[Objective]To investigate the effect of a single subcutaneous dose of an antisense oligonucleotide(ASO) on particle-induced osteolysis.[Method]The murine calvaria osteolysis model was utilized in ICR mice.Bone resorption was measured with the toluidine blue staining.Osteoclasts were detected by tartrate resistant acid phosphatase(TRAP) staining assay and were quantified by a TRAP quantification kit.[Result]Bone resorption was 0.347 ? 0.09 mm2 in animals with particle implantation,and decreased to 0.123 ? 0.05 mm2 and 0.052 ? 0.02 mm2 after ASO treatment in low and high doses,respectively.The bone resorption was reestablished in animals given an additional TNF-?.The number of osteoclasts in animal calvaria treated with ASO was reduced obviously compared with those untreated animals and the quantification results indicated that about 90% osteoclastgenesis was suprressed by the ASO.Additionally,the osteoclastgenesis was reestablished by the addition of TNF-?.[Conclusion]An antisense oligonucleotide targeting an inflammatory factor,TNF-?,has been to suppress the osteolysis induced by particle for the first time.This new finding holds a great promise.It is a therapeutic strategy for the component loosening.

HIV Seropositivity ; Head ; Humans ; Neck ; Otolaryngology ; Otorhinolaryngologic Diseases ; surgery ; virology

Objective: To evaluate the efficacy and safety of acupuncture for the treatment of knee osteoarthritis and to provide evidence for its use in clinical practice. Methods: Eight databases were extensively searched up to March 2018. Randomized controlled trials (RCTs) comparing the efficacy of acupuncture with sham acupuncture or no acupuncture for knee osteoarthritis were included. Study selection, data extraction and quality assessment were independently conducted by two reviewers. The Cochrane Collaboration's tool was used for assessing the risk of bias. Results: A total of 18 RCTs were included, involving a total of 3522 participants. The results showed that acupuncture was superior to sham acupuncture in relieving pain (SMD=-0.34, 95％CI:-0.57 to -0.11, I2=85％, P=0.003) and improving physical function (SMD=-0.34, 95％CI: -0.57 to -0.11, I2=85％, P=0.003). In comparison to the no-acupuncture group, the acupuncture group also showed significant advantages in relieving pain (SMD=-0.79, 95％CI: -1.15 to -0.43, I2=87％, P<0.0001) and improving physical function (SMD=-0.75, 95％CI:-1.19 to -0.31, I2=91％, P=0.0008). Sensitivity analyses suggested that the results were robust, and Egger's test found no potential publication bias. Conclusion: In the treatment of knee osteoarthritis, the acupuncture group had significant advantages over sham acupuncture or no-acupuncture groups in relieving pain and improving physical function.

BACKGROUND: Bag-1 is a multifunctional and anti-apoptotic gene. Its anti-apoptotic ability is enhanced when binding to bcl-2 to form a complex.Now it is considered as a predictive biomarker for the early diagnosis of breast cancer. However, whether it is useful in the assessment of the prognosis of breast cancer is still elusive.OBJECTIVE: To explore the expression of bag-1 in breast cancer and its role for prognosis.DESIGN: A controlled study with breast cancer, benign breast tumor and normal breast tissues as subjects.SETTING: The Vascular and Endocrine Surgery Department of Xijing Hospital of the Fourth Military Medical University of Chinese PLA.MATERIALS:Totally 100 breast cancer specimens were obtained form May 1995 to May 2000. Ten benign breast tumor and 10 normal breast tissues were used as control. All the specimens were paraffin-embedded and came from the Pathological Department of Xijing Hospital Affiliated to Fourth Military Medical University of Chinese PLA.METHODS: Immunohostochemical strept avidin-biotin complex(SABC) method was adopted to detect bag-1 expression in these specimens.pression levels of bag-1.RESULTS: The positive expression rate of bag-1 in breast cancer (85%) was significantly different form those of benign breast tumor (10%) and normal breast (10%) (χ2= 29.98, P = 0.00). While the positive expression rates in breast cancer of different stages (stage Ⅰ, stage Ⅱ and stage Ⅲ ) were 88%, 82% and 88%, respectively, which has no significant difference (χ2 = 0. 61, P = 0.75) . In duct carcinoma, lobular carcinoma and special carcinoma, bag-1 positive expression rate was 86%, 85% and 80%,which was also no significantly different (χ2 =0.16, P =0.95). In the 94followed patients, the 5-year survival rate of positive bag-1 expression was 79% and that of negative bag-1 expression was just 9%. The difference was significant (χ2 = 0. 07, P = 0.04).CONCLUSION: High bag-1 expression exists in breast cancer and its level is not associated with the clinical stages or pathological types of the cancer.Therefore, bag-1 may be used as a predictive marker for the prognosis of breast cancer.

