Objective:To evaluate the outcome and prognostic factors of conventional radiotherapy followed by intensity-modulated radiation therapy (IMRT) as a boost combined with chemotherapy in the treatment of high-grade gliomas (HGG). Methods:From Nov. 2004 to Nov. 2006, 112 HGG patients were treated with conventional radiotherapy followed by IMRT as a boost combined with chemotherapy. The radiotherapy regimen included first-course conventional radiotherapy and latE-course IMRT as a boost with the total radiation dosage of 57.5- 62.5Gy (27-29 fractions in 37-45 days). All the patients received chemotherapy. Sixty-three patients received temozolomidE-based chemotherapy and 49 patients received semustine plus teniposide chemotherapy. The treatment reaction was recorded. The overall survival rate and local progression-free survival rate were calculated. The prognostic factors were analyzed by using multivariate COX regression model. Results:The acute treatment toxicity was the most at grade 1 to grade 2 and no grade 4 adverse reaction was observed. Three cases had late radiation-induced brain necrosis. The overall 1-, 2-, and 3-year survival rates were 78.9%, 54.7%, and 30.8%, respectively. Multivariate analysis revealed that tumor location (P=0.001) and KPS score (P=0.011) were independent prognostic factors. The 1-, 2-, 3-year local progression-free survival rates were 63.8%, 38.9%, and 10.5%, respectively. Multivariate analysis revealed that tumor location (P=0.001), KPS score (P=0.001), and histologic type (P=0.005) were independent prognostic factors. Multivariate analysis did not reveal the significant correlation of temozolomide chemotherapy with the prognosis of the patients. Conclusion:Postoperative conventional radiotherapy followed by IMRT as a boost combined with chemotherapy has better short-term efficacy in the treatment of HGG and the adverse reaction is tolerable. KPS score, tumor location, and histologic type are important prognostic factors. Temozolomide chemotherapy is not associated with the prognosis of patients.

Objective To evaluate the efficacy of the treatment of hilar biliary malignant obstruc tion with multiple stent drainage.Methods One hundred and twenty-seven patients with malignant biliary hilar obstruction were enrolled.The obstructions at the common hepatic duct within less than 1 cm to the junction of the left and the right hepatic duct were found in 66 cases,at the proximal common hepatic duct and the left and the right hepatic ducts in 45 cases,at the right hepatic duct in 5 cases and at the both left and right hepatic duets in 11 cases.Sixty-six patients received stent placement through the right biliary ducts and the common bile duct by puncturing the right mid-axillary line.The other 37 patients received 2 stents placement (disposed"Y"style) through the left and the right hepatic duct punc turing routway.Seven patients received 2 stents placement (disposed"┌"style) through the right hepatic duct and the common bile duct with a stent placed between the left and the right hepatic duct.Three patients had right hepatic duct stent placed first,followed by right hepatic duct and common hepatic duct stent. Twelve patients had stents placed in the right hepatic duct with external drainage from the left hepatic duct. Two patients had multiple strictures at the right hepatic duct,who got multiple external drainages.The total serum bilirubin levels were measured pre-and post-operatively.Results One hundred and twenty-seven patients with bi[iary obstraction had internal stents placed for drainage.The average total bilirubin levels among 121 patients were (283.4?175.4 )?mol/L pre-operation and (63.2?11.8)?mol/L post-operation (P

