Clinicoradiological features associated with epidermal growth factor receptor exon 19 and 21 mutation in lung adenocarcinoma.

AIM: To retrospectively identify clinicopathological and radiological characteristics that could be independent predictors of epidermal growth factor receptor (EGFR) exon 19 and 21 mutation in surgically resected lung adenocarcinomas in a cohort of Asian patients. MATERIALS AND METHODS: Demographics, histopathology data, and preoperative chest computed tomography (CT) images were evaluated retrospectively in 471 surgically resected lung adenocarcinomas. A total of 24 CT descriptors were assessed. Univariate analyses and multivariate logistic regression analyses were performed to identify independent predicted factors of harbouring EGFR mutations. RESULTS: EGFR mutations were existed in 252 (53.5%) of 471 patients, and associated with 11 clinicoradiological features. For the model with both clinical and radiological features, the independent predictors of harbouring EGFR mutation were small maximum diameter (≤3.9 cm), non-smokers, micropapillary pattern, pleural retraction, vascular convergence, and absence of solid pattern. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.784. Multivariable logistic regression analysis indicated that non-smokers, vascular convergence, and absence of solid pattern were important independent predictors of EGFR exon 19 mutation, while non-smokers and vascular convergence were independent predictors of EGFR exon 21 mutation. The AUCs were 0.807 and 0.794, respectively. A lepidic growth pattern appeared more frequently in exon 21 mutant tumours than in exon 19 mutant group (p<0.001). CONCLUSION: CT imaging features of lung adenocarcinomas in combination with clinical variables could be used to prognosticate EGFR mutation status. The separate analysis of EGFR exon 19 or 21 mutation could further improve diagnostic performance.

Carfilzomib combined with ex vivo-expanded patient autologous natural killer cells for myeloma immunotherapy.

Natural killer (NK) cell-based immunotherapy is promising, as NK cells are in the first line of defense against cancer and capital of lysing tumor cells without pre-stimulation. However, NK cells from multiple myeloma (MM) patients are always deficient in numbers and the expression of certain activating receptors, disabling them in cytotoxicity against the cancer. Therefore, effective strategies to expand NK cells and increase NK cell-mediated cytotoxicity against MM are significant. Here, NK cells were efficiently expanded from peripheral blood mononuclear cells (PBMCs) of newly diagnosed MM patients after co-culture with irradiated K562 cells transfected with 41BBL and membrane-bound interleukin (IL)-15 (K562-mb15-41BBL) in the presence of 200 IU/ml human IL-2. The ex vivo-expanded NK cells were demonstrated to vigorously kill both MM cells and autologous primary MM cells without significant lysis of patient normal cells. Further exploration revealed a significant increase in cell surface expression of most activating receptors of NK cells and indicated that expanded NK (exp-NK) cell killing of MM cells was mediated by perforin/granzyme. NK cells are capital of lysing human leukocyte antigen (HLA) I-deficient tumor cells and carfizomib, a selective proteasome inhibitor approved for the treatment of relapsed/refractory MM patient, down-regulates the expression of HLA class I, thus enhancing NK cell-mediated lysis in MM. Here, we found for the first time that carfizomib dramatically augmented ex vivo exp-NK cell cytotoxicity against patient autologous MM cells, suggesting the use of exp-NK alone or in combination with the drug to treat MM patient.

[Clinical study of locking-taper implants in patients treated for periodontitis].

