Fatal, non-fatal burden of cancer in the elderly in China, 2005-2016: a nationwide registry-based study.

BACKGROUND: As populations age, cancer burden becomes increasingly conspicuous. This study quantified the cancer burden of the elderly (≥ 60 years) in China, based on the China Cancer Registry Annual Report to provide epidemiological evidence for cancer prevention and control. METHODS: Data on cancer cases and deaths among the elderly aged ≥ 60 years were collected from the China Cancer Registry Annual Report, 2008-2019. Potential years of life lost (PYLL) and disability-adjusted life years (DALY) were calculated to analyze fatalities and the non-fatal burden. The time trend was analyzed using the Joinpoint model. RESULTS: From 2005 to 2016, the PYLL rate of cancer in the elderly was stable between 45.34‰ and 47.62‰, but the DALY rate for cancer decreased at an average annual rate of 1.18% (95% CI: 0.84-1.52%). The non-fatal cancer burden in the rural elderly was higher than that of the urban elderly. Lung, gastric, liver, esophageal, and colorectal cancers were the main cancers causing the cancer burden in the elderly, and accounted for 74.3% of DALYs. The DALY rate of lung cancer in females in the 60-64 age group increased (annual percentage change [APC] = 1.14%, 95% CI: 0.10-1.82%). Female breast cancer was one of the top five cancers in the 60-64 age group, with DALY rates that also increased (APC = 2.17%, 95% CI: 1.35-3.01%). With increasing age, the burden of liver cancer decreased, while that of colorectal cancer rose. CONCLUSIONS: From 2005 to 2016, the cancer burden in the elderly in China decreased, mainly reflected in the non-fatal burden. Female breast and liver cancer were a more serious burden in the younger elderly, while colorectal cancer burden was mainly observed in the older elderly.

Burden of cardiovascular disease attributable to dietary lead exposure in adolescents and adults in China.

Lead is a naturally occurring metal with a range of industrial applications; however, it can cause adverse health effects upon human exposure. Even if blood lead levels (BLLs) in the human body are in the acceptable range, it is independently associated with cardiovascular disease (CVD), which is the leading cause of death in China. However, the role of lead exposure in CVD outcomes has not been quantified well. A top-down approach was adopted in this study to calculate the population attribution fraction (PAF) by combining pooled BLLs in the Chinese population reported between 2001 and 2022 with the relative risk (RR) of lead-induced CVD. Subsequently, the disease burden (DB) of lead-induced CVD was estimated and expressed in disability-adjusted life years (DALYs), and the attribution analysis about various sources of lead exposure was performed. Among Chinese adolescents and adults, BLLs of 5.50 ±â€¯2.45 µg/dL resulted in an estimated total DB (×106 DALYs) of 2.21 (2.07-2.32) for CVD, including 1.18 (1.12-1.25), 0.71 (0.69-0.74), 0.23 (0.15-0.26), and 0.02 (0.02-0.02) for stroke, and ischemic, hypertensive, and rheumatic heart diseases, respectively. Dietary lead intake was a major contributor to the DB (68.1%), and lead ingested through food was responsible for 15.1 × 105 DALYs of the CVD burden. Guangxi, Hunan, and Yunnan regions in China reported higher BLLs in adolescents and adults, and the DB of lead-induced CVD was higher in Hunan, Henan, and Sichuan. Lead is a risk factor for CVD that can cause significant DB. Further practical and cost-effective efforts to reduce lead exposure are urgently needed.

CSN6 aggravates Ang II-induced cardiomyocyte hypertrophy via inhibiting SIRT2.

The constitutive photomorphogenic 9 (COP9) signalosome complex subunit 6 (COPS6/CSN6) is crucial for structural integrity of the COP9 signalosome complex. CSN6 participates in various aspects of cancer progression, but its role in hypertrophic cardiomyopathy is not clear. Here, we found that the expression of CSN6 was increased in Angiotensin II (Ang II)-induced hypertrophic mice hearts and neonatal rat cardiomyocytes (NRCMs). Inhibition of CSN6 decreased the cardiomyocyte size and fetal genes' expression in Ang II-induced hypertrophic NRCMs, while overexpression of CSN6 aggravated Ang II-induced myocardial hypertrophy. Moreover, we demonstrated that the pro-hypertrophic function of CSN6 was mediated by SIRT2, which acts as a cardioprotective factor in pathological cardiac hypertrophy. CSN6 inhibited the expression of SIRT2, and re-expression of SIRT2 attenuated the myocardial hypertrophy caused by CSN6 overexpression. Further investigation discovered that CSN6 suppressed the expression of SIRT2 via up-regulating Nkx2.2, a transcription suppressor of SIRT2. Mechanistically, CSN6 blocked the ubiquitin proteasome system-mediated degradation of Nkx2.2 protein by interacting with it and inhibiting its ubiquitination directly in cardiomyocytes. Finally, our data showed that CSN6 was partially dependent on the stabilization of Nkx2.2 protein to inhibit SIRT2 and promote myocardial hypertrophy. Overall, our study identified CSN6 as a pro-hypertrophic deubiquitinase, and CSN6 inhibition may be a potential treatment strategy for heart failure.

