Intraarticular Injection of Allogenic Mesenchymal Stem Cells has a Protective Role for the Osteoarthritis.

BACKGROUND: Researchers initially proposed the substitution of apoptotic chondrocytes in the superficial cartilage by injecting mesenchymal stem cells (MSCs) intraarticularly. This effect was termed as bio-resurfacing. Little evidence supporting the treatment of osteoarthritis (OA) by the delivery of a MSC suspension exists. The aim of this study was to investigate the effects of injecting allogenic MSCs intraarticularly in a rat OA model and to evaluate the influence of immobility on the effects of this treatment. METHODS: We established a rat knee OA model after 4 and 6 weeks and cultured primary bone marrow MSCs. A MSC suspension was injected into the articular space once per week for 3 weeks. A subgroup of knee joints was immobilized for 3 days after each injection, while the remaining joints were nonimmobilized. We used toluidine blue staining, Mankin scores, and TdT-mediated dUTP-biotin nick end labeling staining to evaluate the therapeutic effect of the injections. Comparisons between the therapy side and the control side of the knee joint were made using paired t-test, and comparisons between the immobilized and nonimmobilized subgroups were made using the unpaired t-test. A P value < 0.05 was considered significant. RESULTS: The three investigative approaches revealed less degeneration on the therapy sides of the knee joints than the control sides in both the 4- and 6-week groups (P < 0.05), regardless of immobilization. No significant differences were observed between the immobilized and nonimmobilized subgroups (P > 0.05). CONCLUSIONS: Therapy involving the intraarticular injection of allogenic MSCs promoted cartilage repair in a rat arthritis model, and 3-day immobility after injection had little effect on this therapy.

Qingre quyu granule stabilizes plaques through inhibiting the expression of tenascin-C in patients with severe carotid stenosis / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic effects of Qingre Quyu Granule (QQG) on the patients with severe carotid stenosis, and to explore the mechanism of it.</p><p><b>METHODS</b>Ninety-six patients with severe carotid stenosis were enrolled in the study and were classified into a QQG group (n=48) and a control group (n=48) randomly using consecutively numbered envelopes. The patients in the QQG group were given QQG and Western medicine, those in the control group were given Western medicine merely, the course of treatment was 16 weeks. All patients went through endarterectomy after treatment. Plaques were subjected to the analysis of CD3, CD68, soluble intercellular adhesion molecule 1 (ICAM-1), matrix metalloprotease-9 (MMP-9), CD40L, tenascin-C, and collagen content lipid content by immunohistochemistry or polarized light analysis.</p><p><b>RESULTS</b>By the end of experiment, the expressions of CD3, CD68, ICAM-1, MMP9, CD40L and tenascin-C on the plaques were statistically significant lower in the QQG group compared with the control group(P<0.01). The lipid content of the plaque was also significantly lower in the QQG group compared with the control group (P<0.01). The interstitial collagen in the tissue sections of the plaques was also significantly higher in the QQG group in comparison with the control group (P<0.01).</p><p><b>CONCLUSION</b>QQG could stabilize carotid artery plaques through inhibiting pro-inflammation factors and restraining the tenascin-C and MMP9 pathway.</p>

[Dermal hypoesthesia after total knee arthroplasty].

OBJECTIVE: To observe the incidence of skin sensory loss after total knee arthroplasty (TKA) and its natural history over time, and to identify the relationship between numbness area and incision length, tourniquet time, age and gender. METHODS: In the study, 132 patients (20 males and 112 females, with an average age of 69.75 years old, 135 cases of TKA) who underwent primary TKA with midline incisions were chosen and grouped chronologically (4 years, 3 years, 2 years, 1 year, 6 months, 1 month) to the investigation time point from Peking University First Hospital. All the operations were done by the same surgeon team with Stryker NRG and Depuy RP (without patellar resurfacing). Numbness incidence, numbness area, scar length, tourniquet time were recorded from the questionnaires sent to the patients and their medical records. RESULTS: 84.44% of the patients received a reduced skin sensory after TKA, 91.22% of which had a smaller numbness area gradually over time. The numbness area was decreased from the 1 month postoperation group to the 4 years postoperation group (P <0.001). The numbness area in 2 years postoperation group and more were significantly smaller than 1 month postoperation group (P=0.042, 0.004, 0.022), however, the skin flap numbness area had little change after 2 years (P>0.05). The hypoesthesia flap was completely lateral to the incision in 88.60% of the patients, and the numbness area covered the lateral skin and part of media skin to the incision in 11.40% of the patients. Numbness size had no relationship with the patients' gender, age, length of scar and tourniquet time (P>0.05). CONCLUSION: Most but not all the patients have a dermal hypoesthesia after total knee arthroplasty. The numbness area will gradually reduce over time. Numbness size is obviously smaller 2 years postoperation and then it will be stable. Gender, age, length of incision, and tourniquet time have no significant relationship with the size of numbness.

