Real-World Utilization, Barriers, and Factors Associated With the Targeted Treatment of Metastatic Colorectal Cancer Patients in China: A Multi-Center, Hospital-Based Survey Study.

Objectives: To explore the utilization, barriers, and factors associated with the targeted treatment of Chinese metastatic colorectal cancer (mCRC) patients. Methods: A total of 1,688 mCRC patients from 19 hospitals in 14 cities were enrolled from March 2020 to March 2021 using stratified, multistage cluster sampling. The use of targeted therapy and any barriers patients experienced were collected. Logistic regression analyses were conducted to identify the factors associated with initiating targeted treatment. Results: About 51.6% of the patients initiated targeted therapy, of whom 44.5%, 20.2%, and 35.2% started first-, second-, and third-line treatment, respectively. The most reported barriers were high medical costs and a lack of belief in the efficacy of targeted therapy. Patients treated in the general hospital, diagnosed at an older age, less educated, and who had a lower family income, no medical insurance, poor health-related quality of life, metastasis outside the liver/lung or systemic metastasis, a shorter duration of mCRC were less likely to initiate targeted therapy. Conclusion: Reduced medical costs and interventional education to improve public awareness could facilitate the use of targeted treatment for mCRC.

Incidence and mortality of colorectal cancer in 2017 and the time-trend from 2010 to 2017 in Henan province, China: a population-based registry study.

Background: Henan province is an area with a serious disease burden of colorectal cancer (CRC) in China. Understanding the current incidence and mortality and the time-trend is critical to formulate and optimize prevention and control strategies for CRC. However, the current incidence and mortality and time-trend of CRC in Henan province, China have not been reported. Methods: CRC data was got from the Henan Provincial Central Cancer Registry of China in which the data was submitted from local cancer registries. Combined with the census data, the incidence, mortality, proportion, age-standardized rate by Chinese population (ASRC), age-standardized rate by world population (ASRW), and cumulative incidence and mortality (0-74 years old) of CRC by urban and rural population, gender, and age groups were estimated. The average annual percentage change (AAPC) and its 95% confidence interval (CI) of ASRC from 2010 to 2017 were analyzed. Results: In 2017, it was estimated that there were 20,275 new cases and 10,046 deaths of CRC in Henan province. The crude incidence was 18.73/100,000, with an age-standardized incidence rate by Chinese population (ASIRC) of 13.97/100,000 and age-standardized mortality rate by world population (ASIRW) of 13.78/100,000. The cumulative incidence was 1.66%. The mortality rate was 9.28/100,000, with an age-standardized mortality rate by Chinese population (ASMRC) of 6.49/100,000 and an age-standardized mortality rate by world population (ASMRW) of 6.45/100,000. The cumulative mortality rate was 0.69%. The ASIRC and ASMRC were higher in urban areas (15.89/100,000, 7.19/100,000) than in rural areas (13.13/100,000, 6.20/100,000), and higher in males (15.53/100,000, 7.44/100,000) than in females (12.48/100,000, 5.66/100,000). The age-specific incidence reached the peak at age of 80-84, and the age-specific mortality reached the peak at age 85. From 2010 to 2017, the overall ASIRC and ASMRC showed a steady trend (P>0.05), while an upward trend was observed in the mortality rate in urban males (AAPC =3.4, 95% CI: 0.2-6.7, P=0.040). Conclusions: The incidence and mortality of CRC were high in Henan province, and higher in urban areas and males. It is critical to strengthen the prevention and control of CRC, carry out targeted intervention, and promote screening and early diagnosis and treatment, particularly among urban areas and males.

Time-trend of the incidence and mortality of esophageal cancer from 2010 to 2018 and its statistics in 2018 in Henan, China.

