Crizotinib is a tyrosine kinase inhibitor (TKI),which is a target for echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK).It can prolong the progression free survival (PFS)of ALK positive patients with advanced non-small cell lung cancer (NSCLC).The median PFS in the first-line and second-line mPFS is 10.9 months and 7.7 months.However,despite an initial benefit,patients inevitably experience tumor progression,due to the ALK fusion gene amplification and secondary mutations of ALK kinase domain.Clinical trials show the promising efficacy like next generation ALK inhibitors and heat shock protein 90 (HSP90)can overcome acquired resistance.

Aim To establish two new rat models of visceral hypersensitivity in IBS by two chemical irritants.Methods Acetic acid or mustard was infused for six days in intestines of adult rats.After modeling,the rectal distention was performed and the thresholds of abdominal withdrawal reflex were measured.The frequency,peak value,peak-nadir value and area of the gastric and enteric electrical activity were recorded.And the contents of 5-HT in the blood serum were detected.Results Compared with the control group,the colon and rectum's sensitivity(P<0.05)and the frequency(P<0.01) of the acetic acid model were heightened.Meanwhile,the colon and rectum's sensitivity(P<0.01),the frequency(P<0.01),peak value(P<0.05),peak-nadir value(P<0.01)and area(P<0.01),and the contents of 5-HT(P<0.05)in serum of the mustard model were all changed,which indicated the increasing of sensitivity of the model.The colon and rectum's sensitivity,the gastric and enteric electrical activity and the contents of 5-HT in serum of the proving group were recovered to some extent.Conclusion The new rat model of visceral hypersensitivity in IBS is successfully set up by stimulating the intestines of adult rats with chemical substances.

Objective To evaluate the effect of malaria elimination monitoring in Liyang City, so as to provide the evidence for formulating control strategies and measures of malaria elimination. Methods The monitoring data about the epidemic situation, blood tests of feverish patients and epidemiology investigation of individual malaria patients in Liyang City from 2010 to 2016 were collected and analyzed by the descriptive epidemiology method. Results From 2010 to 2016, there were 67 malaria cases in total. Totally 39 196 feverish patients had blood tests for Plasmodium, and 65 of them showed positive and the positive rate was 0.17%. The other 2 cases of microscopy negative were treated with anti-malarial drugs by themselves after the onset of fever, and no Plasmodium was detected in the microscopy, but the tests with malaria rapid diagnostic kit (RDTs) were positive. Among all the 67 cases, there were 49 falciparum malaria cases, 13 ovale malaria cases and 5 vivax malaria cases. All the 67 malaria cases were imported, and the number of cases from Africa was 63 (94.03%). Totally 97.01% (65/67) of the malaria patients were male and most of them were young adults. The patients aged 30 to 49 years accounted for 73.13% (49/67) and 80.60% (54/67) of them were farmers. There were malaria cases in all the 10 towns of the city, and the time of onset had no obvious seasonal characteristics. The timely rate of case report, timely rate of blood film review, standardized treatment rate, epidemiological case investigation rate, and epidemic focus investigation and disposal rate were all 100%. There were 18 076 people with the active case investigation, but no malaria parasite positive carriers were found. The mosquito vector monitoring was performed with the methods of mosquito trap lamp and human bait half night trap, and 187 and 78 Anopheles mosquitoes were captured respectively, and all the parasites were Anopheles sinensis. A total of 88 person-times were performed for the Plasmodium examinations with microscopy and RDTs (one blood sample, two detections) in Liyang City Center for Disease Prevention and Control from 2012 to 2016, and 35 person-times were positive, including 28 person-times of Plasmodium falciparum and 7 person-times of P. ovale, and there was no statistically significant difference between the detection rates of P. falciparum, and P. ovale (adjusted χ² = 0.05, P > 0.05). There were 34 RDTs positive cases, including 14 cases of malignant malaria, and 17 cases of malignant malaria or mixed infections of P. falciparum with other three kinds of Plasmodium parasites, and 3 cases of single infection or mixed infections of other three kinds of Plasmodium parasites, and there was a statistically significant difference among them in the positive RDTs detection rates (adjusted χ² = 13.75, P < 0.05). Conclusions There are still imported malaria cases and there is the risk of malaria retransmission in Liyang City. Therefore, it is necessary to strengthen the malaria surveillance work and the management of infectious sources, so as to consolidate the achievements of malaria elimination in the future.

