OBJECTIVETo evaluate the time course of granulocyte-colony-stimulating-factor (G-CSF), estrogen and various doses of atorvastatin on endothelial progenitor cells (EPCs) mobilization.

METHODA total of 48 male New Zealand White rabbits were treated with placebo, estrogen (0.25 mg.k(-1).d(-1)), Atorvastatin (2.5, 5, or 10 mg) and G-CSF (50 microg/rabbit/d), respectively. Peripheral EPCs number was surveyed weekly for 4 weeks by FACS analysis (double-positive for PE-CD34/FITC-CD133) and under fluorescent microscope (double-positive for FITC-UEA-1/Dil-acLDL). Serum nitric oxide (NO) and lipids were also measured at the third week.

RESULTSPeripheral EPCs was significantly increased in G-CSF treated animals and remained constant for 4 weeks compared to placebo treated animals. Atorvastatin increased peripheral EPCs dose-dependently from 2.5 to 5 mg and peaked at the third week while peripheral EPCs number was not affected by 10 mg.k(-1).d(-1) atorvastatin during the first 3 weeks and was significantly higher only in the fourth week compared to placebo group. Estrogen also significantly increased peripheral EPCs at the third and fourth week compared to placebo group. At the third week, serum NO was similar in G-CSF group, significantly higher in atorvastatin 5 mg.k(-1).d(-1) and estrogen groups while significantly lower in atorvastatin 10 mg.k(-1).d(-1) group compared to placebo group. Serum lipids were similar among various groups.

CONCLUSIONAtorvastatin, estrogen and G-CSF could mobilize EPCs. The mobilization efficacy is as follows: G-CSF > atorvastatin 5 mg.k(-1).d(-1) > estrogen > atorvastatin 2.5 mg.k(-1).d(-1) > atorvastatin 10 mg.k(-1).d(-1). NO might partly contribute to the mobilizing effect of estrogen and atorvastatin.

Animals ; Atorvastatin Calcium ; Endothelial Cells ; cytology ; drug effects ; Estrogens ; pharmacology ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Heptanoic Acids ; pharmacology ; Hypolipidemic Agents ; pharmacology ; Lipids ; blood ; Male ; Nitric Oxide ; blood ; Pyrroles ; pharmacology ; Rabbits ; Recombinant Proteins ; Stem Cells ; drug effects

OBJECTIVEThe Jiangu decoction is used in the treatment of steroid-induced femoral head necrosis in clinical experiences, which has functions of tonifying kidney and activating blood, and invigorating spleen to remove phlegm. The decoction is mainly composed of Radix Polygoni Multiflori, Rhizoma alismatis Rhizoma Drynariae, haw, medlar, Radix Astragali, radix rehmanniae, angelica, Radix Codonopsis, radix salviae miltiorrhizae, Fructus Ligustri Lucidi, licorice, pharmaceutical composition. This study was designed to investigate the influence of Jiangu decoction on peroxisome proliferator-activated receptor gamma (PPARgamma) in the femoral head of rabbits with steroid-induced femoral head necrosis.

METHODSEighteen adult SPF healthy New Zealand rabbits were divided into 3 groups: control group, model group, Jiangu decoction group. The rabbits of Jiangu decoction group orally received Jiangu decoction suspension with a dose of 10 ml/kg each day and the drug content was 0.719 g/ml. The rabbits in control and model groups were given saline with a dose of 10 ml/kg. The methylprednisolone sodium succinate was injected intramuscularly into left leg with a dose of 40 mg/kg. Then the rabbits were fed continuously for 3 weeks. The glucocorticoid levels, PPARgamma and plasma glucocorticoid levels in the femoral head were measured before and after modeling.

RESULTSBefore model established, the plasma glucocorticoid levels had no significant difference among three groups (P=0.301). At 3 weeks after model established,the plasma glucocorticoid level of rabbits in model group increased compared to the control group (P=0.001); and the plasma glucocorticoid level of rabbits in Jiangu decoction group decreased compared with model group (P=0.001). The glucocorticoid level in the local femoral head of rabbits in model group increased compared to the control group (P=0.001); and the glucocorticoid level in the local femoral head of rabbits in Jiangu decoction group decreased compared with model group (P=0.001). The PPARgamma level in the local femoral head of rabbits in model group increased compared to the control group (P=0.018);and the PPARgamma level in the local femoral head of rabbits in Jiangu decoction group decreased compared with model group (P=0.033).

