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  • 1
    In: Cancer Biology & Medicine, China Anti-cancer Association, ( 2022-06-15), p. 1-18
    Abstract: Objective: In various cancers, migration and invasion inhibitory protein (MIIP) is expressed at low level and is involved in cancer pathogenesis. Herein, we sought to explore the function of MIIP in clear cell renal cell carcinoma (ccRCC). Methods: CCK-8, colony formation, cell cycle, and endothelial cell tube formation assays were performed to evaluate the roles of MIIP in ccRCC proliferation and angiogenesis. To explore the underlying mechanism, we conducted RNA-sequencing, GSEA, qRT-PCR, Western blot, ELISA, cell transfection, coimmunoprecipitation, and ubiquitination assays in ccRCC cell lines. Furthermore, xenograft tumor growth in nude mice, and Ki-67 and CD31 staining in xenograft tissues were examined. Finally, the association of MIIP expression with clinical pathology and the expression status of HIF-2α and cysteine-rich 61 (CYR61) were further analyzed in human RCC tissues through Western blot and immunohistochemistry. Results: Both in vitro and in vivo functional experiments indicated that forced expression of MIIP inhibited ccRCC proliferation and angiogenesis, whereas silencing MIIP either in normal HK-2 cells or in ccRCC cells had the opposite effect (P 〈 0.05). Mechanistically, CYR61 was identified as a gene significantly downregulated by MIIP overexpression, and was required for the suppressive role of MIIP in ccRCC. MIIP was found to promote HSP90 acetylation and thus impair its chaperone function toward HIF-2α. Consequently, RACK1 binds HIF-2α and causes its ubiquitination and proteasomal degradation, thus decreasing the transcription of its target, CYR61. Finally, analyses of clinical samples demonstrated that MIIP is significantly downregulated in cancer vs. normal tissues in RCC cases, and its expression is negatively associated with histological grade, metastasis, the prognosis of patients with RCC, and the expression of HIF-2α and CYR61 (P 〈 0.05). Conclusions: MIIP is a novel tumor suppressor in ccRCC via negative regulation of HIF-2α-CYR61 axis.
    Type of Medium: Online Resource
    ISSN: 2095-3941
    Language: Unknown
    Publisher: China Anti-cancer Association
    Publication Date: 2022
    detail.hit.zdb_id: 2676322-9
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  • 2
    In: BMC Neurology, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2023-09-14)
    Abstract: There is uncertainty about the optimum sleep duration for risk of different subtypes of stroke and ischaemic heart disease. Methods The present analyses involved 409,156 adults in the China Kadoorie Biobank study without a prior history of coronary heart disease or stroke or insomnia symptoms. The mean age of study participants was 52 years and 59% were women. Self-reported sleep duration including daytime napping was recorded using a questionnaire. The adjusted hazard ratios (HRs) for disease outcomes associated with sleep duration were estimated by Cox proportional hazards after adjustment for confounding factors. Results The overall mean (SD) sleep duration was 7.4 (1.4) hours. The associations of sleep duration with CVD types were U-shaped, with individuals reporting 7–8 h of sleep having the lowest risks. Compared with those who typically slept 7–8 h, individuals with very short sleep duration (≤ 5 h) had adjusted HRs of 1.10 (95% CI 1.04–1.16), 1.07 (1.01–1.13), 1.19 (1.06–1.33) and 1.23 (1.10–1.37) for total stroke, ischaemic stroke (IS), Intracerebral haemorrhage (ICH) and major coronary events (MCE), respectively. Likewise, individuals with very long sleep duration (≥ 10 h) had HRs of 1.12 (1.07–1.17), 1.08 (1.03–1.14), 1.23 (1.12–1.35) and 1.22 (1.10–1.34) for the same diseases, respectively, with little differences by sex and age. The patterns were similar for all-cause mortality. Conclusions While abnormal sleep duration (≤ 6 h or ≥ 9 h) was associated with higher risks of CVD, the risks were more extreme for those reporting ≤ 5 or ≥ 10 h, respectively and such individuals should be prioritised for more intensive treatment for CVD prevention.
