[Nomogram prediction model of cervical anastomotic leakage after esophageal cancer surgery].

Objective: To retrospectively analyze the risk factors of anastomotic leakage in the neck after esophageal cancer and establish a nomogram prediction model that can accurately predict the occurrence of anastomotic leakage in the neck of the patient. Methods: The study retrospectively analyzed 702 patients who underwent radical esophageal cancer surgery between January 2010 and May 2015 at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. A multivariate logistic regression model was used to determine the risk factors for neck anastomotic leak, and a nomogram model was constructed, internal validation methods were used to evaluate and verify the predictive effectiveness of the nomogram. Results: There were 702 patients in the whole group, 492 in the training group and 210 in the validation group. The incidence of postoperative cervical anastomotic leak was 16.1% (79/492) in 492 patients with esophageal cancer in the training group. Multifactorial analysis revealed calcification of the descending aorta (OR=2.12, 95% CI: 1.14, 3.94, P=0.018), calcification of the celiac artery (OR=2.29, 95% CI: 1.13, 4.64, P=0.022), peripheral vascular disease (OR=5.50, 95% CI: 1.64, 18.40, P=0.006), postoperative ventilator-assisted breathing (OR=5.33, 95% CI: 1.83, 15.56, P=0.002), pleural effusion or septic chest (OR=3.08, 95% CI: 1.11, 8.55, P=0.031), incisional fat liquefaction and infection (OR=3.49, 95% CI: 1.68, 7.27, P=0.001) were independent risk factors for the development of cervical anastomotic leak after esophageal cancer surgery. The results of the nomogram prediction model showed that the consistency indices of the training and external validation groups were 0.73 and 0.74, respectively (P<0.001), suggesting that the prediction model has good predictive efficacy. Conclusion: The nomogram prediction model can intuitively predict the incidence of postoperative cervical anastomotic leakage in patients with high prediction accuracy, which can help provide a clinical basis for preventing cervical anastomotic leak and individualized treatment of patients.

[Effect of circBIRC6 targeting miR-367-3p on cisplatin resistance of ovarian cancer cells].

Objective: To explore the effect of circBIRC6 on cisplatin resistance of ovarian cancer cells and the molecular mechanism. Methods: The ovarian cancer cell line SKOV3 and ovarian cancer cisplatin-resistant cell line SKOV3 / DDP were cultured in vitro, and treated with different concentrations of cisplatin. SKOV3 and SKOV3/DDP cells were transfected with si-NC, si-circBIRC6, si-circBIRC6+ anti-miR-NC, si-circBIRC6+ anti-miR-367-3p by liposome-mediated method, which were denoted as DDP+ si-NC group, DDP+ si-circBIRC6 group, DDP+ si-circBIRC6+ anti-miR-NC group and DDP+ si-circBIRC6+ anti-miR-367-3p group, respectively, and then were treated with 2 µg/ml cisplatin for 24 hours. The cell proliferation inhibition rate was detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide method, and the half inhibitory concentration (IC(50)) value of cisplatin was calculated. Real-time fluorescent quantitative polymerase chain reaction was used to detect the transcriptional levels of circBIRC6 and miR-367-3p. Flow cytometry was used to detect the apoptotic rate. Dual luciferase report experiment verified the targeting relationship of circBIRC6 and miR-367-3p. Western blot was used to detect the expressions of Cyclin D1, Bcl-2, p21, Bax. Results: The expression levels of circBIRC6 in SKOV3 cells were 1.00±0.05, significantly lower than 3.04±0.24 in SKOV3/DDP cells (P<0.001). The expression levels of miR-367-3p in SKOV3 cells were 1.00±0.08, significantly higher than 0.54±0.05 in SKOV3/DDP cells (P<0.001). The cell proliferation inhibition rates of SKOV3 cells and SKOV3/DDP cells were (22.47±2.04)% and (8.84±0.71)%, the IC(50) values of SKOV3 cells and SKOV3/DDP cells were 6.65±0.94 and 28.18±4.91, respectively, with significant difference (P<0.05). The proliferation inhibition rate and apoptosis rate of SKOV3 cells in DDP+ si-NC group[(22.19±2.19)% and (10.98±1.12)%] were lower than those in DDP+ si-circBIRC6 group [(74.18±5.36)% and (32.91±3.19)%, all P<0.05]. The proliferation inhibition rate and apoptosis rate of SKOV3/DDP cells[(8.71±0.87)% and (7.39±0.63)%] were lower than those of DDP+ si-circBIRC6 group [(40.85±4.07)% and (25.31±2.53)%, all P<0.05]. The protein expression levels of Cyclin D1 and Bcl-2 in SKOV3 and SKOV3/DDP cells in DDP+ si-circBIRC6 group were lower than those in DDP+ si-NC group, and the protein expression levels of p21 and Bax were higher than those in DDP+ si-NC group (all P<0.05). The dual luciferase report experiment confirmed that circBIRC6 targeted miR-367-3p. Inhibition of miR-367-3p expression reduced the effect of circBIRC6 deletion on ovarian cancer cell proliferation, apoptosis and cisplatin resistance. Conclusion: Knockdown of circBIRC6 may inhibit the proliferation of ovarian cancer cisplatin-resistant cells and induce apoptosis by up-regulating the expression of miR-367-3p, therefore impair the cisplatin resistance of these cells.

