Objective To explore the radiosensitivity of berberine on esophageal cancer cells under hypoxia condition.Methods MTT assay and clonogenic survival assay were used to evaluate the effect of berberine on proliferation inhibition and radiosensitivity of esophageal cancer cells,respectively.Immunofluorescence was employed to examine the expression of HIF-1.The change of cell cycle distribution and cell apoptosis was assayed by flow cytometry.The expression of HIF-1 was measured by Western blot.DNA damage was detected by γ-H2AX Foci counting.Results With a clear dose and time effect,berberine inhibited cell proliferation and enhanced cell radiosensitivity(t =3.69,P＜0.05)with a sensitizing enhancement ratio(SER)of 1.42.Berberine caused a dose-dependent decrease in HIF-1 protein expression and also significantly increased the cell apoptosis in ECA-109 population(t=4.74,P＜0.05).Compared with the radiation alone group,berberine enhanced X-ray induced DNA double chain breaks(DSB).Conclusions Berberine can increase the radiosensitivity of esophageal cell line ECA-109,which may be associated with decrease of HIF-1 expression and induction of apoptosis in ECA-109 cells.

Objective · To compare urine sample collection methods for measuring urinary concentrations of phenolic endocrine disrupting chemicals including bisphenol A (BPA),triclosan (TCS),and 4-n-nonylphenol (4-n-NP) in pregnant women.Methods· Urine samples were collected from women at late pregnancy by two methods:urine catheter and collection bag (n=176),urine collecting containers made of polypropylene (PP) (n=642).Urinary concentrations of BPA,TCS and 4-n-NP were measured with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)method.Confirmation experiment used PP containers,urine catheter and collection bags,as well as low-density polyethylene (LDPE) tubes and glass containers as both negative controls to collect urine samples from each of the 5 women.Results · Geometric mean (GM) of urinary BPA concentration collected by urine catheter and collection bags was 82.5 ng/mL (95％ CI 71.4-95.4 ng/mL),which was 63 times higher than that from PP containers (GM 1.3 ng/mL;95％ CI 1.3-1.5 ng/mL).Concentrations of urinary 4-n-NP and creatinine were similar between two collection methods.Confirmation experiment showed that urinary BPA concentration collected by urine catheter and collection bags was much higher than those collected by other three methods.Conclusion· In collection of urine samples for measuring phenolic chemicals,PP urine collection container as well as LDPE containers are adequate for use in epidemiologic studies,but urine catheter and collection bag is not.

Objective To study the protective effect of hyperin( Hyp) on the acute liver injury in rats induced by CCl4 . Methods The acute liver injury model was induced by CCl4 . The effect of Hyp on acute liver injury of rat liver histopathology was observed;and the impact of changes of homogenates total superoxide dismutase ( T-SOD) ,glutathione ( GSH) activity and malondialdehyde ( MDA) in liver were de-tected. Results The acute liver injury of tissue induced by CCl4,apparent pathological inflammation and fibrous tissue degeneration and necrosis were observed by HE staining;At the high doses of 60 mg/kg and medium doses of 30 mg/kg treated by Hyp,liver pathology changes was significantly obvious. The T-SOD,GSH activity of liver tissue was significantly increased in the groups of Hyp treatment,MDA content was significantly decreased,which related to the dosages. Conclusion In the rat model of acute liver injury induced by CCl4 . A better therapeu-tic effect of Hyp was shown,the mechanism may be related to its antioxidant activity.

OBJECTIVETo investigate the expression profile of serum micro (mi)RNAs in cholangiocarcinoma (CCA) and investigate the regulatory contribution of miRNAs to the invasive and metastasis.

METHODSMicroarray analysis was carried out using serum samples collected from 30 patients with CCA, bile duct cancer tissues and the corresponding normal tissues collected from 10 patients, and serum samples from 50 healthy volunteers. The miRNAs identified as dysregulated in CCA were verified by RT-PCR. Focused analysis on miR-224 was carried out using the human CCA cell lines HCCC-9810 and RBE to investigate the role of this miRNA in IL-6 expression (using IL-6 induction), cell growth, invasiveness and metastasis (using miR-224 mimic transfection). The one-way ANOVA test was used for statistical analysis.

