What is already known about this topic?:Limited evidence on healthy longevity was provided in the world, and no studies investigated the fractions of healthy longevity attributed to modifiable factors.What is added by this report?:Incidences of longevity and healthy longevity in China are provided. It reveals that the total weighted population attributable fractions for lifestyles and all modifiable factors were 32.8% and 83.7% for longevity, respectively, and 30.4% and 73.4% for healthy longevity, respectively.What are the implications for public health practice?:China has a high potential for longevity and healthy longevity. Strategies may be targeted at education and residence in early life as well as healthy lifestyles, disease prevention, and functional optimization in late life.

Objectives: Previous studies investigated factors associated with mortality. Nevertheless, evidence is limited regarding the determinants of lifespan. We aimed to develop and validate a lifespan prediction model based on the most important predictors. Design: A prospective cohort study.Setting and Participants: A total of 23,892 community-living adults aged 65 years or older with confirmed death records between 1998 and 2018 from 23 provinces in China.Methods: Information including demographic characteristics, lifestyle, functional health, and prevalence of diseases was collected. The risk prediction model was generated using multivariate linear regression, incorporating the most important predictors identified by the Lasso selection method. We used 1000 bootstrap resampling for the internal validation. The model performance was assessed by adjusted R2, root mean square error (RMSE), mean absolute error (MAE), and intraclass correlation coefficient (ICC).Results: Twenty-one predictors were included in the final lifespan prediction model. Older adults with longer lifespans were characterized by older age at baseline, female, minority race, living in rural areas, married, with healthier lifestyles and more leisure engagement, better functional status, and absence of diseases. The predicted lifespans were highly consistent with observed lifespans, with an adjusted R2 of 0.893. RMSE was 2.86 (95% CI 2.84-2.88) and MAE was 2.18 (95% CI 2.16-2.20) years. The ICC between observed and predicted lifespans was 0.971 (95% CI 0.971-0.971).Conclusions and Implications: The lifespan prediction model was validated with good performance, the web-based prediction tool can be easily applied in practical use as it relies on all easily accessible variables.& COPY; 2023 AMDA -The Society for Post-Acute and Long-Term Care Medicine.

PM2.5 can cause airway inflammation and promote the excessive secretion of mucin 5ac (Muc5ac), which can further induce many respiratory diseases. Antisense non-coding RNA in the INK4 locus (ANRIL) might regulate the inflammatory responses mediated by nuclear factor kappa-B (NF-κB) signaling pathway. Beas-2B cells were used to clarify the role of ANRIL in the secretion of Muc5ac induced by PM2.5 . The siRNA was used to silence ANRIL expression. Normal and gene silenced Beas-2B cells were respectively exposed to different doses of PM2.5 for 6, 12, and 24 h. The survival rate of Beas-2B cells was detected by methyl thiazolyl tetrazolium (MTT) assay. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and Muc5ac levels were determined by enzyme linked immunosorbent assay (ELISA). The expression levels of NF-κB family genes and ANRIL were detected by real time polymerase chain reaction (PCR). The levels of NF-κB family proteins and NF-κB family phosphorylated proteins were determined using Western blot. Immunofluorescence experiments were performed to observe the nuclear transposition of RelA. PM2.5 exposure increased the levels of Muc5ac, IL-1β and TNF-α, and ANRIL gene expression (p < .05). With the dose and time of PM2.5 exposure increasing, the protein levels of inhibitory subunit of nuclear factor kappa-B alpha (IκB-α), RelA, and NF-κB1 decreased, the protein levels of phosphorylated RelA (p-RelA) and phosphorylated NF-κB1 (p-NF-κB1) increased, and RelA nuclear translocation increased, which indicated that the NF-κB signaling pathway was activated (p < .05). Silencing ANRIL could decrease the levels of Muc5ac, IL-1β, TNF-α, decrease NF-κB family genes expression, inhibit the degradation of IκB-α and the activation of NF-κB pathway (p < .05). ANRIL played a regulatory role in the secretion of Muc5ac and the inflammation induced by atmospheric PM2.5 via NF-κB pathway in Beas-2B cells. ANRIL could be a target for prevention and treatment of the respiratory diseases caused by PM2.5 .

