BACKGROUNDOver-expression of epidermal growth factor receptor (EGFR) is thought to be related to cell proliferation, invasion, metastasis, resistance to chemoradiotherapy and poor prognosis of various human cancers. Forty percent to fifty percent of glioblastoma multiforme (GBM) possess deregulated EGFR, which may contribute to the aggressive and refractory course of GBM. Therefore, blockade of EGFR signal transduction may be a promising treatment strategy for GBM.

METHODSMTT assay, cell growth curve assay and tumor xenograft model were used to evaluate the antitumor activity of F90 against SHG-44 in vitro and in vivo. Western blot assay was applied to evaluate the expression of p-EGFR, p-ERK1, p-JNK, p-P38, Bcl2 and P53 proteins.

RESULTSF90 inhibited the cell proliferation in a dose-dependent manner in vitro. The growth of SHG-44 tumor xenografts was suppressed by F90 at a high dose level (100 mg x kg(-1) x d(-1)). Phosphorylation of EGFR and activated downstream signaling proteins, such as ERK1, JNK and P38, were found to be depressed after incubation with F90 for 48 hours in vitro. Down-regulated Bcl2 protein and up-regulated P53 protein were also observed.

CONCLUSIONSThe results demonstrate that F90 is effective in inhibiting the proliferation of SHG-44 cells in vitro and tumor growth in vivo, suggesting that F90 may be a new therapeutic option for treatment of GBM.

Animals ; Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Glioblastoma ; drug therapy ; pathology ; Humans ; MAP Kinase Signaling System ; drug effects ; Mice ; Mice, Inbred BALB C ; Phosphorylation ; Protein Kinase Inhibitors ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; Quinazolines ; pharmacology ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; metabolism ; Tumor Suppressor Protein p53 ; analysis

Aim To investigate the effects of salidroside on NeuN and Egrs in the ischemic side of middle cerebral artery occlusion (MCAO) rats by inhibiting complement C3.Methods The rats were subjected to MCAO with suture-occluded method,and the neurologic injury was evaluated.The rats underwent l h ischemia/reperfusion with 1 d and 2d salidroside treatment,and the expressions of NeuN,Egr4,C3 and C1 were tested.Male Sprague Dawley rats were separately injected ventricle C3aR inhibitor and artificial cerebrospinal fluid with the help of ventricle stereotaxic apparatus.Thirty min later,the models of MCAO were finished with 1h reperfusion,drug administration and intracerebroventricular injection for 2d.The expressions of NeuN,Egr4,C3 were detected.Results Compared with models of MCAO,the expression of C3 in MCAO rats treated with salidroside 1 d and 2d decreased significantly,and the expression of NeuN increased markedly.Salidroside had no apparent effect on Egr4 and C1 of administration of 1d,but it could significantly enhance the expression of Egr4 after 2d,and reduce the expression of C1 significantly after 2d.The rats administrated with C3aR inhibitor into cerebral ventricle continueously showed the same result in accordance with the treatment of salidroside.And the treatment of salidroside and C3aR inhibitor did not show remarkable additive effects.Conclusion The neuroprotective effect of salidroside on acute cerebral ischemia/reperfusion injury may be related to the inhibition of the activation of the classical pathway of complement,the regulation of Egrs and the reduction of apoptosis.

OBJECTIVETo develop the techniques of total hip arthroplasty(THA) for Crowe type IV developmental dysplasia of the hip (DDH) with S-ROM prosthesis,and to assess its clinical results.

METHODSFrom October 2000 to October 2011,30 patients (36 hips) with Crowe type IV DDH underwent THA,including 6 patients with bilateral hip involved and 24 patients with unilateral. S-ROM prosthesis was adopted together with subtrochanteric transverse osteotomy. All the cementless acetabular cups were placed at the original anatomic location. The threaded cups were put in or near the level of the true acetabulum in all patients. Full coating stems were used in femoral side. All the patients were evaluated by using the Modified Harris Hip Score. Radiographic evaluations were made preoperatively and during follow-up.

RESULTSTwo patients lost of follow-up. Twenty-seven patients with 32 hips were followed up,and the average duration was 48 months (ranging from 7 to 84 months). There was 1 patient with bilateral THA died from hemorrhagic shock. Two patients could walk freely with the visible fracture lines at 12th and 18th months postoperatively. There were no complications such as infection or nerve injuries. Modified Harris Hip Score improved from preoperative 41.7+/-3.7 to postoperative 89.1+/-2.9. There was no acetabular or femoral component revision because of mal-position or loosening of the prostheses in all patients. Postoperative X-ray showed that all the prostheses in place,good integration between acetabular cups,femoral prosthesis and host bone without loosening. All bone grafts were integrated. All the hips acquired union of osteotomy and bone in-growth. None of the patients had radiographic evidence of aseptic loosening of prosthesis.