Alprostadil liposome microsphere preparation stabilizes vascular plaques and inhibits intra-plaque inflammation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Vulnerable plaques play an important role in the onset of sudden cardiac events and strokes. How to stabilize vulnerable plaques is still a challenge to medical science. Alprostadil is a biologically active substance with strong activity on vessel. Our study assessed the stabilizing effects of an alprostadil liposome microsphere preparation (ALMP) on vulnerable plaques in the brachiocephalic artery of apolipoprotein E (Apo E) knockout mice.</p><p><b>METHODS</b>Seventy-two male Apo E-knockout mice were fed a high-fat diet beginning at eight weeks of age. At week 17, they were divided randomly into groups for treatment with a high dose (3.6 µg×kg(-1)×d(-1)) or low dose (1.8 µg×kg(-1)×d(-1)) of an ALMP, or 0.2 ml/d normal saline (control group). The drug was administered using a micro-capsule pump. Twenty weeks after drug administration, pathological changes in the vulnerable plaques within the brachiocephalic artery were assessed, and levels of anti-mouse monocyte/macrophage monoclonal antibody (MOMA-2) and superoxide anions in the plaques were detected using immunofluorescence. The soluble intercellular adhesion molecule-1 (ICAM-1) expression was measured by ELISA, and the expression of matrix metalloproteinase-9 (MMP-9) and CD40 mRNA was measured using RT-PCR. Thrombospindin-1 (TSP-1) expression was detected using Western blotting.</p><p><b>RESULTS</b>Compared with the control group, ALMP treatment significantly reduced the plaque area in the brachiocephalic artery (P < 0.01), significantly lowered the contents of the lipid core (P < 0.01), significantly reduced the number of ruptured fibrous caps (P < 0.05), and increased the thickness of the fibrous cap and significantly reduced the incidence of intra-plaque hemorrhage (P < 0.05). ALMP treatment significantly reduced the expression of MOMA-2, superoxide anion, MMP-9, ICAM-1 and CD40 in the plaques (P < 0.01), decreased plasma ICAM-1 expression (P < 0.01), and increased the expression of TSP-1.</p><p><b>CONCLUSIONS</b>Treatment with ALMP can stabilize vulnerable plaques by inhibiting inflammation.</p>

Aortic artery elastic lamina degradation, collagen remodeling, oxides stress and inflammation in the apolipoprotein E deficient mice with or without aortic banding / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the elastic lamina degradation and the collagen remodeling of aortic artery as well as oxides stress and inflammation of the apolipoprotein (Apo E) deficient mice with or without experimental hypertension.</p><p><b>METHODS</b>Eighty male Apo E deficient mice were fed with high-fat diet beginning at six weeks of age. At 8-week old, they were randomly divided into hypertension group and control group (n=40 each), the mice in hypertension group were subjected the suprarenal aortic constriction operation and then randomly divided into two subgroups: 15 weeks age and 30 weeks age groups. At the end of experiment, the vascular elastic lamina degradation and the content of collagen were determined by morphological method, plasma ICAM-1 level was measured by ELISA, and the rennin activity measured by radioimmunoassay, the superoxide anion detected by fluorescence, the MOMA-2 observed by immunofluorescence in all animals. mRNA expression of NF-κB P65 and MMP9 was detected by real-time PCR.</p><p><b>RESULT</b>In 15-week old group, the elastic lamina degradation Grade II and the intima-media thickness in the hypertension group were significantly higher than in the control group [(5.4±3.3)% vs. (8.9±2.5)%, P<0.05; (98.66±18.90) µm vs. (70.08±11.71) µm, P<0.05]. In 30-week old group, the elastic lamina degradation Grade III, the III type of collagen and the intima-media thickness were also significantly higher than in the control group [(15.2±3.7)% vs. (8.1±3.3)%, P<0.01; (23.00±7.73)% vs. (11.00±3.82)%, P<0.05; (147.31±22.60) µm vs. (103.98±17.21) µm, P<0.01]. The level of ICAM-1 in hypertension group was significantly higher than that of control group in both 15-week old and in 30-week old mice [(46.3±3.7) µg/ml vs. (40.6±5.7) µg/ml, P<0.05; (56.0±3.1) µg/ml vs. (45.2±2.8) µg/ml, P<0.05]. The superoxide anion, the MOMA-2, mRNA expression of NF-κB P65 and MMP9 in the hypertension group were significantly higher than in the control group in both 15-week old and in the 30-week old mice. The increase in hypertension group was more pronounced in the 30-week old mice than in the 15-week old mice.</p><p><b>CONCLUSION</b>The elastic lamina degradation and the collagen remodeling of aortic artery as well as oxides stress and inflammation are more significant in the Apo E deficient mice with hypertension than in control Apo E deficient mice.</p>

