Incidence and Mortality of Cancers in Female Genital Organs - China, 2022.

Introduction: This study presented the incidence and mortality rates of cancers affecting the female genital organs in China, along with their trends spanning from 2010 to 2018. Methods: 700 population-based cancer registries provided relevant cancer incidence and mortality data for the year 2018. Among these, 106 registries had continuous monitoring data suitable for trend analysis from 2010 to 2018. We focused specifically on cancers affecting female genital organs (ICD10=C51-C54, C56) and projected their incidences and mortalities in China for 2022 based on data from 2018 and the trends observed from 2010 to 2018. Age-standardized incidence rate (ASIR) and mortality rate (ASMR) were calculated using Segi's world standard population. Results: In 2022, there were an estimated 296,300 new cases and 104,900 deaths from female cancers in China. ASIRs for vulva (C51), vagina (C52), cervix uteri (C53), corpus uteri (C54), and ovary (C56) were 0.32, 0.23, 13.83, 6.84, and 5.68 per 100,000 population. ASIRs for corpus uteri and ovary cancers were higher in urban areas. ASMRs for vulva, vagina, cervix, corpus uteri, and ovary cancers were 0.14, 0.08, 4.54, 1.05, and 2.64 per 100,000 population, respectively. ASMR for ovarian cancer was higher in urban areas. ASIRs and ASMRs for most female genital organ cancers increased from 2010 to 2018, although the rate of increase for vulvar and cervical cancers in rural areas has slowed recently. Conclusions: Tailored cancer prevention and control programs specific to each region are necessary to address the growing disease burden.

Plant-based dietary patterns and risk of esophageal cancer: A prospective cohort study spanning 17 years.

Objective: Plant-based diets have multiple health benefits for cancers; however, little is known about the association between plant-based dietary patterns and esophageal cancer (EC).This study presents an investigation of the prospective associations among three predefined indices of plant-based dietary patterns and the risk of EC. Methods: We performed endoscopic screening for 15,709 participants aged 40-69 years from two high-risk areas of China from January 2005 to December 2009 and followed the cohort until December 31, 2022. The overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI), were calculated using survey responses to assess dietary patterns. We applied Cox proportional hazard regression to estimate the multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) of EC across 3 plant-based diet indices and further stratified the analysis by subgroups. Results: The final study sample included 15,184 participants in the cohort. During a follow-up of 219,365 person-years, 176 patients with EC were identified. When the highest quartile was compared with the lowest quartile, the pooled multivariable-adjusted HR of EC was 0.50 (95% CI, 0.32-0.77) for hPDI. In addition, the HR per 10-point increase in the hPDI score was 0.42 (95% CI, 0.27-0.66) for ECs. Conversely, uPDI was positively associated with the risk of EC, and the HR was 1.80 (95% CI, 1.16-2.82). The HR per 10-point increase in the uPDI score was 1.90 (95% CI, 1.26-2.88) for ECs. The associations between these scores and the risk of EC were consistent in most subgroups. These results remained robust in sensitivity analyses. Conclusions: A healthy plant-based dietary pattern was associated with a reduced risk of EC. Emphasizing the healthiness and quality of plant-based diets may be important for preventing the development of EC.

Inhibition of MMP8 effectively alleviates manic-like behavior and reduces neuroinflammation by modulating astrocytic CEBPD.