Association of total bilirubin and indirect bilirubin content with metabolic syndrome among Kazakhs in Xinjiang.

BACKGROUND: Some studies have shown that a high level of bilirubin is a protective factor against metabolic syndrome (MS), while a high level of transaminase is a risk factor for MS. However, the existing results are inconsistent and few cohort studies have been published. METHODS: Using an ambispective cohort study, 565 Kazakhs from Xinjiang, China were selected as the study subjects. The baseline serum bilirubin and transaminase levels of the subjects were divided into quartiles and the relationship between these values and the incidence of MS was analyzed. The definition of MS was based on the Joint Interim Statement (JIS) diagnostic criteria. RESULTS: The average follow-up time for the subjects was 5.72 years. The cumulative incidence of MS was 36.11% (204 of the 565 subjects), and the incidence density was 63.10/1000 person-years. Multivariate Cox regression analysis showed that the levels of total bilirubin (TBIL) and indirect bilirubin (IBIL) were negatively correlated with the occurrence of MS, Compared to the lowest quartile level (Q1), the hazard ratios of MS the TBIL levels at the Q2-Q4 quartiles were: 0.47 (0.31-0.71), 0.53 (0.35-0.79), and 0.48 (0.32-0.72), respectively, while IBIL levels at the Q2-Q4 quartiles showed an MS hazard ratio of 0.48 (0.32-0.72), 0.54(0.36-0.81), and 0.52 (0.35-0.77), respectively, all at a 95% confidence level. However, no relationship was found between transaminase levels and the incidence of MS. CONCLUSION: Serum TBIL and IBIL levels were negatively correlated with the incidence of MS in a Kazakh population in China.

Use of Blood Lipid Indicators as a Screening Tool of Insulin Resistance among Individuals in Low-Income Country Sides of China: A Multiethnic Region Study.

OBJECTIVE: This study is aimed at evaluating the diagnostic value of blood lipid indicators (BLIs) for insulin resistance (IR) among major ethnic groups in Xinjiang, China, to identify the most valuable indicators and appropriate cut-off points for each ethnic group and to lay the foundation for the early detection, diagnosis, and treatment of metabolic diseases in remote rural areas. METHODS: Overall, 418 Uygurs, 331 Kazakhs, and 220 Hans were randomly included in our study. The homeostasis model assessment was the gold standard for identifying IR. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value, and the nomogram was utilized to analyze the predictive value. The size of the area under the curve (AUC) reflected the accuracy of screening and prediction. RESULTS: Differences in races were observed in terms of IR and BLIs, and the Kazakhs had the highest IR level at 5.27 mmol/L. The correlation between IR and BLIs differed among the three races. For the Kazakhs and Hans, all BLIs, except total cholesterol (TC), were correlated to IR. However, for the Uygurs, only the triglyceride (TG) level, TG/high-density lipoprotein cholesterol (HDL-C) ratio, and TC/HDL-C ratio were associated with IR. After further adjustment of confounding factors, these indicators were still correlated to IR. BLIs that independently correlated to IR in the three nationalities had a certain diagnostic value for IR. In terms of the AUC size, the TG level was the highest in Uygurs, the TG/HDL-C ratio was the highest for Kazakhs and Hans, and the corresponding best cut-off points for IR were 1.515, 1.230, and 1.495 mmol/L, respectively. In addition, for each race, when the indicators with a certain diagnostic value were combined, the diagnostic value for IR was higher. CONCLUSION: BLIs had a certain diagnostic value for IR and could be used as a screening tool for IR among Uygurs, Kazakhs, and Hans in Xinjiang. These findings are extremely important for the prevention and treatment of IR and metabolic diseases in remote rural areas.

Effects of Proanthocyanidins on Arsenic Methylation Metabolism and Efflux in Human Hepatocytes L-02.

