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Non-alcoholic fatty liver disease (NAFLD) is one abnormal buildup of fat within the liver, independent of excessive alcohol intake. In type 2 diabetes, the presence of NAFLD can exacerbate chronic kidney diseases and mortality in patients. Hepatocyte nuclear factor 1 homeobox A (HNF1A) predominantly expressed in the liver, owns one crucial role in liver development, function and tumorigenesis. However, the precise regulatory role of HNF1A on the progression of type 2 diabetes combined with NAFLD keep dimness. This investigation uncovered that HNF1A levels, both in protein and mRNA expressions, were elevated in high-fat diet plus hyperglycemia (HFG) mice. Furthermore, liver steatosis was strengthened in the HFG group, which was mitigated following the HNF1A inhibition. Knockdown of HNF1A ameliorated glucose and lipid metabolism disorders in HFG mice. Lastly, the study observed an stimulation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in HFG mice, but this change was neutralized uponHNF1A silencing. In conclusion, knockdown of HNF1A improved type 2 diabetes combined with NAFLD, as well as disorders in glucose and lipid metabolism, and retarded the PI3K/AKT/mTOR signaling pathway. These finding demonstrated that HNF1A may be one serviceable target for ameliorating type 2 diabetes combined with NAFLD.

Abstract BackgroundAs dementia progresses, patients exhibit various psychological and behavioral symptoms, imposing a significant burden on families and society, including behavioral and psychological symptoms of dementia. However, caregivers lack professional care knowledge and skills, making it difficult for them to effectively cope with the diverse challenges of caregiving. Therefore, it is necessary to provide caregivers with professional knowledge and skills guidance. ObjectiveThis study aimed to analyze the impact of internet-based training on behavioral and psychological symptoms of dementia in patients, and explore how this training model affects the caregiving abilities and caregiving burden of the family caregivers of patients with dementia. MethodsUsing a consecutive enrollment method, the Department of Geriatrics at Zhejiang Hospital (Zhejiang, China) recruited 72 informal caregivers of patients with dementia. These caregivers were randomly divided into an intervention group and a control group, with 36 participants in each group. The intervention group underwent caregiver skill training via a web-based platform, whereas the control group initially received face-to-face follow-up guidance and was subsequently offered web-based training after 6 months. To assess the effectiveness of the intervention program, we used the Neuropsychiatric Inventory Questionnaire (NPI-Q), the Chinese version of the Zarit Burden Interview (CZBI), and the Sense of Competence in Dementia Care Staff Scale (SCIDS) for evaluations conducted before the intervention, 3 months after the intervention, and 6 months after the intervention. ResultsBetween July 2019 and December 2020, a total of 66 patients successfully completed the intervention and follow-up. After 6 months of intervention, the NPI-Q score of the intervention group was 3.18 (SD 3.81), the CZBI score was 10.97 (SD 5.43), and the SCIDS score was 71.88 (SD 4.78). The NPI-Q score of the control group was 8.09 (SD 8.52), the CZBI score was 30.30 (SD 13.05), and the SCIDS score was 50.12 (SD 9.10). There were statistically significant differences in NPI-Q (PPPPPPPPPPPP ConclusionsInternet-based training could significantly reduce the level of behavioral symptoms in older patients with dementia and alleviate the burden on caregivers, enhancing their caregiving abilities. Our results confirmed the effectiveness and feasibility of web-based training, which was of great significance in providing caregiving knowledge training for informal caregivers of persons with dementia.

Objective. The destruction of pancreatic β cells causes type 1 diabetes mellitus (T1D), an autoimmune disease. Studies have demonstrated that there is heterogeneity in residual β-cell function in Caucasians; therefore, we aimed to evaluate β-cell function in Chinese autoimmune T1D patients. Methods. β-cell function was determined using oral glucose tolerance testing or standardized steamed bread meal tolerance test in 446 participants with autoantibody-positive T1D. Clinical factors, such as age onset, sex, duration, body mass index, autoantibodies, other autoimmune diseases, diabetic ketoacidosis, hypoglycemia events, glycosylated hemoglobin, and insulin dose, were retrieved. We also analyzed single nucleotide polymorphism (SNP) data for C-peptides from 144 participants enrolled in the Chinese-T1D genome-wide association study. Results. Of 446 T1D patients, 98.5%, 97.4%, 86.9%, and 42.6% of individuals had detectable C-peptide values (≥ 0.003 nmol/L) at durations of < 1 year, 1 to 2 years, 3 to 6 years, and ≥ 7 years, respectively. A total of 60.7% of patients diagnosed at ≥ 18 years old and 15.8% of those diagnosed at < 18 years had detectable C-peptide after ≥ 7 years from the diagnosis. Furthermore, the patients diagnosed at ≥ 18 years old had higher absolute values of stimulated C-peptide (≥ 0.2 nmol/L). Diabetic ketoacidosis, hypoglycemia events, and insulin doses were shown to be associated with β-cell function. SNPs rs1770 and rs55904 were associated with C-peptide levels. Conclusion. Our results have indicated that there are high residuals of β-cell mass in Chinese patients with autoimmune T1D. These findings may aid in the consideration of therapeutic strategies seeking prevention and reversal of β-cell function among Chinese T1D patients. [ABSTRACT FROM AUTHOR]