RESULTSForty-three miRNAs were dysregulated in CCA (vs. non-CCA, P<0.01), of which 22 were upregulated and 21 were downregulated. RT-PCR data showed that the miR-224 was significantly upregulated in serum as well as in cancer tissue from CCA patients. Induction of HCCC-9810 and RBE cells with IL-6 showed a time-dependent upregulation of miR-224. Furthermore, the HCCC-9810 and RBE cells transfected with miR-224 mimic showed enhanced cell growth, invasiveness and migratory ability.

CONCLUSIONIL-6 may promote the invasive and metastatic properties of CCA through upregulated miR-224. Studies of the differentially expressed serum miRNAs in CCA may help to further elucidate the pathogenic processes of this disease and aid in the development of a novel and effective therapeutic strategy.

Bile Ducts, Intrahepatic ; Cell Line, Tumor ; Cell Proliferation ; Cholangiocarcinoma ; Down-Regulation ; Humans ; Interleukin-6 ; MicroRNAs ; Microarray Analysis ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Transfection ; Up-Regulation

Objective To evaluate the application value of low-dose CT (LDCT) in physical examination for coal miners with different exposure time.Methods The consecutive three-year imaging data of 972 coal miners with over 20-year exposure were retrospectively reviewed.All miners were divided into 3 groups according to different exposure time,including 317 cases with less than 10 years,299 cases with 10-20 years and 356 cases with more than 20 years.All subjects underwent LDCT examination every year during three consecutive years.Results Baseline LDCT:As the exposure time was prolonged (with less than 10 years,10-20 years and more than 20 years),the number of coal miners has increased with non-calcified pulmonary nodules,interstitial pulmonary lesions,clinically cured or stable stage of pulmonary tuberculosis,pulmonary calcification and pulmonary fibrous stripes,but without statistically significant difference.The detection rates of lung bullae,aorta and coronary artery sclerosis were also increased mildly,with the prolonged exposure time.There was no significant correlation between exposure time and detection rates of bronchiectasis,pulmonary inflammatory lesions,lymph node enlargement or calcification,pleural lesions.The exposure time of 6 cases of malignant nodules and 2 cases of active tuberculosis was more than 10 years.During a two-year follow-up using LDCT scan,there were no significant changes in most of intrapulmonary,pleural and mediastinal lesions.Neither were in pulmonary nodules less than or equal to 4 mm.Three pulmonary nodules with 4-8 mm diameters were enlarged.Most of the inflammatory lesions have changed in size.Conclusion The LDCT scan has a certain value for chest physical examination of the coal miners with different exposure time.It is very necessary to screen the high-risk population of coal miners with exposure time of more than 10 years using LDCT.LDCT reexamination has significant value for pulmonary nodules and inflammatory lesions with diameter of more than 4 mm.Most of intrapulmonary,pleural and mediastinal lesions have no obvious change in the short term,and make an annual reexamination unnecessary,neither does a negative baseline LDCT.

Objective: To investigate the clinical significance of low-dose CT (LDCT) in coal mine workers with relatively long working years. Methods: A total of 907 coal mine workers with ≥20 working years were enrolled, among whom there were 863 male and 44 female workers with a mean age of 49.5 years. Digital radiography (DR) was performed for these workers in 2013, and LDCT was performed for three consecutive years from 2014 to 2016. Results: A total of 32 workers were found to have lung nodules by DR in 2013, while in 2014, 269 workers were found to have non-calcified lung nodules by LDCT, and there was a significant difference in the number of workers with lung nodules (χ²=233.73, P<0.005) . There was also a significant difference in the detection rate of nodules between the workers with different working years of dust exposure (χ²=6.648, P=0.00) . The male workers had a significantly higher detection rate of nodules than the female workers (χ²=5.690, P=0.017) . There was no significant difference in the number of nodules between workers with different types of work (χ²=16.985, P=0.05) . There were 443 lung nodules in total, among which 71.56% were solid nodules and 55.75% had a size of ≤4mm; malignant nodules were confirmed by surgery in 6 (0.66%) of the 907 workers after baseline LDCT. LDCT reexamination in 2015 and 2016 found new nodules in 8 workers and enlarged nodules in 3 workers, and there was no significant change in the number of nodules with a size of ≤4 mm. Conclusions It is necessary to perform high-risk population screening for coal mine workers by LDCT. The follow-up strategies for nodules with a size of ≤4mm are the same as those for negative results; annual reexamination is recommended for nodules with a size of >4-8 mm, and clinical treatment should be considered for nodules with a size of >8 mm.

