Recent advances of MDM2-p53 inhibitors / 药学学报

Protein-protein interactions (PPI) are involved in a variety of biological processes, including cell-to-cell interactions, metabolism and development control. The misregulation, post-translational modification and interference of PPI are related to a variety of human diseases, making the regulation of these interactions a very attractive field of drug discovery. In recent years, the interaction between MDM2 and p53 has become a research hotspot, which plays an important role in the treatment of tumors. But unfortunately there are no such inhibitors approved all over the world. In this view, recent advances of MDM2-p53 inhibitors were briefly described and its inhibitors with potential therapeutic activities in clinical studies were introduced.

Effect of Banxia Xiexintang-containing Serum on Epithelial-mesenchymal Transition of Peritoneal Mesothelial Cells Induced by Gastric Cancer-derived Exosomes / 中国实验方剂学杂志

Objective:To investigate the effect of Banxia Xiexintang on the epithelial-mesenchymal transition （EMT） of human peritoneal mesothelial cell line （HMrSV5） induced by gastric cancer-derived exosomes （Exo）. Method:Banxia Xiexintang-containing serum was prepared and the human gastric cancer NCI-N87-derived exosomes （NCI-N87-Exo） were extracted， followed by their identification by transmission electron microscopy and Western blotting and labeling with 1，1-dioctadecyl-3，3，3，3- tetramethylindocarbocyanine perchlorate （Dil）. The cells were divided into the blank group， model group， and low-， medium-， and high-dose （13.5，27，54 g·kg^-1） Banxia Xiexintang groups. HMrSV5 cells in the blank group were cultured alone， the ones in the model group with 100 mg·L^-1 NCI-N87-Exo， and those in the low-， medium-， and high-dose Banxia Xiexintang groups with 100 mg·L^-1 NCI-N87-Exo plus low-， medium-， and high-dose 10% Banxia Xiexintang-containing serum， respectively. Confocal laser microscope was used to observe the uptake of NCI-N87-Exo by HMrSV5 cells at 24 h， 48 h and 72 h. Seventy-two hours later， the morphological changes in HMrSV5 cells were observed. The protein expression levels of E-cadherin， cytokeratin 19 （CK19）， <italic>α</italic>-smooth muscle actin （<italic>α</italic>-SMA）， elastin， and transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁）， Smad2/3， and p-Smad2/3 were assayed by Western blot. Result:It was observed under the transmission electron microscope that NCI-N87-Exo showed an oval or dish-shaped vesicle structure with a particle size ranging from 40 to 80 nm. Exo marker proteins CD9 and CD63 were highly expressed while calreticulin was not expressed， implying that the NCI-N87-Exo was confirmed. After 24 h， 48 h， 72 h of co-culture， it was observed under the fluorescence microscope that NCI-N87-Exo were taken up by HMrSV5 cells， which was positively correlated with time. Compared with the blank group， Banxia Xiexintang significantly inhibited the uptake of NCI-N87-Exo by HMrSV5 cells， with better effect noticed in the middle- and high-dose Banxia Xiexintang groups（<italic>P</italic><0.05，<italic>P</italic><0.01）. After intervention with Banxia Xiexintang-containing serum， the HMrSV5 cells were arranged densely， and the intercellular space was significantly reduced， with the most obvious changes present in the high-dose Banxia Xiexintang group. Western blot revealed that the protein expression levels of E-cadherin and CK19 in HMrSV5 cells after being intervened with the medium- and high-dose Banxia Xiexintang-containing serum were increased significantly as compared with those in the blank group， whereas the levels of <italic>α</italic>-SMA and Elastin were decreased significantly （<italic>P</italic><0.01）. Banxia Xiexintang-containing serum at the low， medium， and high doses remarkably down-regulated TGF-<italic>β</italic>₁ and p-Smad2/3 protein expression（<italic>P</italic><0.05，<italic>P</italic><0.01）. However， there was no significant change in Smad2/3. Conclusion:NCI-N87-Exo can be taken up by HMrSV5 cells to induce EMT. Banxia Xiexintang can inhibit the uptake of NCI-N87-Exo by HMrSV5 cells and the resulting EMT induced by NCI-N87-Exo， which is related to the regulation of TGF-<italic>β</italic>₁/Smads signaling pathway.

