Actin cytoskeleton in podocyte is a complicated network structure,and the stability of this structure depend on many proteins which located in slit diaphragm,the apical membrane domain and the basal membrane domain with the stimulus of mechanical stress,the actin cytoskeleton can be adaptive regulated to maintain the normal function of glomerulus,and several signal pathways involve in the process,such as RhoA/Rho kinase signal pathway and TRPC6.

Over-expression of P-glycoprotein (Pgp) is associated with the development of multi-drug resistance ( MDR). Pgp has been focused on as the main target in designing chemotherapy strategy. In this article we review some of the latest advancement in designing and evaluation methods of P- glycoprotein inhibitors.

The development of osteoarthritis (OA) is associated with the synovium around the joints, and the synovitis is closely related to the pain and swelling of OA. The synovitis is not only involved in the early OA, but also played an important role in the progression of OA throughout.

Objective:To retrospectively analyze and summarize the clinical characteristics of 15 glioma cases that led to leptomenin-ges and spinal cord metastases in Department of Glioma, Beijing Shijitan Hospital, Capital Medical University since 2011. Methods:A total of 15 cases were considered, including 5 patients with World Health Organization gradeⅡ, 6 patients with gradeⅢ, and 4 pa-tients with gradeⅣ. One patient had a tumor at the brain stem, two patients had tumors at the spinal cords, and the other patients had tumors at the hemispheres. One case received biopsy, 4 cases received subtotal resection, and 10 cases received complete resec-tion. Results: Symptoms included low back pain, sensory and motor dysfunction, incontinence, and seizures. After the metastases spread to the cerebrospinal region, patients were treated with chemotherapy, whole spine radiotherapy, intrathecal chemotherapy, and target therapy. The median time of leptomeninges and spinal cord metastasis dissemination appearance was 10 months (1.5-80 months) since surgery. The median overall survival time of the 15 patients was 20 months (9-83 months), and the median survival time was 6 months (2-48 months) after leptomeninges and spinal cord metastases. Conclusion:The prognosis of glioma patients with lepto-meninges and spinal cord metastases was poor, and a proportion of the patients who received appropriate treatment might have a better survival.

Objective:The poor prognosis of patients with malignant gliomas (MG) has led to the search for new therapeutic strat-egies. Recently, nimotuzumab has been studied as a new anti-EGFR-receptor humanized monoclonal antibody in patients with MG, who showed improvement of outcome and good tolerability. We conducted phase I of our study to determine the toxicity, tolerated dose, and clinical feasibility of nimotuzumab in combination with concurrent chemoradiotherapy for Chinese MG patients after surgical resection. Methods:Patients with pathologically proven grades 3 and 4 glioma were enrolled in the study. The protocol included infu-sions of nimotuzumab plus standard Stupp schedule (postoperative radiotherapy in a total dose of 60 Gy in combination with daily te-mozolomide). Patients received 6 weekly infusions of nimotuzumab at three levels (100, 200, and 400 mg/week). If none of the first three patients enrolled at a dose level experienced dose-limiting toxicity (DLT), the dose was increased, as appropriate. If DLT was ob-served, another three patients were added to the dose level. Results:Nine patients with MG were enrolled, including 7 with grade 3 MG and 2 with glioblastoma. The treatment was well tolerated, and no evidence of grade 3 or 4 adverse events was detected, even at the highest level (400 mg/week). Grade 1 or 2 myelosuppression was the most common toxicity. Three months after treatment, stable dis-ease occurred in 5 patients, whereas progression disease was observed in 4 patients. Conclusion:Nimotuzumab combined with concur-rent chemoradiotherapy was associated with mild toxicity in Chinese MG patients.

