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- Chen, XD, et al.
(författare)
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Non-invasive early detection of cancer four years before conventional diagnosis using a blood test
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 3475-
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Tidskriftsartikel (refereegranskat)abstract
- Early detection has the potential to reduce cancer mortality, but an effective screening test must demonstrate asymptomatic cancer detection years before conventional diagnosis in a longitudinal study. In the Taizhou Longitudinal Study (TZL), 123,115 healthy subjects provided plasma samples for long-term storage and were then monitored for cancer occurrence. Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation, on TZL plasma samples from 605 asymptomatic individuals, 191 of whom were later diagnosed with stomach, esophageal, colorectal, lung or liver cancer within four years of blood draw. We also assay plasma samples from an additional 223 cancer patients, plus 200 primary tumor and normal tissues. We show that PanSeer detects five common types of cancer in 88% (95% CI: 80–93%) of post-diagnosis patients with a specificity of 96% (95% CI: 93–98%), We also demonstrate that PanSeer detects cancer in 95% (95% CI: 89–98%) of asymptomatic individuals who were later diagnosed, though future longitudinal studies are required to confirm this result. These results demonstrate that cancer can be non-invasively detected up to four years before current standard of care.
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- Ringden, O, et al.
(författare)
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The graft-versus-leukemia effect using matched unrelated donors is not superior to HLA-identical siblings for hematopoietic stem cell transplantation
- 2009
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 113:13, s. 3110-3118
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Tidskriftsartikel (refereegranskat)abstract
- Do some patients benefit from an unrelated donor (URD) transplant because of a stronger graft-versus-leukemia (GVL) effect? We analyzed 4099 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML) undergoing a myeloablative allogeneic hematopoietic cell transplantation (HCT) from an URD (8/8 human leukocyte antigen [HLA]–matched, n = 941) or HLA-identical sibling donor (n = 3158) between 1995 and 2004 reported to the CIBMTR. In the Cox regression model, acute and chronic GVHD were added as time-dependent variables. In multivariate analysis, URD transplant recipients had a higher risk for transplantation-related mortality (TRM; relative risk [RR], 2.76; P < .001) and relapse (RR, 1.50; P < .002) in patients with AML, but not ALL or CML. Chronic GVHD was associated with a lower relapse risk in all diagnoses. Leukemia-free survival (LFS) was decreased in patients with AML without acute GVHD receiving a URD transplant (RR, 2.02; P < .001) but was comparable to those receiving HLA-identical sibling transplants in patients with ALL and CML. In patients without GVHD, multivariate analysis showed similar risk of relapse but decreased LFS for URD transplants for all 3 diagnoses. In conclusion, risk of relapse was the same (ALL, CML) or worse (AML) in URD transplant recipients compared with HLA-identical sibling transplant recipients, suggesting a similar GVL effect.
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- Su, W, et al.
(författare)
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Liver X receptor β increases aquaporin 2 protein level via a posttranscriptional mechanism in renal collecting ducts
- 2017
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Ingår i: American journal of physiology. Renal physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 312:4, s. F619-F628
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Tidskriftsartikel (refereegranskat)abstract
- Liver X receptors (LXRs) including LXRα and LXRβ are nuclear receptor transcription factors and play an important role in lipid and glucose metabolism. It has been previously reported that mice lacking LXRβ but not LXRα develop a severe urine concentrating defect, likely via a central mechanism. Here we provide evidence that LXRβ regulates water homeostasis through increasing aquaporin 2 (AQP2) protein levels in renal collecting ducts. LXRβ−/− mice exhibited a reduced response to desmopressin (dDAVP) stimulation, suggesting that the diabetes insipidus phenotype is of both central and nephrogenic origin. AQP2 protein abundance in the renal inner medulla was significantly reduced in LXRβ−/− mice but with little change in AQP2 mRNA levels. In vitro studies showed that AQP2 protein levels were elevated upon LXR agonist treatment in both primary cultured mouse inner medullary duct cells (mIMCD) and the mIMCD3 cell line with stably expressed AQP2. In addition, LXR agonists including TO901317 and GW3965 failed to induce AQP2 gene transcription but diminished its protein ubiquitination in primary cultured mIMCD cells, thereby inhibiting its degradation. Moreover, LXR activation-induced AQP2 protein expression was abolished by the protease inhibitor MG132 and the ubiquitination-deficient AQP2 (K270R). Taken together, the present study demonstrates that activation of LXRβ increases AQP2 protein levels in the renal collecting ducts via a posttranscriptional mechanism. As such, LXRβ represents a key regulator of body water homeostasis.
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- Xu, L, et al.
(författare)
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Trends in Psychotropic Medication Prescriptions in Urban China From 2013 to 2017: National Population-Based Study
- 2021
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Ingår i: Frontiers in psychiatry. - : Frontiers Media SA. - 1664-0640. ; 12, s. 727453-
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Psychotropic medications are commonly used for treating mental disorders; however, there is currently no study on how commonly they are used in China. This study reported the trends in psychotropic medications prescriptions in urban China.Methods: A national population-based study was conducted using the China Health Insurance Research Association database to estimate the period prescription prevalence of 11 major classes of psychotropic medications annually during 2013–2017. The World Health Organization Anatomical Therapeutic Chemical (ATC) classification codes were used to identify psychotropic medications.Results: The prescription prevalence of any psychotropic medication increased from 8.110% (8.106–8.114%) in 2013 to 11.362% (11.357–11.366%) in 2017. The prescription prevalence of six classes increased significantly during 2013–2017, including sedatives-hypnotics (from 3.177 to 5.388%), anxiolytics (from 1.436 to 2.200%), antiepileptic drugs (from 1.416 to 2.140%), antipsychotics (from 0.809 to 1.156%), antidepressants (from 0.891 to 1.045%), and psycholeptic polypills (from 0.682 to 0.866%). The prescription prevalence of antidementia drugs increased from 0.069 to 0.122%, and mood stabilizers increased from 0.029 to 0.037%, although not statistically significant. The prescription prevalence of nootropic drugs, attention deficit hyperactivity disorder (ADHD) medications and drugs used in the treatment of addictive disorders was largely stable. Psychotropic medication prescription increased with age for all classes except for ADHD medications and mood stabilizers.Conclusion: Increasing trends in prescription prevalence were observed for most classes of psychotropic medications in urban China, although the prevalence was still lower than that in most developed countries. Further research is warranted to explore the potential treatment gap between China and most developed countries.
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