Background: It is great of significance to figure the time-trend of esophageal cancer (EC) and its current status for effective prevention and control, especially in EC high risk areas. As one of world-renowned high-risk areas, the epidemiology of EC in Henan has not been recently updated. Therefore, we aimed to depict the status quo of EC and analyze its time-trend in Henan. Methods: The EC data were extracted from the Henan Provincial Cancer registry database derived from the population based cancer registry system, which covered 30.51% of the whole population in Henan and were qualified according to national and international guidelines. The incidence and mortality of EC were estimated by area (rural/urban), gender, and age groups. The age-standardized rates (ASRs) were calculated according to the Segi's population. Joinpoint regression was used to calculate annual percentage change (APC) and average annual percentage change (AAPC) to evaluate the time-trend of EC. Results: As estimated, there were 29,913 new EC cases in Henan, 2018. The crude incidence and the age-standardized incidence rate by world standard population (ASIRW) was 27.43/105 and 19.96/105, respectively. The incidence in males and rural was 1.83 and 1.51 times higher than that in females and urban areas, respectively. Meanwhile, it was estimated that 22,688 deaths occurred in 2018. The crude mortality and the age-standardized mortality rate by world standard population (ASMRW) were 20.80/105 and 14.47/105, respectively. Similarly, males and rural areas had higher mortality compared with females and urban areas. The age-specific incidence and mortality of EC showed significant increasing after 60-64 years group. In general, the time-trend of incidence (APC: -8.9, P<0.001) and mortality (APC: -7.6, P<0.001) of EC showed a significant decreasing trend since 2014, and downward trend were also observed in rural areas for incidence (APC: -5.2, P<0.001) and mortality (APC: -3.9, P<0.001) from 2010 to 2018. Conclusions: The EC incidence and mortality in Henan has exhibited a significant declining trend in past years. Nonetheless, the disease burden remains high, especially in males and rural areas. Therefore, the ongoing prevention and control strategies of EC should be maintained alongside the establishment of more effective strategies.

Knowledge and awareness of colorectal cancer risk factors, screening, and associated factors in advanced colorectal cancer patients: a multicenter cross-sectional study in China.

Background: Colorectal cancer (CRC) is the 3rd most common malignancy globally, and its disease burden is increasing rapidly in China. But CRC patients' knowledge and awareness of CRC have not yet been examined, which could facilitate the identification of targeted population from public for intervention. Methods: A nationwide multicenter cross-sectional survey was conducted in 19 tertiary hospitals (10 cancer hospitals and 9 general hospitals) from March 2020 to March 2021 in China. During study period, all Stage III and IV CRC patients were invited to complete a semi-structured survey that had been designed to collect information about their socio-demographic characteristics, and knowledge and awareness of CRC risk factors and screening. A multivariate logistic regression model was used to identify factors associated with their knowledge and awareness. Results: In total, 4,589 advanced CRC patients were enrolled in this study, of whom, 46.2% were from tertiary cancer hospitals, and 59.5% were male. Patients had a mean age of 60.1±11.6 years. Before diagnosis, 65.1% of the patients had no related knowledge of the CRC risk factors, and 84.9% were unaware of the CRC screening-related information. Only 30.4% of patients had actively sought to acquire CRC-related knowledge before diagnosis. The 3 most common knowledge sources were relatives or friends who had been diagnosed with CRC (13.2%), popular science television/broadcast shows (12.9%), and community publicity and education (9.6%). Generally, knowledge and awareness were positively associated with better education level [odds ratios (ORs) ranged from 1.49 to 2.54, P<0.001], annual household income ranged from 50,000 Chinese Yuan (CNY) to 100,000 CNY (OR =1.32, P<0.001), being manual laborer (OR =1.25, P<0.001) and being white-collar worker (OR =1.47, P<0.001). Conclusions: Advanced CRC patients' knowledge and awareness of CRC were severely limited before diagnosis. Thus, those who had limited knowledge and awareness should has a priority for intervention.

Status and associated factors of cross-regional healthcare-seeking among patients with advanced colorectal cancer in China: a multicenter cross-sectional study.