Application of case-introduced papers in Clinical Comprehensive Course graduation test for "3+2" assistant general practitioners training of two batches / 中华医学教育探索杂志

Objective:To analyze the design and test results of case-introduced papers in Clinical Comprehensive Course graduation test for assistant general practitioners of batch 2015 and 2016, so as to provide references for enhancing the comprehensive abilities of students to analyze clinical problems during training.Method:Brief cases were introduced to part of the questions in the paper. The difficulty coefficient of the paper and the degree of distinction and reliability of the test results of students in the two batches were calculated and analyzed, and the results of their answers to different questions (single choice questions & brief case-introduced questions) were compared. SPSS 15.0 was used to perform chi-square test or t-test. Results:①The test papers for the two batches and the two parts in the papers all conformed to the testing purpose and have achieved the objective of training. The difficulty coefficient of the paper and the distinction and reliability degrees of the results were all reasonable. ②There was a statistically significant difference in the difficulty coefficient of the single choice questions in the papers of the two batches ( P<0.05), but no significant difference in the brief case-introduced questions ( P>0.05). ③There was no statistical difference in the difficulty coefficient of test questions in the two papers ( P>0.05), but a statistically significant difference was found in the difficulty coefficient of brief case-introduced questions ( P<0.05). ④There was a significant difference in the average scores of students in the two batches ( t=8.18, P<0.01) and in the frequency distribution of each fraction frequency in the "single choice question" ( P<0.01), but no difference in the frequency distribution of brief case-introduced questions ( P>0.05). ⑤There was a significant difference in the average scores of single choice questions of students in the two batches ( P<0.01), and no statistically significant difference in the average scores of brief case-introduced questions ( t=1.22, P>0.05). Conclusion:Students of batch 2015 and 2016 accepted the "brief case-introduced questions". These questions requires students with greater abilities, thus can effectively distinct their training outcomes. Generally speaking, introduction of cases in the teaching of assistant general practitioners has made great achievements.

Expression of the Fra-1 gene in the peripheral blood of children with Wilms tumor / 中国当代儿科杂志

OBJECTIVE@#To study the expression of the Fra-1 gene in the peripheral blood of children with Wilms tumor and its clinical significance.@*METHODS@#Fifty children pathologically diagnosed with Wilms tumor between December 2012 and January 2018 were enrolled as the case group, and 40 healthy children for physical examination were selected as the control group. Among the 45 children with Wilms tumor who were followed up, the children with continuous remission were included in the ideal efficacy group (n=33), and those with recurrence, metastasis or death were included in the poor efficacy group (n=12). Peripheral blood samples were collected from all subjects. Quantitative real-time PCR was used to measure the mRNA expression of Fra-1.@*RESULTS@#The case group had significantly higher mRNA expression of Fra-1 in peripheral blood than the control group (P0.05). The mRNA expression of Fra-1 was significantly lower in the ideal efficacy group than in the poor efficacy group (P<0.05).@*CONCLUSIONS@#Fra-1 may be involved in the development of Wilms tumor and plays a certain role in its development, invasion and metastasis, but the mechanism remains to be further studied.