OBJECTIVE: To observe the in vivo activity of Ranti-HER, a fully human monoclonal antibody, and combined with the doxorubicin or CPT-11 in established human tumor xenografts in nude mice, and to investigate whether EGFR expression is correlated with this activity. METHODS: The overall receptor of EGF was quantified by flow cytometry. The anti-tumor effects of Ranti-HER were evaluated using established, s /c human carcinoma xenografts in nude mice, and the relative growth rate of tumor was used to assess the anti-tumor activity. RESULTS: A431 cells showed highly expression of EGFR by flow cytometry, SW620 showed negative expression, and EGFR were expressed positively in HT29 and SW948 cells, but both of them were showed low expression. Ranti-HER(0.25-1.0 mg) could inhibit the tumor growth in human A431 epidermoid carcinoma xenografts and dose-effect relationship was observed; Ranti-HER(1.0 mg) could also inhibit the tumor growth in human SW948 colon carcinoma xenografts, but no anti-tumor effects of Ranti-HER 1.0 mg were observed in human HT29 and SW620 colon carcinoma xenografts. Therapeutic enhancement was observed in the A431 xenografts after treatment with Ranti-HER combined with doxorubicin. For another combination regimens, Ranti-HER and CPT-11 proved to be significantly more efficacious than Ranti-HER monotherpy in SW948 xenografts. CONCLUSION: Antitumor activity of Ranti-HER are observed in xenografts in athymic nude mice, and the activity of Ranti-HER is correlated with the EGFR expression; synergistic effects are observed when Ranti-HER is combined with chemicals compared to Ranti-HER monotherapy.

Drug-induced arrhythmia is one of the main causes of failure in drug development, and it is also a major cause of drug withdrawal, therefore, accurate prediction of drug-induced arrhythmia in the non-clinical research stage is the best way to reduce cost. Literature was retrieved by formally searching PubMed, Metstr, CNKI and Baidu Scholar, 1 479 published articles were found through search method, 63 full-text articles were included. After reviewed the relevant literatures, the advantages and disadvantages of the different experimental cells and the related evaluation methods are assessed, in order to provide reference for toxicity evaluation.

Objective:To investigate the effect of serum cystatin C level on the occurrence and its long-term prognosis of contrast agent-induced acute kidney injury(CI-AKI)after percutaneous coronary intervention(PCI)in elderly patients.Methods:A total of 848 elderly patients(≥60 years)undergoing PCI in our department between Mar 2015 and Dec 2017 were enrolled in a prospective cohort.The CI-AKI was defined as the increase of serum creatinine ≥44.2 μmol/L within 48-72 h after using iodine contrast agent or more than 25 % higher than base level within 48-72 h after PCI.A receiver operating characteristic curve was used to analyze the optimal cut-off value of Cystatin C for predicting CI-AKI after PCI.Patients were divided into 2 groups based on the optimal cut-off value of Cystatin C: the high Cystatin C group(Cystatin C ≥1.3 mg/L, n=178)and the control group(Cystatin C<1.3 mg/L, n=670). The differences in the incidence of CI-AKI after PCI and major adverse cardiac events(MACE)at 1 year follow-up were compared between the two groups.The Cox regression model was further used to analyze the predictors of the long-term prognosis after PCI.Results:Of 848 patients receiving PCI, the incidence of CI-AKI was 9.4%.The incidence of MACE at 1 year after PCI was higher in the high Cystatin C group than in the control group(15.7% vs.9.3%, χ2=6.524, P=0.011). Cox regression analysis confirmed that the high baseline level of Cystatin C was the most independent predictive factor for MACE at 1 year of follow-up( HR=16.244, P<0.001). Conclusions:The high baseline level of Cystatin C(≥1.3 mg/L)is an independent risk factor for CI-AKI and is also the most important predictor for the occurrence of long-term MACE in elderly patients undergoing PCI.

OBJECTIVETo isolate and purify a new type of lipopolysaccharide binding protein (LBP) from burn rabbit serum, and to investigate its biological functions.

METHODSRabbits subjected to burn injury and endotoxemia were employed. The serum from the rabbits was purified by two-steps of ion-exchange chromatography (Bio-Rex 70 Resin, Mono-Q) and gel chromatography. Furthermore, the serum was identified by flow cytometry analysis, agglomeration test with sheep erythrocyte, and amino end amino acid residue sequencing. The obtained protein was applied to cultured human monocytes (U937), and the cytokine secretion such as TNFalpha from the U937 was observed.

RESULTSThe molecular weight of the harvested protein was 48 kDa, and the 10 amino acid sequence at N end was arranged as GSQGTFTSEE, which was different to the amino acid sequence in NCBI protein bank and was so named P48. P48 possessed similar function to that of LBP and could promote the binding of LPS in a very low concentration with peripheral blood monocytes (PBMC), and also promote the TNFalpha secretion from U937.