Objective Pentamethylquercetin (PMQ) has a role in cardiovascular protection. We investigate the effects of 3,3' ,4' ,5,7-pentamethylquercetin, a derivative of PMQ, on intimal hyperplasia of the vein grafts in rats both in vivo and in vitro. Methods The proliferation of vascular smooth muscle cells ( VSMC ) was induced with Ang Ⅱ (0. 1μmol/L, 24 h)while PMQ was administrated at six different dosages (0. 1, 0.3, 1,3, 10 and 30 μmoL/L). Cell viability was identified with MTT; ROS was measured with DCFH-DA; and the expression of NADPH oxidase subunits Nox1, p47phox, and p22phox mRNA were measured with real-time PCR. For the experiment in vivo, 24 SD rats were randomly assigned to control group and PMQ groups, the latter was further divided into three different dosage groups. In the control group, solvent was administrated daily via gavage. In PMQ groups, PMQ ( 12.5 mg/kg, 25 mg/kg, 50 mg/kg) was administrated daily respectively in the same way.All SD rats received operation performed by one person. Reversed external jugular vein was implanted into the external carotid of the same side with interrupted suture. 4 weeks after operation, all vein grafts were harvested. Status of the vein grafts was observed and tissue sections were analyzed with HE staining. The intimal hyperplasia ( intima/media area index and intima/media thickness index) of the vein grafts was assessed. Results Cell viability and ROS of VSMC induced by Ang Ⅱ were suppressed by PMQ. Cell viability and ROS of VSMC were increased substantially when treated with Ang Ⅱ. The therapeutic effects of PMQ could be initially identified at dose of0. 3 μmol/L, with a peak at 3 μmol/L. The effects decreased from 30μmol/L to 10 μmol/L. PMQ at dose of 0.1 μmol/L had no effect on cell viability and ROS of VSMC induced by Ang Ⅱ. PMQ also downregulated the mRNA expression of NADPH oxidase subunits Nox1, p47phox and p22phox induced by Ang Ⅱ. A peak effect was observed at 3μmoL/L and decreased at 30 μmol/L. PMQ at o. 1 μmol/L had no effect on mRNA expression of NADPH oxidase subunits induced by Ang Ⅱ. As compared with control group, PMQ decreased intima/media area index ( 1. 64 ±0.20 in control, 0. 74 ±0.18 at 12.5 mg/kg, 1.09 ±0.17 at 25 mg/kg, 1.21 ± 0. 21 at 50 mg/kg) and intima/media thickness index ( 1.34 ± 0. 24 in control, 0.67 ± 0. 17 at 12.5 mg/kg, 0. 74 ± 0.14 at 25 mg/kg, 0.93 ± 0. 18 at 50mg/kg) at three dosages after implantation. Conclusion PMQ may suppress the proliferation of VSMC and inhibit neointima hyperplasia of vein grafts in rats. The effects may be attributed to the anti-oxidative activity and the downregulation of mRNA expression of NADPH oxidase subunits Noxl, p47phox and p22phox.

OBJECTIVE Ginsenoside metabolite compound K (CK) is a degradation product of ginsenoside in the intestine by bacteria. The anti-inflammatory and immunomodulatory activities of CK have been reported. This study investigated whether CK exerted its immunoregulatory effect through modulation of dendritic cells (DCs) function. METHODS In vivo, severity of collegen-induced arthritis (CIA), T cells and DCs subsets, phenotype of DC were assayed by flow cytometry, CCL19 and CCL21 level in lymph nodes assayed by ELISA. In vitro, bone marrow-derived DCs from normal mice were matured with lipopolysaccharide and treated with CK for 48 h. In vivo, bone marrow-derived DCs were generated from CIA mice before and 2 weeks into CK treatment. DCs were analyzed for migration, phenotype and T- cell stimulatory capacity. RESULTS CK alleviated the severity of CIA, decreased pDCs and mo-DCs, increased na?ve T cells in CIA mice lymph nodes, and suppressed CCL21 expression in lymph nodes. CK suppressed DCs migration induced by CCL21 and T cells-stimulatory capability of DC, down-regulated LPS-induced expression of CD80, CD86, MHCII and CCR7 on DCs. CONCLUSION This study elucidated the novel immunomodulatory property of CK via impairing function of DCs in priming T cells activation. These results provide an interesting novel insight into the potential mechanism by which CK contribute to the restoration of immunoregulation in autoimmune conditions.