There is an intrinsic relationship between psychiatric disorders and neuroinflammation, including bipolar disorder. Ouabain, an inhibitor of Na+/K+-ATPase, has been implicated in the mouse model with manic-like behavior. However, the molecular mechanisms linking neuroinflammation and manic-like behavior require further investigation. CCAAT/Enhancer-Binding Protein Delta (CEBPD) is an inflammatory transcription factor that contributes to neurological disease progression. In this study, we demonstrated that the expression of CEBPD in astrocytes was increased in ouabain-treated mice. Furthermore, we observed an increase in the expression and transcript levels of CEBPD in human primary astrocytes following ouabain treatment. Transcriptome analysis revealed high MMP8 expression in human primary astrocytes following CEBPD overexpression and ouabain treatment. We confirmed that MMP8 is a CEBPD-regulated gene that mediates ouabain-induced neuroinflammation. In our animal model, treatment of ouabain-injected mice with M8I (an inhibitor of MMP8) resulted in the inhibition of manic-like behavior compared to ouabain-injected mice that were not treated with M8I. Additionally, the reduction in the activation of astrocytes and microglia was observed, particularly in the hippocampal CA1 region. Excessive reactive oxygen species formation was observed in ouabain-injected mice, and treating these mice with M8I resulted in the reduction of oxidative stress, as indicated by nitrotyrosine staining. These findings suggest that MMP8 inhibitors may serve as therapeutic agents in mitigating manic symptoms in bipolar disorder.

Global, regional, and national lifetime risks of developing and dying from gastrointestinal cancers in 185 countries: a population-based systematic analysis of GLOBOCAN.

BACKGROUND: Gastrointestinal cancers account for a quarter of the global cancer incidence and a third of cancer-related deaths. We sought to estimate the lifetime risks of developing and dying from gastrointestinal cancers at the country, world region, and global levels in 2020. METHODS: For this population-based systematic analysis, we obtained estimates of gastrointestinal cancer incidence and mortality rates from GLOBOCAN for 185 countries, alongside all-cause mortality and population data from the UN. Countries were categorised into quartiles of the Human Development Index (HDI). The lifetime risk of gastrointestinal cancers was estimated with a standard method that adjusts for multiple primaries, taking into account competing risks of death from causes other than cancer and life expectancy. FINDINGS: The global lifetime risks of developing and dying from gastrointestinal cancers from birth to death was 8·20% (95% CI 8·18-8·21) and 6·17% (6·16-6·18) in 2020. For men, the risk of developing gastrointestinal cancers was 9·53% (95% CI 9·51-9·55) and of dying from them 7·23% (7·22-7·25); for women, the risk of developing gastrointestinal cancers was 6·84% (6·82-6·85) and of dying from them 5·09% (5·08-5·10). Colorectal cancer presented the highest risk, accounting for 38·5% of the total lifetime risk of developing, and 28·2% of dying from, gastrointestinal cancers, followed by cancers of the stomach, liver, oesophagus, pancreas, and gallbladder. Eastern Asia has the highest lifetime risks for cancers of the stomach, liver, oesophagus, and gallbladder, Australia and New Zealand for colorectal cancer, and Western Europe for pancreatic cancer. The lifetime risk of gastrointestinal cancers increased consistently with increasing level of HDI; however, high HDI countries (the third HDI quartile) had the highest death risk. INTERPRETATION: The global lifetime risk of gastrointestinal cancers translates to one in 12 people developing, and one in 16 people dying from, gastrointestinal cancers. The identified high risk and observed disparities across countries warrants context-specific targeted gastrointestinal cancer control and health systems planning. FUNDING: Beijing Nova Program, CAMS Innovation Fund for Medical Sciences, and Talent Incentive Program of Cancer Hospital, CAMS (Hope Star).

Trends of gastric cancer burdens attributable to risk factors in China from 2000 to 2050.