[Priority setting in scaled-up cancer screening in China: an systematic review of economic evaluation evidences].

Objective: The existed economic evaluations of cancer screening in Chinese population are almost all single-cancer focused, evidence on parallel comparison among multiple cancers is lacking. Thus, the aim of this study was, from a priority setting perspective, to compare the cost-effectiveness of six common cancers(colorectal cancer, breast cancer, liver cancer, lung cancer, esophageal cancer and stomach cancer) to facilitate policy making in future scaled-up screening in populations in China. Methods: Partially based on our previous single-cancer systematic reviews (colorectal cancer, breast cancer, liver cancer, and lung cancer), evidence of economic evaluations of cancer screening in populations in mainland China were systematically updated and integrated. The main updates include: 1) Stomach cancer and esophageal cancer were newly added to the current analysis. 2) The literature searching was extended to 8 literature databases, including PubMed, EMbase, The Cochrane Library, Web of Science, CBM, CNKI, Wanfang Data, and VIP. 3) The period of publication year was updated to the recent 10 years: January 1, 2009 to December 31, 2018. 4) The study focused on populations in mainland China. Following the standard processes of literature searching, inclusion and exclusion from previous systematic reviews, the basic characteristics, evaluation indicators and main results of the included studies were extracted. All the costs were discounted to 2017 value using the by-year consumer price index of medical and health care residents in China and presented in the Chinese Yuan (CNY). The ratios of incremental cost-effectiveness ratio (ICER) to China's per capita GDP in 2017 were calculated (<1 means very cost-effective, 1-3 means cost-effective, >3 means not cost-effective). Given a specific indicator, the median value among all reported screening strategies for each cancer was calculated, based on which priority ranking was then conducted among all cancers when data available. Results: A total of 45 studies were included, 22 for breast cancer, 12 for colorectal cancer, 6 for stomach cancer, 4 for esophageal cancer (all conducted in high-risk areas), 1 for liver cancer and none for lung cancer (was not then considered for next ranking due to limited numbers of studies). When based on the indicator, the median ratio of cost per life-year saved to China's per capita GDP (reported in 12 studies), the lowest ratio (-0.015) was observed in esophageal cancer among 16 strategies of 2 studies (N=2, n=16), followed by 0.297 for colorectal cancer (N=3, n=12), 0.356 for stomach cancer (N=1, n=4) and 0.896 for breast cancer (N=6, n=52, P(75)=3.602). When based on another commonly used ICER indicator, the median ratio of cost per quality-adjusted life-year gained to China's per capita GDP (reported in 13 studies), the least cost was found in stomach cancer (0.495, N=3, n=8, P(75)=3.126), followed by esophageal cancer (0.960, N=1, n=4, P(75)=1.762) and breast cancer (2.056, N=9, n=64, P(75)=4.217). Data was not found for colorectal cancer. In addition, cost per cancer case detected was the most adopted indicator (32 studies). The median cost among all screening strategies for each cancer was 14 759 CNY for stomach cancer (N=5, n=7), 49 680 CNY for colorectal cancer (N=12, n=25) and 171 930 CNY for breast cancer (N=13, n=24), respectively. Data was not available for esophageal cancer and rare for precancer cases detected. Evidence related to cost per disability-adjusted life-year gained was not available. Conclusions: At China's national level and limited to the six cancers covered by the current study, the preliminary analysis suggests that stomach cancer and colorectal cancer were the most cost-effective target cancers and could be given priority in the future scaled-up screening in general populations. Esophageal cancer screening should be prioritized in high-risk areas. Breast cancer was also cost-effective in general but some of the intensive screening strategies were marginal. Data on liver cancer and lung cancer were too limited to conclude, and more well-designed studies and high-quality research evidence should be required. This priority ranking might be changed if other common cancers were involved analyses.