[Acetabular revision using acetabular reinforcement cages with a hook].

OBJECTIVE: To evaluate the effects of cementless revising cup or acetabular reinforcement cages for reconstructing the massive acetabular deficiency. METHODS: From September 2001 to September 2008, 22 loosening acetabular cases (24 hips) were revised using cementless revising cup or acetabular reinforcement cases for reconstructing massive bone defect after particulate bone grafting. There were 2 cases (2 hips) using Lima cementless revising cup, 2 cases (2 hips) using Kerboull ring, and 18 cases (20 hips) using restoration GAP cages. Six cases (6 hips) were male, and 16 cases (18 hips) were female. The mean age was 62 years old (34 - 79 years old). Septic loosening was in 2 cases (2 hips), and aseptic loosening in 20 cases (22 hips). The mean follow-up was 48 months (18 - 84 months). RESULTS: There was no clinical or radiological evidence of loosening for the revising acetabular components at the last follow-up point. The mean Harris hip score was improved significantly from 56 points (44 - 75) before revision to 89 points (78 - 94) at the last follow-up after revision. Excellent and good rate was 95.5% (21/22 cases). The average abduction angle of the three types of acetabular reconstructive cages were 50.1 degrees (39.0 degrees - 66.0 degrees), and almost all cases of the hip rotation center were restored after revision surgery. At the last follow-up, the reinforcement cages were no immigration and breakup, and there was no radiolucent line around the acetabular components. The bone graft integrated well into surrounding acetabular bone. CONCLUSION: The method of revising the massive acetabular bone defect by cementless revising cup and acetabular reinforcement cages restores the normal hip rotation center, supplies the primary stability of the revising component, and protects the bone graft from mechanical overload during its revascularization phase, which is a reliable method for revising the massive acetabular deficiency after total hip arthroplasty.

Effect of Qingre Quyu Granule (清热祛瘀颗粒) on stabilizing plaques in the brachiocephalic artery of apolipoprotein E deficient mice / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Qingre Quyu Granule (清热祛瘀颗粒, QRQYG) on stabilizing vulnerable plaques in apolipoprotein E (ApoE) deficient mice.</p><p><b>METHODS</b>Seventy-two male ApoE deficient mice were given a high-fat diet from 6 weeks of age. At the 16th week, all the mice were randomized into 3 groups: the QRQYG group, the simvastatin group, and the control group. Sixteen weeks after administration of 0.9 g/kg QRQYG, 3 mg/kg simvastatin or 10 mg/kg sodium chloride per day to the respective groups, the animals were euthanized. The pathological morphologic changes in the vulnerable plaques were evaluated, the matrix metalloprotease-9 (MMP-9) expression was measured by immunohistofluorescence, the soluble intercellular adhesion molecule 1 (ICAM-1) was determined by ELISA, the nuclear factor kappaB (NF-κB) subunit p65 was measured by quantitative RT-PCR, and, finally, thrombospondin-1 (TSP-1) was determined by the immunohistochemical method.</p><p><b>RESULTS</b>The plaque cross-sectional area in the brachiocephalic artery (23.7%, P<0.01), the lipid core of the plaque (43.1%±3.1%), and the number of buried fibrotic caps of the plaque were significantly decreased in the QRQYG group compared to the control group (both P<0.01); furthermore, the thickness of the fibrotic cap of the plaque increased and the intra-plaque hemorrhage of the plaque decreased. The serum soluble ICAM-1 (27.1±5.1 μg/mL), the protein expression of MMP-9 and TSP-1 and the p65 mRNA expression increased in the QRQYG group in comparison with the control group (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>QRQYG could stabilize the vulnerable plaque through inhibition of the inflammatory response.</p>

[Polyethylene wear and osteolysis in H/G cementless total hip arthroplasty].

