IMPORTANCE Associations between adverse childhood experiences (ACEs) and chronic diseases among middle-aged or older Chinese individuals have not been well documented. In addition, whether demographic and socioeconomic characteristics modify any such associations has been underexplored. OBJECTIVESTo examine associations between ACEs and subsequent chronic diseases and to assess whether age, sex, educational level, annual per capita household expenditure level, and childhood economic hardship modify these associations. DESIGN, SETTING, AND PARTICIPANTSThis population-based cross-sectional study used data from the China Health and Retirement Longitudinal Study (CHARLS), a survey of residents aged 45 years or older in 28 provinces across China; specifically, the study used data from the CHARLS life history survey conducted from June 1 to December 31, 2014, and a CHARLS follow-up health survey conducted from July 1 to September 30, 2015. The study population included 11 972 respondents aged 45 years or older who had data on at least 1 of 14 specified chronic diseases and information on all 12 of the ACE indicators included in this study. Data analysis was performed from December 1 to 30, 2020. EXPOSURES Any of 12 ACEs (physical abuse, emotional neglect, household substance abuse, household mental illness, domestic violence, incarcerated household member, parental separation or divorce, unsafe neighborhood, bullying, parental death, sibling death, and parental disability), measured by indicators on a questionnaire. The number of ACEs per participant was summed and categorized into 1 of 5 cumulative-score groups: 0, 1, 2, 3, and 4 or more.MAIN OUTCOMES AND MEASURES Hypertension, dyslipidemia, diabetes, heart disease, stroke, chronic lung disease, asthma, liver disease, cancer, digestive disease, kidney disease, arthritis, psychiatric disease, and memory-related disease were defined by self-reported physician diagnoses or in combination with health assessment and medication data. Multimorbidity was defined as the presence of 2 or more of these 14 chronic diseases. Logistic regression models were used to assess associations of the 12 ACEs with the 14 chronic diseases and with multimorbidity. Modification of the associations by demographic and socioeconomic characteristics was assessed by stratified analyses and tests for interaction. RESULTSOf the 11 972 individuals included (mean [SD] age, 59.85 [9.56] years; 6181 [51.6%] were females), 80.9% had been exposed to at least 1 ACE and 18.0% reported exposure to 4 or more ACEs.Compared with those without ACE exposure, participants who experienced 4 or more ACEs had increased risks of dyslipidemia, chronic lung disease, asthma, liver disease, digestive disease, kidney (continued) Key Points Question Are adverse childhood experiences (ACEs) associated with subsequent chronic diseases among middle-aged or older adults in China, and do demographic and socioeconomic characteristics modify these associations? Findings In this cross-sectional study of 11 972 Chinese individuals age...

Beta-amyloid (Aβ ) neurotoxicity is important in Alzheimer’s disease (AD) pathogenesis. Aβ neurotoxicity causes oxidative stress, inflammation and mitochondrial damage resulting in neuronal degeneration and death. Oxidative stress, inflammation and mitochondrial failure are also pathophysiological mechanisms of type 2 diabetes (T2DM) which is characterized by insulin resistance. Interestingly, T2DM increases risk to develop AD which is associated with reduced neuronal insulin sensitivity (central insulin resistance). We studied the potential protective effect of adiponectin (an adipokine with insulin-sensitizing, anti-inflammatory and anti-oxidant properties) against Aβ neurotoxicity in human neuroblastoma cells (SH-SY5Y) transfected with the Swedish amyloid precursor protein (Sw-APP) mutant, which overproduced Aβ with abnormal intracellular Aβ accumulation. Cytotoxicity was measured by assay for lactate dehydrogenase (LDH) released upon cell death and lysis. Our results revealed that Sw-APP transfected SH-SY5Y cells expressed both adiponectin receptor 1 and 2, and had increased AMP-activated protein kinase (AMPK) activation and enhanced nuclear factor-kappa B (NF-κB) activation compared to control empty-vector transfected SH-SY5Y cells. Importantly, adiponectin at physiological concentration of 10 µg/ml protected Sw-APP transfected SH-SY5Y cells against cytotoxicity under oxidative stress induced by hydrogen peroxide. This neuroprotective action of adiponectin against Aβ neurotoxicity-induced cytotoxicity under oxidative stress involved 1) AMPK activation mediated via the endosomal adaptor protein APPL1 (adaptor protein with phosphotyrosine binding, pleckstrin homology domains and leucine zipper motif) and possibly 2) suppression of NF-κB activation. This raises the possibility of novel therapies for AD such as adiponectin receptor agonists.

T helper 17 (Th17) cells are vital components of the adaptive immune system involved in the pathogenesis of most autoimmune and inflammatory syndromes, and adiponectin(ADN) is correlated with inflammatory diseases such as multiple sclerosis (MS) and type II diabetes. However, the regulatory effects of adiponectin on pathogenic Th17 cell and Th17-mediated autoimmune central nervous system (CNS) inflammation are not fully understood. In this study, we demonstrated that ADN could inhibit Th1 and Th17 but not Th2 cells differentiation in vitro. In the in vivo study, we demonstrated that ADN deficiency promoted CNS inflammation and demyelination and exacerbated experimental autoimmune encephalomyelitis (EAE), an animal model of human MS. Furthermore, ADN deficiency increased the Th1 and Th17 cell cytokines of both the peripheral immune system and CNS in mice suffering from EAE. It is worth mentioning that ADN deficiency predominantly promoted the antigen-specific Th17 cells response in autoimmune encephalomyelitis. In addition, in vitro and in vivo, ADN upregulated sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor γ (PPARγ) and inhibited retinoid-related orphan receptor-γt (RORγt); the key transcription factor during Th17 cell differentiation. These results systematically uncovered the role and mechanism of adiponectin on pathogenic Th17 cells and suggested that adiponectin could inhibit Th17 cell-mediated autoimmune CNS inflammation.

Higher circulating fetuin-A levels were associated with increased risk of T2DM. However, the causality deserved further analysis.