Gene expression profiling reveals upregulated FUT1 and MYBPC1 in children with pancreaticobiliary maljunction

Pancreaticobiliary maljunction (PBM) is associated with high risk of epithelial atypical growth and malignant transformation of the bile duct or gallbladder. However, overall changes in genetic expression have not been examined in children with PBM. Genome-wide expression was analyzed using peripheral blood samples from 10 children with PBM and 15 pediatric controls. Differentially expressed genes (DEGs) were identified using microarray. Bioinformatics analysis was conducted using Gene Ontology and KEGG analyses. The top 5 in the up-regulated genes in PBM were verified with qRT-PCR. Receiver operator characteristic curve analysis was conducted to evaluate the predictive accuracy of selected genes for PBM. The microarray experiments identified a total of 876 DEGs in PBM, among which 530 were up-regulated and the remaining 346 were down-regulated. Verification of the top 5 up-regulated genes (TYMS, MYBPC1, FUT1, XAGE2, and GREB1L) by qRT-PCR confirmed the up-regulation of MYBPC1 and FUT1. Receiver operating characteristic curve analysis suggested that FUT1 and MYBPC1 up-regulation could be used to predict PBM, with the area under the curve of 0.873 (95%CI=0.735−1.000) and 0.960 (95%CI=0.891−1.000), respectively. FUT1 and MYBPC1 were up-regulated in children with PBM, and could be used as potential biomarkers for PBM.

LncRNA MALAT-1 regulates expression of miR-205 and affects growth and migration of non-small cell lung cancer cells / 中国免疫学杂志

Objective:To investigate the relationship between LncRNA MALAT-1 and miR-205 in non-small cell lung cancer and the mechanism of biological behavior in lung cancer cells.Methods: The expression of LncRNA MALAT-1 in different non-small cell lung cancer was detected by qPCR.The interaction between MALAT-1 and miR-205 was detected by double luciferase reporter gene.Transwell invasion assay and scratch test were used to detect the changes of invasion and migration abilities of lung cancer cells after silencing MALAT-1 and the recovery the abilities after inhibition of miR-205 expression.The tumor volume and quality of lung cancer cells were detected by subcutaneous tumor formation in nude mice after silencing MALAT-1.Results:Compared with other lung cancer cell lines,the expression of MALAT-1 was the highest and the expression level of miR-205 was the lowest in A549 cells.The double luciferase assay confirmed that MALAT-1 could specifically bind to 3′UTR of miR-205,and could regulate the expression and activity of miR-205.Inhibition of MALAT-1 expression could reduce the migration and invasion of lung cancer cells;while inhibiting the expression of miR-205 level,the migration and invasion of lung cancer cells could recovery.The tumor volume and quality of lung cancer cells were reduced after silencing MALAT-1 in subcutaneous tumorigenesis of nude mice.Conclusion: MALAT-1 can regulate the expression of miR-205 and affect the invasion and migration of lung cancer cell line A549.

Application of case introduction "brief illness example" in clinical integrated curriculum teaching of assistant general practitioners training / 中华医学教育探索杂志

By compiling the practice set of "brief problem examples", we continue to advance case-oriented teaching in the "3+2" assistant general practitioner training "clinical comprehensive course". However, we have found that 10.7% of the questions provided by the instructors are still concerned with large-scale equipment, and operation methods etc., suggesting that parts of the teachers' consciousness in general medicine is still urgent to be enhanced. According to the analysis of the graduation test results of the students of Grade 2015, it is obvious that the average scores of the students after the examination reform have not been significantly affected. The questionnaire survey shows that most of the teachers and students think that it is of positive significance to adopt a "brief medical record problem", and 91.5% of the teachers and 81.7% of the students do not affect the examination paper form and do not affect the answers. As for the compiled 1 exercises, 86.6% of the teachers and 67.8% of the students agreed. In view of the supple-mental effect of the form of "brief medical record problem" to case introduction teaching, it is necessary to compile the exercise set suitable for this course and apply it to specific teaching activities.