[Risk factors of cervical anastomotic leakage after thoracoscopic-lapacoscopic esophagectomy in patients with esophageal carcinoma].

Objective: To analyze the risk factors of cervical anastomotic leakage after thoracoscopic-lapacoscopic esophagectomy. Methods: 530 patients with esophageal cancer underwent thoracoscopic-lapacoscopic esophagectomy at the Cancer Hospital, Chinese Academy of Medical Sciences from Jan 2011 to Dec 2015. The demographic, surgical and clinical data of patients were retrospectively analyzed. Multivariate logistic regression was used to evaluate risk factors of cervical anastomotic leakage in these patients. Results: A total of 530 patients undergoing thoracoscopic-lapacoscopic esophagectomy were enrolled in this study. There were 421 males and 109 females. The mean age was (59.40±8.08) years old, and 91 patients with cervical anastomotic leakage. Sigle factor analysis revealed that the risk grading by American Society of Aneshesiologists, previous history of chest surgery, respiratory comorbidity, diffusion capacity for carbon monoxide of the lung, operation time, anastomosis, average days of postoperative hospitalization, death within 30 days after surgery, respiratory complications, pleural effusion or empyema, and poor healing of the incision were statistically associated with cervical anastomotic leakage (all P<0.05). Multivariate analysis showed that previous history of chest surgery, hepatic insufficiency, manual anastomosis, prolonged postoperative hospitalization, and poor healing of the incision were independent risk factors for cervical anastomotic leakage after thoracoscopic-lapacoscopic esophagectomy (all P<0.05). Conclusions: Previous history of chest surgery, hepatic insufficiency, poor healing of the incision, manual anastomosis and prolonged postoperative hospitalization were significantly associated with cervical anastomotic leakage after thoracoscopic-lapacoscopic esophagectomy. It's important to strengthen perioperative nursing and surgical techniques to prevent anastomotic leakage after thoracoscopic-lapacoscopic esophagectomy.

[The effective mutation of epidermal growth factor receptor in synchronous multiple primary lung cancers: study of clinical, radiographic and pathological factors].