This paper analyses the defects of bubble oxygen inhalators currently used, and investigates into their solutions for improvement.
Oxygen Inhalation Therapy ; instrumentation ; methods ; Oxygenators ; standards

This study was purposed to analyze the clinical characteristics of multiple myeloma (MM) patients with and without renal impairment (RI) and to investigate the effect of bortezomib (Bor) on MM with RI. Clinical data of 39 MM patients (15 cases with RI, 24 cases without RI) received treatment of Bor in department of hematology in our hospital from Jan 2007 to Aug 2011 were collect and analyzed in term of clinical characteristics, curative efficacy, outcome of renal impairment and toxic reaction associated to chemotherapy. The results showed that (1) the obvious difference of the disease type, the creatinine, uric acid, serum calcium and β2-microglobulin levels existed in patients with and without RI, while there were no significant difference in hemoglobin and globin levels; (2) there were no significant difference in overall reaction rate and overall survival rate between MM patients with and without RI, however the median survival time of patients without RI was longer than that of patients with RI; (3) the RI could be reversed after the treatment with Bor, and the effect was most obvious after the first cycle. 20% MM patients with RI had recovered from RI after the first cycle; and the recovery rate from RI got up to 38.4% after the second cycle. The decline of creatinine levels had no difference between MM patients with or without RI after the second cycle. (4) The adverse events included gastrointestinal symptoms, peripheral neuropathy, thrombocytopenia and infection. There was also no difference between the 2 groups. It is concluded that Bor-based regimens for the MM patients with RI are effective and safe, and the renal function would be reversed after 2 cycle of Bor-based regimen.
Adult ; Aged ; Aged, 80 and over ; Boronic Acids ; adverse effects ; therapeutic use ; Bortezomib ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; physiopathology ; Pyrazines ; adverse effects ; therapeutic use ; Renal Insufficiency

BACKGROUNDIntracranial infection is one of the most common complications of open craniocerebral injury and of conventional craniotomy in neurosurgery. The presence of blood-brain barrier leads to lower drug concentrations in the cerebrospinal fluid than in the venous blood. Increasing the intravenous dosage or frequency carries the risk of systemic adverse reactions or infections in other parts of the body. Developing an artificial dura mater (ADM) for sustained antibiotic release for use during neurosurgery can solve the problems perfectly.

METHODSThree types of drug-loaded ADMs made of collagen and containing cefuroxime sodium, ceftriaxone sodium, or norvancomycin were prepared. The antibacterial activity and sustained release characteristics of the ADMs were examined using bacteriostatic and release tests.

RESULTSSingle-layered collagen based ADMs (40 mm×50 mm×5 mm) containing 18 mg cefuroxime sodium or ceftriaxone sodium were not suitable for continued development because of drug preservation and stability issues. Using smaller ADMs (20 mm×30 mm×7 mm), containing 4.86 mg of norvancomycin, with increased collagen density and a three-layered film with two outer drug-free films above and below the antibiotic layer resulted in sustained cumulative release of 2.91 mg (59.9%) of norvancomycin over 72 hours. The similar factor (f2) comparison method proved that products from a same batch were statistically significant similar (f2 > 50).

CONCLUSIONSArtificial ADMs made of collagen can be processed to provide a mature dural repair material for the sustained release of norvancomycin. This system may provide a basis for developing sustained release materials for other drugs.

Anti-Bacterial Agents ; chemistry ; Biocompatible Materials ; chemistry ; Ceftriaxone ; chemistry ; Cefuroxime ; chemistry ; Collagen ; chemistry ; Dura Mater ; chemistry ; Vancomycin ; analogs & derivatives ; chemistry