Comparative Study on Mobilization of Endogenous MSCs in Treatment of Ulcerative Colitis Rats by Shenling Baizhu Powder and Tongxie Yaofang Decoction / 中国中医药信息杂志

Objective To compare mobilization effects of endogeneous MSCs in the treatment of ulcerative colitis rats by Shenling Baizhu Powder and Tongxie Yaofang Decoction. Methods Twenty SD male rats were randomly divided into blank group, model group, Shenling Baizhu Powder group and Tongxie Yaofang Decoction group. TNBS/ethanol method was used to build the ulcerative colitis model. Administration groups were given Shenling Baizhu Powder and Tongxie Yaofang Decoction for gavage and model group and blank group were given normal saline for gavage. After gavage, MSCs from peripheral blood and bone marrow were extracted for primary culture. MSCs of bone marrow and peripheral blood were detected by flow cytometry. Results MSCs from bone marrow showed: Compared with the blank group, the percentage of positive cells in the model group decreased (P<0.05); Compared with the model group, the percentage of positive cells in Shenling Baizhu Powder group and Tongxie Yaofang Decoction group increased, and the expression of Shenling Baizhu Powder group was more obvious (P<0.05). MSCs from peripheral blood showed: Compared with the blank group, the percentage of positive cells in the model group increased (P<0.05); Compared with the model group, the percentage of positive cells in Shenling Baizhu Powder group and Tongxie Yaofang Decoction group decreased, and the expression of Shenling Baizhu Powder group was more obvious (P<0.05). Conclusion Shenling Baizhu Powder and Tongxie Yaofang Decoction have the function of promoting the increase of bone marrow-derived MSCs and the reduction of peripheral blood source of MSCs in model rats, and Shenling Baizhu Powder is better than Tongxie Yaofang Decoction.

Analysis on Clinical Rational Application of Xueshuantong Injection in Gansu Provincial Hospital of Traditional Chinese Medicine / 中国中医药信息杂志

Objective To investigate the influence of TCM Xueshuantong Injection on the clinical benefit and risk factors; To promote rational medication. Methods HIS system of Gansu Province Hospital of Traditional Chinese Medicine was used, and the medical records and information of patients who used Xueshuantong Injection from August 1st,2015 to August 1st,2016 were selected,including patient information, medicine information, and medicine application information. SPSS19.0 software statistics was used for rational analysis on the clinical application of Xueshuantong;two-class Logistic regression analysis was used to look for adverse reactions related factors. Results Totally 1229 patients with 10 974 medical records were included in the study. Irrational use of medicine was mainly for inappropriate indications (accounted for 21.11%), time of unreasonable administration (accounted for 1.87%), and too large dosage (accounted for 0.9%). Regression analysis showed: 1. Patients with history of allergies to food, medicine, and other substances, increased the risk of adverse reactions 8.725 times after application of Xueshuantong Injection; 2. The medicine combination increased the risk of adverse reaction of Xueshuantong Injection 1.799 times; 3. Medicine combination with Xiaozhong Zhitong Mixture, Jianwei Xiaoshi Mixture, ossotide injection, cobamamide, dextran injection, polyene lipid phosphoryl acid choline injection, and glucosamine hydrochloride tablets, may have potential risk factors for adverse reaction of Xueshuantong Injection. Conclusion Clinical irrational medicine use factors of Xueshuantong Injection mainly manifest in the indications are not suitable, the dosage of the drug medicine is too large and the course of treatment is too long. Adverse reactions occur mainly in patients with allergic history,combination of medication and large dosage.

Practice and Exploration of Combined Application Evaluation of Traditional Chinese and Western Medicine / 中国中医药信息杂志

