OBJECTIVETo explore the feasibility of genetic algorithm (GA) on multiple objective blending technology for extractions of Cortex Fraxini.

METHODAccording to that the optimization objective was the combination of fingerprint similarity and the root-mean-square error of multiple key constituents, a new multiple objective optimization model of 10 batches extractions of Cortex Fraxini was built. The blending coefficient was obtained by genetic algorithm. The quality of 10 batches extractions of Cortex Fraxini that after blending was evaluated with the finger print similarity and root-mean-square error as indexes.

RESULTThe quality of 10 batches extractions of Cortex Fraxini that after blending was well improved. Comparing with the fingerprint of the control sample, the similarity was up, but the degree of variation is down. The relative deviation of the key constituents was less than 10%.

CONCLUSIONIt is proved that genetic algorithm works well on multiple objective blending technology for extractions of Cortex Fraxini. This method can be a reference to control the quality of extractions of Cortex Fraxini. Genetic algorithm in blending technology for extractions of Chinese medicines is advisable.

Algorithms ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; analysis ; Medicine, Chinese Traditional ; standards ; Plants, Medicinal ; chemistry ; genetics ; Quality Control

BACKGROUNDTo summarize the preliminary experience on Iressa for refractory non-small cell lung cancer (NSCLC).

METHODSFifty-five patients with NSCLC, who failed after surgery, radiotherapy, chemotherapy or combination of the above modalities, were registered in this clinical trail. Prior to Iressa, 50 patients were in stage IV, and 5 in stage III. Iressa was administered orally at 250 mg, once a day until cancer progressed or severe toxicity occured, which made patients intolerable. The median time for administration of Iressa was 4 months.

RESULTSThe toxicity of Iressa was tolerable with 47% of skin toxicity (rash) and 2%-7% of diarrhea, nausea, orally mucosal ulceration and alopecia. Overall response rate was 20%. Different sites of distant metastases responded to Iressa in different ways with higher response rate for pulmonary disseminations. One quarter of patients felt improvement of their symptoms over 2 weeks. Median survival time for entire group was 5 months (1-17 months). Median time to progression (TTP) was 3.6 months. Survival at 6 months was 67%. Prognostic predictor, which could imply the outcome, was skin toxicity with higher response rate and longer survival time ( P < 0.05), and no relationship with sex, histological types of NSCLC and distant metastasis had been found.

CONCLUSIONSIressa could be tolerated by refractory NSCLC patients with acceptable side-effects, and have palliative effects.

Objective To investigate the effects of modified Yupingfeng Powder medicated serum on the inflammatory response of rat lung epithelial type Ⅱ cells RLE-6TN;To explore the mechanism based on nuclear factor(NF)-κB signaling pathway.Methods The inflammatory reaction of RLE-6TN cells was induced by lipopolysaccharide,and the cells were divided into control group,model group,dexamethasone medicated serum group,and 5%,10%and 20%TCM serum group,and the cell model was intervened with different serum.After 24 hours,the content of lactate dehydrogenase(LDH)in cell supernatant was detected by kit,and the content of reactive oxygen species(ROS)in cells were detected by fluorescence staining,Hoechst/PI double staining was used to observe cell apoptosis,and ELISA was used to detect tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-1β contents in cell supernatant,RT-qPCR was used to detect Toll like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),and NF-κB inhibitory protein α(IκBα)mRNA expression,Western blot was used to detect protein expressions of TLR4,MyD88,NF-κBp65 and IκBα.Results Compared with the control group,the contents of LDH,TNF-α,IL-6,IL-1β in RLE-6TN cell supernatant and ROS content in cells of model group significantly increased(P<0.01),the cell apoptosis rate significantly increased(P<0.01),the expressions of TLR4 and MyD88 mRNA and protein significantly increased(P<0.01),the expression of IκBα mRNA significantly decreased(P<0.01),and the ratio of p-NF-κBp65/NF-κBp65 and p-IκBα/IκBα significantly increased(P<0.01).Compared with the model group,the content of LDH,TNF-α,IL-6,IL-1 in RLE-6TN cell supernatant and ROS content in cells significant decreased in the 20%TCM serum group and dexamethasone medicated serum group(P<0.01),the cell apoptosis rate significantly decreased(P<0.01),the expressions of TLR4 and MyD88 mRNA and protein significantly decreased(P<0.05,P<0.01),the expression of IκBα mRNA significantly increased(P<0.01),and the ratio of p-NF-κBp65/NF-κBp65 and p-IκBα/IκBα significantly decreased(P<0.05,P<0.01).Conclusion Modified Yupingfeng Powder medicated serum can reduce RLE-6TN cells inflammatory reaction,and its mechanism may be related to the regulation of NF-κB signaling pathway.

