Prevalence and Influencing Factors of Irritable Bowel Syndrome Among Nurses in China: A Cross-Sectional Study.

The aims of this study were to investigate the prevalence and influencing factors of irritable bowel syndrome among nurses in order to update the epidemiological data. A questionnaire survey was administered to 1,325 clinical nurses. We used a questionnaire for demographic information, the IBS Severity Scoring System, the IBS Quality of Life questionnaire, the Hospital Anxiety and Depression Scale, the Pittsburgh Sleep Quality Index, and the Maslach Burnout Inventory to conduct our survey. Univariate and multivariate analyses were performed to detect factors influencing irritable bowel syndrome among nurses. The prevalence of irritable bowel syndrome was 13.3%, and the severity of symptoms was mostly moderate. The IBS Quality of Life score was significantly reduced (p < .001). Various foods that caused abdominal pain (egg and dairy products [OR = 4.80], greasy food [OR = 5.80], spicy food [OR = 2.66], raw and cold food [OR = 2.43]), a family history of gastrointestinal diseases (OR = 1.64, 95% CI [1.038, 2.587]), drinking weak green tea (OR = 1.71, 95% CI [1.143, 2.552]), mild depression (OR = 1.78, 95% CI [1.005, 3.156]), and the personal accomplishment dimension of occupational burnout (OR = 2.52, 95% CI [1.039, 6.114]) had important effects on nurses suffering from irritable bowel syndrome. On the contrary, exercising 1-2 hours per week (OR = 0.53, 95% CI [0.327, 0.859]) had a protective effect. The prevalence of irritable bowel syndrome among nurses is relatively high and may be influenced by several factors including genetics, diet, exercise, psychology, and occupational burnout.

Hepatic steatosis aggravates atherosclerosis via small extracellular vesicle-mediated inhibition of cellular cholesterol efflux.

BACKGROUND & AIMS: While it is recognized that non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease (CVD), how NAFLD affects the development and progression of CVD remains unclear and debatable. Hence, we aimed to determine the role of steatotic hepatocyte-derived small extracellular vesicles (sEVs) in foam cell formation and atherosclerosis progression. METHODS: sEVs from steatotic hepatocytes were isolated and characterized. MicroRNA (miRNA) deep sequencing was utilized to identify functional miRNA in sEVs. Lastly, we conducted a cross-sectional study on patients with NAFLD to validate these findings. RESULTS: Treatment of sEVs from steatotic hepatocytes promoted macrophage-derived foam cell formation and atherosclerosis progression via inhibition of ABCA1-mediated cholesterol efflux. Macrophage-specific deletion of Abca1 in ApoE-/- mice abolished the role of steatotic hepatocyte-derived sEVs in atherosclerosis progression. In addition, hepatocyte-specific deletion of Rab27a, which is the key GTPase regulating sEV release, significantly ameliorated high-fat, high-cholesterol diet-induced atherosclerosis progression in ApoE-/- mice. The miRNA deep sequencing results showed that miR-30a-3p was enriched in sEVs from steatotic hepatocytes. miR-30a-3p directly targeted the 3' untranslated region of ABCA1 to inhibit ABCA1 expression and cholesterol efflux. Treatment with antagomiR-30a-3p significantly attenuated atherosclerosis progression in high-fat, high-cholesterol diet-fed ApoE-/- mice. Moreover, serum sEVs from patients with NAFLD and sEV-miR-30a-3p expression were associated with decreased cholesterol efflux levels in foam cells. CONCLUSION: Steatotic hepatocyte-derived sEVs promote foam cell formation and facilitate atherogenesis via the miR-30a-3p/ABCA1 axis. Reducing sEV secretion by steatotic hepatocytes or targeting miR-30a-3p may be potential therapeutic approaches to slow the progression of NAFLD-driven atherosclerosis. IMPACT AND IMPLICATIONS: The presence of hepatic steatosis is strongly correlated with the risk of cardiovascular disease and cardiovascular events, yet the molecular mechanisms linking steatosis to progression of atherosclerosis are unclear. Herein, we identified small extracellular vesicles from steatotic hepatocytes as a trigger that accelerated the progression of atherosclerosis. Steatotic hepatocyte-derived small extracellular vesicles promoted foam cell formation via the miR-30a-3p/ABCA1 axis. Our findings not only provide mechanistic insight into non-alcoholic fatty liver disease-driven atherosclerosis but also provide potential therapeutic targets for patients with atherosclerosis.

Hepatic Fibroblast Growth Factor 21 Is Involved in Mediating Functions of Liraglutide in Mice With Dietary Challenge.