    Type of Medium: Online Resource
    ISSN: 1471-2377
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2041347-6
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  • 3
    In: Breast Cancer Research, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2021-12)
    Abstract: In contrast to developed countries, breast cancer in China is characterized by a rapidly escalating incidence rate in the past two decades, lower survival rate, and vast geographic variation. However, there is no validated risk prediction model in China to aid early detection yet. Methods A large nationwide prospective cohort, China Kadoorie Biobank (CKB), was used to evaluate relative and attributable risks of invasive breast cancer. A total of 300,824 women free of any prior cancer were recruited during 2004–2008 and followed up to Dec 31, 2016. Cox models were used to identify breast cancer risk factors and build a relative risk model. Absolute risks were calculated by incorporating national age- and residence-specific breast cancer incidence and non-breast cancer mortality rates. We used an independent large prospective cohort, Shanghai Women’s Health Study (SWHS), with 73,203 women to externally validate the calibration and discriminating accuracy. Results During a median of 10.2 years of follow-up in the CKB, 2287 cases were observed. The final model included age, residence area, education, BMI, height, family history of overall cancer, parity, and age at menarche. The model was well-calibrated in both the CKB and the SWHS, yielding expected/observed ( E/O ) ratios of 1.01 (95% confidence interval (CI), 0.94–1.09) and 0.94 (95% CI, 0.89–0.99), respectively. After eliminating the effect of age and residence, the model maintained moderate but comparable discriminating accuracy compared with those of some previous externally validated models. The adjusted areas under the receiver operating curve (AUC) were 0.634 (95% CI, 0.608–0.661) and 0.585 (95% CI, 0.564–0.605) in the CKB and the SWHS, respectively. Conclusions Based only on non-laboratory predictors, our model has a good calibration and moderate discriminating capacity. The model may serve as a useful tool to raise individuals’ awareness and aid risk-stratified screening and prevention strategies.
    Type of Medium: Online Resource
    ISSN: 1465-542X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2041618-0
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  • 4
    In: BMC Medicine, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2022-12)
    Abstract: Previous studies of primarily Western populations have reported contrasting associations of dairy consumption with certain cancers, including a positive association with prostate cancer and inverse associations with colorectal and premenopausal breast cancers. However, there are limited data from China where cancer rates and levels of dairy consumption differ importantly from those in Western populations. Methods The prospective China Kadoorie Biobank study recruited ~0.5 million adults from ten diverse (five urban, five rural) areas across China during 2004–2008. Consumption frequency of major food groups, including dairy products, was collected at baseline and subsequent resurveys, using a validated interviewer-administered laptop-based food frequency questionnaire. To quantify the linear association of dairy intake and cancer risk and to account for regression dilution bias, the mean usual consumption amount for each baseline group was estimated via combining the consumption level at both baseline and the second resurvey. During a mean follow-up of 10.8 ( SD 2.0) years, 29,277 incident cancer cases were recorded among the 510,146 participants who were free of cancer at baseline. Cox regression analyses for incident cancers associated with usual dairy intake were stratified by age-at-risk, sex and region and adjusted for cancer family history, education, income, alcohol intake, smoking, physical activity, soy and fresh fruit intake, and body mass index. Results Overall, 20.4% of participants reported consuming dairy products (mainly milk) regularly (i.e. ≥1 day/week), with the estimated mean consumption of 80.8 g/day among regular consumers and of 37.9 g/day among all participants. There were significant positive associations of dairy consumption with risks of total and certain site-specific cancers, with adjusted HRs per 50 g/day usual consumption being 1.07 (95% CI 1.04–1.10), 1.12 (1.02–1.22), 1.19 (1.01–1.41) and 1.17 (1.07–1.29) for total cancer, liver cancer ( n = 3191), female breast cancer ( n = 2582) and lymphoma ( n =915), respectively. However, the association with lymphoma was not statistically significant after correcting for multiple testing. No significant associations were observed for colorectal cancer ( n = 3350, 1.08 [1.00–1.17]) or other site-specific cancers. Conclusion Among Chinese adults who had relatively lower dairy consumption than Western populations, higher dairy intake was associated with higher risks of liver cancer, female breast cancer and, possibly, lymphoma.
