[Global liver cancer incidence and mortality and future trends from 2000 to 2020: GLOBOCAN data analysis].

Objective: To compare the geographical differences and time trends of liver cancer incidence and mortality in different regions around the world so as to predict the future burden of liver cancer. Methods: The incidence and mortality data of liver cancer in different Human Development Index (HDI) countries from 2000 to 2020 were collected from the GLOBOCAN 2020 database. The joinpoint model and annual percent change (APC) were used to analyze the liver cancer global incidence and mortality as well as future epidemic trends from 2000 to 2020. Results: ASMR for male liver cancer was increased from 8.0/100, 000 in 2000 to 7.1/100,000 in 2015 (APC = -0.7, 95%CI: -1.2 ~ -0.3, P = 0.002), while ASMR for female liver cancer was increased from 3.0/100, 000 in 2000 to 2.8/100, 000 in 2015 (APC = -0.5, 95%CI: -0.8 ~ -0.2, P < 0.001). The ratio of male to female ASMR was 2.67:1 in 2000 and 2.51:1 in 2015, indicating a slight narrowing of the difference in mortality between men and women. In 2020, the global ASIR and ASMR for liver cancer were 9.5/100 000 and 8.7/100 000, respectively. Male ASIR and ASMR (14.1/100, 000 and 12.9/100, 000, respectively) were 2 ~ 3 times higher than females (5.2/100, 000 and 4.8/100, 000, respectively). There were significant differences between ASIR and ASMR in different HDI countries and regions (P(ASIR) = 0.008, P(ASMR) < 0.001), and the distributions of ASMR and ASIR were very similar. New cases and deaths were expected to increase by 58.6% (143,6744) and 60.9% (133, 5 375) in 2040, with the number of cases and deaths increasing by 39,7003 and 37,4208 in Asia, respectively. Conclusion: ASMR due to liver cancer worldwide has had a downward trend between 2000 and 2015. However, the latest epidemiological status and predictions of liver cancer in 2020 indicate that prevention and control will still be a major challenge globally in the next 20 years.

[Global incidence and mortality of renal cell carcinoma in 2020].

Objective: To analyze the global epidemiology of renal cell carcinoma (RCC) in 2020. Methods: The incidence and mortality data of RCC in the cooperative database GLOBOCAN 2020 of International Agency for Research on Cancer of WHO and the human development index (HDI) published by the United Nations Development Programme in 2020 were collated. The crude incidence rate (CIR), age-standardized incidence rate (ASIR), crude mortality rate (CMR), age-standardized mortality rate (ASMR) and mortality/incidence ratio (M/I) of RCC were calculated. Kruskale-Wallis test was used to analyze the differences in ASIR or ASMR among HDI countries. Results: In 2020, the global ASIR of RCC was 4.6/100 000, of which 6.1/100 000 for males and 3.2/100 000 for females and ASIR was higher in very high and high HDI countries than that in medium and low HDI countries. With the rapid increase of age after the age of 20, the growth rate of ASIR in males was faster than that in females, and slowed down at the age of 70 to 75. The truncation incidence rate of 35-64 years old was 7.5/100 000 and the cumulative incidence risk of 0-74 years old was 0.52%. The global ASMR of RCC was 1.8/100 000, 2.5/100 000 for males and 1.2/100 000 for females. The ASMR of males in very high and high HDI countries (2.4/100 000-3.7/100 000) was about twice that of males (1.1/100 000-1.4/100 000) in medium and low HDI countries, while the ASMR of female (0.6/100 000-1.5/100 000) did not show significant difference. ASMR continued to increase rapidly with age after the age of 40, and the growth rate of males was faster than that of females. The truncation mortality rate of 35-64 years old was 2.1/100 000, and the cumulative mortality risk of 0-74 years old was 0.20%. M/I decreases with the increase of HDI, with M/I as 0.58 in China, which was higher than the global average of 0.39 and the United States' 0.17. Conclusion: The ASIR and ASMR of RCC presented significant regional and gender disparities globally, and the heaviest burden was in very high HDI countries.

