Objective To establish a platinum resistance nude mice model of epithelial ovarian cancer (EOC) and investigate its resistance to cisplatin (DDP) biological characteristics, so as to provide evidences for exploring chemoresistence mechanisms and screening for reversal targets in vivo micro-environment. Methods The resistance model was produced by repeating a crossover subcutaneous injection of human ovarian cancer SKOV3 cells labelled green fluorescent protein(GFP) and transplatation of tumor fragment into nude mice. Two kinds of cancer cell lines of SKOV3/DDPⅠand SKOV3/DDPⅡwere induced with acquired resistence to DDP. The chemosensitivities of EOC cells to DDP were tested and half maximal inhibitory concentration(IC50) was measured by methyl thiazolyl tetrazolium (MTT) and flow cytometry (FCS). Dynamic analysis among the concentration of DDP treatment and cell apoptosis, cell cycle phase distribution and intracellular DDP concentration. The expression of PTEN, STAT5, XIAP, BRCA1 and MDR1 were examined by real time quantitative reverser transcription PCR (qRT-PCR) in vivo. Results IC50 value of cisplatin for SKOV3/DDPⅡ were 2.83 ± 0.12 and 3.82 ± 0.19 folds than those for SKOV3/GFP by MTT and flow cytometry, separately. SKOV3/DDPⅠwere 2.20±0.16 and 3.40±0.20 folds. The apoptosis rate of SKOV3/DDPⅡ and SKOV3/DDPⅠ were decreased significantly at 29.7 and 39.6μmol/L DDP when treatment for 36 hours,which were lower than that of SKOV3/GFP cells [(57.0±1.4)%vs (37.6 ± 4.36)%vs (83.1 ± 2.71)%,P=0.024;(74.4 ± 2.3)%vs (50.5 ± 3.4)%vs (87.4 ± 4.0)%,P=0.001]. SKOV3/DDPⅠ and SKOV3/DDPⅡ was positively related with cisplatin processing time. Intracellular DDP accumulation of SKOV3/DDPⅡand SKOV3/DDPⅠwere lower than SKOV3-GFP in dynamic processes(P<0.05). Besides intracellular DDP accumulation of SKOV3/DDPⅡ also lower than SKOV3/DDPⅠin dynamic processes (P<0.05). Transplanted tumor of SKOV3/GFP appeared organelle degradation and nuclear membrane imcompleted after five times DDP injection with concentration of 4 mg/kg. SKOV3/DDPⅡand SKOV3/DDPⅠdid not generate these phenomenon untill eighth DDP injections with concentration of 4 mg/kg. STAT5 and BRCA1 of SKOV3/DDPⅡwere increased with DDP treatment at concentration of 4 mg/kg. Expression of XIAP from SKOV3/DDPⅡwas positive correlated with injection times. STAT5,XIAP and BRCA1 of SKOV3/DDPⅡwere up-regulated 3.86,28.1 and 14.6 folds than those in SKOV3/GFP cells after eighth DDP treatment, separately. While PTEN of SKOV3/DDP Ⅱ was decreased 3.77 folds. Conclusions We have successfully established platinum-resistent EOC mice model,which provides a new platform for further study on chemoresistant reversal and individualized clinical treatment. The results shown that potential mechanisms of SKOV3/DDPⅡDDP-resistance included over-expressed BRCA1 gene may be promote DNA damage repair, elevate XIAP gene to decrease cell apoptosis,up-regulated STAT5 gene and decrease PTEN gene to stimulate proliferation.

Objective To investigate the apoptosis of rat glioma C 6 cells induced by defective in-terfering( DI) particles of Sendai virus strain Tianjin .Methods Rat glioma C6 cells were treated with dif-ferent titers of DI particles of Sendai virus strain Tianjin in vitro with culture media as negative control and intact virus as positive control .At different time point , cells were collected and their apoptosis was detected by DNA gel electrophorsis , TUNEL assay and AnnexinⅤ/PI double-labeled flow cytometry .The C6 glioma-bearing rat model was established and then treated with three intratumoral injections of DI particles , intact virus or saline three times at interval of two days .The antitumor effects of ID particles were evaluated through daily measuring of the tumor size .Hematoxylin-eosin( HE) staining was used to observe the patho-logical changes in tumor tissues .TUNEL assay was performed to detect the apoptosis of tumor tissues .Re-sults Rat glioma C6 cells treated with DI particles or intact virus in vitro showed typical DNA ladder pattern in agarose gel electrophoresis in a time-and dose-dependent manner .With the intervention of DI particles , the apoptosis rate of C6 cells showed a time-and dose-dependent manner and was significantly higher than that of the control group (P<0.01) as indicated by flow cytometry assay and TUNEL assay .In vivo, DI par-ticles could markedly inhibit the growth of the tumors in comparison with saline control group .There were fe-wer tumor cells in tumor nodules in DI particles group or intact virus group as shown by histological examina -tion.The TUNEL assay showed that the apoptosis rate of tumor tissues injected with DI particles or intact vi -rus was much higher than that of the saline group (P<0.01), but there was no significant difference between the DI particles group and the intact virus group (P>0.05).Conclusion The DI particles of Sendai virus strain Tianjin could induce apoptosis of rat glioma C 6 cells in a time-and dose-dependent manner both in vitro and in vivo, suggesting that the DI particles might be applicable for the treatment of neurogliocytoma in the future.

