Objective Multimeric cyclic RGD (Arg-Gly-Asp) peptides are capable of improving the integrin αvβ3-binding affinity due to the polyvalence effect.In this study,the authors prepare 99Tcm-la-bearing cyclic RGD tetramer E{E[c(RGDfK)]2}2,and evaluate its biodistribution and imaging in nude mice beating U87 MG human glioma xenografts with integrinαvβ3-positive.Methods 99Tcm-hydrazino-nictinamide (HYNIC)-E{E[c(RGDfK)]2}2 was prepared by two-step method,while HYNIC wag chosen as bifunctional chelator,and tricine and trisodium triphenylphosphine-3,3,3-trisuifonate (TPPTS) as coligands.The af-finity of c (RGDyK) monomer,HYNIC-E[c(RGDfK)]2 dimer and HYNIC-E{E[c(RGDfK)]2}2 tetramer to integrin αvβ3 was compared by in vitro competitive assay against binding of 125I-c(RGDyK)to integrin αvβ3.positive U87 MG human glioma cells.The biodistribution [the percentage of injection dose per gram of tissue(%ID/g)] and imaging were performed in nude mice bearing UB7MG human glioma xenografts.Re-suits The labeling yield of 99Tcm-HYNIC-E{E[c(RGDfK)2}2 was over 95%,and the radiochemical purity was more than 99%after purification with Sop-Pak C18 cartridge.The 50%inhibiting concentration (IC30) val-ues of c(RGDyk),HYNIC-E[c(RGDfK)]2 and HYNIC-E{E[c(RGDfK)]2}2 were 85.9,9.5 and 4.5 nmol/L, respectively.The result indicated that RGD tetramer possessed a significantly higher affinity to in-tegrinαvβ3.The biodistribution data showed that 99Tcm-HYNIC-E{E[c(RGDfK)]2}2 was excreted mainly through kidneys.The tumor uptake of 99Tcm-HYNIC-E{E[c(RGDfK)]2}2 was two times higher than 99Tcm- HYNIC-E[c(RGDfK)]2,at 1h postinjection,with the uptake of(10.32±0.07)%ID/g and(5.15±0.52)%ID/g,respectively,which was consistent with the in vitro competitive binding data.The tumor up-tale of 99Tcm-HYNIC.E{E[c(RGDfK)]2}2 was still as higher as(9.35±1.35)%ID/g at 4 h postinjec-tion, which demonstrated that the retention time of radiotracer in tumor was long enough.The imaging showed that tumor was clearly visualized at 1h postinjection,and the image at 4 h postinjection Was better.Conclusion The higher tumor uptake and longer retention time in tumor make 99Tem-HYNIC-E{E[c(RG-DfK)J 2}2 a promising radiotracer for integrinαvβ3-positive tumors imaging,furthermore,suggest that radi-onuelides(such as 90Y).1abeled RGD tetramer is more suitable for the therapy of integrin αvβ3-positive tumors.

Objective:To explore the protective effect of agmatine on mice with multiple organ failure (MODS) induced by yeast polysaccharide(ZYM) on the expression of inflammatory factors.Methods:ZYM induced inflammation model was established by intraperitoneal injection of ZYM in mice.All mice were divided into blank group,ZYM group and ZYM+AGM group.The mice feeding, white cell count,heart rate and so on were observed before and after the modeling to determine whether the model was successful.The liver function of mice,renal function,myocardial enzymes and other biochemical indicators were detected after the success of the model;and through the qPCR and ELISA method for detection of blood tumor necrosis factor alpha (TNF-alpha),interleukin 1 beta (IL-1 beta),interleukin 6 (IL-6),IL-10 gene and protein secretion level.Results: After the injection of ZYM,mice looked disorganized, activity and reduce consumption;the functional serological indexes of various organs of the mice were detected,which showed that the function of the viscera was serious.Compared with the blank control group,the serum parameters of ZYM group and ZYM+AGM group were significantly higher,and the inflammatory factors TNF-α,IL-1,IL-6 and IL-10 were significantly increased (P<0.05).Compared with ZYM group,ZYM+AGM serum markers of organ function decreased,inflammatory factor TNF-α,IL-1β,IL-6 decreased significantly (P<0.05),while there was no significant difference in IL-10 (P>0.05); and the mouse spirit,eating and activity had no significant change.Conclusion:Intraperitoneal injection of 500 mg/kg ZYM can successfully construct a model of MODS,AGM by reducing the release of inflammatory factors,play a protective role in the function of various organs of MODS mice.