OBJECTIVES: To measure the linear polyethylene wear with use of a computer-assisted two-dimensional method, and to evaluate the relationship between wear and long-term clinic-radiological findings. METHODS: Between December 1991 and December 1995, the senior author performed 40 primary total hip arthroplasties with use of H/G porous-coated acetabular component. Radiographs of 40 H/G cementless total hip arthroplasties were examined for osteolysis, radiolucent line, cup migration and so on. To measure the linear polyethylene wear, migration in the femoral head center relative to the cup shell center was calculated on digitized consecutive radiographs with special computer software program. RESULTS: The minimum follow-up was 10 years. Total linear wear was 2-8 mm, the mean rate of linear polyethylene wear was (0.32+/-0.31) mm/year. Twelve acetabular components (30%) were revised at an average follow-up point of 12 years. Three types of polyethylene liner failure were identified: wear-through of the polyethylene liner with resultant metallosis (5 hips), excessive wear necessitating revision (5 hips), and polyethylene liner dissociation without gross evidence of wear (2 hips). CONCLUSIONS: High wear rates and femoral and acetabular osteolysis have been and still are the main problems in uncemented total hip replacement. There is clear relationship between wear and acetabular osteolysis or loosening of the prostheses. The poor long-term results with these uncemented total hip arthroplasties illustrate the necessity of regular radiographic evaluation in order to detect osteolysis and liner failure, which are both generally asymptomatic until catastrophic failure appears.

Effect of qingre quyu granule on the vulnerable atherosclerotic plaque of carotid artery in patients with stable coronary artery disease / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effect of qingre quyu granule (QQG) for treatment of carotid vulnerable atherosclerotic plaque (CVAP) in patients with coronary heart disease (CHD).</p><p><b>METHODS</b>Eighty-two CHD patients with stable exertional angina, complicated with CVAP and differentiated to phlegm-heat and blood-stasis syndrome type were randomly assigned to two groups equally, the test group treated by Western medical routine therapy combined with QQG, and the control group treated with Western medical routine therapy with placebo. Using high frequency ultrasonography, the number (complex and simple) and Crouse integral of CVAP and the intima-media membranous thickness of carotid artery were measured, and changes in serum levels of CD40L and high-sensitivity C-reactive protein (hs-CRP), liver and renal functions were observed.</p><p><b>RESULTS</b>After treatment, significant improvement were shown in the test group in terms of complex plaques' number, Crouse integral, intima-media thickness and serum levels of CD40L and hs-CRP as compared with that before treatment, also with those in the control group after treatment (P < 0.05 or P < 0.01). No adverse reaction was found in the treatment course.</p><p><b>CONCLUSION</b>QQG has certain stabilizing action on CVAP in patients with CHD.</p>

Effects of perindopril and enalapril on atherosclerosis development of apolipoprotein E knockout mice / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the effects of perindopril and enalapril on the development of atherosclerotic lesions in ApoE knockout mice.</p><p><b>METHODS</b>ApoE knockout mice were treated with perindoprilor (1.5 mg.kg(-1).d(-1), n = 20), enalapril (7.5 mg.kg(-1).d(-1), n = 20) or saline (0.2 ml saline/d, n = 20) per gavage for 20 weeks. Blood pressure and lipids were measured at the study end. Aortic root atherosclerotic plaque was then quantified and the content of collagen and the size of lipid core in the plaque assessed. Cryostat sections were used to quantify the expressions of monocyte/macrophage-2 (MOMA-2), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and matrix metalloproteinases-9 (MMP-9) in the plaque by immunofluorescence method.</p><p><b>RESULTS</b>Blood pressure and lipid profiles were similar among different groups. Compared with control group, the plaque areas of perindopril group and enalapril group displayed significantly decrease (25.33% and 22.86%, respectively, both P < 0.01). However, no significant different were observed in the plaque size between the different ACE inhibitors groups. Perindopril group and enalapril group also significantly decreased the size of lipid core (52.98% and 38.98%, respectively, both P < 0.01) and the expression of MOMA-2 (88.38% and 52.16%, respectively, both P < 0.01), ICAM-1 (80.87% and 49.59%, respectively, both P < 0.01), VCAM-1 (77.56% and 56.44%, respectively, both P < 0.01) and MMP-9 (86.93% and 55.56%, respectively, both P < 0.01), and increased the plaque collagen content (298.36% and 168.14%, respectively, both P < 0.01) and the effects of perindopril was superior to those of enalapril (all P < 0.05).</p><p><b>CONCLUSIONS</b>ACE inhibitors significantly suppressed tissue inflammation and attenuated the development of atherosclerosis in ApoE knockout mice independent of their effects on the lipid and blood pressure. Perindopril is superior to enalapril in stabilizing the plaques and has similar effect on reducing the plaque size as that of enalapril.</p>

