiation and enhance the bone-inducing effect of biomaterials.(6)Static hydrostatic pressure can affect the biological behavior of osteoblasts,including proliferation,differentiation,and apoptosis,and these effects are closely related to the time and intensity of the pressure.Understanding the effects of different biomechanical forces on osteoblasts is of great significance for a deeper understanding of bone growth and maintenance mechanisms.

Inflammatory reaction dominated by defense response will arise against infection and trauma. As an important proinflammatory cytokine, high mobility group box 1 (HMGB1) is widely expressed in all nuclear cells to mediate the inflammatory response. However, the biological functions of HMGB1 in inflammation vary depending on the type of HMGB1 protein modification and the localization in the cell. HMGB1 protein will be modified as acetylation of lysine residues, methylation of lysine residues, oxidation of cysteine residues, phosphorylation of serine residues, glycosylation of asparagine residues, adenosine diphosphate-ribosylation and lactylation of the protein in the nucleus, migrate from the nucleus to the cytoplasm, and release into the extracellular compartment. Extracellular HMGB1 can bind to receptors for advanced glycation end products (RAGE) and Toll-like receptors, activate cells and regulate inflammatory responses. The authors review the research progress in regulatory mechanism of HMGB1 in inflammation response from aspects of its post-translational modifications, releases, biological roles and binding receptors, hoping to provide theoretical basis for finding the targets of inflammation intervention.