Background: The incidence of gastric cancer (GC) decreased in past decades, which was thought largely attributable to risk factors control, yet China still accounts for 44% of global GC burdens. We aimed to estimate changing trajectories of proportions of GC burdens attributable to modifiable risk factors from 2000 to 2050 in China, to inform future targeted preventive strategies. Methods: The incidence and new cases of GC were predicted to 2050 using Bayesian age-period-cohort model based on incidence data by anatomical subsites drawn from 682 cancer registries from National Central Cancer Registry. Population attributable fractions (PAFs) were calculated based on prevalence of risk factors and relative risks with GC. Temporal trends of PAFs were described by sex and categories of risk factors using joinpoint analysis. Findings: We observed declining trends of PAFs of Helicobacter pylori (H. pylori) infection, smoking, pickled vegetable and alcohol consumption, but increasing trends of PAFs of unhealthy body mass index and diabetes for GC in China. The combined PAFs of these risk factors were estimated to decrease by 10.57% from 2000 to 2050 for GC. We estimated there will be 279,707 GC (122,796 cardia gastric cancer [CGC] and 156,911 non-cardia gastric cancer [NCGC]) cases in 2050. Out of these cases, 70.18% of GC cases could be attributable to modifiable risk factors, while H. pylori infection was predicted to be responsible for 40.7% of CGC and 62.1% of NCGC cases in 2050. Interpretation: More than half of GC remained attributable to modifiable risk factors in China. Continued effective strategies on risk factors control are needed to reduce the burden of this highly life-threatening cancer in future. Funding: Beijing Nova Program (No. Z201100006820069), CAMS Innovation Fund for Medical Sciences (CIFMS, grant No. 2021-I2M-1-023), CAMS Innovation Fund for Medical Sciences (CIFMS, grant No. 2021-I2M-1-010), Talent Incentive Program of Cancer Hospital Chinese Academy of Medical Sciences (Hope Star).

Fluvoxamine Exerts Sigma-1R to Rescue Autophagy via Pom121-Mediated Nucleocytoplasmic Transport of TFEB.

Expansion of the GGGGCC-RNA repeat is a known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which currently have no cure. Recent studies have indicated the activation of Sigma-1 receptor plays an important role in providing neuroprotection, especially in ALS and Alzheimer's disease. Nevertheless, the mechanisms underlying Sigma-1R activation and its effect on (G4C2)n-RNA-induced cell death remain unclear. In this study, we demonstrated that fluvoxamine is a Sigma-1R agonist that can increase chaperone activity and stabilize the protein expression of Pom121 in (G4C2)31-RNA-expressing NSC34 cells, leading to increased colocalization at the nuclear envelope. Interestingly, fluvoxamine treatment increased Pom121 protein expression without affecting transcription. In C9orf72-ALS, the nuclear translocation of TFEB autophagy factor decreased owing to nucleocytoplasmic transport defects. Our results showed that pretreatment of NSC34 cells with fluvoxamine promoted the shuttling of TFEB into the nucleus and elevated the expression of LC3-II compared to the overexpression of (G4C2)31-RNA alone. Additionally, even when used alone, fluvoxamine increases Pom121 expression and TFEB translocation. To summarize, fluvoxamine may act as a promising repurposed medicine for patients with C9orf72-ALS, as it stabilizes the nucleoporin Pom121 and promotes the translocation of TFEB in (G4C2)31-RNA-expressing NSC34 cells.

Gastric tubular adenocarcinoma with diffuse neutrophils infiltrating: characteristics and probable treatment strategy.

BACKGROUND: Gastric adenocarcinoma is a highly heterogeneous malignancy with varying prognoses. In clinicopathological practice, we noticed a special tubular adenocarcinoma with diffuse neutrophils infiltrating (TADNI). However, the proportion and characteristics of TADNI remain unclear. This study aimed to evaluate the features of TADNI and explore probable treatments. METHODS: We divided 289 tubular adenocarcinoma cases into the TADNI and non-TADNI (nTADNI) groups by histological neutrophil quantity and performed immunohistochemistry of treatment-associated markers (CXCR1, CXCR2, PD-L1, CD8, HER2 and VEGFR2). Then we evaluated the clinical and morphological features in these cases. We also compared the value of histological features and peripheral blood neutrophil test. In addition, multiomics bioinformatic analyses were performed using the public datasets. RESULTS: In our cohort, TADNI accounted for 10.4% of all tubular adenocarcinoma cases. These cases had worse prognoses (especially the neutrophils mainly outside the tubes) than nTADNI cases. The histological identification of TADNI had more prognostic value than peripheral blood neutrophils. CXCR1/CXCR2 expression was significantly high in TADNI group which indicated that CXCR1/CXCR2 inhibitors might be beneficial for TADNI patients. There were no significant differences in the expression of PD-L1, CD8, HER2 and VEGFR2. The analyses of TCGA data confirmed that TADNI cases had poorer prognoses and higher CXCR1/CXCR2 expression. Bioinformatic results also revealed molecular features (more hsa-mir-223 expression, fewer CD8-positive T cells and regulatory T cells, tighter communication between tumor cells' CXCR1/CXCR2 and neutrophils' CXCL5/CXCL8) of this type. CONCLUSIONS: TADNI is a special morphological subtype with poorer prognoses and unique molecular characteristics, which might benefit from CXCR1/CXCR2 inhibitors.