    Type of Medium: Online Resource
    ISSN: 1741-7015
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2131669-7
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  • 5
    In: International Journal of Epidemiology, Oxford University Press (OUP), Vol. 51, No. 2 ( 2022-05-09), p. 567-578
    Abstract: The relative importance of healthy lifestyle factors and cardiovascular health metrics for the risk of heart failure is uncertain in Chinese populations. We aimed to compare the strength of associations between healthy lifestyle factors and ideal cardiovascular health metrics in the risk of heart failure in middle-aged Chinese adults. Methods A healthy lifestyle score (HLS) was constructed using smoking, drinking, physical activity, diet, body mass index and waist circumference, and compared with a more comprehensive set of metrics that included cardiovascular-disease risk biomarkers (blood pressure, blood glucose and blood lipids) in addition to the HLS. This broader set of factors [called ‘ideal cardiovascular health metrics’ (ICVHMs)] was evaluated in 487 197 participants in the China Kadoorie Biobank. Results A total of 4208 incident cases of heart failure were recorded during a median follow-up of 10 years. Both HLS [hazard ratio (HR), 0.88; 95% confidence interval (CI), 0.85, 0.91] and ICVHMs (0.87: 0.84, 0.89) were inversely associated with risk of heart failure (P  & lt; 0.001 for linear trend). Compared with participants with 0–1 HLS, the multivariable-adjusted HR of those with 4–5 HLS was 0.68 (0.59, 0.77). Compared with participants with 0–2 ICVHMs, the adjusted HR (95% CIs) of those who had 7–8 ICVHMs was 0.47 (0.36, 0.60). ICVHMs were more strongly predictive of risk of heart failure (area under curve, 0.61 vs 0.58, P  & lt; 0.001) than healthy lifestyle factors alone. Conclusions Higher levels of healthy lifestyle factors and ICVHMs were each inversely associated with heart failure, and lifestyle factors combined with cardiometabolic factors improved the prediction of heart failure compared with healthy lifestyle factors alone.
    Type of Medium: Online Resource
    ISSN: 0300-5771 , 1464-3685
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1494592-7
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  • 6
    In: BMC Medicine, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2021-12)
    Abstract: Both genetic and cardiovascular factors contribute to the risk of developing heart failure (HF), but whether idea cardiovascular health metrics (ICVHMs) offset the genetic association with incident HF remains unclear. Objectives To investigate the genetic association with incident HF as well as the modification effect of ICVHMs on such genetic association in Chinese and British populations. Methods An ICVHMs based on smoking, drinking, physical activity, diets, body mass index, waist circumference, blood pressure, blood glucose, and blood lipids, and a polygenic risk score (PRS) for HF were constructed in the China Kadoorie Biobank (CKB) of 96,014 participants and UK Biobank (UKB) of 335,782 participants which were free from HF and severe chronic diseases at baseline. Results During the median follow-up of 11.38 and 8.73 years, 1451 and 3169 incident HF events were documented in CKB and UKB, respectively. HF risk increased monotonically with the increase of PRS per standard deviation (CKB: hazard ratio [ HR ], 1.19; 95% confidence interval [ CI ], 1.07, 1.32; UKB: 1.07; 1.03, 1.11; P for trend 〈 0.001). Each point increase in ICVHMs was associated with 15% and 20% lower risk of incident HF in CKB (0.85; 0.81, 0.90) and UKB (0.80; 0.77, 0.82), respectively. Compared with unfavorable ICVHMs, favorable ICVHMs was associated with a lower HF risk, with 0.71 (0.44, 1.15), 0.41 (0.22, 0.77), and 0.48 (0.30, 0.77) in the low, intermediate, and high genetic risk in CKB and 0.34 (0.26, 0.44), 0.32 (0.25, 0.41), and 0.37 (0.28, 0.47) in UKB ( P for multiplicative interaction 〉 0.05). Participants with low genetic risk and favorable ICVHMs, as compared with high genetic risk and unfavorable ICVHMs, had 56~72% lower risk of HF (CKB 0.44; 0.28, 0.70; UKB 0.28; 0.22, 0.37). No additive interaction between PRS and ICVHMs was observed (relative excess risk due to interaction was 0.05 [−0.22, 0.33] in CKB and 0.04 [−0.14, 0.22] in UKB). Conclusions In CKB and UKB, genetic risk and ICVHMs were independently associated with the risk of incident HF, which suggested that adherence to favorable cardiovascular health status was associated with a lower HF risk among participants with all gradients of genetic risk.