Objective: To investigate the clinical, pathological and CT features associated with the effective mutation of epidermal growth factor receptor (EGFR) in multiple primary lung cancers (MPLCs) , and to determine the target population of EGFR mutations tests. Methods: A total of 558 nodules from 232 patients with MPLCs who underwent surgery in the Cancer Hospital of Chinese Academy of Medical Sciences from August 2017 to December 2017 were selected. Two hundreds and sixteen nodules were detected by DNA direct sequencing. Chi-square test and Mann-Whitney U test were used to compare the clinical, pathological and CT features of 216 nodules in the EGFR effective mutation group and the non-effective mutation group. Logistic regression analysis was used to explore the independent risk factors of EGFR mutation. The cut off value was determined using the receiver operating characteristic(ROC) curve. Of 232 cases 558 nodules of surgically resected MPLCs, EGFR mutation of 216 nodules was determined by direct DNA sequencing. Results: There were 58 males and 174 females with MPLCs(male︰female=1︰3). There were 117 cases of age ≥59 years old and 115 cases of age <59 years old. There were 192 non-smokers, accounting for 82.8% of all patients. There were 2-7 nodules in the patient's lungs, of which 170 patients had two nodules in the lungs, 44 patients had 3 nodules, and another patient had 7 nodules. Among them, 216 nodules were detected by EGFR gene, 136 were effective mutations, and 80 were non-effective mutations (including wild type and null mutation). EGFR effective mutation group and non-effective mutation group were statistically significant in lung adenocarcinoma patients with different gender, age, smoking history, histological type, and differentiation degree (P=0.006, 0.002, 0.002, 0.015, 0.025).Among them, the effective mutation group were 107 females, 85 cases≥ 59 years old, 117 cases with no smoking history, 68 acinar-based, 89 moderate differentiation. In the count data, 127 nodule edges were lobed, and only 9 nodule edges were smooth. Among the measurement data, the GGO CT value was approximately (-459±147) HU in the EGFR mutation group, with statistical difference (P=0.037). The GGO diameter was approximately (11±9)mm,P=0.279.Multivariate Logistic regression analysis showed that GGO diameter (OR=0.873, 95%CI: 0.780-0.997; P=0.018) and smooth margins (OR=0.183,95%CI: 0.041-0.824; P=0.027) were independent protective factors of effective mutations of EGFR. Conclusions: In MPLCs, effective EGFR mutation is more common, and associated with elder female, age≥59 years, non-smoking, GGO attenuation <-548 HU, moderately differentiated, predominant invasive papillary adenocarcinoma. Patients with MPLCs and these risk factors may be encouraged to have postoperative EGFR molecular test.

[Cancer epidemics and the cancer prevention and control strategies in the United States: a review study].

In the past two decades,the United States made an impressed progress in the prevention and control of cancer that the overall morbidity and mortality of cancer had shown a downward trend, while China had seen an opposite trend. Cancer, one of the major public health concerns in China, has imposed an enormous burden onthe society and individuals. Therefore,in order to scientifically formulate cancer prevention and control policies, it is essential to make a comprehensive understanding of the practical experience in the field of cancer prevention and control from the United States. This article reviews the relevant literature on cancer trends as well as the prevention and control strategies in the United States,depictsthe cancer epidemic situation in the United States in the past 30 years, and summarizes the influencing factors, strategies and intervention experiences that lead to the improvement of cancer epidemic. It highlights the policy support, surveillance and intervention adopted by the United States for the cancer prevention and control. This article is expected to provide some implications and reference for the cancer prevention and control in China.

[Health economic evidence for colorectal cancer screening programs in China: an update from 2009-2018].