CONCLUSIONThe Jiangu decoction is effective to inhibit the femoral head adipogenic differentiation by decrease the PPAR content, so as to prevent and treat steroid-induced femoral head necrosis.

Animals ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Femur Head Necrosis ; chemically induced ; drug therapy ; pathology ; Glucocorticoids ; blood ; toxicity ; Male ; Medicine, Chinese Traditional ; PPAR gamma ; analysis ; Rabbits

BACKGROUNDNon-adhesive liquid embolic agents are increasingly gaining importance in the embolization of cerebral arteriovenous malformations (AVMs). We investigated the use of poly (N-isopropylacrylamide) (PNIPAM) as a non-adhesive embolic agent in swine rete mirabile.

METHODSThe PNIPAM hydrogel was mixed with iohexol and embolization was performed in swine rete mirabile in 30 animals. The microcatheter was examined after embolization. Follow-up angiography was performed for embolic efficacy after embolization. Embolized retia were examined histopathologically, and the alterations of inside rete and surrounding tissue were observed.

RESULTSThe copolymer hydrogel was used for rete embolization in 30 swine, 28 swine survived the procedure, 2 swine died, 1 swine died of cerebrum infarction and the other died of embolic agent reflux into the occipital artery. The inside wall of the microcatheter was smooth, without copolymer adhering to it. Follow-up angiography was performed in 22 swine, there was no rete recanalization in 20 swine and partial rete recanalization in 2 swine because of the trunk embolization of ascending pharyngeal arteries. Histopathologically, the copolymer was found diffused into vessels of 100 - 150 microm in diameter. In acute group, neutrophils scattered surrounding the copolymer and endothelial integrity was observed, without endothelial denuding and necrosis. In subacute and chronic groups, the copolymer was found inside retia, a few mononuclear cells and eosinocytes scattered inside and surrounding it. The muscular layer was loosened with most muscular nuclei degraded.

CONCLUSIONExperimental rete embolization with PNIPAM, made radiopaque with iohexol, is technically feasible in swine. Because of its properties, PNIPAM has great potential as a therapeutic non-adhesive embolic agent.

Acrylic Resins ; Animals ; Embolization, Therapeutic ; methods ; Intracranial Arteriovenous Malformations ; therapy ; Swine

OBJECTIVETo investigate whether hepatitis B e antigen (HBeAg) can modulate the ability of dendritic cells (DCs) to produce inflammatory cytokines (IL-12/IL-6) upon stimulation in vitro.

METHODSPurified adherent mononuclear cells isolated by Ficoll-hypaque density gradient centrifugation were cultured in complete medium containing granulocyte macrophage colony-stimulating factor plus interleukin (IL)-4 to generate immature (i)DCs. Microscopic analysis and flow cytometry were performed to define the phenotypic characteristics of the iDCs. Then, different concentrations (1, 2 and 5 mug/ml) of HBeAg were added to the culture medium and for 24 hrs of incubation. To induce iDCs' maturation, the various groups of cells were incubated for 24 hrs in differentiation culture with lipopolysaccharide (LPS). Effects on secreted inflammatory cytokines were determined by enzyme-linked immunosorbent assay of the cells' supernatants.

RESULTSAll concentrations of HBeAg led to significant reductions in IL-6 (all P less than 0.05). Similar significant reduction trends were seen for IL-12 at the HBeAg concentrations of 2 and 5 mug/ml (both P less than 0.05), but not at the 1 mug/ml concentration.

CONCLUSIONHBeAg may suppress the production of cytokines from DCs; this mechanism may contribute to the immune escape of HBV that supports persistent infection.

Cells, Cultured ; Dendritic Cells ; immunology ; metabolism ; Hepatitis B e Antigens ; immunology ; Humans ; Interleukin-12 ; metabolism ; Interleukin-6 ; metabolism ; Lipopolysaccharides ; adverse effects