Objective To study the relationship between activity of thorax and each spinal intervertebral angle in patients with ankylosing spondylitis. Methods Each spinal intervertebral angle of 41 patients with ankylosing spondylitis were measured by Spinalmouse in different postures. And the activity of thorax was measured. Correlation between activity of thorax and shape of spinal were analyzed. Results The activity of thorax positively correlated with the entire lumbar spinal column in flexion (P<0.01), as well as the intervertebral angle of L1/2, L2/3 and L4/5 in flexion (P<0.05), but negatively correlated with the intervertebral angle of L1/2 and L2/3, curvature of the entire lumbar spinal column in upright and the intervertebral angle of L1/2, L3/4, curvature of the entire lumbar spinal column in extension. Conclusion There was a significant relation between activity of thorax and lumbar vertebra motor ability.

BACKGROUND: Harmful stimuli induce increased production of calcitonin gene-related peptide(CGRP) in the spinal cord and dorsal root ganglion, causing also intense dilation of the microvessels. But it remains unknown whether vessel dilation and pain relief were accompanied by increased CGRP production when negative pressure is applied on the limbs for treatment of peripheral arterial occlusion diseases (PAOD).OBJECTIVE: To examine the changes of calcitonin gene-related peptide (GGRP) -immunoractive nerve fibers in the spinal cord and dorsal root ganglion in dogs with PAOD treated with negative pressure on the limbs.DESIGN: A randomized controlled retrospective study.SETTING: The department of general surgery of a military medical university.MATERIALS: This study was carried out at Xijing Hospital of the Fourth Military Medical University of Chinese PLA between January and August 2003. Seventeen adult male dogs weighing 12 - 18 kg, regardless of the gender, were selected.INTERVENTIONS: Seventeen dogs were randomly divided into three groups, namely the treatment group( n = 10), model group( n = 5), and the normal control group( n = 2). Posterior left leg ischemia was induced in dogs in the treatment and model groups, and those in the treatment group, but not the model group, were treated with negative limb pressure for 10 days 14days after model establishment. The spinal cord and dorsal ganglion at L1-5of these two groups were collected and stained immunohistochemically for observing the changes of GGRP-immunreactive nerve fibers. The dogs in the normal control group were also sampled in similar manner for immunohistochemical staining.MAIN OUTCOME MEASURES: Distribution of CGRP-immunoreactive nerve fibers in the spinal cord and dorsal ganglions of the three groups of dogs.RESULTS: In the dogs of the model group, GGRP-immunoreactive nerve fibers in the spinal cord and dorsal ganglions was significantly more numerous[ (75. 00 ±4. 30)%, (68.20 ± 2.60)% ] than those in the treatment and normal control groups[ (58. 20 ±5. 10)%, (52. 20 ±6.20)%; (37.00±4. 20)%, (34. 00 ± 1.40)%, P ＜ 0.01]. The positive nerve fibers were less strongly stained in the treatment group than those in the model group,but still stronger stained those in the normal control group, with significant difference between the three groups( P ＜ 0.01).CONCLUSION: Negative pressure on the limbs may attenuate the synthesis of CGRP-immunoreactive nerve fibers in the spinal cord and dorsal root ganglion and pain conduction following PAOD in dogs, so that harmful afferent stimuli are inhibited to relieve the pain in the limbs.

BACKGROUND: Limb negative pressure treatment can dilate limb vessels and improve terminal microcirculation. P-substance has strong vasodilative activity and is involved in the sensation of the skin to traumatic stimulation and the modulation of local vascular function.OBJECTIVE: To observe the influence of limb negative pressure on cutaneous P-substance immunoreactive nerve fibers in dogs with peripheral arterial occlusive disease.DESIGN: Randomized controlled experiment.SETTING: The 3rd Department of General Surgery, Xijing Hospital Affiliated to the Fourth Military Medical University of Chinese PLA.MATERIALS: This experiment was conducted at the Animal Laboratory of Xijing Hospital Affiliated to the Fourth Military Medical University of Chinese PLA between April 2003 and May 2004. Totally 17 healthy hybrid dogs were randomized into 3 groups, namely, treatment group of 10 dogs,non-treatment group of 5 dogs, and normal control group of 2 dogs.INTERVENTIONS: Negative pressure treatment on affected limbs: After superficial anesthesia, the left hindlimbs of the animals were put into the home-made negative cabin for negative pressure treatment with pressure designed as -12kPa, for 15 minutes, once a day for consecutive 10 days.[1] Treatment group: The left hindlimb ischemic model was prepared 14days before starting 10-day negative pressure treatment; after that the animals were subjected to infusion, the skin of the 2nd toe of affected limbs, as well as L1-5 spinal cords and dorsal root ganglion were obtained for immunohistochemical (IHC) staining. Meanwhile prostaglandin E1 immunoreactive nerve fibers were detected. [2] Non-treatment group: The animals received the same treatment and examination as treatment group except for negative pressure. [3] Normal control group: No ischemic model was prepared or negative pressure treatment was given except for IHC staining.MAIN OUTCOME MEASURES: Changes of cutaneous P-substance immunoreactive nerve fiber in each group. RESULTS: Totally 17 dogs entered the result analysis. Changes of cutaneous P-substance immunoreactive nerve fibers: The cutaneous P-substance immunoreactive nerve fibers in dermis connective tissues and layer vessels were reduced in treatment group compared to those in non-treatment group[(24.70±4.6), (43.49±6.3) μm/mm2, P ＜ 0.01], but still higher than those in control group [(18.10±5.4) μm/mm2, P ＜ 0.01]; dermis P-substance immunoreactive nerve fibers in non-treatment group were more than those in normal control group (P ＜ 0.01), with P-substance immunoreactive nerve fibers increased and deeply stained in dermis connective tissues and small vessels. In contrast, P-substance immunoreactive nerve fibers were not observed in the horny layer but in the dermis of the toe in normal control group.CONCLUSION: Results of the present study suggest that limb negative pressure can enhance P-substance release from cutaneous sensory nerve fibers.