[Spatiotemporal changes of COVID-19 outbreak in Shanghai].

Objective: To clarify the epidemiological characteristics and spatiotemporal clustering dynamics of COVID-19 in Shanghai in 2022. Methods: The COVID-19 data presented on the official websites of Municipal Health Commissions of Shanghai during March 1, 2022 and May 31, 2022 were collected for a spatial autocorrelation analysis by GeoDa software. A logistic growth model was used to fit the epidemic situation and make a comparison with the actual infection situation. Results: Pudong district had the highest number of symptomatic and asymptomatic infectants, accounting for 29.30% and 35.58% of the total infectants. Differences in cumulative attack rates and infection rates among 16 districts (P<0.001) were significant. The rates were significantly higher in Huangpu district than in other districts. The attack rate of COVID-19 from March 1, 2022 to May 31, 2022 had a global spatial positive correlation (P<0.05). Spatial distribution of COVID-19 attack rate was different at different periods. The global autocorrelation coefficient from March 16 to March 29, April 6 to April 12 and May 18 to May 24 had no statistical significance (P>0.05). Our local autocorrelation analysis showed that 22 high-high clustering areas were detected in eight periods.The high-risk hot-spot areas have experienced a "less-more-less" change process. The growth model fitting results were consistent with the actual infection situation. Conclusion: There was a clear spatiotemporal correlation in the distribution of COVID-19 in Shanghai. The comprehensive prevention and control measures of COVID-19 epidemic in Shanghai have effectively prohibited the growth of the epidemic, not only curbing the spatially spread of high-risk epidemic areas, but also reducing the risk of transmission to other cities.

[Molecular mechanism and research progress of hepatocellular carcinoma induced by hepatitis B virus mutation].

Hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV) is the first cause of cancer-caused death in China. This study, from the perspective of HBV genomic epidemiology, systematically investigated the evolution of HBV and their interaction with host genetic factors in each stage of HBV carcinogenesis and comprehensively analyzed the role of apolipoprotein B mRNA editing enzyme catalytic polypeptides (APOBEC) family in the inflammation-to-cancer transformation. Based on our findings and related studies, we proposed "cancer evolution and development" (Cancer Evo-Dev) theoretical system suitable for most cancer types. Cancer Evo-Dev lays a theoretical foundation for understanding the mechanism of inflammation to promote the development of cancer, which is of great significance for the specific prevention, prediction, early diagnosis, and targeted therapy of malignant diseases.

[Consideration on improving public health emergency management ability of current medical health system].

COVID-19 is a Public Health Emergency of International Concern (PHEIC). Direct economic loss is expected to be much more than that of SARS outbreak in 2003. The risk factors of COVID-19 epidemic at the early stage included the misjudgment of the epidemic, delay in reporting this emerging infectious disease, nosocomial infection-caused transmission of the virus into local communities, and weak public health interventions. The infection rate (or the incidence) reflects the prophylactic effect in population. Case fatality reflects the therapeutic effect of clinical intervention. There were sufficient medical resources at the national top levels accumulated in Wuhan. Furthermore, medical professionals and sufficient medical supplies from other provinces have been assigned to join in the fighting against the epidemic in Wuhan. However, the case fatality in Wuhan has been kept the highest in China, indicating that clinical treatment for this virus-caused emerging infectious disease, whose pathogenesis remains to be elucidated, with limited effect in controlling this epidemic. The unusual, extremely costly public health interventions including the temporarily city quarantine and transportation ban issued by the central government are crucial in controlling this epidemic. The control of epidemic indicates the importance of public health measures but also reflected its insufficient capacity in China. Recently, profit-seeking mechanism run in Chinese health service system disorganized the balance of clinical service and public health service patterns in China, promoting the vicious circle of "attaching importance to clinical treatment and despising disease prophylaxis" , damaging the infrastructure of public health capacity, thus contributing to the formation of the inevitability in various fortuities of public health emergency. To strength the capacity of our medical service system to respond to public health emergency efficiently, two key issues should be considered. First, public health service, which should be fixed as the health section of the governments' public services by the law, must be greatly improved to meet the increasing health needs of the publics. Second, the vicious circle of profit-seeking-caused "attaching importance to clinical treatment and despising disease prophylaxis" should be immediately broken to optimize the national health service system in China by increasing the investment in public health service.