Objective To analyze the rationality of the combined application prescriptions of traditional Chinese and Western medicine; To discuss the problems in the evaluation of the combined application of traditional Chinese and Western Medicine. Methods A total of 12 issue monthly outpatient combination application prescriptions of traditional Chinese and Western medicine were randomly selected in Gansu Provincial Hospital of Traditional Chinese Medicine (Here in after referred to as "this hospital"). According to the relevant laws and regulations, evaluation rules of the combined application traditional Chinese and Western medicine was developed, reviewed and statistically summarized. Results Totally 1900 prescriptions were sampled in the study and accounted for 8.67% in all prescriptions (including prescription of traditional Chinese herbal medicine) and accounted for 20.87% of all prescription of pure Western medicine and pure traditional Chinese patent medicine in the same period, which meet the requirements of sampling rate. Prescriptions of department of orthopedics accounted for the majority. The average number of drugs and the average amount of each prescription of department of orthopedics were lower than the overall average. The sample consisted of 1852 patients, 796 males and 1056 females. Middle-aged patients (36-60 years old) of combined medication were up to 49.46% of the total number of patients. 3990 terms of diagnosis were involved, including 1908 terms of traditional Chinese medicine diagnosis and 2082 terms of Western medicine diagnosis. Orthopedics disease diagnosis accounted for more than 50%. The main problems of the combined application of traditional Chinese and Western medicine were the non syndrome differeentiationg use of medicine, inappropriate usage and dosage, and the lack of attention to medicine interactions. Conclusion The combined application prescriptions of traditional Chinese and Western medicine of this hospital account for a small proportion. Prescription structure adapts with the size of the department, patient age and disease diagnosis. In the future, the prescription evaluation and intervention of syndrome differeentiationg application and dosage and medicine interaction should be strengthened.

Impact of village-based health education of tobacco control on the current smoking rate in Chinese rural areas / 华中科技大学学报（医学）（英德文版）

The number of smokers in Chinese rural areas is more than 200 million, which is twice that in cities. It is very significant to carry out tobacco control interventions in rural areas. We performed this community intervention study to evaluate the efficacy of village-based health education of tobacco control on the male current smoking rate in rural areas. The population of this study was the males above 15 years old from 6 villages in rural areas. The villages were randomly assigned to intervention group or control group (3 villages in each group). Self-designed smoking questionnaire was applied. The intervention group received the village-based health education of tobacco control for one year. The primary outcome measurement was the male current smoking rate. In the baseline investigation, completed surveys were returned by 814 male residents from the control group and 831 male residents from the intervention group. The male current smoking rate in the control group and the intervention group was 61.2% and 58.5%, respectively, before intervention. There was no significant difference between these two groups (P>0.05). After one-year intervention, the current smoking rate in the intervention group (51.2%) was significantly lower than that in the control group (62.8%) (P<0.001). Our study suggested that the village-based health education of tobacco control was effective in lowering the male current smoking rate in rural areas, which could be a suitable and feasible way for tobacco control in the Chinese rural areas.

"The assessment and analysis of the graduation papers of ""3+2"" assistant general practitioners training ""comprehensive clinical course""" / 中华医学教育探索杂志

Objective Based on the objective test (A type) results of the 2014 comprehensive clinical course graduation test of 3+2 assistant general practitioners training,this article analyzed the differences between different teaching units,so as to provide objective basis for improving the teaching level of each unit.Method We established a database with EXCEL 2000,and put each question's ID and points,and the score of each student into the computer,so we could get the difficulty coefficient,distinction degree and reliability of the test paper,and calculate the difficulty coefficient and difference of each question.Then we analyzed the difficulty coefficient,the difference and the reliability of the 122 students' testing results,and compared the accuracy to the same question of the 6 teaching units.Result The objective test's (A type) difficulty coefficient is 0.77,distinction degree is 0.19,and reliability is 0.99.The highest score of the 122 students is 47 points,and the lowest score is 28 points,the average score is (38.5 ± 3.9) points.In the 50 questions,3 questions' difficulty coefficient is less than 0.4,14 questions' difficulty coefficient is between 0.4-0.7,33 questions' difficulty coefficient is above 0.7,so the difficulty degree of the paper is relatively low.In the 50 questions,23 questions' distinction degree is less than 0.15,17 questions' distinction degree is between 0.15-0.30,10 questions' distinction degree is above 0.30,so the distinction degree of the paper is relatively high.In the 50 questions,20 questions' accuracy appears larger differences between each unit:9 questions' accuracy has decreased significantly among 1-2 units,4 questions' accuracy decreased significantly among 3 units,3 questions' accuracy decreased significantly among 4 units,only 1 unit has high accuracy among 2 questions,and 2 questions' accuracy decreased significantly among all units.These problems are related to the teachers' teaching ability,the difficulty in mastering the key points of the curriculum,the lack of the concept of the general practitioners training.Conclusion The design of the examination paper is basically in line with the study purpose and the objectives of the training course.This examination paper was highly reliable,and suitable for the professional theory and ability test.There are site differences between each unit,which can provide an objective basis for improving the teaching level of different teaching unit,and we will solve the problems in the form of collective preparation next step.