Introduction: About half of adults aged ≥80 years suffer from frailty. Exercise is considered effective in preventing frailty but may be inapplicable to adults aged ≥80 years due to physical limitations. As an alternative, we aimed to explore the association of leisure activities with frailty and identify potential interaction with established polygenic risk score (PRS) among adults aged ≥80 years. Methods: Analyses were performed in a prospective cohort study of 7,471 community-living older adults aged ≥80 years who were recruited between 2002 and 2014 from 23 provinces in China. Leisure activity was assessed using a seven-question leisure activity index and frailty was defined as a frailty index ≥0.25 using a validated 39-item health-related scale. The PRS was constructed using 59 single-nucleotide polymorphisms associated with frailty in a subsample of 2,541 older adults. Cox proportional hazards models were used to explore the associations of leisure activities, PRS with frailty. Results: The mean age of participants was 89.4 ± 6.6 years (range: 80–116). In total, 2,930 cases of frailty were identified during 42,216 person-years of follow-up. Each 1 unit increase in the leisure activity index was associated with 12% lower risk of frailty (hazard ratio: 0.88 [95% confidence interval, 0.85–0.91]). Participants with high genetic risk (PRS >2.47 × 10−4) suffered from 26% higher risk of frailty. Interaction between leisure activity and genetic risk was not observed. Conclusion: Evidence is presented for the independent association of leisure activities and genetic risk with frailty. Engagement in leisure activities is suggested to be associated with lower risk of frailty across all levels of genetic risk among adults aged ≥80 years.

Di-(2-ethylhexyl) phthalate (DEHP) and mono-2-ethylhexyl phthalate (MEHP) can induce hepatic lipid metabolism disorders, while the molecular mechanism still remain unknown. We aim to explore the underlying mechanism of Notch signaling pathway on hepatic lipid accumulation induced by DEHP/MEHP. A total of 40 male wistar rats were exposed to DEHP (0, 5, 50, and 500 mg/kg/d) for 8 weeks, BRL-3A hepatocytes were exposed to MEHP (0, 10, 50, 100, and 200 μM) for 24 h. About 50 μM DAPT and 100 μg/mL Aspirin were used to inhibit Notch pathway and prevent inflammation, respectively. Real-Time PCR was performed to detect the mRNA expression, western blot and immunofluorescence were used to detect the protein expression. Lipids and inflammatory factors levels were determined by commercial kits. The results showed that DEHP/MEHP promoted the expression of Notch pathway molecules and lipids accumulation in rat livers/BRL-3A cells. The up-regulated Notch receptors were correlated with the TG levels in the rat liver. MEHP increased the levels of IL-8 and IL-1β. The lipids levels were reduced after anti-inflammation. The inhibition of Notch pathway reversed the elevation of inflammation and lipid accumulation caused by MEHP. In conclusion, this study demonstrated that DEHP/MEHP led to lipid accumulation in hepatocytes by up-regulating Notch pathway and the inflammation might play a key role in the process.

Di(2-ethylhexyl) phthalate (DEHP) could induce thyroid injury but the mechanism was unclear. This study combined in vivo and in vitro experiments to clarify the mechanism. In vivo, the offspring of Sprague Dawley rats were gavaged with different doses of DEHP (5, 50, and 250 mg/[kg⋅d]) from in utero to 12 weeks-old. Transcriptome sequencing was used to detect the mRNA expression profile of the offspring's thyroids. Differentially expressed genes were identified, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. In vitro, Nthy-ori 3-1 cells were exposed to DEHP's metabolite mono (2-ethylhexyl) phthalate (MEHP) to verify the pathway we found by KEGG analysis. The results indicated that DEHP could disorder the thyroid hormones. Compared with the offspring in control group, the mRNA levels of 656 genes were upregulated in the offspring exposed to 50 mg/(kg⋅d) DEHP. The upregulated genes were enriched in the pathway of "protein processing in the endoplasmic reticulum (ER)." It indicated that the ER stress might play significant role in the thyroid toxicity induced by DEHP. In vitro, the mitochondrial membrane potential (ΔΨm) level of cells was decreased while the reactive oxygen species level was increased after MEHP exposure. MEHP increased the intracellular Ca2+ level and induced ER stress. After ER stress was inhibited by the 4-phenylbutyric acid, the thyroid toxicity caused by MEHP was alleviated. Taken together, our results indicated that DEHP could induce thyroid toxicity by activating ER stress.

Neuroblastoma（NB） is the most common extracranial solid tumor of childhood. It accounts for 8%–10% of all malignant tumors in children[1] and results in a heavy burden to the life and health of children. NB is a complex disease, and its occurrence is related to exposure to environmental risk factors.