BACKGROUND:Antibiotic loaded bone cement has been well studied in clinical prevention and treatment of postoperative infection after artificial joint replacement. However, little is reported on antituberculotic-loaded bone cement. OBJECTIVE:To investigate the drug release properties of polymethyl methacrylate bone cement carrying antituberculosis drugs in a simulated body fluid (phosphate buffer solution, PBS). METHODS:The bone cement SimpLex P and antituberculosis drugs, including pyrazinamide, isoniazid, rifapentine, prothionamide, capreomycin, rifampicin, moxifloxacin, and amikacin, were mixed at 40 g:1.5 g and 40 g: 2.5 g ratios to prepare 16 groups of experimental specimens (n=5 per group). In addition, 40 g of bone cement powder was mixed with the liquid monomer to prepare a group of non-loaded bone cement specimens (control group,n=5). Either experimental or control specimens were soaked in PBS simulated body fluid, and then the extractions were taken at different time points to measure concentrations of antituberculosis drugs by high performance liquid chromatography. RESULTS AND CONCLUSION:The effective sustained-releasing time in the PBS simulated body fluid was 45 and 60 days for 1.5 g and 2.5 g groups of pyrazinamide, was 60 and 45 days for 1.5 g and 2.5 g groups of isoniazid, was 60 and 45 days for 1.5 g and 2.5 g groups of rifapentine, was 150 and 150 days for 1.5 g and 2.5 g groups of protionamide, was 150 and 150 days for 1.5 g and 2.5 g groups of capreomycin, was 45 and 60 days for 1.5 g and 2.5g groups of rifampicin, was 90 and 90 days for 1.5 g and 2.5 g groups of moxifloxacin, and was 60 and 90 days for 1.5 g and 2.5 g groups of amikacin, respectively. All the drug carriers had good drug release characteristics. Especially the 1.5 g and 2.5 g groups of protionamide, 1.5 g and 2.5 g groups of capreomycin, 1.5 g and 2.5 g groups of moxifloxacin and 2.5 g group of amikacin showed a longer period of drug release in accordance with the clinical need. However, our preliminary findings showed that the mechanical strength of the composite bone cement was considerably reduced by isoniazid, rifampicin, rifapentine, or protionamide, while the SimpLex P bone cement carrying pyrazinamide, amikacin, moxifloxacin, or capreomycin showed no changes in the mechanical strength. Therefore, pyrazinamide, amikacin, moxifloxacin, and capreomycin are suitable for the preparation of bone cements carrying antituberculosis drugs.

Adult ; China ; epidemiology ; Female ; Humans ; Male ; Mental Health ; Middle Aged ; Police ; Young Adult