[A bibliometric analysis on cohort study of liver cancer in China].

Objective: To retrospectively analyze the application trend of cohort study in the field of liver cancer in past 27 years and to look forward to the future development trend. Methods: Chinese and English papers reporting the cohort studies of liver cancer conducted in the mainland of China since 1991 were included. The literature management software was used to analyze the publication time, institution, type and objective of the studies and the follow-up performance. Statistical analysis was carried out by using SPSS 21.0. Results: The number and quality of the papers reporting liver cancer-related cohort studies increased significantly in past 27 years and a core English journal group of this field has formed. The average annual growth rates of Chinese and English papers published were 20.4% and 35.2% respectively. About 52.3% of the Chinese papers and 73.5% of the English papers were published in past five years and the quality of these papers was high. The Chinese papers published on Chinese core journals accounted for 49.2%, and the English papers published on SCI periodicals (IF>3) accounted for 47.3%. For the study objective, those published on the domestic journals mainly focused on the pathogenesis of hepatoma (41.5%), studies with large sample size was the common form. The SCI studies mainly focused on the prognosis of liver cancer (40.7%). High-quality SCI papers are more interested in the studies of prognosis, and survival analysis was the common form. Conclusions: The application of cohort study in the field of liver cancer gradually increased in China. Large-scale study and prognosis analysis were conducted commonly. However, it is necessary to further improve the researchers' understanding of cohort study, improve the follow-up quality, and increase the application of scientific evaluation methods, such as survival analysis, for the better solving of clinical problems.

[Mortality trend and age-period-cohort analysis of colorectal cancer among residents in Yangpu District of Shanghai from 1975 to 2014].

Objective: To describe the 40-years trend for the mortality of colorectal cancer (CRC) in Shanghai and to estimate the effect of age, period, and birth cohort with Age-Period-Cohort (APC) model. Methods: Data on tumor-releated death from 1975 Janurary 1 to 2014 December 31 was derived from the Yangpu District of Shanghai Center for Diseases Prevention and Control tumor registration system. Colonrectal cancer cases (C18.2-C18.9 and C20 in ICD10) were selected for analyses. Crude mortality, age-adjusted mortality, and Average Annual Percent Changes (AAPCs) were calculated for colon cancer and rectal cancer. The difference of AAPCs between male/female and different age groups were tested. An APC model (reference cohort and period were 1900 and 1975, respectively) was constructed to estimate the age-effect, period-effect, and cohort-effect on the colorectal cancer death. Results: During 1975-2014, 6 725 cases died of colorectal cancer (the cased of colon and rectal cancer were 3 684 and 3 041, respectively). The crude mortality and age-adjusted mortality of colon cancer was 8.83/100 000 and 6.76/100 000, respectively. The crude mortality and age-adjusted mortality of rectal cancer were 7.32/100 000 and 5.67/100 000, respectively. For population in Yangpu District, the crude mortality and age-adjusted mortality of colon cancer increased with time, and the crude mortality of rectal cancer increased with time (P<0.001). AAPC of the crude mortality rate (5.6%) and age-adjusted mortality rate (2.3%) of colon cancer were higher than those in rectal cancer (3.0% and -0.3%), respectively (both P values <0.001). AAPC of the crude mortality rate (males vs. females was 6.2% vs. 5.0%, P<0.05) and age-adjusted mortality rate (males vs. females was 2.7% vs. 1.7%, P<0.05) of colon cancer were higher in males than in females. APC model indicted that CRC-related death increased with age. During 1901 to 1941, the RR values of cohort effects for colon and rectal cancer death were 1.09-5.57 and from 1.04-2.28, respectively; During 1946 to 1991, the RR values of cohort effects for colon cancer and rectal cancer were 5.51-4.32 and 2.16-0.89. Conclusion: From 1975 to 2014, the mortality of CRC in Yangpu District increased gradually, and colon cancer mortality in males increased faster than that in females. The risk of death from colorectal cancer in the 1946-1991 birth cohort declined.