Chronic kidney disease (CKD) has become a worldwide health and social problem. Retarding its progression to end-stage renal disease is beneficial both to the patients and the healthcare system. Plenty of clinical trials have indicated that enema with Chinese medicine could effectively prevent chronic renal failure, and was widely used in the clinical practice. However, studies on mechanism were still nearly blank, which may prevent further improvement of therapeutic efficacy. Recent studies had discovered that colon was an important organ where uremic toxins were generated. The uremic toxins involved could not only promote CKD progression, but also was closely correlated with CKD mortality. Reducing production and promoting excretion of toxins were confirmed to reduce renal tubule interstitial fibrosis and delay renal progression. On the basis of the theory of gut-kidney axis above, we had conducted pilot clinical researches to evaluate the effect of enema with Chinese medicine on the intestinal flora, gut barrier, enterogenous uremic toxins and renal protection. The preliminary results revealed that rheum enema through colon could accelerate intestinal dynamics, improve intestinal barrier function, regulate intestinal flora and reduce production and absorption of intestine-derived uremic toxins such as indoxyl sulfate, which may reduce renal fibrosis and delay renal progression. Further studies could provide more evidence for colon as a new therapeutic target for the treatment of CKD with Chinese medicine.
Colon ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Enema ; Humans ; Kidney ; drug effects ; pathology ; Renal Insufficiency, Chronic ; drug therapy ; pathology ; Treatment Outcome

OBJECTIVETo investigate the clinical therapeutic results of allograft tendon for anatomical reconstruction of medial patellofemoral ligament (MPFL) for the treatment of patellar dislocations.

METHODSFrom September 2008 to June 2013, 16 patients with patellar dislocation underwent MPFL reconstructions. There were 2 males and 14 females, aged 11 to 27 years old (16 years old on average). Patellar dislocations occurred in 11 left and 5 right knees. The disease course ranged from 3 to 10 years. The frequency of dislocation ranged from 9 to 33 times (19 times on average). Affected knee joints showed patellar instability; the range of action for patella obviously increased. The X-ray films showed patellar dislocation. The preoperative Q angle was (36 ± 9)°, and the congruence angle was (63 ± 18)°. Reconstruction was performed via allograft tendon. Allograft tendon was fixed through the superomedial pole of the patella, and the other end was fixed at the natural MPFL insertion site near the medial femoral condyle with an interference screw in a bone tunnel. All the patients were evaluated postoperatively; Kujala patellofemoral scores, objective knee function, complications, and reoperations were assessed.

RESULTSPrimary healing was achieved in all cases. No infection or necrosis and absorption of grafts was observed. All the patients were followed up for an average of 16.4 months (ranged, 10 to 24 months) postoperatively. At the latest follow-up, all the patients had no pain, swelling and patellar instability; neither patella redislocation nor fracture occurred. The X-ray films showed good position of tunnel 6 months after operation, and the congruence angle was (5 ± 9)°, showing statistically significant difference when compared with preoperation (P < 0.05). The postoperative Q angle was (17 ± 8)°, the Kujala knee function score improved significantly from 45.20 ± 9.20 to 89.30 ± 6.40 at the latest follow-up, showing statistically significant difference (P < 0.05).

CONCLUSIONMPFL reconstruction improves clinical symptoms. Anatomical MPFL reconstruction is effective for patellar dislocation, and it offers good recovery of the premorbid patella mechanics. The interference screw provides firm fixation. Allograft can avoid the graft harvest site morbidity, but it increases the cost of the surgery.

Adolescent ; Adult ; Allografts ; Child ; Female ; Humans ; Ligaments, Articular ; surgery ; Male ; Patellar Dislocation ; surgery ; Patellofemoral Joint ; surgery ; Reconstructive Surgical Procedures ; methods ; Tendons ; transplantation

Objective To analyze the effect of NexusTM coils for endovascular occlusion of intracranial aneurysms. Methods In 41 patients with intracranial aneurysms, endovascular occlusion of 43 aneurysms was performed using NexusTM coils. The follow-up data of the patients for 6 to 12 months were reviewed, and the imaging data from digital subtraction angiography (DSA), CT angiography (CTA) or magnetic resonance arthrography (MRA) alter the treatment were analyzed. Results In the 41 patients, 1 died, 1 had aneurysm recurrence, 3 had cerebral infarction, 1 showed ocular paralysis, and 2 developed hydrocephalus after the surgery. Evaluation with modified Rankin Scale showed grade 0 in 8 cases, grade 1 in 19 cases, grade 2 in 7 cases, grade 3 in 3 cases, grade 4 in 1 case, grade 5 in 1 ease and grade 6 in 1 case. Conclusion Endovascular embolization with NexusTM coils is effective for treatment of intracranial aneurysms especially in cases of small aneurysms and parent artery occlusion. Caution should be taken with the coil for endovascular occlusion of the neck of anterior and middle cerebral artery aneurysms with thin parent arteries, as the fibers in the coil may cause thrombosis and potential cerebral infarction.