IntroductionThis study explored the associations of intrinsic capacity (IC), fall risk, and frailty in geriatric inpatients.MethodsA total of 703 hospitalized patients aged 75 years or older were recruited for this retrospective observational study from Zhejiang Hospital using a comprehensive geriatric assessment. The IC composite score was constructed from the scores of the Chinese version of the Mini-Mental State Examination, Short Physical Performance Battery, Short Form Mini Nutritional Assessment, 15-item Geriatric Depression Scale, and self-reported hearing and vision impairment. Adverse outcomes were recorded as the fall risk and frailty using the Morse Fall Scale and the Clinical Frailty Scale. Spearman’s correlation coefficient analyses and multivariate logistic regression models were used to explore the associations between IC, high fall risk, and frailty.ResultsDeclined IC composite scores were associated with increased risks of falls [odds ratio (OR) = 0.64, 95% confidence interval (CI): 0.57–0.72] and frailty (OR = 0.45, 95%CI: 0.37–0.54) among older hospitalized patients after adjusting for the related potential confounders. In addition, decreased cognitive, vitality, locomotion, and psychological scores were associated with increased adverse health conditions, with ORs ranging from 0.26 to 0.70. Vision impairment was observed to increase the risk of frailty (OR = 0.42, 95%CI: 0.23–0.76) after adjusting for the related potential confounders.DiscussionThis study indicated that declined IC was associated with fall risk and frailty in older inpatients. Further prospective studies are needed to explore the longitudinal associations between baseline IC and subsequent risk of falls and frailty.

Abstract Background Orthostatic Hypotension (OH) and malnutrition, are common health problems in elderly hypertensive patients. This study aimed to analyze the relationship between malnutrition and OH in elderly hypertensive patients. Methods This is a cross-sectional single-center study. All participants underwent a Comprehensive Geriatric Assessment (CGA), in which malnutrition was defined according to the Global Leadership Initiative on Malnutrition (GLIM) criteria based on four different methods of diagnosing muscle mass loss. Furthermore, the accuracy of these methods was verified by Receiver Operating Characteristic (ROC) analysis. Univariate and multivariate logistic regression analyses were used to identify risk factors for OH in elderly hypertensive patients. Results For GLIM criteria, when Fat-Free Mass Index (FFMI) was the gold standard for muscle mass loss, the Area Under ROC Curve (AUC) values for Upper Arm Circumference (UAC), Calf Circumference (CC), and Hand Grip Strength (HGS) were 0.784, 0.805, and 0.832, with moderate accuracy in diagnosing malnutrition. Multivariate analysis showed that females, Diabetes Mellitus (DM), diuretics, and malnutrition diagnosed by GLIM-UAC were risk factors for OH in elderly hypertensive patients. Conclusion Prompt detection of malnutrition in the elderly and attention to changes in UAC may be critical. Similarly, we should strengthen medication and disease management in elderly hypertensive patients.