Clinical study on effect of Garlicin in stabilizing the carotid artery atherosclerotic plaque in patients with primary hypertension and coronary artery disease / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of garlicin in treating carotid artery atherosclerotic plaque (CAAP) in patients with primary hypertension and coronary heart disease (PHT-CHD).</p><p><b>METHODS</b>Seventy-nine patients with PHT-CHD were randomly divided into the treated group (39 patients) treated with garlicin and fosinopril and the control group (40 patients) treated with fosinopril alone. The change of CAAP was evaluated by high frequency ultrasonic examination every six months, and the changes of intercellular adhesion molecule-1 (ICAM-1) and high sensitive C-reactive protein (hs-CRP) were measured by ELISA, with the observation proceeding for 52 weeks totally.</p><p><b>RESULTS</b>By the end of the experiment, the number of complex plaques, Crouse integrals, intima-media thickness, serum ICAM-1 and hs-CRP were significantly lower in the treated group than those in the control group with significant difference (P < 0.05).</p><p><b>CONCLUSION</b>Garlicin could stabilize CAAP to a certain extent and shows a definite vascular protective effect in patients with PHT-CHD.</p>

Fosinopril but not metoprolol attenuated the increased matrix metallo-proteinases 9 expression at mRNA and protein levels of human umbilical vein endothelial cells exposed to oscillatory flow / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of fosinopril and metoprolol on metalloproteinases 9 (MMP9) expression of human umbilical vein endothelial cells (HUVECs) stimulated by oscillatory flow.</p><p><b>METHODS</b>HUVECs were exposed to steady laminar flow or oscillatory flow, laminar flow or oscillatory flow plus various concentrations (1 x 10(-7) mol/L, 1 x 10(-5) mol/L) of fosinopril and metoprolol for 4 and 24 hours. MMP9 mRNA and protein expressions of HUVECs were determined by RT-PCR and Western blot, respectively.</p><p><b>RESULTS</b>MMP9 expression at mRNA and protein levels were significantly increased in HUVECs exposed to oscillatory flow than that to laminar flow and these could be down-regulated by coincubation with fosinopril (1 x 10(-7) mol/L, 1 x 10(-5) mol/L, P < 0.01, P < 0.05, respectively) but not by co-incubation with metoprolol.</p><p><b>CONCLUSION</b>Fosinopril can attenuate the increased MMP9 expression at mRNA and protein levels of HUVECs exposed to oscillatory flow.</p>

Effects and the mechanism of carvedilol on gap junctional intercellular communication in rat myocardium / 中华心血管病杂志

<p><b>OBJECTIVE</b>To examine the effects of carvedilol on myocardial ischemia and reperfusion injury and on gap junctional intercellular communication (GJIC).</p><p><b>METHODS</b>The left coronary artery was occluded for 30 min and reperfused for 4 h. The activity of creatine phosphokinase (CK), lactate dehydrogenase (LDH) and the infarct size were measured. Isolated buffer-perfused hearts were divided randomly into four groups, sham operation (SO), myocardial ischemia and reperfusion (IR), carvedilol (CV) and heptanol (a gap junctional inhibitor) (HT). The effect of carvedilol on GJIC was measured by a modification of Scrape-loading and dye transfer method, and the state of CX43 phosphorylation was evaluated by Western blot.</p><p><b>RESULTS</b>Compared with the SO group, Increased CK, LDH and infarct size were found in the IR group after 4 h reperfusion. GJIC in the IR group was not inhibited, but dephosphorylated CX43 was increased after 30 minutes of ischemia. Carvedilol decreased CK, LDH and infarct size compared with the IR rats; after 30 minutes of ischemia, both carvedilol and heptanol significantly reduced the GJIC, associated with a significant augmentation of dephosphorylated CX43.</p><p><b>CONCLUSIONS</b>These results suggest that carvedilol reduces GJIC during ischemia presumably by dephosphorylating Cx43, which may be one of the mechanisms of lessening myocardial ischemia-reperfusion injury.</p>