Geographic, sex and socioeconomic disparities in esophageal cancer incidence in China: A population-based study.

Geographic and sex differences in esophageal cancer have been reported in China, but data are lacking at the local level. We aimed to investigate geographic and sex disparities in esophageal cancer incidence among Chinese counties and whether county-level socioeconomic status was associated with these variations. We obtained esophageal cancer data from 2015 to 2017 for 782 counties from population-based cancer registries in China. We calculated age-standardized incidence rates and male-to-female incidence rate ratios (IRRs) by county. We performed hotspot analysis to identify geographical clusters. We used negative binomial regression models to analyze the association between incidence rates and county-level socioeconomic factors. There were significant geographic disparities in esophageal cancer incidence, with 8.1 times higher rate in the 90th-percentile county than in the 10th-percentile county (23.7 vs 2.9 per 100 000 person-years). Clusters of elevated rates were prominent across north-central China. Nationally, men had 2.9 times higher incidence of esophageal cancer than women. By county, the male-to-female IRRs ranged from 1.1 to 21.1. Clusters of high male-to-female IRRs were observed in northeast China. Rurality (IRR 1.16, 95% CI 1.10-1.22), per capita gross domestic product (IRR 0.95, 0.92-0.98) and percentage of people with a high school diploma (IRR 0.86, 0.84-0.87) in a county were significantly associated with esophageal cancer incidence. The male-to-female IRRs were higher in counties with higher socioeconomic status. Substantial differences in incidence rates and sex ratios of esophageal cancer exist between Chinese counties, and county-level socioeconomic status was associated with these variations. These findings may inform interventions to reduce these disparities.

Synthesis and biological activity assay of novel camptothecin-peptidic conjugates based on PEPT1.

Camptothecin (CPT) and its derivatives are potent candidates for cancer treatment. However, the clinical applications are largely restricted by non-selectivity and severe toxicities. The peptide transporter 1 (PEPT1), which is highly expressed in human intestines, has been found to be overexpressed in several cancer cells. This discovery suggests that PEPT1 has the potential to serve as a therapeutic target for both improving bioavailability and cancer-targeting treatment. Therefore, a prodrug approach for CPT targeting at PEPT1 highly expressed cancer cells was adopted in the present study. Eighteen CPT prodrugs, its peptidic conjugates, were synthesized and the structures were confirmed by NMR and HRMS. The protein expression profiles of PEPT1 in different cell lines were performed using immunofluorescence assay and western blotting analysis. The cytotoxicity of CPT prodrugs and their uptake via competition with Gly-Sar, a typical substrate of PEPT1, were evaluated in both PEPT1-overexpressed and under expressed cells. The results demonstrated that most CPT prodrugs significantly impaired Gly-Sar uptake, suggesting a higher affinity of CPT-peptidic conjugates for PEPT1 and PEPT1 overexpression cells. In addition, these prodrugs demonstrated a higher capability for inhibiting cell growth in PEPT1 highly-expressed cancer cells compared to PEPT1 under expressed cells. These results indicated that this peptidic prodrug strategy might offer great potential for improved tumor selectivity and chemotherapeutic efficacy of CPT.

A systematic review and meta-analysis on the relative and attributable risk of Helicobacter pylori infection and cardia and non-cardia gastric cancer.

