Process quality, diagnosis quality, and patient satisfaction of primary care in Rural Western China: A study using standardized patients.

OBJECTIVES: Patient satisfaction is an essential indicator of the doctor-patient relationship. This study aimed to investigate the relationship between primary care quality and patient satisfaction for non-communicable diseases (NCDs) in rural western China. METHODS: The study utilized the standardized patients (SPs) approach to present typical symptoms of unstable angina and diabetes to rural healthcare providers. After the consultations, the SPs completed a satisfaction survey. Ordinary least squares and quantile regression were used to examine the association between quality of primary care and patient satisfaction. RESULTS: We examined 178 anonymous SPs visits. The results showed that higher process quality for angina SPs was correlated with stronger satisfaction for provider ability at a low quantile of ability satisfaction. For diabetes SPs, higher process quality increased overall satisfaction at a low quantile of overall satisfaction, whereas a correct diagnosis significantly contributed to communication satisfaction at a high quantile of communication satisfaction. CONCLUSIONS: The study found positive associations between process and diagnosis quality and SPs satisfaction. Notably, the influence of process quality was most significant among patients with lower satisfaction levels. PRACTICE IMPLICATIONS: Provider's process quality could be a key area of improving the satisfaction levels, especially for patients with lower levels of satisfaction.

In-Hospital Formula Feeding Hindered Exclusive Breastfeeding: Breastfeeding Self-Efficacy as a Mediating Factor.

Breastfeeding self-efficacy (BSE), defined as a mother's confidence in her ability to breastfeed, has been confirmed to predict the uptake of exclusive breastfeeding (EBF). Early experiences during the birth hospital stay, especially in-hospital formula feeding (IHFF), can impact both EBF and maternal breastfeeding confidence. Therefore, our objective was to examine the association between IHFF and EBF outcomes and investigate whether this association is influenced by BSE. The study included 778 infants from a larger cohort study conducted in 2021, with a one-year follow-up in rural areas of Sichuan Province, China. We used a causal mediation analysis to estimate the total effect (TE), natural direct (NDE), and nature indirect effects (NIE) using the paramed command in Stata. Causal mediation analyses revealed that IHFF was negatively associated with EBF (TE odds ratio = 0.47; 95% CI, 0.29 to 0.76); 28% of this association was mediated by BSE. In the subgroup analysis, there were no significant differences in the effects between parity subgroups, as well as between infant delivery subgroups. Our study found that IHFF hindered later EBF and that BSE mediated this association. Limiting the occurrence of in-hospital formula feeding or improving maternal breastfeeding self-efficacy is likely to improve exclusive breastfeeding outcomes.

PP2Ac knockdown attenuates lipotoxicity­induced pancreatic ß­cell dysfunction and apoptosis.

Protein phosphatase 2A (PP2A) is one of the most common serine/threonine phosphatases in mammalian cells, and it primarily functions to regulate cell signaling, glycolipid metabolism and apoptosis. The catalytic subunit of PP2A (PP2Ac) plays an important role in the functions of the protein. However, there are few reports on the regulatory role of PP2Ac in pancreatic ß-cells under lipotoxic conditions. In the present study, mouse insulinoma 6 (MIN6) pancreatic cells were transfected with short hairpin RNAs to generate PP2Ac knockdown cells and incubated with palmitate (PA) to establish a lipotoxicity model. Serine/threonine phosphatase assay system, Cell Counting Kit-8, flow cytometry, enzyme-linked immunosorbent assay and western blotting were used to measure PP2A activity, cell viability, apoptosis, oxidative stress and insulin secretion in the cells. In addition, a mouse model of lipotoxicity was established with a high-fat diet (HFD) and the knockdown of PP2Ac using adeno-associated viruses to interfere with PP2Ac expression in the pancreatic tissues. The activity of PP2A in the mouse pancreatic tissue and the serum insulin level were measured. Furthermore, the proliferation of mouse pancreatic ß-cells was assessed using pancreatic tissue immunofluorescence. PP2Ac knockdown inhibited lipotoxicity-induced PP2A hyperactivation, increased the resistance of pancreatic ß-cells to lipotoxicity and attenuated PA-induced apoptosis in MIN6 cells. It also protected the endoplasmic reticulum and mitochondria, and ameliorated insulin secretion. The results of mRNA sequencing and western blotting analysis suggested that the protective effects of PP2Ac knockdown in MIN6 cells may be mediated via the MAPK pathway. Moreover, the results of the animal experiments suggested that specific knockdown of pancreatic PP2Ac effectively attenuated HFD-induced insulin resistance and reduced the compensatory proliferation of pancreatic ß-cells in mice. In summary, the present study revealed the effects of interfering with PP2Ac gene expression on pancreatic ß-cells in vivo and in vitro and the underlying mechanisms, which may provide insights for the treatment of type 2 diabetes mellitus in the clinic.