Objective To study the application of accreditation standards for trainers of general practitioners (GPs) in community health centers.Methods The questionnaire was designed according to the accreditation standards for GP trainers in community health centers,which involved professional quality,clinical competence in primary care and teaching abilities.According to typical sampling,583 trainers from 56 community teaching bases in Shanghai were selected for the survey.Results Among 583 participants,the effective respondents were 505 with a response rate of 86.6％.The professional quality was highly recognized by the participants,and more than 80％ of trainers met the requirement.For the ability of primary care,81.4％ (411/505),79.8 ％ (403/505) and 69.5 ％ (351/505) of participants were well qualified with the abilities of management for hypertension,type 2 diabetes and coronary heart disease,respectively,while only about 40％ had abilities of management for epilepsy,hypothyroidism and chronic mental diseases.75.4％ (381/505) participants fully mastered the principle of first aid skills and CPR,while only 24.8％ (125/505) had abilities of management for conjunctival foreign body and nasal foreign body,34.5％ (174/505) had the abilities of debridement and gastrolavage.For the index of teaching abilities,most trainers had insufficient teaching capacity and experience in the community.Only 48.5％ (245/505) and 40.2％ (203/505) of trainers were familiar with the teaching methods of cased-based learning and problem-based learning,respectively.Significant difference was found in the scores of teaching abilities among trainers from community health centers in different locations (P ＜ 0.05),such as using appropriate teaching methods (F =3.45,P =0.033),monthly assessment and feedback to students (F =5.14,P =0.006) and ensure at least 4 hours of teaching time every week(F =4.96,P =0.007).No significant differences were found in the scores of professional quality and clinical competences in primary care (P ＞ 0.5).Conclusion The trainers of general practitioners in community health centers meet the requirement of accreditation standards in the aspects of professional quality and clinical competences in primary care,while the teaching abilities remained to be improved and should be strengthened in the future.

Chondroblastoma ; pathology ; Chondroma ; pathology ; Chondrosarcoma ; metabolism ; pathology ; surgery ; Cricoid Cartilage ; Diagnosis, Differential ; Humans ; Laryngeal Neoplasms ; metabolism ; pathology ; surgery ; Laryngectomy ; Lymph Node Excision ; Male ; Middle Aged ; Osteoblastoma ; pathology ; Osteosarcoma ; pathology ; S100 Proteins ; metabolism ; Sarcoma, Clear Cell ; metabolism ; pathology ; surgery ; Vimentin ; metabolism

Objective:To optimize the matrix formulation of Erhuang analgesic gels. Methods:Central composite design-response surface methodology was adopted to optimize the best formulation of Erhuang analgesic gels by using carbomer 940, triethanolamine and glycerine as independent variables, the appearance, stability, viscosity and in vitro release of berberine hydrochloride as comprehensive evaluation indices. Results:The fitting regressing equation was Y= 82.25 + 4.95 A+ 5.19 B + 1.41 C+ 1.51 AB + 0.904 0 AC- 0.531 9 BC- 2.92 A2-1.80 B2-0.182 1 C2. P value of the model was less than 0.000 1, and the correlation coefficient r value was 0.977. The optimal formulation of Erhuang analgesic gels consisted of 1.84% carbomer 940, 1.30 times triethanolamine of carbomer 940 and 13.99 grams of glycerine. The average comprehensive scores of three verification experiments was 88.56, and the deviations from the predicted values were 2.93%, 2.85% and 1.55%. Conclusion:The formulation process by central composite design-response surface methodology was stable and the formulation of Erhuang analgesic gels has been optimized.