Background: The imbalanced allocation of medical resources leads to the occurrence of cross-regional healthcare-seeking in China. Due to the low cure rate, advanced colorectal cancer (CRC) patients may seek cross-regional healthcare for high-level medical facilities. Investigating status of cross-regional healthcare-seeking and its associated factors among advanced CRC patients is important for policymakers to understand access to health services and improve the quality of oncology services. Methods: From March 2020 to March 2021, a cross­sectional, nation-wide, hospital-based, multi-center survey was conducted. Nineteen hospitals in seven regions were selected by multi-stage stratified sampling. All eligible CRC patients in the selected hospitals were invited to participate in the current study. The outcome variable, cross-regional healthcare-seeking, was defined as seeking health facilities outside the local administration policy of medical insurance. The demographics, clinical information, and medical treatment history of each eligible CRC patient in stage III or IV, were collected through the patients' self-reporting or medical records by trained interviewers. Univariate and multivariate logistic analyses were used to explore the associated factors of cross-regional healthcare-seeking. All statistical analyses were conducted using SAS 9.4. Results: A total of 4,589 individuals with advanced CRC were included. The average age of the patients was 60.1±11.6 years, and 59.5% were males. About 37.5% of the patients suffered from metastatic CRC at first diagnosis. Approximately 36.5% of the patients had sought cross-regional health care previously, and among them, 31.9% had encountered problems. The most common problems included complicated procedures (95.3%), unreimbursed expenses of outpatient service (71.0%), and reimbursement delay (59.4%). Logistic regression analysis showed that patients who completed undergraduate or above [odds ratio (OR) =1.40, 95% confidence interval (CI): 1.13-1.73], had an annual household income of more than 100,000 Chinse Yuan (CNY) (OR =1.46, 95% CI: 1.21-1.78), and had metastasis at diagnosis (OR =1.33, 95% CI: 1.18-1.51) were more likely to seek cross-regional health care. Conclusions: About one third of advanced CRC patients seek cross-regional health care, and 31.9% had encountered problems. There is a need to simplify procedures of reimbursement, optimize direct settlement system and referral mechanisms in order to improve the equality of health services.

The choice of medical facility and associated factors among Chinese advanced colorectal cancer patients: a cross-sectional multi-center study.

Background: Colorectal cancer (CRC) poses a significant public health burden worldwide. The investigation of the choice of medical facility among CRC patients is helpful for understanding access to health services and improving quality of oncology services to optimize health outcomes. However, there are limited studies on the topic. The objective of this study was to investigate the choice of medical facility and its associated factors among advanced CRC patients. Methods: This cross-sectional multi-center study included a total of 4,589 individuals with advanced CRC from 19 hospitals in 7 geographic regions in China. Participants were recruited by multi-stage stratified sampling. In the first stage, two cities in each geographic region were selected through simple random sampling. In the second stage, one tertiary cancer hospital and/or one general hospital were selected in each city. Data on medical experience and demographics were collected via a questionnaire during face-to-face interviews. Explanatory variables were selected based on the Andersen behavioral model. Multinomial logistic regression analyses were performed to explore the factors associated with the level of medical facility for the first treatment. Results: Hospitals at the prefecture level were the most common medical facility sought by advanced CRC patients for initial medical care (44.9%), the first definite diagnosis (46.3%), the first treatment (39.5%), and regular follow-up (38.9%). However, the first priority was changed to hospitals at the national level for the second treatment (38.0%) and after recurrence and metastasis (45.9%). Female {odds ratios (ORs) ranged from 1.31 [95% confidence interval (CI): 1.01-1.71] to 1.41 (95% CI: 1.07-1.87)} and relatively well-educated individuals [ORs ranged from 1.74 (95% CI: 1.20-2.53) to 7.26 (95% CI: 4.18-12.60)] preferred to seek higher-level health facilities. Individuals with metastatic CRC at diagnosis were more likely to visit hospitals in provincial capitals versus hospitals at the county level (OR =1.68, 95% CI: 1.27-2.22). Individuals with "good" health-related quality of life (HRQOL) (OR =0.63, 95% CI: 0.49-0.81) were less likely to seek hospitals at the prefecture level compared with hospitals at the county level. Conclusions: There is a need to improve the oncology services for CRC patients, including the optimization of referral reform policy and the promotion of quality of primary healthcare service. The results may provide evidence to fill the policy-implementation gap and potentially contribute to the improvement of the efficiency of the healthcare system.