[Risk factors analysis and a new risk scoring system predicting hepatocarcinogenesis for chronic genotype C HBV infected patients].

Objective: To investigate the effects of hepatitis B virus (HBV) genotype and mutations on the development of hepatocellular carcinoma (HCC) and to establish a new qualified HCC risk scores. Methods: A cohort study enrolling patients with chronic HBV infection was conducted. HBV genotypes were identified by nested multiplex PCR. HBV mutations in the basic core promoter region and PreS region were sequenced after PCR amplification. Scores on risk factors were set based on nomogram. Results: Totally, 1 525 patients were followed-up in this research. A total of 1 110 patients infected with genotype C were followed-up for 8.52 (Q(R): 5.36-11.68) years on average, of whom the incidence of HCC was 11.93/1 000 person-years. In genotype C HBV infected patients, male gender, aged 40 years and over, and four DNA mutations (T1674CG, A1762T/G1764A, A3120T, and A2962G) can increase the risk of HCC (P<0.05); interferon therapy can reduce the risk of HCC (P<0.05). A new HCC predicting model was established according to the results. After validation, the predicted disease-free survival rate was consistent with the real one. Conclusions: Hepatitis B virus genotypes and mutations were closely associated with HCC. The new risk scoring system can well predict HCC occurrence in genotype C HBV infected patients.

[Epidemic characteristics and prophylaxis/control measures of infectious diseases caused by hydrological disasters].

Hydrological disasters are associated with infectious disease outbreaks and epidemics. Hydrological disasters will lead to water pollution, increased vulnerability to diseases, and increased density of vectors. These factors will facilitate the outbreaks of water-borne/food-borne diseases, vector-borne diseases, and air-borne/contagious diseases. Pre-event preparedness for disasters and post-event reconstruction of both disease surveillance system and water-supply system are key measures to prevent infectious disease outbreaks caused by hydrological disasters. This study reviews the domestic and overseas experiences of controlling infectious diseases after hydrologic disasters, outlines the spectrum of post-disaster infectious disease as well as their epidemiological characteristics, and provides practicable suggestions accordingly.

[Research on reform of epidemiology teaching].

Epidemiology is a traditional subject mainly based on principles and concepts, and its teaching method needs further improving to meet the requirement of the new trend of education reform. Lecture-based teaching, problem-based teaching, case-based teaching, and internet based teaching, such as flip class, massive open online course and micro-lecture, all have its own unique merits in the practice of epidemiology teaching. So the combination of traditional teaching and online teaching is the most promising mode. "Rain class" , a mixed mode, is an efficient tool to present the epidemiology case more actually in class. Thus, teaching design and application of "rain class" are worth research.

[Indispensability of cohort study in tumor prevention and prognosis assessment].

Cancer is one of the major causes of human death. Early diagnosis and treatment are widely believed to be important in decreasing cancer mortality rate. However, biological factors (such as tumor heterogeneity) and social factors (such as profits driving), over-diagnosis and over-treatment exist in the practice of cancer diagnosis and treatment. The keys to avoid such issues are to identify what kinds of precancerous lesions are more likely to progress into malignant tumors, what kind of early cancer are prone to invading surrounding tissues, and what kinds of prophylactic and therapeutic options are of benefit to effective survival of patients. All above need to be accurately evaluated by cohort studies. Cohort study is the most reliable method to crystallize causal relationship of the exposures (interventions) with the development and recurrence of cancers and define the directions of cancer screening and therapy. Cohort studies shed light on the prediction, screening, and active prophylaxis for the occurrence and recurrence of cancers with specific types. Moreover, the prognostic effects of a given clinical treatment can be precisely evaluated in cohort study, rather than experience-directed clinical activity. Therefore, cohort study is indispensable for cancer research.

[Qidong Chronic Hepatitis B Cohort: participants enrollment and comparison of baseline characteristics by gender stratification].