Objective:To evaluate the performance of magnetic beads extraction method (MGE) for the measurement of catecholamine metabolites by liquid chromatography tandem mass spectrometry.Methods:This is a methodological evaluation study. The linearity, limit of quantitation, recovery, precision, and matrix effect of catecholamine metabolites 3-methoxyepinephrine (MN), 3-methoxynorepinephrine (NMN) and 3-methoxytyramine (3-MT) extracted by MGE method were evaluated according to CLSI C62-A. Consensus of method development and validation of liquid chromatography-tandem mass spectrometry in clinical laboratories and other guidelines, 132 clinical residual plasma samples were collected and extracted by automated MGE and traditional solid phase extraction (SPE) method to compare the harmonization of the two extraction methods.Results:The linearity of MN, NMN and 3-MT extracted by automated MGE was>0.99, and the LOQ for MN, NMN and 3-MT were 0.033 5 nmol/L, 0.054 7 nmol/L and 0.011 0 nmol/L, respectively. The repeatability of MN, NMN and 3-MT were 1.3%-5.1%, 2.2%-5.6% and 1.7%-7.1%, respectively. The total imprecision in the laboratory were 1.5%-8.2%, 2.2%-7.7%, 2.1%-11.2%. Although the absolute recovery is low, the average relative recoveries of MN, NMN and 3-MT were 91.5%-108.5%, 92.0%-108.6%, and 89.3%-104.1%, respectively, and the percentage deviation from the expected concentration was within 15%. After isotope internal standard correction, the relative matrix effect is close to 100%, which can compensate for the potential matrix effect. The results of MGE and SPE of MN, NMN and 3-MT showeda good correlation (correlation coefficient r>0.99). The average relative deviations of MN, NMN and 3-MT were 0.2%, -1.4% and 1.0%, respectively. Conclusion:The automatic MGE method hasa good performance in extracting catecholamine metabolites, and is expected to be used in high-throughput analysis of samples in clinical in the future.

Objective:To investigate the relationship between spread through air spaces(STAS) of peripheral stage ⅠA small adenocarcinoma of the lung(≤2 cm) and related factors such as clinical and CT morphological features, and to construct a nomogram model.Methods:Relevant clinical, pathological and imaging data of patients who underwent lung surgery and were diagnosed as peripheral stage ⅠA small lung adenocarcinoma by postoperative pathology in the Affiliated Hospital of Nantong University from 2017 to 2022 were collected, of which cases that met the inclusion criteria from 2017 to 2021 served as the training group, and those that met the inclusion criteria in 2022 served as the validation group. The independent risk factors for the occurrence of STAS in peripheral stage ⅠA lung small adenocarcinoma were investigated by using univariate analysis and multifactorial logistic regression analysis, based on which a nomogram prediction model was constructed, and the subjects were analyzed by using the receiver operating characteristic curve( ROC), correction model, etc. were used to evaluate the model. Results:A total of 430 patients who met the criteria were included, including 351 patients in the training group(109 STAS-positive and 242 STAS-negative) and 79 patients in the validation group(23 STAS-positive and 56 STAS-negative). Univariate analysis showed that the patients in the two groups showed a significant difference in age(>58 years old), gender, smoking history, tumor location(subpleural, non-subpleural), pleural pull, nodule type, nodule maximal diameter, solid component maximal diameter, consolidation tumor ratio(CTR), lobulation sign, burr sign, bronchial truncation sign, vascular sign(includes thickening and distortion of blood vessels in/around the nodes), satellite lesions, and ground-glass band sign were statistically significant( P<0.05). The results of multifactorial logistic regression analysis showed that CTR( OR=4.98, P<0.001), lobulation sign( OR=4.07, P=0.013), burr sign( OR=3.66, P<0.001), and satellite lesions( OR=3.56, P=0.009) were the independent risk factors for the occurrence of STAS. Applying the above factors to construct the nomogram model and validate the model, the results showed that the ROC curve was plotted by the nomogram prediction model, and the area under the ROC curve( AUC) of the training set was 0.840(sensitivity 0.835, specificity 0.734), and the validation set had an AUC value of 0.852(sensitivity 0.786, specificity 0.783), and the training set and validation set calibration curves have good overlap with the ideal curve. Conclusion:CTR, lobular sign, burr sign, and satellite lesions are independent risk factors for STAS, and the nomogram model constructed in this study has good predictive value.