Impact of village-based health education of tobacco control on the current smoking rate in Chinese rural areas / 华中科技大学学报（医学）（英德文版）

The number of smokers in Chinese rural areas is more than 200 million, which is twice that in cities. It is very significant to carry out tobacco control interventions in rural areas. We performed this community intervention study to evaluate the efficacy of village-based health education of tobacco control on the male current smoking rate in rural areas. The population of this study was the males above 15 years old from 6 villages in rural areas. The villages were randomly assigned to intervention group or control group (3 villages in each group). Self-designed smoking questionnaire was applied. The intervention group received the village-based health education of tobacco control for one year. The primary outcome measurement was the male current smoking rate. In the baseline investigation, completed surveys were returned by 814 male residents from the control group and 831 male residents from the intervention group. The male current smoking rate in the control group and the intervention group was 61.2% and 58.5%, respectively, before intervention. There was no significant difference between these two groups (P>0.05). After one-year intervention, the current smoking rate in the intervention group (51.2%) was significantly lower than that in the control group (62.8%) (P<0.001). Our study suggested that the village-based health education of tobacco control was effective in lowering the male current smoking rate in rural areas, which could be a suitable and feasible way for tobacco control in the Chinese rural areas.

Preparation of pueratin/MCM-41 assemblies and pharmacokinetic study in rats / 中国药学杂志

OBJECTIVE: To synthesize MCM41 mesoporous molecular sieves, prepare pueratin/MCM 41 assemblies, and study their pharmacokinetics in rats. METHODS: MCM-41 mesoporous molecular sieves were synthesized using TEOS as silicon source and CTAB as templates under basic condition. Pueratin was loaded into MCM-41 by immersion method. Pueratin-loaded MCM-41 (PU-MCM) was characterized by X-ray diffraction (XRD), N2 adsorption-desorption and FT-IR spectroscopy. Pharmacokinetic parameters were calculated from the plasma concentrations determined by HPLC after administration of pueratin suspension (PU-SUS) and PU-MCM orally to rats. RESULTS: Pueratin was loaded into the pores of MCM-41 successfully with a drug loading rate of 12.6%. The pharmacokinetic parameters in rats after administration of PU-SUN and PU-MCM were as follows: ρmax were (2.43 ± 0.75) and (3.98 ± 1.15) μg · mL-1, tmax were (0.79 ± 0.19) and (0.67 ± 0.20) h, and AUC0~t were (5.35 ± 1.42) and (10.41 ± 2.64) μg · h · mL-1, respectively. CONCLUSION: PU-MCM was prepared successfully, which showed significantly increased release rate, longer residence time and higher bioavailability than PU-SUS after administration in rats.

Inhibitory effect of dexamethasone on expression of cysteine-rich 61 protein in airway epithelial cells of allergic mouse models / 华中科技大学学报（医学）（英德文版）