CONCLUSIONP48, a new type of LBP, could be isolated and purified from the burn rabbit serum. P48 possessed similar biological activities to that of LBP and could promote the process of inflammatory reaction.

Acute-Phase Proteins ; Amino Acid Sequence ; Animals ; Binding, Competitive ; drug effects ; Blood Proteins ; chemistry ; isolation & purification ; pharmacology ; Burns ; blood ; Carrier Proteins ; chemistry ; isolation & purification ; pharmacology ; Chromatography, Gel ; Chromatography, Ion Exchange ; Female ; Flow Cytometry ; Humans ; Leukocytes, Mononuclear ; cytology ; drug effects ; metabolism ; Lipopolysaccharides ; metabolism ; Male ; Membrane Glycoproteins ; Rabbits ; Sequence Analysis, Protein ; Tumor Necrosis Factor-alpha ; secretion ; U937 Cells

BACKGROUNDIncreasing evidence suggests that many neurons may die through apoptosis in Alzheimer's disease (AD). Mitochondrial dysfunction has been implicated in this process of neuronal cell death. One promising approach for preventing AD is based upon anti-apoptosis to decrease death of nerve cells. In this study, we observed the memory improving properties of curcumin in mice and investigated the neuroprotective effect of curcumin in vitro and in vivo.

METHODSThe mice were given AlCl(3) orally and injections of D-galactose intraperitoneally for 90 days to establish the AD animal model. From day 45, the curcumin group was treated with curcumin for 45 days. Subsequently, the step-through test, neuropathological changes in the hippocampus and the expression of Bax and Bcl-2 were carried out to evaluate the effect of curcumin on the AD model mice. In cultured PC12 cells, AlCl(3) exposure induced apoptosis. The MTT assay was used to measure cell viabilities; flow cytometric analysis to survey the rate of cell apoptosis; DNA-binding fluorochrome Hoechst 33258 to observe nuclei changes in apoptotic cells and Western blot analysis of Bax, Bcl-2 to investigate the mechanisms by which curcumin protects cells from toxicity.

RESULTSCurcumin significantly improved the memory ability of AD mice in the step-through test, as indicated by the reduced number of step-through errors (P < 0.05) and prolonged step-through latency (P < 0.05). Curcumin also attenuated the neuropathological changes in the hippocampus and inhibited apoptosis accompanied by an increase in Bcl-2 level (P < 0.05), but the activity of Bax did not change (P > 0.05). AlCl(3) significantly reduced the viability of PC12 cells (P < 0.01). Curcumin increased cell viability in the presence of AlCl(3) (P < 0.01). The rate of apoptosis decreased significantly in the curcumin group (P < 0.05) when measured by flow cytometric analysis. Curcumin protected cells by increasing Bcl-2 level (P < 0.05), but the level of Bax did not change (P > 0.05).

CONCLUSIONSThis study demonstrates that curcumin improves the memory ability of AD mice and inhibits apoptosis in cultured PC12 cells induced by AlCl(3). Its mechanism may involve enhancing the level of Bcl-2.

Aluminum Compounds ; toxicity ; Alzheimer Disease ; drug therapy ; psychology ; Animals ; Apoptosis ; drug effects ; Cells, Cultured ; Chlorides ; toxicity ; Curcumin ; pharmacology ; therapeutic use ; Disease Models, Animal ; Female ; Learning ; drug effects ; Memory ; drug effects ; Mice ; Neuroprotective Agents ; pharmacology ; PC12 Cells ; Rats