Objective: To establish a study cohort of chronic hepatitis B (CHB) in Qidong and evaluate its baseline characteristics. Methods: CHB outpatients of the Third People's Hospital of Qidong were invited to participate in baseline survey from January 1, 2016, including questionnaire survey, liver function detection, serum detection of HBV infection and upper abdomen ultrasound detection. Anticipated sample size was at least one thousand. Baseline data were inputted by EpiData 3.1 software and then cleaned and analyzed by SAS 9.3 software. Results: As of 18 July, 2016, a total of 1 006 participants had been enrolled into the current study, including 615 males with an average age of (44.26±9.97) years and 391 females with an average age of (46.66±11.17) years. The difference in family history of liver disease was not significant between males and females (P>0.05), while the differences in other key information, such as age, education level, tobacco consumption, alcohol drinking, tea consumption, and antiviral intervention, were significant between males and females (P<0.05). Among the key clinical parameters, such as ALT, HBeAg, HBsAg, HBV DNA, albumin, and width of splenic vein and portal vein, only the abnormal rates of ALT and total bilirubin levels were higher in males than in females, the difference was significant (P<0.05). Conclusion: Outpatient department-based CHB cohort was established successfully in Qidong, and sub-cohort could be divided according to the differences on baseline characteristics.

[Hepatocellular carcinoma: co - evolution of hepatocytes and hepatitis B virus].

Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC). In the process from chronic HBV infection to the development of HCC, there is a phenomenon of co-evolution of hepatocytes and HBV. The evolution of hepatocytes includes dedifferentiation and reverse evolution, while the evolution of HBV is mainly "telemorphosis" . Since HBV evolution occurs earlier than the development of HCC, the interaction between them is mainly reflected in the promotion of HCC evolution by HBV mutation. This article briefly summarizes the novel theory termed as cancer evolution and development and elucidates the molecular mechanism of HCC caused by HBV from the perspective of evolution.

[Effects of application of vancomycin in the early stage of patients with extremely severe burn].

Objective: To evaluate the effects of application of vancomycin in the early stage of patients with extremely severe burn, in order to provide reference to drug for anti-infection treatment in the early stage of patients with extremely severe burn. Methods: Data of 15 patients of Kunshan explosion on August 2nd, 2014, admitted to the Department of Intensive Care in our hospital were retrospectively analyzed. The clinical efficacy of continuously intravenous dripping of vancomycin (combined with imipenem) in the early stage of burns (before and on post burn day 14) was analyzed. (1) The steady state plasma concentration of vancomycin was monitored respectively 30 min before the third, sixth, and tenth medication with direct chemiluminescent imaging method. (2) The distribution of Gram-positive bacteria of patients during hospitalization and their drug resistance to 14 antibiotics commonly used in clinic were analyzed. (3) Serum level of procalcitonin (PCT), white blood cell count, percentage of neutrophils before and after treatment, and efficacy grade of anti-infection treatment in the early stage of burns were analyzed. (4) Serum levels of aspartate transaminase (AST), alanine aminotransferase (ALT), creatinine before and after treatment, and the adverse effects during medication were analyzed. The WHONET 5.5 statistical software was used to analyze the distribution of Gram-positive bacteria in all the pathogens, and the status of drug resistance of Gram-positive bacteria to 14 antibiotics. Data were processed with Wilcoxon rank sum test. Results: (1) Twenty-nine times of steady state plasma concentration monitoring were performed in the patients in total, with the steady state plasma concentration of vancomycin from 4.3 to 42.1 µg/mL. In the monitoring before third, sixth, and tenth medication, the percentages of result reaching the standard were respectively 1, 3/14, and 2/7. (2) A total of 79 Gram-positive bacteria were isolated, including 49 (62.03%) strains of Staphylococcus aureus, 9 (11.39%) strains of Staphylococcus haemolyticus, 7 (8.86%) strains of Staphylococcus epidermidis, 12 (15.19%) strains of Enterococcus faecium, and 2 (2.53%) strains of Enterococcus faecalis. The above-mentioned Staphylococcus strains were with high drug resistance to antibiotics including penicillins, erythromycin, ciprofloxacin, and low drug resistance to linezolid, teicoplanin, and nitrofurantoin. The above-mentioned Enterococcus strains were with high drug resistance to antibiotics including erythromycin, ciprofloxacin, gentamicin, and low drug resistance to linezolid and teicoplanin. The above-mentioned Staphylococcus strains were all sensitive to vancomycin. Two strains of vancomycin-resistant Enterococcus were detected in the above-mentioned Enterococcus strains. (3) Serum level of PCT, white blood cell count, percentage of neutrophils of patients were (8.1±7.5) ng/mL, (24±10)×10(9)/L, and 0.898±0.029 before treatment, which were significantly higher than (3.0±2.8) ng/mL, (12±5)×10(9)/L, and 0.867±0.016 after treatment (with Z values respectively -2.103, -3.237, and -3.068, P<0.05 or P<0.01). After the early treatment, excellence, progess, and invalid results were achieved in 7, 5, and 3 patients, with the effective percentage of 4/5 in clinic. (4) There were no statistically significant differences in serum levels of AST, ALT, and creatinine of patients between before and after treatment (with Z values respectively-0.057, -1.508, and -1.363, P values above 0.05). Only one patient had liver and renal dysfunction during treatment. Conclusions: The positive and reasonable use of vancomycin can remove most of the Gram-positive bacteria, and control the development of sepsis combined with imipenem in the early stage of patients with extremely severe burn. However, the dose of vancomycin should be individualized and the steady state plasma concentration should be monitored to maintain the blood concentration within the safe and effective range, so as to improve the rational use of vancomycin.