Five compounds (tenuifoliside C, tenuifoliside D, telephiose A, telephiose C and polygalaxanthone III) from polygala tenuifolia wild were incubated together with CYP probe substrate in human liver microsomes to investigate the inhibitory effect towards CYP450 enzyme. Phenacetin (CYP1A2), coumarin (CYP2A6), paclitaxel (CYP2C8), diclofenac (CYP2C9), S-mepheriytoin (CYP2C19), dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1), midazolam (CYP3A) were selected as the isoforfn specific substrate. And the formation of paracetamol, 7-hydroxycoumarin, 6alpha-hydroxy paclitaxel, 4'-hydroxydiclofenac, dextrorphan, 6-hydroxychlorzoxazone, 1'-hydroxymidazolam, 4'-hydroxymephenytoin were detected respectively to measure the effect towards CYP450 by high-pressure liquid chromatography (HPLC). The result shows that five compounds from polygala tenuifolia willd significantly inhibit chlorzoxazone 6-hydroxylation catalyzed by CYP2E1, while showed no effect towards CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A. And IC50 value was 38.73, 54.14, 61.77, 62.22, 50.56 micromol x L(-1), respectively.
Cytochrome P-450 Enzyme System ; metabolism ; Esters ; pharmacology ; Glycosides ; pharmacology ; Humans ; Microsomes, Liver ; drug effects ; enzymology ; Oligosaccharides ; pharmacology ; Polygala ; chemistry ; Xanthones ; pharmacology

A sensitive and selective liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of betamethasone in human plasma. The analyte was isocratically eluted on a Venusil XBP C8 column (200 mm x 3.9 mm ID, 5 microm) with methanol-water mol x L(-1) ammonium formate) (80:20) at a flow rate of 0.4 mL x min(-1), and detected (containing 5 mmol x L(-1) ammonium formate) (80:20) at a flow rate of 0.4 mL x min(-1), and detected with a triple quad LC-MS/MS using ESI with positive ionization. Ions monitored in the multiple reaction monitoring (MRM) mode were m/z 393.3-->355.2 for betamethasone and m/z 361.3-->343.2 for prednisolone (IS). Betamethasone was extracted from 0.5 mL human plasma with ethyl acetate. The average recovery is 88.24% and the low limit of quantitation (LLOQ) was 0.5 ng x mL(-1). The 3-day validation study demonstrated excellent precision and accuracy across the calibration range of 0.5-80.0 ng x mL(-1). The method was successfully applied to the pharmacokinetic study of compound betamethason injection in healthy Chinese volunteers.
Anti-Inflammatory Agents ; blood ; pharmacokinetics ; Area Under Curve ; Betamethasone ; blood ; pharmacokinetics ; Chromatography, Liquid ; methods ; Humans ; Injections, Intramuscular ; Male ; Spectrometry, Mass, Electrospray Ionization ; methods ; Tandem Mass Spectrometry ; methods ; Young Adult

Objective To develop a clinically applicable approach to enhance repair of cartilage defects by constructing an in vivo non-viral gene transfer system targeting chondrocytes. Methods High molecular weight chitosan (HMWC) was degraded to produce low molecular weight chitosan (LM-WC) that was combined with transforming growth factor-β1 (TGF-β1) plasmid to form stable nano-sizc complexes. After being tested in vitro firstly, these nano-size complexes were injected into the knee joint of New Zealand white rabbit models with full-thickness cartilage defects to detect their feasibility of delive-ring the growth factor gent in vivo. Results The results showed that LMWC/DNA nano-sizc comple-xes could deliver the gone into the cultured chondroeytes and cartilage tissue efficiently in vitro. When used in vivo, LMWC/TGF-β1 gene nano-size complexes could enhance the transfection efficiency and prolong the expression of TGF-β1 gone. In the animal models of articular osteechondral defect of rabbits, better healing and gentler degeneration could be observed in comparison with the control. Conclusion In vivo transfection of LMWC/TGF-β1 nano-size complexe is a safe and effective method to early promote the repair of osteochondral defects.