Radiotherapy is a treatment for cancer with undesired by-effects. In order to develop a new radiation protective agent that could reduce the by-effects, we tried to express and purify human cryptochrome 1 (hCRY1). The coding sequence of hCRY1 was inserted into prokaryotic expression plasmid pET28a(+), and this protein was purified from Escherichia coli BL21(DE3) after IPTG induction, ultrasonication, inclusion body dissolution, gradient dialysis, nickel column purification and ultrafiltration. The yield of hCRY1 in 1 L E. coli culture (LB medium) was about 10-15 mg. The radiation protective efficiency of hCRY1 was monitored by detecting X-ray-induced H2A.X foci in HaCaT cells. The results of immunofluorescence show that hCRY1 significantly reduces X-ray stimulated DNA damage response. The apoptosis of HaCaT cell was also detected, and the repression of H2A.X foci formation was not due to hCRY1's cytotoxity. All these data suggest a potential application of recombinant hCRY1 as a protective agent for radiotherapy.
Cryptochromes ; biosynthesis ; Escherichia coli ; Humans ; Plasmids ; Radiation-Protective Agents ; Recombinant Proteins ; biosynthesis

BACKGROUNDThe American Heart Association/American Stroke Association proposed a metric called Life's Simple 7 (LS7) to define cardiovascular health (CVH). The presence of a large number of ideal components of CVH is associated with lower cardiovascular disease and all-cause mortality. We aimed to assess CVH using LS7 in a Chinese population undergoing primary and secondary stroke prevention.

METHODSPatients with either ischemic stroke or cardiovascular risk factors were enrolled in the study from October 2010 to July 2013. LS7 components were scored as poor (0 points), intermediate (1 point), or ideal (2 points). The overall LS7 score was categorized as inadequate (0-4), average (5-9), or optimal (10-14) CVH. The Chi-square test, Mann-Whitney U-test, and Kruskal-Wallis test were used.

RESULTSIn total, 706 patients were enrolled. (1) The distribution of the overall LS7 score (n = 255) indicated that 9.4%, 82.4%, and 8.2% of the patients had inadequate, average, and optimal CVH, respectively. The proportion of patients with optimal CVH undergoing secondary stroke prevention was lower than that for patients undergoing primary stroke prevention (3.8% vs. 12.8%, P = 0.005). The vast majority of participants (76.1%) presented with ≤2 ideal health components. (2) The proportions of patients with poor, intermediate, and ideal status, respectively, for the following LS7 components were assessed : t0 otal cholesterol (n = 275; 5.1%, 73.8%, and 21.1%), blood pressure (n = 351; 32.5%, 59.0%, and 8.5%), blood glucose (n = 280; 9.3%, 39.6%, and 51.1%), physical activity (n = 540; 90.7%, 8.7%, and 0.6%), diet (n = 524; 0.2%, 92.4%, and 7.4%), smoking (n = 619; 20.7%, 2.9%, and 76.4%), and body mass index (n = 259; 6.6%, 35.5%, and 57.9%).

CONCLUSIONSFew Chinese patients undergoing stroke prevention had optimal CVH (determined using LS7). Additionally, fewer patients undergoing secondary prevention had optimal CVH than those undergoing primary prevention. In particular, physical activity and diet status in this population require improvement.

Aged ; Aged, 80 and over ; American Heart Association ; Blood Glucose ; metabolism ; Blood Pressure ; physiology ; Body Mass Index ; Cholesterol ; blood ; Female ; Humans ; Male ; Middle Aged ; Motor Activity ; physiology ; Risk Factors ; Smoking ; adverse effects ; Stroke ; blood ; prevention & control ; United States

The high price of the reference substances is an obstacle for the HPLC analysis of Lonicerae Japonicae Flos. To solve this problem, a new method based on the standard reference extract (SRE) was proposed. In this study, the extract of Lonicerae Japonicae Flos was calibrated, and the long-term stability was investigated. Different concentration solutions of SRE were prepared for establishment of the calibration profiles, and 6 organic acids were determined. T-test was used for the comparison of the determination results via reference substances and SRE, and the results demonstrated that there is no significant difference between the two methods. The presented method can be used for the quality control of Lonicerae Japonicae Flos, and will also offer reference to resolve similar problems.
Flowers ; chemistry ; Lonicera ; chemistry ; Plant Extracts ; standards ; Quality Control ; Reference Standards