In order to study whether cysteine-rich 61 protein (cyr61) is involved in the pathogenesis of asthma and its relation to airway inflammation, the effect of dexamethasone (Dxm) on the expression of cyr61 in the lung tissues of asthmatic mice was investigated. Forty BALB/c mice were divided into asthma group (n=15), control group (n=10) and Dxm group (n=15). The asthma group was sensitized and challenged by ovalbumin (OVA). The mice in Dxm group were intraperitoneally administered with Dxm after OVA challenge. The expression of cyr61 in the lung tissues was detected by using immunohistochemistry, and that of eotaxin protein in the bronchoalveolar lavage fluid (BALF) by using enzyme-linked immunosorbent assay (ELISA). The number of inflammatory cells in BALF was also analyzed. The results showed that the cyr61 expression was highest in asthma group (P<0.05), followed by Dxm group (P<0.05) and control group. The cyr61 had a positive correlation with the total nucleated cells (r=0.867, P<0.05), especially eosinophils (r=0.856, P<0.05), and eotaxin level (r=0.983, P<0.05) in the BALF. Our findings suggested that cyr61 is expressed in airway epithelial cells and has a positive correlation with eotaxin and number of airway infiltrating eosinophils.

Genotoxicity and reduced heat shock protein 70 in human airway smooth muscle cells exposed to cigarette smoke extract / 华中科技大学学报（医学）（英德文版）

Cigarette smoke is associated with the development of several diseases, such as chronic obstructive pulmonary disease (COPD). The purpose of this study was to investigate genotoxicity and heat shock protein 70 (Hsp70) in human airway smooth muscle cells (HASMCs) exposed to cigarette smoke extract (CSE). HASMCs was exposed to CSE with different doses for 24 h. The level of 8-hydroxydeoxyguanosine (8-OHdG) was determined by using HPLC-ECD, the DNA damage was analyzed by using comet assay, and apoptosis was examined by using Annexin-FITC/PI staining. The production of Hsp70 after CSE stimulation was tested. Results indicated that CSE significantly increased the level of 8-OHdG, DNA damage and cell apoptosis, and reduced the production of Hsp70. In particular, levels of Hsp70 were inversely correlated with 8-OHdG, DNA damage and cell apoptosis. It was concluded that cigarette smoke induced genotoxicity and decreased the production of cell protective protein Hsp70, which may contribute to the development of some airway diseases.

Genotoxicity and reduced heat shock protein 70 in human airway smooth muscle cells exposed to cigarette smoke extract / 华中科技大学学报（医学）（英德文版）

Cigarette smoke is associated with the development of several diseases, such as chronic obstructive pulmonary disease (COPD). The purpose of this study was to investigate genotoxicity and heat shock protein 70 (Hsp70) in human airway smooth muscle cells (HASMCs) exposed to cigarette smoke extract (CSE). HASMCs was exposed to CSE with different doses for 24 h. The level of 8-hydroxydeoxyguanosine (8-OHdG) was determined by using HPLC-ECD, the DNA damage was analyzed by using comet assay, and apoptosis was examined by using Annexin-FITC/PI staining. The production of Hsp70 after CSE stimulation was tested. Results indicated that CSE significantly increased the level of 8-OHdG, DNA damage and cell apoptosis, and reduced the production of Hsp70. In particular, levels of Hsp70 were inversely correlated with 8-OHdG, DNA damage and cell apoptosis. It was concluded that cigarette smoke induced genotoxicity and decreased the production of cell protective protein Hsp70, which may contribute to the development of some airway diseases.

Inhibitory effect of dexamethasone on expression of cysteine-rich 61 protein in airway epithelial cells of allergic mouse models / 华中科技大学学报（医学）（英德文版）

In order to study whether cysteine-rich 61 protein (cyr61) is involved in the pathogenesis of asthma and its relation to airway inflammation, the effect of dexamethasone (Dxm) on the expression of cyr61 in the lung tissues of asthmatic mice was investigated. Forty BALB/c mice were divided into asthma group (n=15), control group (n=10) and Dxm group (n=15). The asthma group was sensitized and challenged by ovalbumin (OVA). The mice in Dxm group were intraperitoneally administered with Dxm after OVA challenge. The expression of cyr61 in the lung tissues was detected by using immunohistochemistry, and that of eotaxin protein in the bronchoalveolar lavage fluid (BALF) by using enzyme-linked immunosorbent assay (ELISA). The number of inflammatory cells in BALF was also analyzed. The results showed that the cyr61 expression was highest in asthma group (P<0.05), followed by Dxm group (P<0.05) and control group. The cyr61 had a positive correlation with the total nucleated cells (r=0.867, P<0.05), especially eosinophils (r=0.856, P<0.05), and eotaxin level (r=0.983, P<0.05) in the BALF. Our findings suggested that cyr61 is expressed in airway epithelial cells and has a positive correlation with eotaxin and number of airway infiltrating eosinophils.