INTRODUCTION: This study aimed to update the association between Helicobacter pylori (H. pylori) infection and gastric cancer (GC). METHODS: We searched PubMed, Embase, and Cochrane Library from 1990 to December 2021 to identify prospective studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were summarized to validate the relationship between H. pylori infection and GC. RESULTS: Including 27 studies, findings indicated a strong link between H. pylori and non-cardia gastric cancer (NCGC) in both Europe/North America (OR=5.37, 95%CI:4.39-6.57) and Asia (OR = 2.50, 95%CI:1.89-3.32), and a positive association with cardia gastric cancer (CGC) in Asia (OR = 1.74, 95%CI:1.38-2.19), but an inverse association in European/American populations (OR = 0.64, 95%CI: 0.51 to 0.79). Furthermore, the strength of association was greater in studies that detected H. pylori by immunoblotting versus ELISA, and also in studies testing for H. pylori detection further back in time prior to cancer diagnosis (Ptrend<0.05). Approximately 79% of NCGC in Asia and 87% in Europe/North America, along with 62% of CGC in Asia, could be attributable to H. pylori infection. CONCLUSIONS: The meta-analysis supports the significant attributable risk of H. pylori infection for GC and underscores the potential impact of targeting H. pylori in GC prevention programs. PROSPERO REGISTRATION: CRD42021274120.

Global, regional, and national lifetime probabilities of developing cancer in 2020.

The lifetime risk of cancer is a measure of the cumulative risk of cancer over a specific age range and has a clear, intuitive appeal. However, comparative assessments of cancer-specific risk across populations are limited. We used the adjusted for multiple primaries method to estimate the lifetime risk of cancer from the obtained data from GLOBOCAN for 185 countries/regions for the year 2020, alongside all-cause mortality and population data from the United Nations. The estimated global lifetime risk of cancer from birth to death was 25.10% (95% confidence interval (CI): 25.08%-25.11%) in 2020; the risk was 26.27% (95% CI: 26.24%-26.30%) in men and 23.96% (95% CI: 23.93%-23.98%) in women. Significant differences were observed in the risks between countries/regions within world areas and by the human development level. The lifetime risk of cancer was 38.48%, 25.38%, 11.36%, and 10.34% in countries/regions with very high, high, medium, and low Human Development Index, respectively. Globally, prostate and breast cancers were associated with the greatest lifetime risks among men and women (4.65% and 5.90%, respectively). The lifetime risk of cancer decreased with age, with a remaining risk of 12.61% (95% CI: 12.60%-12.63%) from the age of 70 years. The lifetime risk from birth to death translates to approximately one in four persons developing cancer, with men and women having similar risk levels. The identified age-specific variations in cancer risk at the population level can provide crucial information to support targeted cancer prevention and health system planning.

Survival differences between the USA and an urban population from China for all cancer types and 20 individual cancers: a population-based study.

Background: The systematic comparison of cancer survival between China and the USA is rare. Here we aimed to assess the magnitude of survival disparities and disentangle the impact of the stage at diagnosis between a Chinese metropolitan city and the USA on cancer survival. Methods: We included 11,046 newly diagnosed cancer patients in Dalian Cancer Registry, China, 2015, with the follow-up data for vital status until December 2020. We estimated age-standardised 5-year relative survival and quantified the excess hazard ratio (EHR) of death using generalised linear models for all cancers and 20 individual cancers. We compared these estimates with 17 cancer registries' data from the USA, using the Surveillance, Epidemiology, and End Results database. We further estimated the stage-specific survival for five major cancers by region. Findings: Age-standardised 5-year relative survival for all patients in Dalian was lower than that in the USA (49.9% vs 67.9%). By cancer types, twelve cancers with poorer prognosis were observed in Dalian compared to the USA, with the largest gap seen in prostate cancer (Dalian: 55.8% vs USA: 96.0%). However, Dalian had a better survival for lung cancer, cervical cancer, and bladder cancer. Dalian patients had a lower percentage of stage Ⅰ colorectal cancer (Dalian: 17.9% vs USA: 24.2%) and female breast cancer (Dalian: 40.9% vs USA: 48.9%). However, we observed better stage-specific survival among stage Ⅰ-Ⅱ lung cancer patients in Dalian than in the USA. Interpretation: This study suggests that although the overall prognosis for patients was better in the USA than in Dalian, China, survival deficits existed in both countries. Improvement in cancer early detection and cancer care are needed in both countries. Funding: National Key R&D Program (2021YFC2501900, 2022YFC3600805), Major State Basic Innovation Program of the Chinese Academy of Medical Sciences (2021-I2M-1-010, 2021-I2M-1-046), and Talent Incentive Program of Cancer Hospital of Chinese Academy of Medical Sciences.