Abstract Background Sleep disturbance, chronic pain and depressive symptoms later in life are modifiable risk factors and may contribute to frailty. However, much less is known about sex differences in the association between these concurrent symptoms and frailty in older patients. Therefore, we conducted this study to explore the associations of poor sleep quality, chronic pain, and depressive symptoms with frailty in older patients, and the sex-specific associations. Methods In an observational population-based study, 540 older hospitalized patients from Zhejiang Hospital in China were enrolled. We collected data on poor sleep quality, pain, depressive symptoms and frailty using the Pittsburgh Sleep Quality Index, the Numerical Rating Scale, the 15-item Geriatric Depression Scale, and the Clinical Frailty Scale. Multivariate logistic regression models were used to explore the total sample and sex-specific associations among symptom burdens, symptom combination patterns and symptom counts, and frailty. Results After adjusting for the potential covariates, concurrent poor sleep quality and depressive symptoms (OR = 4.02, 95% CI 1.57–10.26), concurrent poor sleep quality and chronic pain (OR = 2.05, 95% CI 1.04–4.05), and having three symptoms (OR = 3.52, 95% CI 1.19–10.44) were associated with a higher likelihood of frailty in older inpatients. In addition, older patients with 2 or 3 symptoms (2 and 3 vs. 0 symptoms) had a higher risk of frailty, and the odds ratios were 2.40 and 3.51, respectively. Interaction analysis and sex-stratified associations exhibited conflicting results. The nonsignificant effect of the interaction of sex and symptoms on frailty, but not the sex-stratified associations, showed that individual symptoms, symptom combination patterns, and symptom counts were associated with elevated risks of frailty in older male patients, but not in older female patients. Conclusions Increased symptom burdens were associated with a higher risk of frailty in older inpatients, especially in those with poor sleep quality concurrent with at least one of the other two symptoms. Thus, a multidisciplinary program addressing these common symptoms is required to reduce adverse outcomes.

BackgroundTo demonstrate the real-word situation of burdens that are attributed to the risk factor of high low-density lipoprotein cholesterol (LDL-C) at the global, regional, national levels, among different age groups and between genders.MethodsWe analyzed data from the Global Burden of Disease study 2019 related to global deaths, disability-adjusted life years (DALYs), summary exposure value (SEV), average annual percentage change (AAPC), and observed to expected ratios (O/E ratios) attributable to high LDL-C from 1990 to 2019.ResultsGlobally, in 2019, the total numbers of deaths and DALYs attributed to high LDL cholesterol were 1.47 and 1.41 times higher than that in 1990. The age-standardized deaths and DALYs rate was 1.45 and 1.70 times in males compared to females, while the age-standardized SEVs rate was 1.10 times in females compared to males. The deaths, DALYs, and SEV rates increased with age. In 2019, the highest age-standardized rates of both deaths and DALYs occurred in Eastern Europe while the lowest occurred in high-income Asia Pacific. High-income North America experienced a dramatic reduction of risk related to high LDL-C. Correlation analysis identified that the age-standardized SEV rate was positively correlated with Socio-demographic Index (SDI; r = 0.7753, P < 0.001). The average annual percentage change (AAPC) of age-standardized SEV rate decreased in the high SDI and high-middle SDI regions but increased in the middle SDI, low-middle SDI, and low SDI regions. High LDL-C mainly contributed to ischemic heart diseases.ConclusionHigh LDL-C contributed considerably to health burden worldwide. Males suffered worse health outcomes attributed to high LDL-C when compared to females. The burden attributed to high LDL-C increased with age. Lower SDI regions and countries experienced more health problem challenges attributed to high LDL-C as the result of social development and this should be reflected in policymaking.

Abstract Background Genotyping of the rs174547 polymorphism in the fatty acid desaturase 1 gene (FADS1) shows that it is associated with the FA composition of plasma phospholipids and lipid metabolic indices among several ethnic groups. However, this association requires further confirmation in the Chinese population, and little is known about the effect of polymorphisms in fatty acid-related genes on body fat distribution. Methods Anthropometric measurements of 951 Chinese adults aged 18–79 were obtained and body fat distribution was estimated using dual-energy X-ray absorptiometry. The FA composition of plasma phospholipids was measured by gas chromatography. Multiple linear regression assessed whether the rs174547 genotype was associated with FA composition, body fat distribution, and metabolic traits in additive, dominant, and recessive models. Results The rs174547 C minor allele was associated with a higher proportion of linoleic acid, lower arachidonic acid and docosahexaenoic acid, as well as lower delta-6-desaturase and delta-5-desaturase activity. Female C allele carriers had lower android fat percentages and lower levels of low-density lipoprotein-cholesterol, while male C allele carriers had lower gynoid fat percentages and higher triglyceride after adjusting for age, income, BMI, behavioral risk factors, and regional fat percentages. Conclusion An association of FADS1 rs174547 with the FA composition of plasma phospholipids was identified among this Chinese adult population. The association with body fat distribution and lipid metabolic indices differed between men and women, which might explain sexual differences in body fat distribution and lipid metabolism.