OBJECTIVE: To evaluate the survival rate and peri-implant clinical parameters of Locking-Taper implants in patients having lost their teeth due to non-periodontitis (NP) reasons, chronic periodontitis (CP) and aggressive periodontitis (AgP). METHODS: In the study, 145 subjects were installed with 315 Bicon Locking-Taper implants and followed up for 1-5 years. The subjects and implants were classified into three groups, tooth loss by NP, CP and AgP. NP included 44 subjects with 100 implants, CP 70 subjects with 132 implants and AgP 31 subjects with 83 implants. Periodontal parameters before subgingival scaling and root planning (T0), at the end of active periodontal therapy (T1) and at the time of last recall (T2) were recorded. Right after the installation of final restoration and at the time of last recall (T2), peri-implant probing parameters were recorded. RESULTS: After active periodontal therapy, mean probing depth (PD) in CP and AgP were reduced from 4.05 mm, 5.20 mm at T0 to 3.07 mm, 2.96 mm at T1 (P<0.001, P<0.001), (PD≥6 mm)% were reduced from 33.2%, 58.5% at T0 to 14.4%, 10.5% at T1 (P<0.001, P<0.001). The periodontal parameters remained stable at T2 compared with T1 (P>0.05). Cumulative survival rates of implants in NP, CP and AgP were 100%, 97.6% and 100% for 1-5 years' follow-ups with no statistical significance found. At T2, mean implant PD was 2.78 mm, 2.96 mm and 2.97 mm in NP, CP and AgP, with NP significantly lower than the other two groups (P=0.006, P=0.01). The percentage of implant sites with PD≥6 mm was 3.7% in CP and 4.8% in AgP, both significantly higher than NP (P=0.003, P<0.001). 8.4% implant sites showed at least 2 mm deeper than those at prosthesis installation were found in CP group, significantly higher than NP (4.3%, P=0.003). CONCLUSION: Periodontal conditions of patients having lost their teeth for chronic and aggressive periodontitis were significantly improved after active periodontal therapy and remained stable during 1-5 years. Short-term survival rates of Locking-Taper implants in patients treated for CP and AgP was no less than those who lost their teeth for non-periodontitis reasons. More sites with increasing peri-implant probing depth were found in CP and AgP patients, compared with NP.

[Efficacy of subgingival glycine air polishing on patients with early peri-implant diseases].

Objective: To compare the clinical efficacies of subgingival glycine air polishing and ultrasonic scaling combined with 0.12% chlorhexidine rinsing on patients with early peri-implant diseases (peri-implant mucositis and early peri-implantitis). Methods: Twenty-two systemically healthy patients with totally 42 implants and early peri-implant diseases, were recruited in this study. The patients were randomly divided into the test group and the control group. Patients in the test group were treated with subgingival glycine air polishing and patients in the control group were treated with ultrasonic scalers combined with 0.12% chlorhexidine rinsing. Periodontal parameters such as probing depth, bleeding index, plaque index and clinical attachment loss, at baseline and 2 months after treatment, respectively, were collected and compared between the test and control groups. Results: For the natural teeth, the parameters of probing depth, bleeding index, plaque index and attachment loss in the two groups were significantly improved after treatments (medians were 0.48 mm vs 0.22 mm, 1.00 vs-0.13, 0.38 vs 0.50, 0.48 mm vs 0.22 mm, respectively for test and control group). There was no statistical difference of median between the two groups after treatment except for that of the attachment loss (medians, 0.48 mm vs 0.22 mm, P=0.034). For the implants, differences of parameters in the two groups at baseline were insignificant. After treatments, the probing depths significantly decreased by 0.67 mm and 0.33 mm in the test group and the control group, respectively. The inter-group differences, however, were insignificant. Significant difference of the bleeding index after treatment was found in the test group (P=0.019), but not in the control group. No adverse reactions were found on patients in the two groups after treatments. Conclusions: Efficacy of subgingival glycine air polishing and ultrasonic scaling combined with 0.12% chlorhexidine rinsing is competitive on patients with early peri-implant diseases. However, the former treatment may be more effective oncontrolling the early peri-implant inflammation.

Left atrial diameter, flow-mediated dilation of brachial artery and target organ damage in Chinese patients with hypertension.