    Type of Medium: Online Resource
    ISSN: 1741-7015
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2131669-7
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  • 7
    In: European Journal of Preventive Cardiology, Oxford University Press (OUP), ( 2024-01-10)
    Abstract: Lowering low-density lipoprotein cholesterol (LDL-C) through PCSK9 inhibition represents a new therapeutic approach to preventing and treating cardiovascular disease (CVD). Phenome-wide analyses of PCSK9 genetic variants in large biobanks can help to identify unexpected effects of PCSK9 inhibition. Methods and results In the prospective China Kadoorie Biobank, we constructed a genetic score using three variants at the PCSK9 locus associated with directly measured LDL-C [PCSK9 genetic score (PCSK9-GS)]. Logistic regression gave estimated odds ratios (ORs) for PCSK9-GS associations with CVD and non-CVD outcomes, scaled to 1 SD lower LDL-C. PCSK9-GS was associated with lower risks of carotid plaque [n = 8340 cases; OR = 0.61 (95% confidence interval: 0.45–0.83); P = 0.0015] , major occlusive vascular events [n = 15 752; 0.80 (0.67–0.95); P = 0.011], and ischaemic stroke [n = 11 467; 0.80 (0.66–0.98); P = 0.029] . However, PCSK9-GS was also associated with higher risk of hospitalization with chronic obstructive pulmonary disease [COPD: n = 6836; 1.38 (1.08–1.76); P = 0.0089] and with even higher risk of fatal exacerbations amongst individuals with pre-existing COPD [n = 730; 3.61 (1.71–7.60); P = 7.3 × 10−4] . We also replicated associations for a PCSK9 variant, reported in UK Biobank, with increased risks of acute upper respiratory tract infection (URTI) [pooled OR after meta-analysis of 1.87 (1.38–2.54); P = 5.4 × 10−5] and self-reported asthma [pooled OR of 1.17 (1.04–1.30); P = 0.0071] . There was no association of a polygenic LDL-C score with COPD hospitalization, COPD exacerbation, or URTI. Conclusion The LDL-C-lowering PCSK9 genetic variants are associated with lower risk of subclinical and clinical atherosclerotic vascular disease but higher risks of respiratory diseases. Pharmacovigilance studies may be required to monitor patients treated with therapeutic PCSK9 inhibitors for exacerbations of respiratory diseases or respiratory tract infections. Lay summary Genetic analyses of over 100 000 participants of the China Kadoorie Biobank, mimicking the effect of new drugs intended to reduce cholesterol by targeting the PCSK9 protein, have identified potential severe effects of lower PCSK9 activity in patients with existing respiratory disease.
    Type of Medium: Online Resource
    ISSN: 2047-4873 , 2047-4881
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 2646239-4
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  • 8
    In: Nutrition, Metabolism and Cardiovascular Diseases, Elsevier BV, Vol. 31, No. 8 ( 2021-07), p. 2328-2337
    Type of Medium: Online Resource
    ISSN: 0939-4753
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2050914-5
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  • 9
    In: The Lancet Public Health, Elsevier BV, Vol. 7, No. 12 ( 2022-12), p. e1014-e1026
    Type of Medium: Online Resource
    ISSN: 2468-2667
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2917200-7
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  • 10
    In: Angewandte Chemie, Wiley, Vol. 134, No. 32 ( 2022-08-08)
    Abstract: Construction of an intimate film/substrate interface is of great importance for a photoelectrode to achieve efficient photoelectrochemical performance. Inspired by coordination chemistry, a polymeric carbon nitride (PCN) film is intimately grown on a Ti‐coated substrate by an in situ thermal condensation process. The as‐prepared PCN photoanode exhibits a record low onset potential ( E onset ) of −0.38 V versus the reversible hydrogen electrode (RHE) and a decent photocurrent density of 242 μA cm −2 at 1.23 V RHE for water splitting. Detailed characterization confirms that the origin of the ultralow onset potential is mainly attributed to the substantially reduced interfacial resistance between the Ti‐coated substrate and the PCN film benefitting from the constructed interfacial sp 2 N→Ti coordination bonds. For the first time, the ultralow onset potential enables the PCN photoanode to drive water splitting without external bias with a stable photocurrent density of ≈9 μA cm −2 up to 1 hour.
    Type of Medium: Online Resource
    ISSN: 0044-8249 , 1521-3757
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 505868-5
    detail.hit.zdb_id: 506609-8
    detail.hit.zdb_id: 514305-6
    detail.hit.zdb_id: 505872-7
    detail.hit.zdb_id: 1479266-7
    detail.hit.zdb_id: 505867-3
    detail.hit.zdb_id: 506259-7
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