Corrigendum: Construction and Validation of a Lung Cancer Risk Prediction Model for Non-Smokers in China.

[This corrects the article DOI: 10.3389/fonc.2021.766939.].

A risk prediction model for selecting high-risk population for computed tomography lung cancer screening in China.

OBJECTIVE: Two large randomized controlled trials (RCTs) have demonstrated that low dose computed tomography (LDCT) screening reduces lung cancer mortality. Risk-prediction models have been proved to select individuals for lung cancer screening effectively. With the focus on established risk factors for lung cancer routinely available in general cancer screening settings, we aimed to develop and internally validated a risk prediction model for lung cancer. MATERIALS AND METHODS: Using data from the Cancer Screening Program in Urban China (CanSPUC) in Henan province, China between 2013 and 2019, we conducted a prospective cohort study consisting of 282,254 participants including 126,445 males and 155,809 females. Detailed questionnaire, physical assessment and follow-up were completed for all participants. Using Cox proportional risk regression analysis, we developed the Henan Lung Cancer Risk Models based on simplified questionnaire. Model discrimination was evaluated by concordance statistics (C-statistics), and model calibration was evaluated by the bootstrap sampling, respectively. RESULTS: By 2020, a total of 589 lung cancer cases occurred in the follow-up yielding an incident density of 64.91/100,000 person-years (pyrs). Age, gender, smoking, history of tuberculosis and history of emphysema were included into the model. The C-index of the model for 1-year lung cancer risk was 0.766 and 0.741 in the training set and validation set, respectively. In stratified analysis, the model showed better predictive power in males, younger participants, and former or current smoking participants. The model calibrated well across the deciles of predicted risk in both the overall population and all subgroups. CONCLUSIONS: We developed and internally validated a simple risk prediction model for lung cancer, which may be useful to identify high-risk individuals for more intensive screening for cancer prevention.

Construction and Validation of a Lung Cancer Risk Prediction Model for Non-Smokers in China.

BACKGROUND: About 15% of lung cancers in men and 53% in women are not attributable to smoking worldwide. The aim was to develop and validate a simple and non-invasive model which could assess and stratify lung cancer risk in non-smokers in China. METHODS: A large-sample size, population-based study was conducted under the framework of the Cancer Screening Program in Urban China (CanSPUC). Data on the lung cancer screening in Henan province, China, from October 2013 to October 2019 were used and randomly divided into the training and validation sets. Related risk factors were identified through multivariable Cox regression analysis, followed by establishment of risk prediction nomogram. Discrimination [area under the curve (AUC)] and calibration were further performed to assess the validation of risk prediction nomogram in the training set, and then validated by the validation set. RESULTS: A total of 214,764 eligible subjects were included, with a mean age of 55.19 years. Subjects were randomly divided into the training (107,382) and validation (107,382) sets. Elder age, being male, a low education level, family history of lung cancer, history of tuberculosis, and without a history of hyperlipidemia were the independent risk factors for lung cancer. Using these six variables, we plotted 1-year, 3-year, and 5-year lung cancer risk prediction nomogram. The AUC was 0.753, 0.752, and 0.755 for the 1-, 3- and 5-year lung cancer risk in the training set, respectively. In the validation set, the model showed a moderate predictive discrimination, with the AUC was 0.668, 0.678, and 0.685 for the 1-, 3- and 5-year lung cancer risk. CONCLUSIONS: We developed and validated a simple and non-invasive lung cancer risk model in non-smokers. This model can be applied to identify and triage patients at high risk for developing lung cancers in non-smokers.