Maternal Dietary Diversity and Small for Gestational Age: The Effect Modification by Pre-Pregnancy Body Mass Index and Gestational Weight Gain in a Prospective Study within Rural Sichuan, China (2021-2022).

Infants born small for gestational age (SGA) remains a significant global public health concern, with potential interconnections among maternal diet, pre-pregnancy BMI, gestational weight gain (GWG), and SGA. This prospective study investigated the association between dietary diversity (DD) during pregnancy and the risk of SGA, as well as the synergistic effect of DD with pre-pregnancy BMI and GWG on SGA. Maternal dietary intake during pregnancy was assessed using 24 h dietary recalls, and dietary diversity scores (DDS) were calculated based on the FAO's Minimum Dietary Diversity for Women index. Infant information was followed up. The Poisson regression model was employed to determine the association between maternal DD and SGA. Interactions between DD and pre-pregnancy BMI or GWG were evaluated under additive and multiplicative models. Among the 560 singleton live births, 62 (11.07%) were classified as SGA. After adjusting for potential confounders, the DDS exhibited a protective effect against SGA (aRR: 0.76; 95% CI: 0.62-0.95). DD modified the association between being underweight prior to pregnancy and SGA on the additive scale (interaction contrast ratio = 7.39; 95% CI: 5.84, 8.94). These findings suggest that improving dietary diversity during pregnancy, particularly among women with a low pre-pregnancy BMI, may be a feasible strategy to reduce the risk of SGA newborns.

Dietary Diversity and Its Contribution to the Magnitude of Anaemia among Pregnant Women: Evidence from Rural Areas of Western China.

BACKGROUND: Prenatal anaemia causes serious consequences for both mother and foetus, and dietary factors are suggested to be associated with anaemia. However, research in pregnant women living in rural areas is limited. We aim to assess the contribution of dietary diversity to the magnitude of prenatal anaemia in rural China and identify the interactions between dietary diversity and several sociodemographic and maternal characteristics in relation to anaemia. METHODS: A multi-stage random cluster sampling method was used to select pregnant women in rural western China. The Woman's Dietary Diversity Score was created to measure dietary diversity, which was recoded into terciles. Multinomial logistic regression models were used to assess the associations between dietary diversity score terciles and the magnitude of prenatal anaemia. Multiplicative interactions were tested by adding the product term of dietary diversity and several sociodemographic and maternal characteristics into the regression models. RESULTS: Out of 969 participants, 54.3% were measured as anaemic, with 28.6% mildly anaemic and 25.7% moderately to severely anaemic. There was an absence of agreement between self-reported and measured anaemia status (κ = 0.28, 95% CI [0.22-0.34]). Participants in the highest dietary diversity score tercile had lower odds of being moderately to severely anaemic after adjusting for potential confounders (RRR = 0.65, 95% CI [0.44, 0.98]). In participants with moderate to severe anaemia, significant interactions were found between dietary diversity score terciles, age, and parity (p for interaction < 0.05). CONCLUSIONS: The prevalence of prenatal anaemia in rural China remains high, and pregnant women living in these areas are insufficiently aware of their anaemia status. Improving dietary diversity is needed to manage prenatal anaemia in rural areas.