Objective To investigate the clinical significance of joint application of carcinoembryionic and carbohydrate antigen 19-9 for improving the prognosis of patients with gallbladder cancer.Methods A retrospective analysis of clinical-pathological features and prognosis were conducted including 390 patients with gallbladder cancer,who were treated from January 2003 to December 2013 at Eastern Hepatobiliary Surgery Hospital of Second Military Medical University.The clinical value of joint application of careinoembryionic and carbohydrate antigen 19-9 in prognosis was explored.The survival of patients was followed up by telephone or outpatient.Continuous variables were indicated as median (average) and categorical variables were expressed as number(n).Mann-Whitney U test was applied for continuous variables.Categorical variables were compared by the Chi-square test or Fisher probability method.The survival curve was drawn by the Kaplan-Meier method.The univariate analysis and multivariate analysis of prognosis were respectively done using the Log-rank test and COX regression model.Results Of the 390 patients,327 had complete data.The median (range) follow-up time was 49 (1-123) months.Both carcinoembryionic and carbohydrate antigen 19-9 could be used to predict prognosis of gallbladder cancer.A linear combination of carcinoembryionic and carbohydrate antigen 19-9 was significantly better(0.9365) than carbohydrate antigen 19-9 (0.7619) as well as carcinoembryionic (0.7937) alone in term of specificity.Preoperative blood test carcinoembryionic and carbohydrate antigen 19-9 nature showed double-negative group had the best prognosis,with a median survival of 27.06 months,R0 radical rate was 86.1％.Doublepositive group had the worst prognosis,with a median survival of 6.17 months,R0 radical rate was 45.1％.Conclusions Combinations of pretherapeutic tumor makers carcinoembryionic and carbohydrate antigen 19-9 can improve the accuracy of predicting prognostic in patients with gallbladder cancer,and the clinical application is practical.

Background The current treatment program with penehyclidine hydrochloride (PHC) for acute severe organophosphorus pesticide poisoning (ASOPP) patients exerts a positive effect but with concerned adverse reactions. Objective To evaluate the treatment effect of a revised ASOPP treatment program with PHC. Methods A prospective single-blind randomized controlled trial was conducted. A total of 157 patients with ASOPP were divided into a revised treatment group (82 cases) and a conventional treatment group (75 cases) by random number table. The two groups received the same basic treatment measures including active life support, routine gastric lavage, catharsis, and pralidoxime treatment. The revised treatment group followed a revised PHC treatment protocol initiated by first a small dose of PHC and followed by small doses of PHC administration/discontinuation through frequent observations at different time points. The conventional treatment group received the conventional program. Treatment effects and incidence rates of possible adverse reactions were compared between the two groups. Results Compared with the conventional treatment group, the revised treatment group obtained delay in penetrogenation time point, higher success rate in catharsis, earlier cholinesterase-turning time, and shorter hospitalization period with statistical significance (all Ps＜0.05). No differences were found in terms of time for symptoms of poisoning to disappear, incidence rates of intermediate myasthenic syndrome and delayed polyneuropathy, mechanical ventilation time, and cure rate (all Ps＞0.05). Less adverse reactions occurred in the revised treatment group including tachycardia and delirium than in the conventional treatment control group (all Ps＜0.05). Conclusion The revised ASOPP treatment program with PHC is similar to the current recommended treatment program in treatment effects, but with less adverse reactions.