The Potential Benefits of HPV E6/E7 mRNA Test in Cervical Cancer Screening in China.

This study aims to evaluate the clinical performance of the HPV E6/E7 mRNA test in cervical cancer screening in China. A hospital-based study was conducted with mRNA, DNA, and liquid-based cytology (LBC) as primary screening tests. Each woman with a positive result received colposcopy with lesion-targeted-biopsy. Histopathological diagnosis was used as the gold standard. The total agreement of HPV DNA and mRNA was 90.7% (95%CI: 87.9, 92.9) with a kappa value of 0.81. The positive rates of HPV DNA, mRNA, and LBC increased with the severity of histopathology diagnosis, from 25.5, 19.1, and 11.4% in normal to 100.0% in SCC, respectively. The sensitivities for mRNA to detect CIN2+ and CIN3+ were 93.8% (95%CI: 89.7-96.4) and 95.7% (95%CI: 91.3-97.9), respectively, which were not different from HPV DNA testing (95.7% [95%CI: 92.0-97.7], 96.3% [95%CI: 92.1-98.3]), but higher than LBC (80.4% [95%CI: 74.5-85.2] and 88.8% [95%CI: 83.0-92.8]). The specificities for mRNA to detect CIN2+ (79.0% [95%CI: 74.2-83.0]) and CIN3+ (70.5% [95%CI: 65.7-74.9]) were higher than HPV DNA testing (71.0% [95%CI: 65.9-75.7], 62.8% [95%CI: 57.8-67.5]), but lower than LBC (84.5% [95%CI: 80.1-88.0] 79.8% [95%CI: 75.4-83.6]). All tests were more effective in women older than 30 years. HPV mRNA test showed excellent agreement with the DNA test, with similar sensitivity and a higher specificity in detecting high-grade cervical lesions. It is promising that mRNA test could be used for the national cervical cancer screening to reduce false positive without losing sensitivity.

The relative survival and cure fraction of gastric cancer estimated through flexible parametric models using data from population-based cancer registration during 2003-2012 in Linzhou, China.

PURPOSE: The proportion of cured gastric cancer patients has drawn the attention of patients, physicians, and healthcare providers after comprehensive prevention and control measures were carried out for several years. Therefore, the relative survival and cure fraction were estimated in our study. METHODS: Population-based cancer registration data were used to estimate survival and cure fraction. A total of 7585 gastric cancer cases (ICD10:C16.0 ~ C16.9) were extracted and included in the final analysis. Cases were diagnosed in 2003-2012 and followed until the end of 2017. Relative survival was calculated as the ratio between the observed survival through the life-table method. The expected survival was estimated by the Ederer II method. The cure fraction was estimated using flexible parametric cure models stratified by age and calendar period when the cases were diagnosed. RESULTS: The 5-year relative survival of cardia gastric cancer increased with the calendar period of 2003-2004, 2005-2006, 2007-2008, 2009-2010, and 2011-2012 (27.5%, 28.3%, 33.5%, 38.2%, and 46.8%, respectively). The increasing trend along with the calendar periods was also observed in cure proportion of cardia gastric cancer (24.8%, 25.2%, 31.7%, 36.0%, and 43.1%, respectively). Notable improvement of cure proportion was observed in the period of 2011-2012, compared with the initial period of 2003-2004. There was an improvement of 79.8% among all gastric cancer subjects, and it was 74.1% and 55.7% in cardia gastric and noncardia gastric cancer subjects, respectively. The median survival of "uncured" patients showed no significant improvement along with the calendar periods in all age groups. CONCLUSIONS: Notable improvement of gastric cancer relative survival and cure proportion was observed in Linzhou during 2003-2012.