This study investigated the effects of proanthocyanidins (PC) on arsenic methylation metabolism and efflux in human hepatocytes (L-02), as well as the relationships between PC and GSH, MRP1 and other molecules. Cells were randomly divided into blank control group, arsenic trioxide exposure group (ATO, As2O3, 25µmol/L), and PC-treated arsenic exposure group (10, 25, 50mg/L). After 24/48h, the contents of different forms of arsenic were determined, and the methylation indexes were calculated. Intracellular S-adenosyl methionine (SAM), arsenic (+3 oxidation state) methyltransferase (AS3MT), multidrug resistance-associated protein 1 (MRP1), and reduced glutathione (GSH) were ascertained. Changing trends were observed and the correlation between arsenic metabolism and efflux related factors and arsenic metabolites was analyzed. We observed that cells showed increased levels of content/constituent ratio of methyl arsenic, primary/secondary methylation index, methylation growth efficiency/rate, and the difference of methyl arsenic content in cells and culture medium (P<0.05, resp.). Compared with ATO exposure group, the intracellular SAM content in PC-treated group decreased, and the contents of GSH, AS3MT, and MRP1 increased (P<0.05, resp.). There was a positive correlation between the content of intracellular GSH/AS3MT and methyl arsenic. The content of MRP1 was positively correlated with the difference of methyl arsenic content in cell and culture medium; conversely, the SAM content was negatively correlated with intracellular methyl arsenic content (P<0.05, resp.). Taken together, these results prove that PC can promote arsenic methylation metabolism and efflux in L-02 cells, which may be related to the upregulation of GSH, MRP1, and AS3MT levels by PC.

[Trend in the prevalence of prostate cancer in Shihezi, Xinjiang from 2009 to 2017].

OBJECTIVE: To analyze the trend in the prevalence and mortality of prostate cancer in Shihezi, Xinjiang from 2009 to 2017 and provide some evidence for the prevention and control of the malignance. METHODS: We collected the data on the cancer registries in the Shihezi area between 2009 and 2017, calculated the incidence and mortality rates of prostate cancer, and analyzed the annual percent change (APC) and prevalence trend of the disease. RESULTS: The crude incidence rate, age-standardized incidence rate by Chinese standard population (ASIRC), age-standardized incidence rate by world standard population (ASIRW) and cumulative incidence rate of prostate cancer (in 0－74-year-olds) in Shihezi between 2009 and 2017 were 16.94, 10.33, 8.98 and 2.29 per 100 000, respectively. The crude mortality rate, age-standardized mortality rate by Chinese standard population (ASMRC), age-standardized mortality rate by world standard population (ASMRW) and cumulative incidence rate (in 0－74-year-olds) were 9.03, 5.39 and 4.72 and 0.49 per 100 000, respectively. Both the incidence and mortality rates showed an increasing trend from 2009 to 2017, with an APC of 16.69% (P < 0.05) and 19.71% (P < 0.05), respectively. From 2011 to 2017, the increase rates of incidence and mortality of prostate cancer in the >60-year-olds were 86.20% and 89.30%, with the peak values shifted from the 70－74 to the 80－84 years old males. CONCLUSIONS: The incidence and mortality of prostate cancer in Shihezi showed an increasing trend from 2009 to 2017, chiefly in the males aged over 60 years, with the peak value moving towards an older age.

The Bidirectional Effects of Arsenic on miRNA-21: A Systematic Review and Meta-analysis.

OBJECTIVE: Arsenic is a metalloid environmental carcinogen involved in the occurrence and development of many cancers. miRNA-21 plays a crucial role in arsenic-induced carcinogenesis. We aimed to elucidate the mechanism by which miRNA-21 influences arsenic-induced cancer. METHODS: We used meta-analysis of published studies to determine how arsenic induces cancerous cells through miRNA-21. RESULTS: Low-dose arsenic exposure (⪕ 5 µmol/L) can increase miRNA-21 and phosphorylated signal transducter and activator of transcription 3 (pSTAT3) expression, and decrease programmed cell death protein 4 (PDCD4) and protein sprouty homolog 1 (Spry1) expression. High-dose arsenic exposure (> 5 µmol/L), can increase miRNA-21 expression, and decrease Spry1 and E-cadherin expression. Short-term arsenic exposure (⪕ 24 h) can increase miRNA-21 and pSTAT3 expression, and decrease PDCD4 expression. Moreover, long-term arsenic exposure (> 24 h) can increase the miRNA-21, STAT3, and pSTAT3 expression, and decrease PDCD4 expression. We found that activation of miRNA-21 and pSTAT3 were most pronounced following long-term arsenic exposure at low doses, and the effects on PDCD4 expression were most pronounced following short-term arsenic exposure at low doses. miRNA-21 inhibitors increased the expression of tumor suppressor genes PDCD4, PTEN, and Spry1 and miRNA-21-mimics suppressed the expression of these tumor suppressor genes. CONCLUSION: Arsenic can cause cancer by activating miRNA-21 and inhibiting the expression of PDCD4, PTEN, and Spry1.