CONCLUSIONFor the complex DDH, follow methods should be used to improve therapeutic effects:good exposure of the true acetabulum,deepen acetabulum, femoral shortening, oblique osteotomy, using the S-ROM prosthesis.

Adult ; Aged ; Arthroplasty, Replacement, Hip ; methods ; Female ; Hip Dislocation, Congenital ; surgery ; Hip Prosthesis ; Humans ; Male ; Middle Aged

OBJECTIVETo explore clinical efficacy of hip replacement for hip-joint diseases with Parkinson disease.

METHODSFrom December 2011 to December 2016, 18 patients with hip-joint diseases with Parkinson disease treated by hip replacement, including 8 males and 10 females aged from 59 to 87 years old with an average of 71 years old. Among them, 3 cases were developmental dysplasia of hip, 3 cases were femoral head necrosis and 12 cases were femoral neck fracture. All patients manifested with obvious pain and limitation of stepping ability. Postoperative complications were observed and Harris score were used to compare hip joint function after operation.

RESULTSThe incision were healed well, and pain were alleviated or disappeared, and hip joint function were improved. Eighteen patients were followed up from 1 to 3 years with an average of 2.3 years. At the latest follow up, 14 cases recovered freedom-walk, 2 cases could walk with walking stick, 1 case could walk with walking aid and 1 case was died. Among 18 patients, 2 cases were occurred dislocation, and 1 case were died for cardiac disease at 3 months after operation. Four patients were occurred slight pain. There were significant differences in Harris scores among preoperative (41.7±1.4), 6 months after operation(80.1±5.4) and the final follow-up (83.4±2.1), and 10 cases got excellent result, 4 good, 1 fair and 2 poor.

CONCLUSIONSApplication of hip replacement for hip-joint diseases with Parkinson disease is a safe and effective clinical therapy, and has advantages of less complications and rapid recovery of hip joint function.

OBJECTIVETo investigate and evaluate the effectiveness of neuroendoscopic therapy for arachnoid cysts of middle cranial fossa.

METHODSFrom January 2004 to June 2009, 32 patients with arachnoid cysts of middle cranial fossa who were treated with endoscopic cystocisternal fenestration were retrospectively analyzed. There were 21 male patients and 11 female patients, aged from 6 months to 39 years. The clinical and neuroradiological presentation, indications, surgical technique, complications, and clinical and neuroradiological follow-up were analyzed.

RESULTSThe cysts were reduced in size in 20 patients and completely disappeared in 4 patients. For the 27 patients with symptoms before operation, the symptoms disappeared in 8 cases and improved in 17 cases after operation. There were asymptomatic subdural hydroma in 4 patients, intracranial infection and incision cerebro-spinal fluid leakage in 1 patient respectively. The complication incidence rate was 18.8%.

CONCLUSIONSEndoscopic fenestration is an effective treatment for symptomatic arachnoid cysts of middle cranial fossa and could be performed as the first surgical choice for these patients.

Adolescent ; Adult ; Arachnoid Cysts ; surgery ; Child ; Child, Preschool ; Cranial Fossa, Middle ; Endoscopy ; methods ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Retrospective Studies ; Treatment Outcome ; Young Adult

BACKGROUNDCongenital heart disease is a diverse group of diseases determined by genetic and environmental factors. Considerable research has been done on genes associated with development of the heart. A recent focus is the role of transcription factor TBX5 in the development of atria, left ventricle and conduction system. As part of a larger study, high density, single nucleotide polymorphism (SNP) scanning was used to explore the relationship between TBX5 gene polymorphism and susceptibility to ventricular septal defect not associated with forelimb malformation in the Chinese Han population.

METHODSOne hundred and ninety two paediatric patients with congenital ventricular septal defect and 192 matched healthy control subjects were studied. The haplotype reconstructions were calculated by PHASE2.0 software. Haploview software was used to perform linkage disequilibrium assessment and defining of haplotype blocks. The algorithm used for defining of blocks was the confidence interval method.

RESULTSThe TBX5 gene region can be divided into 3 haplotype blocks of 27, 15 and 2 SNPs. Strong linkage disequilibrium exists within each block. SNP rs11067075 within the TBX5 gene had significant correlation with ventricular septal defect (P = 0.0037) by single marker association analysis. In addition, a 20 kb haplotype composed of 27 SNPs correlated with ventricular septal defect (P = 0.05, multiple loci regression analyses based on reconstructed haplotype blocks).

