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1.
JAMA Pediatr ; 2024 Jun 10.
Article En | MEDLINE | ID: mdl-38856986

Importance: Overweight and obesity in childhood and adolescence is a global health issue associated with adverse outcomes throughout the life course. Objective: To estimate worldwide prevalence of overweight and obesity in children and adolescents from 2000 to 2023 and to assess potential risk factors for and comorbidities of obesity. Data Sources: MEDLINE, Web of Science, Embase, and Cochrane. Study Selection: The inclusion criteria were: (1) studies provided adequate information, (2) diagnosis based on body mass index cutoffs proposed by accepted references, (3) studies performed on general population between January 2000 and March 2023, (4) participants were younger than 18 years. Data Extraction and Synthesis: The current study was performed in accordance with the Meta-analysis of Observational Studies in Epidemiology guidelines. DerSimonian-Laird random-effects model with Free-Tukey double arcsine transformation was used for data analysis. Sensitivity analysis, meta-regression, and subgroup analysis of obesity among children and adolescents were conducted. Main Outcomes and Measures: Prevalence of overweight and obesity among children and adolescents assessed by World Health Organization, International Obesity Task Force, the US Centers for Disease Control and Prevention, or other national references. Results: A total of 2033 studies from 154 different countries or regions involving 45 890 555 individuals were included. The overall prevalence of obesity in children and adolescents was 8.5% (95% CI 8.2-8.8). We found that the prevalence varied across countries, ranging from 0.4% (Vanuatu) to 28.4% (Puerto Rico). Higher prevalence of obesity among children and adolescents was reported in countries with Human Development Index scores of 0.8 or greater and high-income countries or regions. Compared to 2000 to 2011, a 1.5-fold increase in the prevalence of obesity was observed in 2012 to 2023. Substantial differences in rates of obesity were noted when stratified by 11 risk factors. Children and adolescents with obesity had a high risk of depression and hypertension. The pooled estimates of overweight and excess weight in children and adolescents were 14.8% (95% CI 14.5-15.1) and 22.2% (95% CI 21.6-22.8), respectively. Conclusions and Relevance: This study's findings indicated 1 of 5 children or adolescents experienced excess weight and that rates of excess weight varied by regional income and Human Development Index. Excess weight among children and adolescents was associated with a mix of inherent, behavioral, environmental, and sociocultural influences that need the attention and committed intervention of primary care professionals, clinicians, health authorities, and the general public.

3.
Nat Commun ; 13(1): 4308, 2022 07 25.
Article En | MEDLINE | ID: mdl-35879297

Cancer associated fibroblasts (CAFs) support tumors via multiple mechanisms, including maintaining the immunosuppressive tumor microenvironment and limiting infiltration of immune cells. The prolyl isomerase Pin1, whose overexpression in CAFs has not been fully profiled yet, plays critical roles in tumor initiation and progression. To decipher effects of selective Pin1 inhibition in CAFs on pancreatic cancer, here we formulate a DNA-barcoded micellular system (DMS) encapsulating the Pin1 inhibitor AG17724. DMS functionalized with CAF-targeting anti-FAP-α antibodies (antiCAFs-DMS) can selectively inhibit Pin1 in CAFs, leading to efficacious but transient tumor growth inhibition. We further integrate DNA aptamers (AptT), which can engage CD8+ T lymphocytes, to obtain a bispecific antiCAFs-DMS-AptT system. AntiCAFs-DMS-AptT inhibits tumor growth in subcutaneous and orthotopic pancreatic cancer models.


Cancer-Associated Fibroblasts , Pancreatic Neoplasms , Cancer-Associated Fibroblasts/pathology , Cell Line, Tumor , Fibroblasts/pathology , Humans , NIMA-Interacting Peptidylprolyl Isomerase/genetics , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Tumor Microenvironment , Pancreatic Neoplasms
4.
BMC Cancer ; 20(1): 97, 2020 Feb 04.
Article En | MEDLINE | ID: mdl-32019501

BACKGROUND: For selected locally advanced prostate cancer (PCa) patients, radical prostatectomy (RP) is one of the first-line treatments. We aimed to develop a preoperative nomogram to identify what kinds of patients can get the most survival benefits after RP. METHODS: We conducted analyses with data from the Surveillance, Epidemiology, and End Results (SEER) database. Covariates used for analyses included age at diagnosis, marital status, race, American Joint Committee on Cancer (AJCC) 7th TNM stage, Prostate specific antigen, Gleason biopsy score (GS), percent of positive cores. We estimated the cumulative incidence function for cause-specific death. The Fine and Gray's proportional subdistribution hazard approach was used to perform multivariable competing risk analyses and reveal prognostic factors. A nomogram was built by these factors (including GS, percent of positive cores and N stage) and validated by concordance index and calibration curves. Risk stratification was established based on the nomogram. RESULTS: We studied 14,185 patients. N stage, GS, and percent of positive cores were the independent prognostic factors used to construct the nomogram. For validating, in the training cohort, the C-index was 0.779 (95% CI 0.736-0.822), and in the validation cohort, the C-index was 0.773 (95% CI 0.710-0.836). Calibration curves showed that the predicted survival and actual survival were very close. The nomogram performed better over the AJCC staging system (C-index 0.779 versus 0.764 for training cohort, and 0.773 versus 0.744 for validation cohort). The new stratification of risk groups based on the nomogram also showed better discrimination than the AJCC staging system. CONCLUSIONS: The preoperative nomogram can provide favorable prognosis stratification ability to help clinicians identify patients who are suitable for surgery.


Nomograms , Prostatectomy/methods , Prostatic Neoplasms/surgery , Aged , Cohort Studies , Humans , Male , Middle Aged , Neoplasm Grading , Preoperative Period , Prognosis , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , SEER Program , Survival Analysis , Treatment Outcome
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