Objective:To investigate the effect of GluA2-3Y which is an inhibitor of AMPA(α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid) receptor internalization on cognitive function and hippocampal postsynaptic protein expression in rats with chronic cerebral hypoperfusion.Methods:Forty-eight adult male SD rats were randomly divided into Sham group, 2VO group, high-dose GluA2-3Y group and low-dose GluA2-3Y group according to random number table, with 12 rats in each group.The chronic cerebral hypoperfusion model of rat was established by two vessel occlusion (2VO) while the Sham operation was performed in rats of Sham group.The rats in high dose GluA2-3Y group and low dose GluA2-3Y group were intraperitoneal injected with 3 μmol/kg and 0.03 μmol/kg GluA2-3Y respectively once a day for 2 weeks. Rats in 2VO group and Sham group were intraperitoneally injected with control peptide. Morris water maze test and new object recognition test were performed to evaluate the learning and memory ability of rats, and Western blot was used to evaluate the expression of Akt1、GSK3β、p-GSK3β、GluA2 and PSD-95 in rat hippocampus. The expressions of GluA2 and PSD-95 in rat hippocampus were evaluated by immunofluorescence. SPSS 23.0 software was used for data analysis. The comparison between multiple groups was analyzed by one-way ANOVA and repeated measurement ANOVA was used to analyze Morris water maze results. And independent-samples t-test was used for pairwise comparisons. Results:(1)In Morris water maze trials, the results of repeated measurement ANOVA showed that the interaction between group and time of escape latency of rats in each group was not significant ( F=0.79, P>0.05), and the group main effect and time main effect were significant ( F=24.44, 40.42, both P<0.05). On the 5th day of navigation trials, the escape latency of rats in 2VO group was longer than that in sham group ( t=5.87, P<0.05). The escape latency of rats in low dose GluA2-3Y group and high dose GluA2-3Y group were significantly shorter than that in 2VO group ( t=2.20, 3.41, both P<0.05), but there was no significant difference between low dose GluA2-3Y group and high dose GluA2-3Y group ( t=1.37, P>0.05). The target quadrant residence time and resolution coefficient ((14.57±1.40)s, (0.15±0.10)) in 2VO group were significantly lower than those in Sham group ((23.71±2.57)s, (0.40±0.06)) ( t=3.23, 2.24, both P<0.05), while the target quadrant residence time in high dose GluA2-3Y group ((20.19±1.53)s) and low dose GluA2-3Y group ((20.31±2.06)s) were longer than that in 2VO group( t=2.71, 2.35, both P<0.05). The discrimination coefficients in high dose GluA2-3Y group (0.47±0.10) and low dose GluA2-3Y group (0.59±0.06) were higher than that of 2VO group ( t=2.21, 3.94, both P<0.05). (2)The Western blot results showed that the expression of PSD-95 and GluA2 in hippocampus of rats in 2VO group were significantly lower than those in Sham group ( t=2.31, 2.20, both P<0.05), and the expression of PSD-95 in high dose GluA2-3Y group (1.026±0.056) was significantly higher than that in 2VO group ((0.760±0.061), t=2.49, P<0.05), while there was no significant difference between low-dose GluA2-3Y group and 2VO group( t=0.96, P>0.05). The expression of GluA2 in low-dose GluA2-3Y group was higher than that in 2VO Group ((1.130±0.087), (0.766±0.080), t=2.37, P<0.05), but there was no significant difference between high-dose GluA2-3Y group and 2VO group( t=1.06, P>0.05). (3) Immunofluorescence showed that compared with Sham group, the expression of PSD-95 and GluA2 in 2VO group decreased ( t=4.23, 2.57, P<0.05). Compared with 2VO group, the expression of PSD-95 and GluA2 in high dose GluA2-3Y group and low dose GluA2-3Y group increased significantly, and the differences were statistically significant (PSD-95: (7.757±0.578), (12.057±0.578), t=3.14, 6.96, both P<0.05; (9.721±0.950), (16.610±0.950), t=4.56, 9.34, both P<0.05). (4) The results of Western blot showed that the expression GSK3β in hippocampus of rats in each group were not statistically different( F=2.03, P>0.05). There were significant differences in the expression of Akt1, p-GSK3β and the percentage of p-GSK3β/GSK3β in hippocampus of rats in each group ( F=8.30, 4.76, 3.57, all P<0.05). Compared with Sham group, the levels of Akt1, p-GSK3β and the percentage of p-GSK3β/GSK3β in 2VO group were significantly lower ( t=3.00, 2.81, 3.17, all P<0.05). Compared with 2VO group, the levels of Akt1, p-GSK3β and p-GSK3β/GSK3β percentage in low dose GluA2-3Y group and high-dose GluA2-3Y group were significantly higher (Akt1: t=2.05, 5.20, both P<0.05; p-GSK3β: t=2.49, 4.15, both P<0.05; p-GSK3β/GSK3β percentage: t=2.30, 2.97, both P<0.05). Conclusion:GluA2-3Y, an AMPA receptor internalization inhibitor, can alleviate the cognitive impairment in rats with chronic cerebral hypoperfusion, which may be related to the increased expression of Akt1, p-GSK3β and postsynaptic proteins.

Objective:To establish the TLC identification method and content determination method of ferulic acid, ligustilide, hydroxysafflor yellow A and paeoniflorin in Shangke Huoxue Decoction for quality evaluation.Methods:Ferulic acid, ligustilide, hydroxysafflor yellow A and paeoniflorin were qualitatively identified by TLC method, and the content was determined by HPLC method. Waters Symmetry ShieldTM RP18 column (4.6 mm×250 mm, 5 μm) was set, the mobile phase consisted of acetonitrile-0.15% phosphoric acid water with gradient elution at a flow of 1.0 ml/min, and the column temperature was 30 ℃.The detection wavelength was 320 nm (33-50 min for ferulic acid, 55-70 min for ligustilide), 403 nm (7-31 min for hydroxysafflor yellow A) and 230 nm (7-31 min for paeoniflorin).Results:The TLC spots were clear. The linear relationships of ferulic acid, ligustilide, and hydroxysafflor yellow A were good in the range of 3.05-48.74 μg, 3.50-26.24 μg, 21.34-213.44 μg. The method was stable, repeatable with good recovery rate.Conclusion:The TLC and HPLC method for the simutanous determination of the four effective components in Shangke Huoxue Decoction were established, and the methods are suitable for the quality evaluation of Shangke Huoxue Decoction.