CONCLUSIONSTBX5 is associated with the occurrence of ventricular septal defect and may be a predisposing gene to congenital heart disease in Han Chinese. This finding has set a direction for further genetic and functional studies.

Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; genetics ; Heart Septal Defects, Ventricular ; genetics ; Humans ; Linkage Disequilibrium ; genetics ; Polymorphism, Genetic ; genetics ; Polymorphism, Single Nucleotide ; T-Box Domain Proteins ; genetics

BACKGROUNDThe mammalian target of rapamycin (mTOR) pathway, a key cellular signaling pathway associated with various cellular functions, has distinct roles in the inflammatory process. In this study, the mTOR inhibitor rapamycin (Rapa) was used to test whether inhibition of mTOR activation attenuates lipopolysaccharide (LPS)-induced acute lung injury (ALI) in a murine model.

METHODSMice pretreated with Rapa or vehicle were given LPS intratracheally. Local cell numbers and inflammatory cytokines present in the bronchoalveolar lavage fluid (BAL), wet-to-dry weight ratio, histopathology of the lungs, and survival were evaluated.

RESULTSThe phosphorylation of S6, a major downstream target of mTOR, had a 3-fold increase in lung tissue after LPS stimulation, but the increase was blocked by Rapa. Rapa reduced the levels of TNF-α (LPS vs. LPS + Rapa, (1672.74 ± 193.73) vs. (539.17 ± 140.48) pg/ml, respectively; P < 0.01) and IL-6 (LPS vs. LPS + Rapa: (7790.88 ± 1170.54) vs. (1968.57 ± 474.62) pg/ml, respectively; P < 0.01) in the BAL fluid. However, Rapa had limited effects on the overall severity of ALI, as determined by the wet-to-dry weight ratio of the lungs, number of neutrophils in the BAL fluid, and changes in histopathology. In addition, Rapa failed to reduce mortality in the LPS-induced ALI model.

CONCLUSIONSWe confirmed that mTOR was activated during LPS-induced ALI and strongly inhibited by Rapa. Although Rapa reduced the levels of the mediators of inflammation, the overall severity and survival of the ALI murine model were unchanged.

Acute Lung Injury ; chemically induced ; drug therapy ; Animals ; Lipopolysaccharides ; Mice ; Mice, Inbred C57BL ; Phosphorylation ; Sirolimus ; pharmacology ; therapeutic use ; TOR Serine-Threonine Kinases ; drug effects

Objective To study the sensitivity and specificity of gold-immunochromatography assay (GICA) for detection of Yersiniapestis(Y. pestis ) F1 antigen. Methods Viscera organ(liver and spleen) specimens of 308 mice with virulent Y. pestis infection and 225 control specimens of rats(217 Spermophilus dauricus, 5 mice,3 guinea pigs) were detected by GICA dipstick with monoclonal antibody against plague F1 antigen (F1MAb).Meanwhile, micro-method of reverse indirect hemagglutination assay(RIHA) and bacteria culture were carried out for parallel testing. Results Bacteriological examination of 225 control specimens, and F1 antigen detected with GICA and RIHA were all negative. No cross-reaction with related Yersinia pseudotuberculosis at 1 x 108 cfu/ml level was found in GICA and RIHA. Detection sensitivity of Y. pestis by GICA and RIHA were 2.5 × 105 cfu/ml and 2.0 × 105 cfu/ml, respectively, and of F1 antigen were 1μg/L and 10 μg/L, respectively. Coincidence was 97.94% (522/533) between GICA and bacteriological test, Kappa = 0.959, and the difference was statistically insignificant(x2 = 0.36, P ＞ 0.05); and 97.94%(522/533) between GICA and RIHA, Kappa = 0.959, with statistically significant difference in the positive detection rates(x2 = 9.09, P ＜ 0.05). Out of the 308 infected mice, 284 were positive of plague bacterial cultured, In 284 samples with positive bacterial culture, there were 280 of positive detected by GICA for F1 antigen, positive rate of F1 antigen was 98.59%, higher than that by RIHA[the positive rate of 96.13%(522/533)], with statistically significant difference(x2 = 5.14, P ＜ 0.05). Sensitivity of GICA was 98.59% (280/284), specificity was 97.19% (242/249), positive predictive value (PPV) was 97.56% (280/287),negative predictive value ( NPV ) was 98.37% (242/246), and Youden index was 0.9578. Conclusions GICA is sensitive and specific, fast and simple in detection of F1 antigen of the plague. It's a valuable detection technique for early and rapid diagnosis of plague.

OBJECTIVETo explore the effect of puerarin combined with felodipine on the mRNA and protein expression of apelin and APJ in renal tissue of renovascular hypertensive rat.