To investigate the relationship between left atrial (LA) size, endothelial dysfunction and different markers of target organ damage (TOD), we measured left atrial diameter (LAD) and endothelial function in hypertensive patients with or without TOD. In this study, 197 patients with hypertension were divided into four groups as follows: no TOD (Group I, n=40), one TOD (Group II, n=76), two TOD (Group III, n=46) and ≥3 TOD (Group IV, n=35). Endothelial function was assessed by endothelium-dependent vasodilatation (flow-mediated dilation, FMD) of the brachial artery. We also assessed serum creatinine, the urinary albumin-creatinine ratio (UACR), the intima-media thickness (IMT) of the common carotid, carotid to femoral pulse wave velocity (cf-PWV) and left ventricular mass index (LVMI). Our results were as follows: LA size was increased in 50.8% of patients and was associated with the number of TOD. LAD was larger in the patient groups with ≥3 TOD as compared with patients with two TOD, one TOD and no TOD. FMD was lower in patients with LAD enlargement. LAD exhibited significant relationships with serum creatinine, UACR, cf-PWV, IMT and LVMI. In stepwise multivariate regression analysis, LVMI (ß=0.37, P<0.001), BMI (ß=0.33, P<0.001), duration of hypertension (ß=0.20, P=0.001) and FMD (ß=-0.17, P=0.006) were the independent predictors of LAD. FMD significantly correlated with LAD (ß=-0.26, P=0.001), male sex (ß=-0.23, P=0.004) and pulse pressure (PP) (ß=-0.16, P<0.05). In conclusions, enlargement of LAD may be an important predictor of endothelial dysfunction and may be considered to be an indicator for evaluating TOD in hypertensive patients.

Repellent effect of pea (Pisum sativum) fractions against stored-product insects.

Peas (Pisum sativum) are toxic to some stored-product insects. The repellent effect of fractions of pea seed to stored-product insects was evaluated in multiple-choice tests in which wheat kernels were dusted with fractions rich in either protein, fibre or starch at 0.001 to 10% (wt:wt). There was a negative correlation between pea protein concentration and the number of adults found in grain for Cryptolestes ferrugineus and Sitophilus oryzae, but not for Tribolium castaneum. Pea fibre repelled C. ferrugineus adults but not S. oryzae and T. castaneum. Pea starch did not repel any of the insects. One-week old and 6-week old C. ferrugineus were equally repelled by pea protein. Repellency was detectable 1h after exposure. Cryptolestes ferrugineus and S. oryzae did not become habituated to the repellent action of pea protein even after 4 weeks of exposure. Habituation was observed, however, when C. ferrugineus was exposed to pea fibre for 4 weeks. In a two-choice bioassay (0 vs. 0.1% and 0 vs. 1% pea protein), the pea-protein-treated grain had significantly fewer insects (C. ferrugineus, S. oryzae, Sitophilus zeamais, T. castaneum, and Tribolium confusum) than untreated grain. The properties of the pea protein fractions seem well suited for developing a natural stored grain protectant.

[Electrophysiological effects of guan-fu base A on action potentials of guinea pig ventricular papillary muscles].

Guan-fu base A (GA), an alkaloid first isolated in China, 50 mg.L-1 decreased the action potential amplitude and the maximal rate of depolarization (Vmax) of guinea pig papillary muscles in vitro. GA shortened the action potential period at 90% repolarization (APD90) without significant effect on the effective refractory period (ERP), resulting in an increased ERP/APD90 ratio. GA 50 mg.L-1 also slowed the conduction speed. The inhibiting effect of GA on Vmax showed frequency- and potential-dependent manners.

[Predictive and diagnostic value of fibronectin levels in pregnancy-induced hypertension].

Serum fibronectin (FN) level was assayed using ELISA monoclonal antifibronectin antibody of 152 normal gravida tested in the second and third trimesters, 24 cases who showed higher serum FN (309 +/- 13 mg/l, means +/- s means) than the normal (163 +/- 4 mg/l) developed pregnancy induced hypertension (PIH) later on. The serum FN level of 30 PIH patients was significantly higher than that of 128 normal gravidae (P less than 0.01). A serum FN level of 255 mg/l is suggested as the critical value in predicting the occurrence of PIH. The sensitivity was 79.2%, the specificity 95.3%, the index of diagnosis 174.5%, the efficiency of diagnosis 92.8%, the positive predictive value 76.0%, and the negative predictive value 96.1%.