The occurence of cancer in ageing populations at global and regional levels, 1990 to 2019.

BACKGROUND: population ageing contributes to increased cancer cases and deaths and has profound implications for global healthcare systems. We estimated the trends of cancer cases and deaths in ageing populations at global and regional levels. METHODS: using data from the Global Burden of Disease Study 2019, we analysed the change in cancer cases and deaths associated with population ageing, population growth and epidemiological factors from 1990 to 2019 using decomposition analysis. Additionally, we estimated the proportions of people aged 65 years and over accounting for total cases and deaths, and investigated relationships between the proportions and the Sociodemographic Index (SDI) using the Pearson correlation coefficient. RESULTS: from 1990 to 2019, there was an increase of 128.9% for total cases and 74.8% for total deaths in all cancers combined; the percentages of older people increased from 48.6% to 56.4% for cases and from 52.0% to 61.9% for deaths. Population ageing contributed to the largest increase in global cancer occurrence, with 56.5% for cases and 63.3% for deaths. However, the changes attributed to epidemiological factors was 5.2% for cancer cases and -33.4% for cancer deaths. The proportions of total cases and deaths of older adults were positively correlated with socioeconomic development of the country. CONCLUSION: our findings revealed that the main contributor to increased cancer cases and deaths has changed from comprehensive epidemiological factors to demographic shifts. To respond to the rapidly growing occurrence of cancer in ageing populations, the global health priority should focus on meeting the rising demand for cancer diagnosis, treatment and care services for older people.

Changes in Geographic Variation and Socioeconomic Inequalities in Esophageal Cancer Mortality in China, 1973-2017.

BACKGROUND: Geographic variability in esophageal cancer has been reported in China, but data are lacking at the local level. We aimed to investigate changes in disparities in esophageal cancer-related mortality among Chinese counties and whether county-level socioeconomic status was associated with this variation. METHODS: We used data from a nationwide survey and population-based cancer registries to calculate esophageal cancer-related mortality rates for 782 Chinese counties for the periods of 1973-1975 and 2015-2017. We performed hotspot analysis to identify spatial clusters. We used a multivariable negative binomial regression model to estimate the associations between county-level socioeconomic factors and mortality. RESULTS: From 1973-1975 to 2015-2017, the age-standardized esophageal cancer-related mortality rate decreased from 27 to 8 per 100,000 person-years in China. By county, 577 (74%) of 782 counties experienced decreasing mortality. Geographic disparities in mortality substantially narrowed, with the gap in mortality rates between 90th and 10th percentile counties decreasing from 55 per 100,000 person-years in 1973-1975 to 16 in 2015-2017. However, clusters of elevated rates persisted across north-central China. Rurality [adjusted mortality rate ratio (MRR) 1.15; 95% confidence interval (CI), 1.10-1.21], per capita gross domestic product (adjusted MRR, 0.95; 95% CI, 0.91-0.98), and percentage of people with a high-school diploma (adjusted MRR, 0.86; 95% CI, 0.84-0.87) in a county were significantly associated esophageal cancer-related mortality rates. CONCLUSIONS: China has made substantial progress in reducing esophageal cancer-related mortality and disparities, but the intercounty differences remain large. IMPACT: Continued efforts are needed to address the geographical and socioeconomic disparities in esophageal cancer.

Trends in Incidence Rates, Mortality Rates, and Age-Period-Cohort Effects of Female Breast Cancer - China, 2003-2017.