Objective To observe the clinical efficacy of arthroscopy and fibula osteotomy in the treatment of medial knee osteoarthritis.Methods Thirty-six patients with medial knee osteoarthritis treated in our hospital from September 2014 to September 2016 were divided into two groups according to the acceptable surgical protocol.The control group was treated by fibula osteotomy,and the observation group received arthroscopy combined with fibula osteotomy.The clinical signs and symptoms,VAS and ISOA scores were evaluated and compared between the two groups.Results The control group of 18 cases,clinical recovery in 0 cases,markedly effective in 7 cases,effective in 8 cases,3 cases with no effect,the effective rate was 38.9％;observation group of 18 cases,3 cases clinically cured,effective in 10 cases,effective in 5 cases,the effective rate was 72.2％.The effective rate of observation group was better than that of the control group,the difference was signicant (P ＜ 0.05).VAS and ISOA in both groups were significantly improved after operation,the difference was signicant (P ＜ 0.05);VAS improvement in observation group was better than that in control group,the difference was signicant(P ＜ 0.05),ISOA score in observation group was significantly better than that in control group,the difference was signicant(P ＜0.01).The clinical signs and symptoms(pain and numbness,walking,living and working abilities,tenderness,straight leg raising test,knee and Achilles reflex,total score) in two groups were improved respectively compared with those before treatment,and the differences were statistically significant(P ＜ 0.05).The pain and numbness,walking,tenderness,straight leg raising test and total score in the observation group were significantly different from those in the control group(P ＜ 0.05).Conclusion The arthroscopy and fibula osteotomy is safe and feasible to treat patients of medial knee osteoarthritis with less traumatic,more effective and better functional recovery.

OBJECTIVETo evaluate the association of C-reactive protein/albumin ratio (CAR) with the prognosis of patients with colorectal cancer and compare the prognostic value of CAR with other inflammation-based prognostic scoring systems.

METHODSWe retrospectively evaluated 163 newly diagnosed colorectal cancer patients in Nanfang Hospital between January, 2007 and December, 2014. All recommended cutoff values of the clinicopathological factors were defined using receiver- operating characteristic (ROC) curve analyses. We evaluated the prognostic value of CAR in comparison with Glasgow Prognostic Score (GPS) and neutrophil lymphocyte ratio (NLR) with the area under the ROC curve. Univariate and multivariate analyses using the Cox proportional hazards model were performed to identify the factors closely associated with overall survival of the patients. Kaplan-Meier analysis was used to compare overall survival curves between patients with a high CAR and those with a low CAR.

RESULTSThe recommended cutoff value of CAR was 0.132. Kaplan-Meier analysis and log rank test demonstrated a significant difference in the overall survival between patients with a low CAR (<0.132) and those with a high CAR (≥0.132) (2157.0∓395.3 vs 1661.0∓136.4 days, P<0.001). The area under the ROC curve of CAR, NLR and GPS was 0.656, 0.550 and 0.642, respectively, indicating a better prognostic value of CAR. Univariate analyses showed that age, C-reactive protein, albumin, CAR, NLR, GPS, platelet, TMN stage, Dukes stage and chemotherapy regimens were associated with the overall survival of the patients (P<0.05). Multivariate analyses showed that TMN stage [HR=1.689 (95%CI: 1.146-2.488), P=0.008] and Dukes stage [HR=2.447 (95%CI: 1.349-4.441), P=0.003] were associated with the overall survival of the patients.

CONCLUSIONSSimilar to the previously reported inflammation-based prognostic systems (GPS and NLR), CAR is useful for predicting the survival of patients with colorectal cancer and can be complementary to the two prognostic scoring systems.

OBJECTIVETo explore the CT criteria for evaluating lymph node (LN) metastasis and preoperative N-staging of gastric cancer through the comparison of CT signs and surgical pathology.

METHODSEighty-nine patients with gastric cancer underwent CT examinations before radical resections. A soft-reading method on PACS workstation was employed to evaluate the detection of LNs. The size and number of LNs were registered, and the accumulated size of LNs was calculated in every case. The pathological N-staging (pN(0-3)) was considered on the basis of pathological examination of excised specimens according to UICC TNM-staging system (6th edition, 2002). The relationships between LN metastases and CT findings were analyzed by SPSS using t test and one-way ANOVA analysis.

RESULTSThe distribution of maximal size, CT detection number and accumulated size were significantly different among different pN stages (P<0.01). All these 3 indicators were significantly different between LN metastasis group and non-metastasis group (P<0.01). There was no significant difference of maximal size among different pN stages in positive metastasis LNs (P>0.05), while significant difference could be found in CT detection number between pN1 and pN3 (P<0.01), pN2 and pN3 (P<0.01), and in accumulated size between pN1 and pN3 (P<0.01), pN1 and pN2 (P<0.01).