FUNDC1 modulates mitochondrial defects and pancreatic ß-cell dysfunction under lipotoxicity.

Insulin resistance and many metabolic disorders are causally linked to mitochondrial dysfunction or defective mitochondrial quality control. Mitophagy is a highly selective mechanism that recognizes and removes damaged mitochondria to maintain mitochondrial homeostasis. Here, we addressed the potential role of FUNDC1, a mediator of mitophagy, in pancreatic ß-cell dysfunction under lipotoxicity. In pancreatic MIN6 cells, FUNDC1 deficiency aggravated palmitate-induced mitochondrial dysfunction, which led to cell death and insulin insensitivity. Interestingly, FUNDC1 overexpression prevented these cellular harms brought on by palmitate. In mice models, pancreatic-specific FUNDC1 overexpression alleviated high-fat diet (HFD)-induced insulin resistance and obesity. Mechanistically, pancreatic-specific overexpression of FUNDC1 ameliorated mitochondrial defects and endoplasmic reticulum (ER) stress upon HFD. Our research indicates that FUNDC1 plays an essential role in apoptosis and dysfunction of pancreatic ß-cells via modulating lipotoxicity-induced mitochondrial defects.

Hepatic IDH2 regulates glycolysis and gluconeogenesis.

BACKGROUND AND AIMS: The liver plays a central role in controlling glucose and lipid metabolism. IDH2, a mitochondrial protein, controls TCA cycle flux. However, its role in regulating metabolism in obesity is still unclear. This study intends to investigate the impact of hepatic IDH2 expression on overnutrition-regulated glucose and lipid metabolism. METHODS: Hepatic IDH2 was knocked-out in mice by the approach of CRISPR-Cas9. Mice were subjected to starvation and refeeding for hepatic glucose and lipid studies in vivo. Primary hepatocytes and mouse normal liver cell line, AML12 cells were used for experiments in vitro. RESULTS: This study found that IDH2 protein levels were elevated in the livers of obese people and mice with high-fat diet consumption or hepatic steatosis. Liver IDH2-deletion mice (IDH2LKO) were resistant to high-fat diet-induced body weight gain, with lower serum glucose and TG levels, increased insulin sensitivity, and higher FGF21 secretion, despite the higher TG content in the liver. Consistently, overexpression of IDH2 in hepatocytes promoted gluconeogenesis and enhanced glycogenesis. By performing mass spectrometry and proteomics analyses, we further demonstrated that IDH2-deficiency in hepatocytes accelerated ATP production by increasing forward TCA cycle flux, thus promoting glycolysis pathway and decreasing glycogen synthesis at refeeding state, and inhibiting hepatic gluconeogenesis, increasing ß-oxidation during starvation. Moreover, experiments in vivo demonstrated that IDH2-knockout might not exacerbate hepatic inflammatory responses in the NASH model. CONCLUSIONS: Elevated hepatic IDH2 under over-nutrition state contributes to elevated gluconeogenesis and glycogen synthesis. Inhibition of IDH2 in the liver could be a potential therapeutic target for obesity and diabetes.

Sigma­1 receptor overexpression promotes proliferation and ameliorates cell apoptosis in ß­cells.