Objective To clarify the characteristics and postoperative benefit of gallbladder carcinoma in elderly patients (≥ 65 years old).Methods Two hundred and seventy-three patients of gallbladder carcinoma were collected,who were treated intent resection from January 2004 to December 2012 in the Department of Hepatobiliary Surgery,Eastern Hepatobiliary Hospital,Second Military Medical University.More than 65 years old was defined as the elderly,else was defined as the younger.The clinical-pathological features and prognosis of 85 elderly patients(elderly group) and 188 younger patients (younger group) were retrospectively analyzed.The survival of patients were followed up by telephone or outpatient.The incidence of hypertension,incidence of diabetes,TNM staging,and median CA19-9 were compared between the two groups.Continuous variables using a two-sample t test or Mann-Whitney U test.Categorical variables were compared by the Chi-square test or Fisher probability method.The survival curve was drawn by the Kaplan-Meier method.The univariate analysis and multivariate analysis of prognosis were respectively done using the Log-rank test and COX regression model.Results The incidence of hypertension,incidence of diabetes,TNM stage ratio (Ⅲ + Ⅳ/Ⅰ + Ⅱ),and CA19-9 median in the elderly group were 30.6％,11.8％,27.6 and 69.3 U/ml,respectively.The differences in the younger group were 13.8％,4.8％,7.9 and 28.2 U/ml,respectively,with statistically significant difference between the two groups (all P ＜ 0.05).The incidence of complications was 54.1％ in the elderly group and 48.9％ in the younger group,with no significant difference between the two groups (P =0.302).The median survival of the elderly group was 28.01 months,and the median survival of the younger group was 36.20 months,with no statistical difference between the two groups (P =0.131).Cox analysis showed that independent prognostic risk factors for the elderly patients with gallbladder cancer included liver invasion (HR =2.386,95％ CI:1.379-4.127,P =0.002) and lymph node metastasis (HR =1.866,95 ％ CI:1.100-3.167,P =0.021).Conclusions Radical resection is safe and feasible for elderly patients with gallbladder carcinoma.Age is not a contraindication for surgery.Radical resection can get the same benefits as young people.Liver invasion and lymph node metastasis are independent risk factors affecting the prognosis of the elderly patients with gallbladder carcinoma.

Objective:To explore the screening scheme of gastric cancer in large-scale natural population in Wuxi.Methods:From December 2016 to December 2019, 105 865 residents of 19 communities (villages) in six streets of Xinwu District, Wuxi were randomly enrolled in this study by random number table. A household epidemiological questionnaire survey was conducted among 50 063 target population subjects (aged 40-69), and then, respondents were divided into four categories, category Ⅰ: HP (-), PG (-); category Ⅱ: HP (+ ), PG (-); category Ⅲ: HP (+ ), PG (+ ); category Ⅳ: HP (-), PG (+ )according to the serological Helicobacter pylori ( HP) antibodies and pepsinogen (PG) test results. People in category Ⅲ and Ⅳ were all selected into group C and group D respectively, then individuals 3 times of group D were randomly selected from category Ⅰ to assign to group A, and individuals 3 times of group C from category Ⅱwere assigned to group B in the same way. Remaining individuals in category Ⅰ and Ⅱ who had first-degree family history of gastric cancer were also included in group A and group B, respectively. Endoscopic and pathological examination were performed on the above enrolled subjects for high grade intraepithelialneoplasia (HGIN), early gastric cancer and gastric cancer. Results:Of the 50 063 target subjects, 31 508 questionnaires were finally collected, with a participation rate of 62.9%. A total of 19 745 people were tested for serology, and the participation rate was 39.4% (19 745/50 063). Serological results showed that there were 11 152 people (56.48%) in category Ⅰ, 8 170 (41.38%) in category Ⅱ, 124 (0.63%) in category Ⅲ, and 299 (1.51%) in category Ⅳ. According to the exclusion criteria and principle of voluntariness, 3 400 individuals were candidates to undergo gastroscopy. Finally, a total of 2 389 people came to the hospital for gastroscopy, 1 263 in group A, 814 in group B, 86 in group C and 226 in group D, with an overall response rate of 70.3% (2 389/3 400), target population participation rate of 4.8% (389/50 063), and the overall population participation rate of 2.3% (2 389/105 865). In the 2 389 cases, there were 32 cases (1.34%) of HGIN and gastric cancer by gastroscopy and biopsy pathology, among which 1 case (3.125%) aged 40-49, 9 (28.125%) aged 50-59, and 22 (68.750%) aged 60-69. Among the 32 cases, 25 cases (78.13%)were pathologically confirmed as having HGIN or early gastric cancer by endoscopic submucosal dissection or surgical operation. By eliminating 810 people (including 3 gastric cancer) without first-degree family history with gastric cancer in group Ⅰ and Ⅱ, and increasing the gastroscopy screening age to 50 years (exluding 214 people aged 40-49, including 1 gastric cancer), the number of people who should undergo gastroscopy could be reduced from 2 389 to 1 365, and 28 cases of HGIN or gastric cancer were still detected, including 22 HGIN or early gastric cancer.Conclusion:Gastroscopy after the screening with epidemiological, serological tests, age and first-degree relative with gastric cancer family history is suitable for gastric cancer screening in Wuxi. Based on Chinese national conditions, a new community gastric cancer screening program is recommended in Wuxi considering cost-effectiveness, which includes those over 50 years old, serological PG (+ ) and first-degree relatives with family history of gastric cancer.