[Innovations on technology, management and concept are indispensible for scientific research, prevention and treatment of malignant tumor in China].

Malignant tumor has become the top cause of deaths before the average life expectancy in Chinese population. From the variations in the morbidity rate and mortality rate of malignant tumor in the mainland of China between 2000 and 2011, the primary prevention targeting the risk factors/etiological agents significantly reduced the morbidity rates of gastric cancer, esophageal cancer, and primary liver cancer, therefore reduced the mortality rates of these cancers. However, the contribution of clinical treatments to the mortality reduction was not obviously improved during this period. Importantly, it is necessary to conduct research to identify precancerous lesions and early tumors which are prone to progress to aggressive diseases for the active secondary prevention to avoid over-diagnosis and over-treatment. Multi-center, prospective randomized controlled clinical trials and prognosis evaluation independently carried out by third parts are needed to evaluate the longterm effectiveness of some clinical treatment efficiency for cancers with different histological types. On the basis of a series of population-based studies in China, the prevention and clinical treatments for malignant tumor need innovations on technology, management, and even concept; the mechanisms of "forward placement of strategic pass" for the prevention and control of malignant tumor should be established and improved to reduce the increasing disease burden due to malignant tumor in China.

Meteorological factors affect the hand, foot, and mouth disease epidemic in Qingdao, China, 2007-2014.

Hand, foot, and mouth disease (HFMD) has caused public health concerns worldwide. We aimed to investigate the effect of meteorological factors on the HFMD epidemic in Qingdao, a port city in China. A total of 78641 cases were reported in Qingdao between January 2007 and December 2014. Of those, 71084 (90·39%) occurred in children aged 0-5 years, with an incidence of 1691·2/100000. The incidence increased from early spring, peaked between spring and summer, and decreased in late summer. Aetiological agents in all severe cases and selected mild cases were characterized by examining throat swabs. Except for enterovirus 71 (EV71) and coxsackievirus A16 (CA16), other EVs caused >50% of the HFMD cases between 2011 and 2014. EV71 was more frequent in the off-peak months than in the peak months and prone to causing more severe cases compared to CA16 (χ 2 = 46·3, P < 0·001). CA10 caused more severe HFMD than did CA6 (χ 2 = 20·49, P < 0·001) and all non-CA10 EVs (χ 2 = 41·01, P < 0·001). Community-derived HFMD cases accounted for 65·11%. Spearman rank correlation analysis showed that HFMD incidence in children aged 0-5 years was positively correlated with atmospheric temperature (r s = 0·77, P < 0·001), relative humidity (r s = 0·507, P < 0·001), and precipitation (r s = 0·328, P < 0·001). Climate changes and CA10 surveillance in communities should be integrated into the current prophylactic programme.