Talk teaching is an effective form of teaching research activity.It focuses on the teachers,teaching ideas and their abilities of curriculum development,curriculum designing and teaching practice.It is of great significance in optimizing pathophysiologic teaching,improving the teaching effect and teachers'quality.It is worth discussing and promoting.Talk teaching should be the basic skill necessary to the teachers of basic medicine.

OBJECTIVE:To study the technical conditions and parameters of DiaionHP-20 macroporous adsorption resin for the purification of the anti-PMOP(primary Type I osteoporosis) active fraction from Camellia semiserrata seed.METHODS: With the elution ratios and purity of total flavonoids and polyphenol from Camellia semiserrata as indexes,the technical parameters of DiaionHP-20 macroporous adsorption resin including the adsorption quantity,the loading sample,the elution concentration and volume of alcohol were investigated.RESULTS: The adsorption quantity of DiaionHP-20 macroporous resin on total flavonoids and polyphenol were 59.5 mg?g-1 and 23.9 mg?g-1 respectively.The optimal technical conditions were as follows:the quantity of drug was 10.5 times that of resin;water-soluble foreign substance was washed off with distilled water weighing 3 times the weight of resin,and total flavonoids and polyphenol were eluted using 25% ethanol weighing 13.5 times the weight of resin.CONCLUSION:DiaionHP-20 macroporous resin had good purification effects on total flavonoids and polyphenol from Camellia semiserrata seeds.The process is simple,low cost,and suitable for lavge-scale production.

AIM: To explore the effect of atorvastatin on the expression of α-SMA and TGF-β1 in the adventi-tia of ApoE-/-mice with atherosclerosis, and to investigate the underlying mechanism of atorvastatin therapy.METHODS:Male ApoE-/-mice (n =40) at 6-weeks of age were used to establish the atherosclerosis model by feeding with high fat diet. The mice were randomly divided into model group and atorvastatin group.In atorvastatin group, the mice were lavaged with atorvastatin at dose of 20 mg? kg-1? d-1 .The mice in model group were given normal saline.C57BL/6 mice of the same age served as control group, feeding with ordinary food.The mice were respectively sacrificed at the time points of 10 and 15 weeks after feeding with different diets.The ascending aorta was removed for serial sectioning.Some sections were per-formed with Movat staining in order to observe the morphological changes of the tissues, and to measure the relative athero-sclerotic plaque area and the thickness of the adventitia.Some sections were stained with Sirius red to identify the collagen synthesis.Immunohistochemistry assay was prepared to observe the expression of α-SMA and TGF-β1 in the adventitia at different time points.The expression of TGF-β1 at mRNA and protein levels in the thoracoabdominal aorta was measured by RT-qPCR and Western blot.RESULTS: Compared with model group, the formation of plaque in atorvastatin group signifi-cantly descended.Meanwhile the adventitial thickness and collagen synthesis also decreased.The results of immunohisto-
chemical staining showed that compared with 10 weeks-model group, α-SMA and TGF-β1 in 15 weeks-model group was in-creased.The expression of α-SMA and TGF-β1 in atorvastatin group decreased significantly compared with model group. The expression of TGF-β1 at mRNA and protein levels in model group were higher than those in control group.They de-creased in atorvastatin group compared with model group.Compared with 10 weeks-model group, the mRNA and protein of TGF-β1 in 15 weeks-model group were increased.CONCLUSION: Atorvastatin modulates adventitial fibroblast phenotype differentiation by suppressing expression of TGF-β1 and intervenes atherosclerotic development in ApoE.