Background Non-adhesive liquid embolic agents are increasingly gaining importance in the embolization of cerebral arteriovenous malformations (AVMs). We investigated the use of poly (N-isopropylacrylamide)(PNIPAM) as a non-adhesive embolic agent in swine rete mirabile.Methods The PNIPAM hydrogel was mixed with iohexol and embolization was performed in swine rete mirabile in 30 animals. The microcatheter was examined after embolization. Follow-up angiography was performed for embolic efficacy after embolization. Embolized retia were examined histopatholgically, and the alterations of inside rete and surrounding tissue were observed.Results The copolymer hydrogel was used for rete embolization in 30 swine, 28 swine survived the procedure,2 swine died, 1 swine died of cerebrum infarction and the other died of embolic agent reflux into the occipital artery. The inside wall of the microcatheter was smooth, without copolymer adhering to it. Follow-up angiography was performed in 22 swine, there was no rete recanalization in 20 swine and partial rete recanalization in 2 swine because of the trunk embolization of ascending pharyngeal arteries. Histopatholgically,the copolymer was found diffused into vessels of 100-150 μm in diameter. In acute group, neutrophils scattered surrounding the copolymer and endothelial integrity was observed, without endothelial denuding and necrosis. In subacute and chronic groups, the copolymer was found inside retia, a few mononuclear cells and eosinocytes scattered inside and surrounding it. The muscular layer was loosened with most muscular nuclei degraded.Conclusion Experimental rete embolization with PNIPAM, made radiopaque with iohexol, is technically feasible in swine. Because of its properties, PNIPAM has great potential as a therapeutic non-adhesive embolic agent.

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC. Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January 2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups. Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszel χ2 test,P<0.001,Pearson's R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

BACKGROUND AND OBJECTIVECytokine-induced killer (CIK) cells and autologous dendritic cells-CIK (DC-CIK) cells co-cultured with autologous dendritic cells (DCs) and CIK cells are commonly used for immunotherapy recently. We compared the anti-tumor immune response of CIK cells, autologous DC-CIK cells, and semi-allogeneic DC-CIK cells to explore a more effective anti-tumor adoptive immunotherapy approach.

METHODSPeripheral monocytes were isolated from patients with renal carcinoma, lung cancer, or maxillary squamous cell carcinoma and their healthy adult children. Isolated cells were cultured and induced as DCs and CIK cells in vitro. CIK cells from patients were co-cultured with autologous DCs and DCs from their children respectively, generating DC-CIK cells and semi-allogeneic DC-CIK cells. The anti-tumor activities of autologous CIK cells, autologous DC-CIK cells, and semi-allogeneic DC-CIK cells were measured by LDH assay. Intracellular staining was used to test the secretion of cytokines. Flow cytometry was applied for detecting the phonotype changes of these three types of cells. Cell proliferation and cell apoptosis were detected by 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) and Annexin V/PI respectively.

RESULTSCompared with autologous CIK cells and DC-CIK cells, semi-allogeneic DC-CIK cells significantly enhanced the anti-tumor activity and IFN-gamma secretion, reduced IL-4 secretion, increased the ratio of CD3(+)CD56(+) cells and CD3(+)CD8(+) cells, decreased the number of CD4(+)CD25(+) cells, promoted cell proliferation, and lessened cell apoptosis.

CONCLUSIONSSemi-allogeneic DC-CIK cells had a stronger anti-tumor effect than did autologous CIK cells and DC-CIK cells. Our results provided experimental evidence for clinical application of DC-CIK cells.

Apoptosis ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Cells, Cultured ; Coculture Techniques ; Cytokine-Induced Killer Cells ; cytology ; immunology ; metabolism ; Cytokines ; metabolism ; Cytotoxicity, Immunologic ; Dendritic Cells ; cytology ; immunology ; metabolism ; Hep G2 Cells ; Humans ; Immunotherapy, Adoptive ; Interferon-gamma ; secretion ; Interleukin-4 ; secretion ; K562 Cells ; Kidney Neoplasms ; metabolism ; pathology ; L-Lactate Dehydrogenase ; metabolism ; Lung Neoplasms ; metabolism ; pathology ; Maxillary Neoplasms ; metabolism ; pathology