Introduction: This study reported the trends in female breast cancer incidence and mortality rates in China, and analyzed the corresponding age-period-cohort effects. Methods: Data from 22 population-based cancer registries in China between 2003 and 2017 were analyzed. Age-standardized incidence rates (ASIR) and mortality rates (ASMR) were calculated using Segi's world standard population. Joinpoint regression was employed to evaluate trends, and age-period-cohort effects were examined using the intrinsic estimator method. Results: The ASIR for female breast cancer exhibited a more rapid increase in rural areas compared to urban areas across all age groups. The most substantial increase was observed in the 20-34 age group in rural areas [annual percent change (APC)=9.0%, 95% confidence interval (CI): 7.0%-11.0%, P<0.001]. The ASMR for females under 50 years old remained stable from 2003 to 2017 in both urban and rural areas. However, the ASMR for females over 50 in rural areas and those over 65 in urban areas demonstrated a significant increase, with the most pronounced increase observed among females over 65 in rural areas (APC=4.9%, 95% CI: 2.8%-7.0%, P<0.001). Age-period-cohort analysis revealed increasing period effects and decreasing cohort effects for female breast cancer incidence and mortality rates in both urban and rural settings. Notably, the cohort effect for incidence displayed a slight upward trend for females born between 1983 and 1992 in rural areas. Conclusions: Our study revealed a rapid increase in breast cancer incidence among younger generations and an accelerated mortality rate in older populations residing in rural areas. To effectively address the growing burden of female breast cancer in China, it is essential to develop and implement targeted intervention strategies.

Incidence and survival of neuroendocrine neoplasms in China with comparison to the United States.

BACKGROUND: Neuroendocrine neoplasms (NENs) are rare tumors characterized by variable biology and delayed diagnosis. However, the nationwide epidemiology of NENs has never been reported in China. We aimed to estimate the incidence and survival statistics of NENs in China, in comparison to those in the United States during the same period. METHODS: Based on the data from 246 population-based cancer registries covering 272.5 million people of China, we calculated age-specific incidence on NENs in 2017 and multiplied by corresponding national population to estimate the nationwide incidence in China. The data of 22 population-based cancer registries were used to estimate the trends of NENs incidence from 2000 to 2017 through the Joinpoint regression model. We used the cohort approach to analyze the 5-year age-standardized relative survival by sex, age group, and urban-rural area between 2008 and 2013, based on data from 176 high-quality cancer registries. We used data from the Surveillance, Epidemiology, and End Results (SEER) 18 program to estimate the comparable incidence and survival of NENs in the United States. RESULTS: The overall age-standardized rate (ASR) of NENs incidence was lower in China (1.14 per 100,000) than in the United States (6.26 per 100,000). The most common primary sites were lungs, pancreas, stomach, and rectum in China. The ASRs of NENs incidence increased by 9.8% and 3.6% per year in China and the United States, respectively. The overall 5-year relative survival in China (36.2%) was lower than in the United States (63.9%). The 5-year relative survival was higher for female patients than male patients, and was higher in urban areas than in rural areas. CONCLUSIONS: The disparities in burden of NENs persist across sex, area, age group, and site in China and the United States. These findings may provide a scientific basis on prevention and control of NENs in the two countries.

Hepatocellular carcinoma and intrahepatic cholangiocarcinoma incidence between 2006 and 2015 in China: estimates based on data from 188 population-based cancer registries.