Objective:This study aims to systematically sort out the effectiveness evaluation of the general education teaching models in epidemiology at home and abroad and provide a reference for the development and reform of epidemiology education.Methods:A systematic search of English databases such as PubMed, Embase, and Web of Science and Chinese databases such as CNKI, Sinomed, Wanfang, etc., were used to screen out the literature on different general teaching models of education in epidemiology. Each literature's teaching effect will be summarized and evaluated to conduct a systematic qualitative review in the narrative integration method, Results:A total of 45 articles (28 in Chinese and 17 in English) were included in this study, involving 14 teaching models, including mixed teaching models, PBL (problem-based learning), project designing models, and CBL (case-based learning) and other teaching models. Except for some teaching models such as project design, network platform, and flipped classroom model, the teaching effect of other innovative models is better than that of the traditional model. The distribution of teaching models was different in Chinese and foreign literature. Foreign teaching models were diverse, mainly concentrated in mixed teaching models and software/network platform learning. Domestic teaching models were relatively fixed. The mixed teaching model and PBL model were the most widely used in China, and there were fewer comparative studies between different teaching models than in foreign countries.Conclusion:General education in epidemiology is still in the early exploration stage. Compared with the traditional lecture model, the effect of various innovative teaching models has been improved. According to teaching objectives and student characteristics, we encourage extensive use of different teaching strategies, combining theoretical knowledge with practical applications and integrating epidemiological knowledge with inter-professional knowledge. Thus, students who can apply what they learn are becoming interdisciplinary talents our society needs.

Objective:To explore the differences of physical activity levels between Chinese and British patients with cardiovascular disease (CVD) and its influencing factors.Methods:Based on the baseline survey of China Kadoorie Biobank (CKB) and United Kingdom Biobank (UKB), we identified the case and control group according to the self-reported disease history in the questionnaire. Metabolic equivalent of task, as the assessment of physical activity level, was graded according to the tertiles of specific ages and genders. Multiple logistic regression models were used to analyze the correlation between CVD status and physical activity levels.Results:We included 509 170 Chinese adults and 360 360 British adults in the analysis. After adjusting for multiple factors, we found a positive correlation between CVD patients and low physical activity levels in both CKB and UKB populations (CKB: OR=1.21, 95% CI:1.17-1.25; UKB: OR=1.24, 95% CI:1.20-1.28). There was a high correlation between the prevalence of CVD and low physical activity levels in males with CKB ( OR=1.33, 95% CI:1.27-1.40).Unlike the UKB population, as the length of CVD increased, the physical activity levels of CKB patients gradually approached that of the non-CVD population, and stroke was positively correlated with low physical activity levels ( OR=1.46, 95% CI:1.38-1.53). The decline in physical activity was more pronounced among CKB and UKB CVD patients with lower educational levels, current or former smokers or drinkers, and those with other chronic diseases. In CKB, there showed a high correlation between CVD disease and low physical activity levels in rural areas and non-retired populations. In UKB, there appeared a higher correlation between CVD disease and low physical activity levels in urban and non-working populations. Conclusions:The physical activity levels of CVD patients in both China and the UK were lower than that in non-CVD population. In addition to low-educated individuals, current or former smokers or drinkers, and those with other chronic diseases, it is critical to pay attention to the physical activity levels of rural, male, and non-retirees among Chinese patients.

Objective:To compare physical activity and its influencing factors in patients with chronic obstructive pulmonary disease (COPD) between China and the United Kingdom.Methods:We analyzed baseline data from China Kadoorie Biobank and the United Kingdom Biobank among COPD patients who were diagnosed with a one-second rate (FEV 1/FVC) less than 70%. Physical activity level was calculated as metabolic equivalent (MET) and divided into three levels: low, medium, and high, according to tertiles stratified by gender and age. Multiple logistic regression was used to estimate ORs and 95% CIs for COPD and Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade about physical activity level, and subgroup analysis was conducted. Results:A total of 506 073 Chinese adults and 231 884 British adults were included. After adjusting for potential confounders, COPD was associated with lower physical activity levels in both Chinese and British COPD patients, with OR (95% CI) of 1.07(1.03-1.10) and 1.03(1.01-1.06) compared with non COPD patients, respectively. The GOLD grade was inversely correlated with physical activity level, particularly in a dose-response manner in the CKB population (trend test P<0.001). The negative relationship was stronger among the elderly, people with less education and lower economic status, and those with a smoking or chronic disease history. Chinese rural COPD patients were at high risk of decline of physical activity. Conclusions:Physical activity is inversely related to COPD, with a dose-response connection to GOLD grade. Therefore, physical activity maintenance and improvement should be encouraged and promoted in COPD patients, especially in high-risk groups.