Effect of transformer noise on the neurophysiology of SD rats.

Transformer noise is a type of environmental sound that causes discomfort to individuals. The aim of the present study was to determine the effect of relatively long-term periods of transformer noise on the behavior and neurophysiology of SD rats. A total of 90 healthy SD rats with normal hearing were randomly divided into two experimental groups (65 and 60 dB group) and a control group. The experimental groups were exposed to recorded transformer noise for 8 weeks (sound level limits: 65 or 60 dB) and the control group was maintained under the same conditions without noise stimulation. Changes in physiological growth (weight tests), behavior (tail suspension and open field behavior tests) and neurophysiology (glutamate, γ-aminobutyric acid, dopamine, 5-hydroxytryptamine, the morphologies of hippocampi) following noise exposure were recorded and compared. The results revealed that rats exhibited normal physiological growth, with no significant difference between the experimental and control groups. Following noise exposure, no significant differences were observed in the results of behavioral experiments (tail suspension and open field behavior tests) between the experimental and control groups. In addition, there were no significant differences in glutamate, γ-aminobutyric acid, dopamine and 5-hydroxytryptamine levels or in the morphologies of hippocampi between groups. In conclusion, exposure to transformer noise with a sound level limit of 65 dB sound pressure level (SPL) or 60 dB SPL (spectral range, 100-800 Hz) for 8 weeks (10 h/day) had no significant impact on the behavior and neurophysiology of SD rats.

Medical expenditure for esophageal cancer in China: a 10-year multicenter retrospective survey (2002-2011).

BACKGROUND: Esophageal cancer is associated with substantial disease burden in China, and data on the economic burden are fundamental for setting priorities in cancer interventions. The medical expenditure for the diagnosis and treatment of esophageal cancer in China has not been fully quantified. This study aimed to examine the medical expenditure of Chinese patients with esophageal cancer and the associated trends. METHODS: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 37 hospitals in 13 provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. For each esophageal cancer patient diagnosed between 2002 and 2011, clinical information and expense data were extracted by using structured questionnaires. All expense data were reported in Chinese Yuan (CNY; 1 CNY = 0.155 USD) based on the 2011 value and inflated using the year-specific health care consumer price index for China. RESULTS: A total of 14,967 esophageal cancer patients were included in the analysis. It was estimated that the overall average expenditure per patient was 38,666 CNY, and an average annual increase of 6.27% was observed from 2002 (25,111 CNY) to 2011 (46,124 CNY). The average expenditures were 34,460 CNY for stage I, 39,302 CNY for stage II, 40,353 CNY for stage III, and 37,432 CNY for stage IV diseases (P < 0.01). The expenditure also differed by the therapy type, which was 38,492 CNY for surgery, 27,933 CNY for radiotherapy, and 27,805 CNY for chemotherapy (P < 0.05). Drugs contributed to 45.02% of the overall expenditure. CONCLUSIONS: These conservative estimates suggested that medical expenditures for esophageal cancer in China substantially increased in the last 10 years, treatment for early-stage esophageal cancer costs less than that for advanced cases, and spending on drugs continued to account for a considerable proportion of the overall expenditure.

[Analysis of cancer incidence and mortality in Henan province, 2009].