METHODSixty-two Sprague-Dawley rats were used, of which 8 rats were randomly chosen as sham-operation group. The remaining rats were made for the rat model with renovascular hypertension. The renovascular hypertensive rats were randomly divided into 5 groups as follows: 4 groups which were treated with felodipine (0.8 mg x kg(-1) x d(-1)), puerarin (50 mg x kg(-1) x d(-1)), puerarin combined with felodipine (puerarin 25 mg x kg(-1) x d(-1) + felodipine 0.4 mg x kg(-1) x d(-1)) or captopril combined with felodipine (captopril 15 mg x kg(-1) x d(-1) x felodipine 0.4 mg x kg(-1) x d(-1)), and 1 group which was treated with distilled water. Drugs or distilled water were administered for 8 weeks. The expression of apelin and APJ mRNA and protein in ischemic and non-ischemic kidneys was assessed by RT-PCR or Western blot.

RESULTCompared with sham-operation group, the expression of apelin mRNA and protein in ischemic and non-ischemic kidneys in model group was increased significantly (P < 0.01); the expression of APJ mRNA and protein in ischemic kidneys had no significance, while that in non-ischemic kidneys was decreased (P < 0. 01). Compared with model group, the expression of apelin mRNA and protein in ischemic and non-ischemic kidneys was decreased significantly in all drug-treated groups (P < 0.01); while that of APJ mRNA and protein in non-ischemic kidneys was upregulated (P < 0.01). Compared with felodipine group, the expression of apelin mRNA and protein in ischemic and non-ischemic kidneys was decreased (P < 0.01 or P < 0.05) in the group treated with both puerarin and felodipine; and the expression of APJ mRNA and protein in ischemic kidneys did not reach significant level, however, that was upregulated in non-ischemic kidneys (P < 0.01 or P < 0.05).

CONCLUSIONPuerarin downregulates the expression of apelin mRNA and protein in ischemic and non-ischemic kidneys, and upregulates that of APJ mRNA and protein in non-ischemic kidneys. Combination of puerarin and felodipine enhances the above-mentioned effects and shows no significant difference versus the combination of felodipine and captopril. The results suggest that puerarin regulates blood pressure and protects target organ through apelin/APJ pathway and that puerarin has synergetic effects with CCB.

Animals ; Antihypertensive Agents ; pharmacology ; Apelin ; Apelin Receptors ; Blotting, Western ; Captopril ; pharmacology ; Drug Synergism ; Felodipine ; pharmacology ; Gene Expression ; drug effects ; Hypertension, Renovascular ; genetics ; metabolism ; Intercellular Signaling Peptides and Proteins ; genetics ; metabolism ; Ischemia ; Isoflavones ; pharmacology ; Kidney ; blood supply ; drug effects ; metabolism ; Male ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Vasodilator Agents ; pharmacology

OBJECTIVETo examine the correlation between the health-related quality of life measured by the St. George's Respiratory Questionnaire (SGRQ) and the commonly used physiological measures in lymphangioleiomyomatosis (LAM).

METHODSThis study retrospectively analyzed the SGRQ scores and other measures (the Borg scale of breathlessness at rest, 6-minute walking distance, blood oxygen levels, and pulmonary function) of patients diagnosed and confirmed with LAM. Altogether 38 patients between June 2007 and November 2009 were included.

RESULTSThe mean values of the SGRQ three components (symptoms, activity, and impacts) and total scores in the LAM patients were 46.95 +/- 28.90, 58.47 +/- 25.41, 47.89 +/- 29.66, and 51.11 +/- 26.35, respectively. The SGRQ total or component scores were correlated well with the Borg scale of breathlessness, 6-minute walking distance, partial pressure of oxygen in arterial blood, spirometry and diffusion capacity of lung. There were poor correlations between SGRQ score and residual volume or total lung capacity. In our preliminary observation, sirolimus improved the SGRQ total and three component scores and the Borg scale of breathlessness significantly after 101-200 days of treatment (n = 6).

CONCLUSIONSThe SGRQ score in LAM is correlated well with physiological measures (Borg scale of breathlessness, 6-minute walking distance, blood oxygen levels, and pulmonary function tests). The SGRQ could therefore be recommended in baseline and follow-up evaluation of patients with LAM. Treatment with sirolimus, an inhibitor of mammalian target of rapamycin, may improve the quality of life and patient's perception of breathlessness in LAM.

Adult ; Forced Expiratory Volume ; Humans ; Lymphangioleiomyomatosis ; physiopathology ; psychology ; Middle Aged ; Quality of Life ; Residual Volume ; Surveys and Questionnaires ; Vital Capacity