Objective:To explore the effect of combining hand-brain perception training with hand-brain motor training based on mirror neuron theory on the recovery of upper limb function after a stroke.Methods:A group of 105 stroke survivors with upper limb dysfunction were randomly divided into a hand-brain perception (HP) group, a hand-brain motor (HM) group, and a combination (C) group, each of 35. In addition to conventional rehabilitation treatment (including exercise therapy, occupational therapy and physical factor therapy), the HP and HM groups were given hand-brain perception training and hand-brain motor training respectively, while group C was provided with both. Before the intervention and after 4 weeks, the upper limb motor functioning of all of the participants was assessed using the simplified version of the Fugl-Meyer upper limb motor function scale (FMA-UE). Sensory functioning was quantified using the tactile Semmes Weinstein monofilament examination (SWME), and the modified Barthel index (MBI) was used to quantify the participants′ ability in the activities of daily living.Results:After the intervention the average FMA-UE, MBI and SWME scores of all three groups had improved significantly, with group C′s average FMA-UE and MBI scores significantly better than the other two groups′ averages. The average SWME score of group C was then significantly better than that of group HM.Conclusions:Hand-brain perception combined with hand-brain motor training based on mirror neuron theory can further promote the recovery of upper limb sensory and motor functioning of stroke survivors., Such therapy is worthy of clinical promotion and application.

Objective To explore the feasibility and safety of flexible ureteroscope with tubeless in the treatment of middle or upper calyx renal calculi.Methods The clinical data of 107 patients with renal calculi treated from January 2015 to October 2018 were analyzed retrospectively.Age ranged from 18 to 55 years,with mean of (32.1 ± 5.2) years.Calculi was single,locating in the middle or upper calyx,with the diameter less than 2.0 cm,the CT value ≤ 800 HU,and mild renal hydronephrosis.All patients were routinely indwelling double-J tube using cystoscopy 2 weeks preoperatively,and ureteroscopic lithotripsy was performed.Fifty patients in group A were received tubeless treatment,and 57 patients in group B were given routinely indwelling double-J tube.The 50 patients in group A were (30.4 ± 5.9) years of age,including 33 males and 17 females,28 cases on the left and 22 cases on the right,24 cases locating in the upper calyx and 26 cases locating in the middle calyx,and calculi diameter of (1.3 ± 0.5) cm.The 57 patients in group B were (31.3 ± 5.4) years of age,including 35 males and 22 females,26 cases on the left and 31 cases on the right,27 cases locating in the upper calyx and 30 cases locating in the middle calyx,and diameter of (1.4 ± 0.4) cm.There were no significant difference in the demographics between the two groups (P ＞ 0.05).Results There were no obvious ureteral malformations,stenosis,polyps or tumors in the 107 cases intraoperatively,and the flexible ureteroscope sheath was placed smoothly.The operation time in group A [(48.2 ± 9.7) min] was significantly lower than that in group B [(51.7 ± 7.8) min,P ＜ 0.05].There was no significant difference in the calculi clearance rate between the two groups on the first day [92.0％ (46/50) vs.91.2％ (52/57)] and two weeks[96.0％ (48/50) vs.98.2％ (56/57)] after operation(P ＞ 0.05),and the calculi clearance rate reached 100％ at 1 month after operation.The incidence of hematuria in group A [24.0％ (12/50)] was significantly lower than that in group B [54.4％ (31/57),P =0.001].The incidence of bladder irritative symptoms in group A [14.0％ (7/50)] was significantly lower than that in group B [36.8％ (21/57),P =0.007].The incidence of lumbar and abdominal pain at 1 week,2 weeks and 1 month after operation was significantly lower in group A [32.0％ (16/50),8.0％ (4/50),2.0％ (1/50)] than that in group B [57.9％ (33/57),49.1％ (28/57),33.3％ (19/57),P ＜ 0.05].There was no significant difference between the two groups about the incidence of lumbar and abdominal pain at first day after operation [86.0％ (43/50) vs.84.2％ (48/57),P ＞ 0.05].Conclusions It was feasibility and safety to perform flexible ureteroscope with tubeless for the patients with renal primary and single calculi,ideal ureteral conditions (no malformations,stenosis,polyps or tumors),mild renal hydronephrosis,calculi,diameter ＜ 2.0 cm,CT value ≤ 800 HU,locating in the middle or upper calyx,and no history of urinary calculi.This procedure had not only similar calculi clearance rate compared with routinely indwelling double-J tube,but also has a lower incidence of complications (hematuria,bladder irritative symptoms,lumbar or abdominal pain).