Sigma­1 receptor (Sig­1R) is a class of orphan receptors, the potential role of which in pancreatic islet cells remains poorly understood. The present study aimed to investigate the role of Sig­1R in islet ß­cell proliferation and examine the effects of Sig­1R on islet ß­cell injury under lipotoxic conditions. Sig­1R­overexpressing MIN6 cells were generated by lentiviral vector transfection. The effect of Sig­1R overexpression on cell proliferation detected by EdU staining, cell cycle progression by propidium iodide (PI), apoptosis by Annexin V­APC/PI, mitochondrial membrane potential by Mitolite Red and cytoplasmic Ca2+ levelsby Fura­2/AM in islet ß­cells were measured by flow cytometry. Western blot analysis was used to measure protein expression levels of endoplasmic reticulum (ER) stress markers glucose­regulated protein 78 and C/EBP homologous protein, mitochondrial apoptotic proteins Bcl­2­associated X and Bcl­2 and cytochrome c. In addition, ATP levels and insulin secretion were separately measured using ATP Assay and mouse insulin ELISA. Mitochondria­associated ER membrane (MAM) structures in MIN6 cells were then detected using transmission electron microscopy. Protein disulfide isomerase expression and possible colocalization between inositol 1,4,5­trisphosphate receptor and voltage­dependent anion channel 1 were examined using immunofluorescence. Sig­1R overexpression was found to promote ß­cell proliferation by accelerating cell cycle progression. Furthermore, Sig­1R overexpression ameliorated the apoptosis rate whilst impairing insulin secretion induced by palmitic acid by relieving ER stress and mitochondrial dysfunction in MIN6 cells. Sig­1R overexpression also promoted Ca2+ transport between mitochondria and ER by increasing the quantity of ER adjacent to mitochondria in the 50­nm range. It was concluded that Sig­1R overexpression conferred protective effects on ß­cells against lipotoxicity as a result of the promotion of cell proliferation and inhibition of ER stress and oxidative stress, by regulating the structure of MAM.

Nr2e1 deficiency aggravates insulin resistance and chronic inflammation of visceral adipose tissues in a diet-induced obese mice model.

AIMS: To investigate the nuclear receptor subfamily 2 group E member 1 (Nr2e1) expression in adipose tissues of obese mice and assess the role of Nr2e1 in insulin resistance and chronic inflammation of the adipose tissues. MAIN METHODS: An obese model was established in Nr2e1 knockout (KO) mice and their wild type (WT) littermates through a long-term high-fat diet (HFD) feeding regime. The epididymal fat weight, body weight, and daily food intake were recorded. The blood lipid profile, blood inflammatory factors, and the levels of fasting blood glucose (FBG) and fasting insulin were determined. We estimated insulin resistance by the homeostasis model assessment (HOMA). The expression of inflammatory factors and F4/80 was examined by polymerase chain reaction (PCR) and western blotting to assess adipose tissues inflammation. We also determined the molecules of insulin signaling and the nuclear factor kappa B (NF-κB) pathway by western blotting. KEY FINDINGS: The Nr2e1 expression was upregulated in WT obese mice when compared with that in control mice. Despite a lower body weight and epididymal fat mass in Nr2e1-/- mice, these rats showed increased inflammatory cytokines secretion, more pronounced hyperlipidemia, and impaired insulin sensitivity after HFD treatment. Further investigation revealed that Nr2e1 deletion affected the expression of insulin signaling and NF-κB pathway-related molecules in visceral adipose tissues. SIGNIFICANCE: Nr2e1 may act as a potential target to improve insulin sensitivity and inflammation in obesity and related complications.

Nr2e1 ablation impairs liver glucolipid metabolism and induces inflammation, high-fat diets amplify the damage.

Nonalcoholic fatty liver disease (NAFLD) is a common and complex metabolic disorder. Despite the widespread concern, there are still few effective treatments except lifestyle interventions. Nuclear receptor subfamily 2 group E member 1 (Nr2e1) is a transcription factor which regulates many biological processes, including development, growth, and differentiation of nerve cells. However, its specific function in hepatocyte is still unknown. In the present study, we found that the expression of Nr2e1 decreased in the livers of high-fat diet-fed mice. We generated Nr2e1 knockout (KO) mice and studied whether Nr2e1 ablation was related to NAFLD. We found that typical pathological features of NAFLD, including insulin resistance, hepatic steatosis, and inflammation, were present in Nr2e1-KO mice or high-fat diet-induced mice models. In conclusion, Nr2e1 ablation promotes liver steatosis and systemic insulin resistance. Nr2e1 may play a protective role in the formation of NAFLD and may serve as a worthy therapeutic target for NAFLD.