OBJECTIVE: To analyze the cancer incidence and mortality of Henan province in 2009. METHODS: On basis of the criteria of data quality from the National Central Cancer Registry (NCCR), data from 6 registries in Henan province were evaluated, covering 6 061 564 people, accounting for 6.45% of the total population in Henan in 2009. There were 3 104 991 people of males, and 2 956 573 people of females. The incidence, mortality, 10 most common cancers, constitution and cumulative rate (0-74 years old) were then calculated. The age-standardized rate was calculated and adjusted by the Chinese standard population in 1982 as well as the Segi's world standard population. RESULTS: There were 12 091 new diagnosed cancer and 8040 death cases registered in Henan province in 2009. The rate of pathological diagnosis was 68.2% (8246/12 901) and only 1.75% (2116/12 901) had death certificates. The ratio of mortality and incidence was 0.66 (8040/12 091). The incidence rate was 199.47/100 000 (12 091/6 061 564) in total, and it was 216.36/100 000(6718/3 104 991) in males and 181.73/100 000(5373/2 956 573) among females. The standardized incidence by Chinese population was 126.50/100 000 and it was 166.08/100 000 by world's population. The cumulative rate was 19.95% between 0 and 74 years old. The incidence was the highest in Linzhou city, whose standardized incidence was 156.87/100 000 by Chinese population and the incidence was the lowest in Shenqiu city, whose standardized incidence was 104.82/100 000 by Chinese population. The morphology verified cases accounted for 68.2% (8246/12 091), death certification cases only accounted for 1.75% (2116/12 091), and mortality to incidence ratio was 0.66 (8040/12 091). The crude incidence in cancer registration areas of Henan province was 199.47/10 000 (12 091/6 061 564), 216.36/10 000(6718/3 104 991) for males, 181.73/10 000 (5373/2 956 573) for females, age-standardized incidence rates by Chinese standard population and by world standard population were 126.50/10 000 and 166.08/10 000 with cumulative incidence rate (0-74 age years old) of 19.95%. The crude mortality in cancer registration areas of Henan province was 132.64/100 000 (8040/6 061 564), separately 160.58/100 000 (4986/3 104 991) for males and 103.30/10 000 (3054/2 956 573) for females. The age-standardized mortality rates by Chinese standard population and by world's standard population were 78.41/10 000 and 107.49/10 000. The cumulative mortality rate (0-74 age years old) was 12.18%. The mortality rate was the highest in Linzhou city, whose standardized rate was 93.35/100 000 by Chinese population, and the lowest mortality rate was in Yuzhou city, whose standardized rate was 67.95/100 000. The most common cancers were lung cancer, esophageal cancer, gastric cancer, liver cancer, breast cancer, rectum cancer, brain nervous system cancer, colon cancer, cervical cancer and uterus cancer, all of which accounted for 82.23% (9943/12 091) of the registered cancers.Lung cancer, esophageal cancer, gastric cancer, liver cancer, breast cancer, rectum cancer, brain nervous system cancer, pancreas cancer, colon cancer and gallbladder carcinoma were the major causes for the death, accounting for 86.30% (6938/8040) of all cancer deaths. CONCLUSION: Both incidence and mortality of cancer in Henan province were lower than the level in China, prevention and control should be implemented based on practical situation.

Metabolism-based synthesis, biological evaluation and structure-activity relationship analysis of spirotetramat analogues as potential lipid biosynthesis inhibitors.

BACKGROUND: In previous studies, scientists found that, when spirotetramat was introduced into plants or animals, it was mainly metabolised at positions C-4 and C-8. That is to say, these two functional positions potentially played an important role in spirotetramat's bioactivities. In order to develop novel insecticides or miticides, the present authors designed and synthesised 35 spirotetramat analogues based on metabolite structures. RESULTS: All of the analogues have been identified on the basis of (1)H NMR, ESI-MS and elemental analysis data. The activities of these analogues were evaluated against three organisms, and biological assays indicated that compounds 5f, 5h and 5u possessed better insecticidal activities against bean aphids (Aphis fabae) than the lead compound spirotetramat. The LC50 of 5f, 5h and 5u against bean aphids reached 0.42, 0.28 and 2.53 mg L(-1) respectively. Moreover, some compounds possessed comparable activities against carmine spider mite (Tetranychus cinnabarinus) and oriental armyworm (Mythimna sepatara) with spirotetramat. The structure-activity relationships (SARs) indicated that the flexible bridge at position C-4 of spirotetramat was important for its bioactivities, and the size of the group at position C-8 would have great influence on the activities. Furthermore, the log P values lower than 6.0 may be favourable for insecticidal activities. CONCLUSION: The present work demonstrates that some spirotetramat analogues can be used as potential lead compounds for developing novel insecticides, and preliminary SAR analysis would provide information for the utilisation of spirotetramat analogues as potential lipid biosynthesis inhibitors.