Objective: This study was to systematically update the economic evaluation evidence of colorectal cancer screening in mainland China. Methods: Based on a systematic review published in 2015, we expanded the scope of retrieval database (PubMed, EMbase, The Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP, CBM) and extended it to December 2018. Focusing on the evidence for nearly 10 years (2009-2018), basic characteristics and main results were extracted. Costs were discounted to 2017 using the consumer price index of medical and health care being provided to the residents, and the ratio of incremental cost-effectiveness ratio (ICER) to per capita GDP in corresponding years were calculated. Results: A total of 12 articles (8 new ones) were included, of which 9 were population-based (all cross-sectional studies) and 3 were model-based. Most of the initial screening age was 40 years (7 articles), and most of the frequency was once in a lifetime (11 articles). Technologies used for primary screening included: questionnaire assessment, immunological fecal occult blood test (iFOBT) and endoscopy. The most commonly used indicator was the cost per colorectal cancer detected, and the median (range) of the 20 screening schemes was 52 307 Chinese Yuan (12 967-3 769 801, n=20). The cost per adenoma detected was 9 220 Yuan (1 859-40 535, n=10). In 3 articles, the cost per life year saved (compared with noscreening) was mentioned and the ratio of ICER to GDP was 0.673 (-0.013-2.459, n=11), which was considered by WHO as "very cost-effective" ; The range of ratios overlapped greatly among different technologies and screening frequencies, but the initial age for screening seemed more cost-effective at the age of 50 years (0.002, -0.013-0.015, n=3), than at the 40 year-olds (0.781, 0.321-2.459, n=8). Conclusions: Results from the population-based studies showed that the cost per adenoma detected was only 1/6 of the cost per colorectal cancer detected, and limited ICER evidence suggested that screening for colorectal cancer was generally cost-effective in Chinese population. Despite the inconclusiveness of the optimal screening technology, the findings suggested that the initial screening might be more cost-effective at older age. No high-level evidence such as randomized controlled trial evaluation was found.

Validation of the classification criteria commonly used in Korea and a modified set of preliminary criteria for Behçet's disease: a multi-center study.

OBJECTIVE: Recently we have proposed a modified set of criteria to settle the questions raised regarding the International Study Group (ISG) criteria for Behçet's disease (BD). The aim of the present study was to validate the two pre-existing criteria sets commonly used in Korea, the ISG criteria and the criteria of the Behçet's Disease Research Committee of Japan (Japanese criteria), as well as the proposed modified criteria. METHODS: The study population included 155 consecutive patients with BD and 170 controls with non-Behçet's rheumatic diseases. Detailed data for all of the subjects were recorded prospectively by the participating physicians on a standard form that listed the clinical features of BD. The sensitivity, specificity, and accuracy of each set of the criteria were measured. RESULTS: Of the three criteria sets employed, the modified criteria were the most accurate, with an accuracy of 96.3%. The ISG criteria often failed to classify the following patients with BD: patients with only oral and genital ulcerations, certain patients with intestinal ulcerations, patients who did not manifest oral ulcerations, and patients with acute disease but fewer than three recurrent oral ulceration relapses in a 1-year period. The Japanese criteria also failed to categorize the following patients with BD: patients with oral and genital ulcerations, and patients with oral ulcerations, skin lesions, and a positive pathergy reaction. In addition, the Japanese criteria misclassified some of the control subjects with non-Behçet's uveitis as having BD. CONCLUSIONS: The results of this study suggest that there are some points that need to be reconsidered in the clinical application of the two pre-existing sets of criteria. Although the modified criteria were the most accurate, further validation studies will be required in other ethnic populations.

Biosynthesis of cadmium sulfide nanoparticles by photosynthetic bacteria Rhodopseudomonas palustris.

A simple route for the synthesis of cadmium sulfide nanoparticles by photosynthetic bacteria Rhodopseudomonas palustris has been demonstrated in this work. The cadmium sulfate solution incubated with R. palustris biomass changed to a yellow color from 48 h onward, indicating the formation of cadmium sulfide nanoparticles. The purified solution yielded the maximum absorbance peak at 425 nm due to CdS particles in the quantum size regime. Also, X-ray analysis of the purified nanoparticles confirmed the formation of cadmium sulfide. Transmission electron microscopic analysis of the samples showed a uniform distribution of nanoparticles, having an average size of 8.01+/-0.25 nm, and its corresponding electron diffraction pattern confirmed the face-centered cubic (fcc) crystalline structure of cadmium sulfide. Furthermore, it was observed that the cysteine desulfhydrase producing S(2-) in the R. palustris was located in cytoplasm, and the content of cysteine desulfhydrase depending on the growth phase of cells was responsible for the formation of CdS nanocrystal, while protein secreted by the R. palustris stabilized the cadmium sulfide nanoparticles. In addition, R. palustris was able to efficiently transport CdS nanoparticles out of the cell.