Delivery of biotinylated IGF-1 with biotinylated self-assembling peptides combined with bone marrow stem cell transplantation promotes cell therapy for myocardial infarction.

Cell therapy is a promising approach for cardiac repair. The aim of the present study was to determine the feasibility of using biotinylated insulin-like growth factor 1 (IGF-1) with biotinylated self-assembling peptides (tethered IGF-1) combined with bone marrow stem cells (BMSCs) transplantation for the treatment of heart failure. Tethered IGF-1 was synthesized and its effect on H9c2 cells was analyzed. Reverse transcription-quantitative polymerase chain reaction and western blot assays demonstrated that tethered IGF-1 did not significantly affect the expression and phosphorylation of AKT, whereas it significantly increased the expression of cardiac troponin T (P<0.01). A rabbit myocardial infarction model was constructed and rabbits were divided into four groups: Control group (no treatment), group 1 (G1; BMSC transplantation), group 2 (G2; BMSCs + non-biotinylated IGF-1) and group 3 (G3; BMSCs + tethered IGF-1). At 4 weeks after modeling, cardiac tissues were obtained for analysis. In the control group, myocardial fibers were disordered, a large number of inflammatory cells infiltrated the cardiac tissues, and apoptosis occurred in ~50% of cells. However, in G1, G2 and G3, muscle cells were well ordered, and a lesser degree of myocardial degeneration and inflammatory cell infiltration was observed. Compared with the control group, the apoptosis rates of myocardial cells in G1-G3 were significantly decreased (P<0.01). Furthermore, compared with G1 and G2, tissue morphology was improved in G3and the number of apoptotic myocardial cells was significantly decreased (P<0.01). These results suggest that treatment with tethered IGF-1 + BMSCs significantly suppresses cell apoptosis and induces the expression of cardiac maturation proteins. These findings provide a novel insight into how the delivery of tethered IGF-1 with BMSCs could potentially enhance the prognosis of patients with heart failure treatment.

[Analysis of clinical features of pregnant women with hypertrophic cardiomyopathy].

OBJECTIVE: To discuss the clinical features of pregnant women with hypertrophic cardiomyopathy (HCM). METHODS: There were 28 patients with HCM who delivered in Renji hospital of Shanghai Jiaotong University from January 2000 to August 2012. Clinical data were analyzed, including diagnosis, cardiac functional grading, gestational weeks of delivery, delivery mode, birth weight, Apgar scores, etc. RESULTS: (1) Of all the 28 patients, 14 (50%) were diagnosed before pregnancy and others (50%) were diagnosed during pregnancy.(2) Four cases were obstructive HCM (14%), 3 with cardiac function grade I and 1 with grade II. Twenty four cases were non-obstructive HCM (86%), 14 with cardiac function grade I, 9 with grade II and 1 with grade IV. (3) Of all the 28 patients, 4 had family history, 18 (64%) had clinical symptoms or signs which occurred in 8-32 gestational weeks. Twenty-three cases had abnormal ECG (82%). Among them 21 had non-obstructive HCM (88%), with average interventricular septal thickness of (22 ± 3) mm. The other 2 patients had obstructive HCM, with average interventricular septal thickness of (23 ± 4) mm.7 patients (7/28, 25%) had mild-to-moderate pulmonary hypertension [6 with non-obstructive HCM (6/24, 25%) ], and 10 patients had abnormal myocardial enzyme spectrum or troponin levels [9 with non-obstructive HCM (9/24, 38%) ].(4) Among all the patients, only one had vaginal delivery and others received cesarean section. Twenty-two patients had term pregnancies and 6 had preterm birth. The average gestational weeks of delivery in non-obstructive HCM and obstructive HCM were (36.5 ± 2.5) and (38.5 ± 0.4) weeks, respectively. The average birth weight of neonates were (2684 ± 563) and (3164 ± 321) g, and Apgar scores were 9.9 and 10 (10 minutes) respectively. Patients transferred to NICU after delivery were 8 and 0. There was 1 maternal death (with non-obstructive HCM whose ejection fraction was only 26%) and no perinatal death. CONCLUSIONS: More attention should be paid to the clinical signs and abnormal ECG.HCM could be definitely diagnosed by timely echocardiography. Patients with hypertrophic cardiomyopathy were mainly non-obstructive HCM, with cardiac function grade I and II. Monitoring the change of ejection fraction during pregnancy would help. Perinatal outcomes were fine.