[The effects of glucose fluctuation on resistin].

OBJECTIVE: To explore the effect of glucose fluctuation on resistin. METHODS: The phorbol-12-myristate-13-acetate(PMA)-activated and differentiated U937 cells were exposed to experimental condition for 3 days, three groups of cells were formed, each one receiving the following fresh medium every 6 hours, respectively: (1) continuous 11.1 mmol/L glucose concentration medium (Con group), (2) continuous 22.2 mmol/L glucose concentration medium (CHG group), (3) alternating 11.1 mmol/L glucose concentration and 22.2 mmol/L glucose concentration medium every 6 hours (IHG group). The supernatants of cell median at the last 6 hours were collected to test resistin concentration. Besides, 92 subjects were selected and classified into three groups according to the results of oral glucose tolerance test: normal glucose tolerance group (NGT group, n=30), impaired glucose tolerance patients (IGT group, n=31) and newly diagnosed type 2 diabetes patients (T2DM group, n=31). Blood glucose and serum resistin levels were measured at 0 h and 1 h during oral glucose tolerance test (OGTT) to compare the glucose fluctuation (ΔGlu1-0) and the change of serum resistin level (ΔlnRes1-0) among the three groups. RESULTS: Resistin concentration in the Con, CHG and IHG group was (73.62±5.07) ng/L, (97.78±7.00) ng/L and (212.49±28.81) ng/L respectively and in IHG group it was higher as compared with the other two groups (P<0.05). ΔGlu1-0 in NGT, IGT and T2DM group was (2.31±2.30) mmol/L, (5.70±2.08) mmol/L and (8.41±2.63) mmol/L respectively; ΔGlu1-0 increased gradually in all the three groups (P<0.05). Serum resistin level from 0 h to 1 h in the NGT group was 6.41 (1.52-15.76) µg/L to 6.96 (1.52-22.70) µg/L, in the IGT group 5.47 (1.49-24.09) µg/L to 9.12 (1.27-21.94) µg/L and in the T2DM group 5.77 (1.11-30.10) µg/L to 9.27(1.02-48.15) µg/L. In the IGT and T2DM group serum resistin level increased from 0 h to 1 h (P<0.05), but no difference was observed in the NGT group (P>0.05). ΔlnRes1-0 in these 3 groups was (0.05±0.05) µg/L, (0.25±0.04) µg/L and (0.37±0.03) µg/L respectively and the change in the T2DM group was significant as compared with that in the NGT group, ΔlnRes1-0 was positively correlated with ΔGlu1-0 (r=0.23, P=0.02). CONCLUSION: Glucose fluctuation induced monocyte/macrophage to secrete resistin, greater the glucose fluctuation, greater the change of amplitude of serum resistin.

Dihalogenated trichodermin (4ß-acet-oxy-9,10-dibromo-12,13-epoxy-tri-chothec).

In the title dihalogenated trichodermin mol-ecule, C(17)H(24)Br(2)O(4) (systematic name: 9,10-dibromo-12,13-epoxy-trichothec-9-en-4ß-yl acetate), the five-membered ring displays an envelope conformation, whereas the two six-membered rings show the same conformation, viz. chair. As for the seven-membered ring, the dihedral angle between the mean planes formed by the four C atoms of the envelope unit and the three C and one O atoms of the six-membered chair is 69.08 (4)°; these two mean planes are nearly perpendicular to the ep-oxy ring with angles of 87.53 (4) and 88.67 (4)°, respectively.