Background: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common subtypes of primary liver cancer, but nationwide incidence of both liver cancer subtypes have never been reported in China. We aimed to estimate the most recent incidence of HCC and ICC and temporal trends in China based on the most updated data from high qualified population-based cancer registries (covering 13.1% of the national population), in comparison to those in the United States at the same period. Methods: We used data from 188 Chinese population-based cancer registries covering 180.6 million population of China to estimate the nationwide incidence of HCC and ICC in 2015. And 22 population-based cancer registries' data were used to estimate the trends of HCC and ICC incidence from 2006 to 2015. Multiple imputation by chained equations method was used to impute liver cancer cases with unknown subtype (50.8%). We used data from 18 population-based registries from the Surveillance, Epidemiology, and End Results program to analyze incidence of HCC and ICC in the United States. Results: In China, an estimated 301,500 and 61,900 newly diagnosed HCC and ICC occurred in 2015. The overall age-standardized rates (ASRs) of HCC incidence decreased by 3.9% per year. For ICC incidence, the overall ASR was relatively stable, but increased in the population of over 65 years old. Subgroup analysis by age showed that the ASR of HCC incidence had the sharpest decline in population who were less than 14 years old and received neonatally hepatitis B virus (HBV) vaccination. In the United States, though the incidence of HCC and ICC were lower than those in China, the overall HCC and ICC incidence increased by 3.3% and 9.2% per year. Conclusions: China still faces with a heavy burden of liver cancer incidence. Our results may further support the beneficial effect of Hepatitis B vaccination on reduction of HCC incidence. Both healthy lifestyle promotion and infection control are needed for future liver cancer control and prevention for China and the United States.

Clinical characteristics and changing trajectories of esophageal cancer and gastric cancer in China from 2010 to 2019: An analysis of a hospital-based database of 24,327 patients.

Purpose: This analysis aimed to investigate the clinical characteristics and changing trajectories of gastric cancer (GC) and esophageal cancer (EC). Methods: We collected data from a large cancer hospital in Beijing, China, from 2010 to 2019. Joinpoint regression was used to analyze the trends of histological characteristics and comorbidities. Results: From 2010 to 2019, there were a total of 10,083 EC patients and 14,244 GC patients. Patients were mainly men and diagnosed at 55-64 years old. Metabolic comorbidity was the most common comorbidity, with hypertension being predominant. The percentages of stage I showed significant increases for EC [average annual percent change (AAPC): 10.5%] and GC (AAPC: 9.7%) patients. We also observed an increasing trend of EC and GC patients over 65 years old. For EC patients, esophageal squamous cell carcinoma (93.1%) remained as the prioritized subtype, and the middle third of the esophagus was the most common site. EC patients with three or more comorbidities increased from 0.1% to 2.2% (AAPC, 27.7%; 95% CI, 14.7% to 42.2%). For GC patients, adenocarcinoma accounts for 86.9% of the total cases, and cardia was the most common site. The ulcerative comorbidity rate decreased from 2.0% to 1.2% (AAPC, -6.1%; 95% CI, -11.6% to -0.3%). Conclusion: ESCC remained as the prioritized histological subtype, and the middle third of the esophagus was the most common site of EC. The majority of GC patients had adenocarcinoma, and the cardia was the most common site. There was an increasing trend of patients diagnosed at stage I. These findings provide scientific evidence to guide future treatment.

Astrocytic Cebpd Regulates Pentraxin 3 Expression to Promote Fibrotic Scar Formation After Spinal Cord Injury.

Astroglial-fibrotic scars resulted from spinal cord injury affect motor and sensory function, leading to paralysis. In particular, the fibrotic scar is a main barrier that disrupts neuronal regeneration after spinal cord injury. However, the association between astrocytes and fibrotic scar formation is not yet understood. We have previously demonstrated that the transcriptional factor Cebpd contributes to astrogliosis, which promotes glial scar formation after spinal cord injury. Herein, we show that fibrotic scar formation was decreased in the epicenter region in Cebpd-/- mice after contusive spinal cord injury and astrocytic Cebpd promoted fibroblast migration through secretion of Ptx3. Furthermore, the expression of Mmp3 was increased under recombinant protein Ptx3 treatment in fibroblasts by observing microarray data, resulting in fibroblast migration. In addition, regulation of Mmp3 occurs through the NFκB signaling pathway by using an irreversible inhibitor of IκBα phosphorylation in pretreated fibroblasts. Of note, we used the synthetic peptide RI37, which blocks fibroblast migration and decreases fibroblast Mmp3 expression in IL-1ß-treated astrocyte conditioned media. Collectively, our data suggest that fibroblast migration can be affected by astrocytic Cebpd through the Ptx3/NFκB/Mmp3 axis pathway and that the RI37 peptide may act as a therapeutic medicine to inhibit fibrotic scar formation after spinal cord injury.