CONCLUSIONSThe involvement of LNs in gastric cancer and pN staging are associated with size, number, and accumulated size of CT detection. CT detection number is more valuable in the evaluation of N staging than LNs size. CT detection number combined with accumulated size of LNs can provide meaningful information for preoperative N-staging.

Adult ; Aged ; Female ; Humans ; Lymphatic Metastasis ; diagnostic imaging ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; methods ; Stomach Neoplasms ; diagnostic imaging ; pathology ; Tomography, X-Ray Computed

OBJECTIVETo investigate the correlation of the mRNA expression level of excision repair cross-complementing group 1 (ERCC1) gene with clinicopathological parameters and clinical outcome in patients with non-small cell lung cancer (NSCLC) receiving platinum-based chemotherapy.

METHODSThe mRNA expression of ERCC1 in formalin-fixed paraffin-embedded primary tumor specimens was measured by real-time quantitative reverse transcriptase polymerase chain reaction. The association between ERCC1 expression levels and clinicopathological parameters in NSCLC patients was analyzed.

RESULTSThe median value of ERCC1 mRNA expression level compared with beta-actin in tumor specimens of 61 NSCLC patients was 0.48. There was no correlation between ERCC1 expression and clinicopathological parameters. Patients with low expression of ERCC1 mRNA (less than 0.35, 0.28, respectively) had a significantly longer median time to progression (TTP) (14.3 vs. 8.0 months, P = 0.028) and overall survival (OS) (28.4 vs. 12.9 months, P = 0.0064) than those with high expression. Multivariate analysis showed that a low ERCC1 mRNA expression was an independent factor for OS.

CONCLUSIONOur findings suggest that intratumoral ERCC1 mRNA expression level, although is uncorrelated with clinicopathological parameters, is an independent predictive marker for survival of the patients with NSCLC receiving platinum-based chemotherapy, and may provide critical information for personalized chemotherapy.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Neoplasms ; secondary ; Brain Neoplasms ; secondary ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; metabolism ; pathology ; secondary ; Cisplatin ; administration & dosage ; DNA-Binding Proteins ; genetics ; metabolism ; Disease-Free Survival ; Endonucleases ; genetics ; metabolism ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; drug therapy ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Paraffin Embedding ; Platinum ; administration & dosage ; Proportional Hazards Models ; RNA, Messenger ; metabolism ; Survival Rate