Objective:To analyze the effect of ultrasound contrast agent targeting gelatin on uptake of high lymphatic metastasis cell lines of mouse hepatocellular carcinoma with peritoneal effusion.Methods:The modified double emulsifying solvent evaporation method was used to construct the macromolecule contrast agent PLGA-Cooh. The carbodiimide was used to connect the monoclonal antibody of gelatin with the contrast agent PLGA-Cooh, and the targeted ultrasound contrast agent Gsn-PLGA was established. The particle size and Zeta potential of the targeted ultrasound contrast agent were measured by laser particle size analyzer. The surface binding of the contrast agent to the gelatin monoclonal antibody was evaluated by immunofluorescence. Hca-F cells with high lymphatic metastasis were cultured in mice with peritoneal effusion hepatocellular carcinoma. Target-seeking ability in vitro was evaluated by in vitro uptake test, and the imaging effect of the contrast agent in vitro was evaluated by in vitro developing test. Results:The contrast agent is white powder with good water solubility. The average particle size and surface potential were (569.68±6.96) nm and (-10.95±2.43) mV, respectively. The fluorescent antibody binding rate of non-targeted and targeted ultrasound contrast agent labeled with DiI were 0.84% and 95.89%, respectively. The results showed that the targeted ultrasound contrast agent Gsn-PLGA had a better of developing effect in vitro. Hca-F cells with high expression of gelsolin protein had stronger uptake ability of targeted ultrasound contrast agent and stronger green fluorescence in vitro than those with low expression of gelsolin protein ( P<0.05). Moreover, targeted ultrasound contrast agent Gsn-PLGA had stronger targeting to the gelsolin protein. The echo of the targeted ultrasound contrast agent Gsn-PLGA was uniform and fine, without attenuating echo of the back. Simultaneously, the development effect was more obvious with the increase of contrast agent concentration ( P<0.05). Conclusion:Ultrasound contrast agent Gsn-PLGA targeting gelatin can bind Hca-F cells with high expression of gelatin and display a good imaging effect in vitro.

Objective:To analyze the effect of ultrasound contrast agent targeting gelatin on uptake of high lymphatic metastasis cell lines of mouse hepatocellular carcinoma with peritoneal effusion.Methods:The modified double emulsifying solvent evaporation method was used to construct the macromolecule contrast agent PLGA-Cooh. The carbodiimide was used to connect the monoclonal antibody of gelatin with the contrast agent PLGA-Cooh, and the targeted ultrasound contrast agent Gsn-PLGA was established. The particle size and Zeta potential of the targeted ultrasound contrast agent were measured by laser particle size analyzer. The surface binding of the contrast agent to the gelatin monoclonal antibody was evaluated by immunofluorescence. Hca-F cells with high lymphatic metastasis were cultured in mice with peritoneal effusion hepatocellular carcinoma. Target-seeking ability in vitro was evaluated by in vitro uptake test, and the imaging effect of the contrast agent in vitro was evaluated by in vitro developing test. Results:The contrast agent is white powder with good water solubility. The average particle size and surface potential were (569.68±6.96) nm and (-10.95±2.43) mV, respectively. The fluorescent antibody binding rate of non-targeted and targeted ultrasound contrast agent labeled with DiI were 0.84% and 95.89%, respectively. The results showed that the targeted ultrasound contrast agent Gsn-PLGA had a better of developing effect in vitro. Hca-F cells with high expression of gelsolin protein had stronger uptake ability of targeted ultrasound contrast agent and stronger green fluorescence in vitro than those with low expression of gelsolin protein ( P<0.05). Moreover, targeted ultrasound contrast agent Gsn-PLGA had stronger targeting to the gelsolin protein. The echo of the targeted ultrasound contrast agent Gsn-PLGA was uniform and fine, without attenuating echo of the back. Simultaneously, the development effect was more obvious with the increase of contrast agent concentration ( P<0.05). Conclusion:Ultrasound contrast agent Gsn-PLGA targeting gelatin can bind Hca-F cells with high expression of gelatin and display a good imaging effect in vitro.