Evolution of hepatitis B virus quasispecies during lamivudine-entecavir sequential therapy / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To study the evolution of HBV quasispecies under the pressures of lamivudine (LAM) - entecavir (ETV) sequential therapy and its clinical significance.</p><p><b>METHODS</b>Consecutive serum samples from 2 patients underwent LAM-ETV sequential therapy were extensively studied for HBV quasispecies composition and evolution, using PCR-cloning-sequencing method. Maximum likelihood trees were built to analyze the genetic relationship between representative sequences. Correlation between HBV quasispecies evolution and serological/virological data was analyzed to determined the clinical significance of the evolution of HBV quasispecies during prolonged nucleotide analog therapy.</p><p><b>RESULTS</b>Virological breakthrough was observed in both patients. Patient I acquired sustained virological response after switching to ETV rescue therapy, whereas Patient II suffered from virological breakthrough after 72 weeks of ETV therapy. Each virological breakthrough was accompanied with the replacement of previous drug susceptible dominant quasispecies with a drug resistant variant, indicating a close correlation between quasispecies composition and drug susceptibility. The rtL180M+S202G+M204V triple mutant, which was most likely a descendant of the LAM resistant rtL180M+M204V variant, was closely correlated with ETV resistant in Patient II.</p><p><b>CONCLUSION</b>Quasispecies composition of HBV is closely correlated with nucleotide analog susceptibility. ETV resistant variant can emerge from a LAM resistant viral population. Dynamic monitoring of HBV quasispecies composition is of great importance during nucleotide analog therapy.</p>

Assessment of percutaneous vertebroplasty and percutaneous kyphoplasty for treatment of senile osteoporotic vertebral compression fractures / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the clinical effects and safety of vertebroplasty and kyphoplasty for the senile osteoporotic vertebral compression fractures.</p><p><b>METHODS</b>From December 2004 to June 2008, 28 patients (40 vertebrae) with osteoporotic vertebral compression fractures were treated with percutaneous vertebroplasty (PVP group), there were 11 males (14 vertebrae) and 17 females (26 vertebrae), with an average age of 72 years (ranged, 70 to 91 years). The fracture site of vertebral body was from T5 to L5. Other 31 patients (43 vertebrae) were treated with percutaneous kyphoplasty (PKP group), there were 13 males (18 vertebrae) and 18 females (25 vertebrae), with an average age of 74 years (ranged, 70 to 92 years). The fracture site of vertebral body was from T4 to L5. Theapeutic effects of all the patients were observed after operation, the item included visual analog scale (VAS), Oswestry score, Cobb angle, the height of anterior and middle column vertebra, and the incidence of cement leakage.</p><p><b>RESULTS</b>There was significant decrease in VAS score and Oswestry score after operation in both groups, there was significant difference between preoperative and postoperative (P < 0.01). There was no significant difference in VAS score and Oswestry score between two groups (P > 0.05). There was no significant difference in Cobb angles and the height of anterior and middle column vertebra between two groups before and after operation (P > 0.05). Among them, there were 3 vertebrae cement leakage in PVP group (7.5%) and 2 in PKP group (4.7%), but no clinical sympton occurred. There was no significant difference in the incidence of cement leakage between two groups (P > 0.05).</p><p><b>CONCLUSION</b>Vertebroplasty and kyphoplasty are safe and effective methods in treating senile osteoporotic vertebral compression fractures, which can restore the height of fractured vertebra, relieve pain and improve function as well as minimize the incidence of cement leakage.</p>