Cancer Evolution-Development: experience of hepatitis B virus-induced hepatocarcinogenesis.

Here, we present the basic concept and theoretical framework of a scientific hypothesis called Cancer Evolution-Development ("Cancer Evo-Dev"), based on our recent studies of the molecular mechanisms by which chronic infection with the hepatitis B virus induces hepatocarcinogenesis, together with related advances in that field. Several aspects central to our hypothesis are presented: ■ Immune imbalance-caused by the interaction of genetic predispositions and environmental exposures such as viral infection-is responsible for the maintenance of chronic non-resolving inflammation. Non-resolving inflammation promotes the occurrence and progression of cancers, characterized by an evolutionary process of "mutation-selection-adaptation" for both viruses and host cells.■ Under a microenvironment of non-resolving inflammation, proinflammatory factors promote mutations in viral or host genomes by transactivation of the expression of cytidine deaminases and their analogues. Most cells with genomic mutations and mutated viruses are eliminated in the competition for survival in the inflammatory microenvironment. Only a small percentage of the mutated cells that alter their survival signal pathways and exhibit the characteristics of "stem-ness" can survive and function as cancer-initiating cells.■ Cancers generally develop with properties of "backward evolution" and "retro-differentiation," indicating the indispensability of stem-like signal pathways in the evolution and development of cancers. The hypothesis of Cancer Evo-Dev not only lays the theoretical foundation for understanding the mechanisms by which inflammation promotes the development of cancers, but also plays an important role in specific prophylaxis, prediction, early diagnosis, and targeted treatment of cancers.

Secreted protein acidic and rich in cysteine expression in human colorectal cancer predicts postoperative prognosis.

OBJECTIVE: Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix glycoprotein involved in cell proliferation, migration and angiogenesis. The aim of this study was to assess its expression in colorectal cancer, see whether and how it correlates with clinicopathological features, and evaluate its potential prognostic significance. PATIENTS AND METHODS: SPARC expression was detected by microarrays containing 847 immunohistochemically stained specimens, and further correlated with the clinicopathological and prognostic data. The prognostic significance of its expression was assessed using Kaplan-Meier survival with log-rank tests. Multivariate regression utilizing Cox's proportional hazard model was used to evaluate prognostic factors. RESULTS: SPARC expression in the normal colorectal mucosa and colorectal cancer tissue was significantly different (p < 0.001). Low SPARC expression was found to be associated with poor prognosis, and it was unfavorably correlated with overall survival and disease-free survival in colorectal cancer patients. In addition, SPARC expression in surrounding mesenchymal and stromal cells, bowel wall invasion, lymph node metastasis, and distant metastasis were independent prognostic factors for overall survival and disease-free survival. CONCLUSIONS: Reduced expression of SPARC in colorectal cancer tissue is associated with poor prognosis and aggressive clinicopathological features. Therefore, SPARC expression could potentially be used as a prognostic predictor for colorectal cancer patients.

p28(GANK) associates with p300 to attenuate the acetylation of RelA.

Oncoprotein p28(GANK), overexpressed in hepatocellular carcinomas (HCC), binds to RelA and retains NF-κB in the cytoplasm to suppress NF-κB transactivation. However, the mechanism has not yet been elucidated. In this study, we clarified the mechanism of NF-κB regulated by p28(GANK). p28(GANK) reduced TNF-α-induced nuclear translocation of RelA/NF-κB independent of HDAC3. p28(GANK) interacted with p300 to attenuate assembly of RelA with p300, which lessened acetylation of RelA on the lysine 310 sites. Moreover, overexpression of p28(GANK) attenuated the capability of NF-κB binding to the target gene IκBα promoter, but also weakened adriamycin-induced NF-κB pro-apoptotic gene Fas and FasL expression, which subsequently made p53-deficient tumor cells resistance to adriamycin. These results present mechanistic insight into the key role of p28(GANK) in post-translational regulation of RelA/NF-κB.