Using a combination of various chromatographic techniques including column chromatography over silica gel, Sephadex LH-20, macroporous adsorbent resin, and reversed-phase HPLC, 115 compounds including diterpenes, sesquiterpenes, treterpenes, coumarins, lignans, fatty acid derivatives, and simple aromatic derivatives were isolated from an ethanol extract of branch of Fraxinus sieboldiana (Oleaceaue), and their structures of the compounds were elucidated by spectroscopic methods including 1 D, 2D NMR and MS techniques. Among them, 41 compounds were new. In previous reports, we have been described the isolation, structure elucidation, and bioactivities of the 41 new compounds and 22 known orii including 8 coumarins, 4 phenolic and 12 phenylethanoidal glycosides. As a consequence, we herein reported the isolation and structure elucidation of the remaining 50 known compounds including 8- hydroxy-12-oxoabieta-9(11),13-dien-20-oic 8, 20-lactone(1), 6beta-hydroxyfcrruginol(2),(+)-pisiferic acid(3), (+)-pisiferal(4),(+)-7-dehydroabiet6none(5), 1-oxomiltirone(6), subdigitatone(7), linarionoside B(8), (9S)-linarionoside B(9), (3R,9R)-3-hydroxy-7,8-dihydro-beta-ionol 9-O-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside(10), ursolic acid(11), betulinic acid(12), euscaphic acid(13), (+)-syringaresinol(14), (+)-fraxiresinol(15), (+)-1-hydroxysyringaresinol(16), pinoresinol(17), medioresinol(18), 8-acetoxypinoresinol(19), epipinoresinol(20), (-)-olivil(21), (+)-cyclo-olivil(22), 3,3'-dimethoxy-4,4',9-trihydroxy-7,9'-epoxylignan-7'-one(23),(+)-1-hydroxypinoresinol 4'-O-beta-D-glucopyranoside (24), (+)-1-hydroxypinoresinol 4"-O-beta-D-glucopyranoside(25),(+)-syringaresinol O-beta-D-glucopyranoside (26), liriodendrin (27), ehletianol D(28), icariside E5(29) (-)-(7R, 8R)-threo-1-C-syringylglycerol(30),(-)-(7R, 8S)-erythro-guaiacylglycerol (31),(-)-(7R, 8R)-threo-guaiacylglycerol(32), 3-(4-beta-D-glucopyranosyloxy-3-methoxy)-phenyl-2E-propenol(33),2,3-dihydroxy-l-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone(34), 2,3-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)-1-propanone (35), 3-hydroxy-l-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone(36), omega-hydroxypropioguaiacone(37), sinapyladehyde(38), trans-p-hydroxycinnamaldehyde(39), syringic acid(40), vanilic acid(41), vanillin(42), 4-hydroxy-benzaldehyde (43), (24R)-24-ethyl-5alpha-cholestane-3beta,5,6beta-triol(44), beta-sitosterol(45), daucosterol(46), 2,6-dimethoxy-I,4-benzoquinone(47), 2,6-dimethoxy-pyran-4-one(48), 1-(beta-D-ribofuranosyl)uracil(49), and mannitol(50). Compouds 1-7,12,18,28-37,44 and 48 were obtained from the genus Fraxinus for the first time.
Fraxinus ; chemistry ; Magnetic Resonance Spectroscopy ; Mass Spectrometry ; Plant Extracts ; analysis

OBJECTIVE: To explore whether MRI fusion technology (combined T2-weighted imaging [T2WI] and fat-suppressed T2WI [T2WI-(FS)]) improves signal differences between anal fistulas and surrounding structures. MATERIALS AND METHODS: A total of 32 patients with confirmed diagnoses of anal fistula were retrospectively studied. All available T2WI and T2WI-(FS) images for each patient were used to generate fusion image (T2WI-(Fusion)) based on the addition of gray values obtained from each pixel via an MR post-processing work station. The discriminability of fistula, perianal sphincter, and perianal fat in T2WI, T2WI-(FS), and T2WI-(Fusion) images was quantified with Fisher's scoring algorithm. For subjective visual image assessment by researchers, five-point scale scores were determined using a modified double-stimulus continuous quality-scale test to evaluate T2WI-(FS), T2WI, enhanced axial three-dimensional-volumetric interpolated breath-hold examination (3D-VIBE), and T2WI-(Fusion) sequence images. The differences were subsequently compared. RESULTS: Mean Fisher scores for fistulas vs. sphincters obtained from T2WI-(Fusion) (F(Fusion-fistula) = 6.56) were significantly higher than those from T2WI (F(T2WI-fistula) = 3.35) (p = 0.001). Mean Fisher scores for sphincters vs. fat from T2WI-(Fusion) (F(Fusion-sphincter) = 10.84) were significantly higher than those from T2WI-(FS) (FS(FS-sphincter) = 2.57) (p = 0.001). In human assessment, T2WI-(Fusion) showed the same fistula discriminability as T2WI-(FS), and better sphincter discriminability than T2WI. Overall, T2WI-(Fusion) showed better discriminability than T2WI, T2WI-(FS), and enhanced 3D-VIBE images. CONCLUSION: T2WI and T2WI-(FS) fusion technology improves signal differences between anal fistulas and surrounding structures, and may facilitate better evaluation of anal fistulas and sphincters.
Anal Canal ; Diagnosis ; Fistula ; Humans ; Magnetic Resonance Imaging ; Rectal Fistula ; Retrospective Studies