Colorectal polyp has been considered as the precancerous lesion of colorectal cancer, to which serum lipid levels are closely related. At present, there is no consensus on the relationship between colorectal polyps and serum lipid levels. We performed a meta-analysis to explore the effects of lipid levels on colorectal polyps. Relevant articles published from 2000 to 2020 were searched in PubMed, Web of Science, EMBASE, and Cochrane Library databases. The mean value and SD of serum lipid indexes and body mass index in colorectal polyps groups and control groups were extracted from the included articles. Combined weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated to assess the effect size of serum lipid levels on colorectal polyps. The publication bias of the included studies were assessed based on the Egger test. Thirty-seven articles containing 19,464 cases and 63,979 controls were included. There were no significant publication bias. The levels of high-density lipoprotein cholesterol in the cases were lower than those in the controls (WMD: −2.589 mg/dL, 95% CI: −3.273, −1.906). While the levels of triglyceride (WMD: 16.933 mg/dL, 95% CI: 13.131, 20.736), total cholesterol (WMD: 5.561 mg/dL, 95% CI: 3.477, 7.645), low-density lipoprotein cholesterol (WMD: 3.109 mg/dL, 95% CI: 0.859, 5.359) and body mass index (WMD: 0.747 mg/dL, 95% CI: 0.588, 0.906) were higher in the cases. Colorectal polyps were associated with serum lipid levels and obesity. Hyperlipidemia and obesity may be the risk factors for colorectal polyps.

Fine particulate matter (PM2.5) exposure can cause the injury of vascular endothelial cells by inflammatory response. CD40 works in inflammation of endothelial cells and it may be regulated by the miRNAs. This study aimed to clarify the role and mechanism of CD40 and miR-145-5p in PM2.5-induced injury of human umbilical vein endothelial cells (HUVECs). HUVECs were treated with different concentrations of PM2.5 exposure (0, 100, 200, 400 μg/mL) for 24 h. The si-RNA was used for CD40 gene silencing (0, 200 μg/mL PM2.5, siRNA-CD40 and siRNA-CD40 + 200 μg/mL PM2.5). Mimics was used for overexpression of miR-145-5p (0, 200 μg/mL PM2.5, mimics and mimics+200 μg/mL PM2.5). The cell viability of HUVECs was detected with Cell Counting Kit8 (CCK8) kit. The level of cell apoptosis was detected by flow cytometry. The inflammation-related factor including interleukin-1β (IL-1β), interleukin-18 (IL-18), tumor necrosis factor α (TNF-α) and C1q complement/tumor necrosis factor (TNF)-associated proteins9 (CTRP9) were tested with enzyme-linked immunosorbent assay (ELISA) kits. The mRNA and protein expression levels of CD40, CD40L, caspase1, NLRP3 (Nod-like receptor family pyrin domain-containing 3) and IKKB were detected with quantitative real-time PCR (qRT-PCR), Western blot and Immunofluorescence. Compared with the control group, the cell viability of HUVECs exposed to PM2.5 was significantly decreased (p < 0.05); the levels of IL-Iβ and TNF-α were significantly increased, while the level of CTRP9 was significantly decreased (p < 0.05). The proportion of apoptotic cells was increased after being treated with PM2.5 (p < 0.05). Besides, the mRNA and protein levels of CD40, CD40L, IKKB, NLRP3 and caspase1 were increased comparing with the control group (p < 0.05). After CD40 silencing, the condition of inflammation and apoptosis in HUVECs exposed to PM2.5 was alleviated, and the expression levels of CD40L, IKKB, NLRP3 and caspase1 were significantly decreased (p < 0.05). Furthermore, miR-145-5p was significantly down-regulated after exposure to 200μg/mL PM2.5 (p < 0.05). After over-expression of miR-145-5p, the expression level of CD40 was decreased (p < 0.05). Taken together, PM2.5 can cause inflammation and apoptosis of HUVECs via the activation of CD40, which can be regulated by miR-145-5p. Over-expression of miR-145-5p can down-regulate CD40, further inhibiting the inflammation and apoptosis of HUVECs induced by PM2.5.

Neuroblastoma (NB) is an estrogen-dependent tumor. Mono-2-ethylhexyl phthalate (MEHP) has an estrogen-like effect. However, the effects of MEHP on the progression of NB are not well illustrated. This study was to clarify the effect of Notch pathway on proliferation and cell cycle of SH-SY5Y cell induced by MEHP. The viability of SH-SY5Y and BE2C cells were detected by CCK8; cell cycle and apoptosis were detected by flow cytometry; the protein expression levels of Notch pathway and cell cycle related proteins were detected by Western-blot. Results show that MEHP exposure can promote cell proliferation and altered the cell cycle. MEHP exposure can up-regulate the expression of C-MYC, Cyclin D1, Bcl-2 and affected the Notch pathway. In conclusion, MEHP exposure can promote NB cell proliferation and affect the cell cycle and apoptosis. Notch pathway plays a critical role in accelerating the cell cycle and inhibiting the apoptosis of SH-SY5Y cells caused by MEHP.