BACKGROUND AND AIMS: Several studies have shown that expression of hepatic fibroblast growth factor 21 (FGF21) can be stimulated by glucagon-like peptide 1 (GLP-1)-based diabetes drugs. As GLP-1 receptor (GLP-1R) is unlikely to be expressed in hepatocytes, we aimed to compare such stimulation in mice and in mouse hepatocytes, determine the involvement of GLP-1R, and clarify whether FGF21 mediates certain functions of the GLP-1R agonist liraglutide. APPROACH AND RESULTS: Liver FGF21 expression was assessed in mice receiving a daily liraglutide injection for 3 days or in mouse primary hepatocytes (MPHs) undergoing direct liraglutide treatment. The effects of liraglutide on metabolic improvement and FGF21 expression were then assessed in high-fat diet (HFD)-fed mice and compared with the effects of the dipeptidyl-peptidase 4 inhibitor sitagliptin. Animal studies were also performed in Glp1r-/- mice and liver-specific FGF21-knockout (lFgf21-KO) mice. In wild-type mouse liver that underwent RNA sequencing and quantitative reverse-transcription PCR, we observed liraglutide-stimulated hepatic Fgf21 expression and a lack of Glp1r expression. In MPHs, liraglutide did not stimulate Fgf21. In mice with HFD-induced obesity, liraglutide or sitagliptin treatment reduced plasma triglyceride levels, whereas their effect on reducing body-weight gain was different. Importantly, increased hepatic FGF21 expression was observed in liraglutide-treated mice but was not observed in sitagliptin-treated mice. In HFD-fed Glp1r-/- mice, liraglutide showed no beneficial effects and could not stimulate Fgf21 expression. In lFgf21-KO mice undergoing dietary challenge, the body-weight-gain attenuation and lipid homeostatic effects of liraglutide were lost or significantly reduced. CONCLUSIONS: We suggest that liraglutide-stimulated hepatic Fgf21 expression may require GLP-1R to be expressed in extrahepatic organs. Importantly, we revealed that hepatic FGF21 is required for liraglutide to lower body weight and improve hepatic lipid homeostasis. These observations advanced our mechanistic understanding of the function of GLP-1-based drugs in NAFLD.

Estrogen-Wnt signaling cascade regulates expression of hepatic fibroblast growth factor 21.

We have generated the transgenic mouse line LTCFDN in which dominant negative TCF7L2 (TCF7L2DN) is specifically expressed in the liver during adulthood. Male but not female LTCFDN mice showed elevated hepatic and plasma triglyceride (TG) levels, indicating the existence of estrogen-ß-cat/TCF signaling cascade that regulates hepatic lipid homeostasis. We show here that hepatic fibroblast growth factor 21 (FGF21) expression was reduced in male but not in female LTCFDN mice. The reduction was not associated with altered hepatic expression of peroxisome proliferator-activated receptor α (PPARα). In mouse primary hepatocytes (MPH), Wnt-3a treatment increased FGF21 expression in the presence of PPARα inhibitor. Results from our luciferase-reporter assay and chromatin immunoprecipitation suggest that evolutionarily conserved TCF binding motifs (TCFBs) on Fgf21 promoter mediate Wnt-3a-induced Fgf21 transactivation. Female mice showed reduced hepatic FGF21 production and circulating FGF21 level following ovariectomy (OVX), associated with reduced hepatic TCF expression and ß-catenin S675 phosphorylation. Finally, in MPH, estradiol (E2) treatment enhanced FGF21 expression, as well as binding of TCF7L2 and ribonucleic acid (RNA) polymerase II to the Fgf21 promoter; and the enhancement can be attenuated by the G-protein-coupled estrogen receptor 1 (GPER) antagonist G15. Our observations hence indicate that hepatic FGF21 is among the effectors of the newly recognized E2-ß-cat/TCF signaling cascade.NEW & NOTEWORTHY FGF21 is mainly produced in the liver. Therapeutic effect of FGF21 analogues has been demonstrated in clinical trials on reducing hyperlipidemia. We show here that Fgf21 transcription is positively regulated by Wnt pathway effector ß-cat/TCF. Importantly, hepatic ß-cat/TCF activity can be regulated by the female hormone estradiol, involving GPER. The investigation enriched our understanding on hepatic FGF21 hormone production, and expanded our view on metabolic functions of the Wnt pathway in the liver.

The accumulation, histopathology, and intestinal microorganism effects of waterborne cadmium on Carassius auratus gibelio.

Cadmium (Cd) is known to be a potentially toxic heavy metals to the fish health and growth. Carassius auratus gibelio (C. a. gibelio) specimens were exposed to waterborne Cd (0, 0.05, 0.10, 0.15, and 0.20 mg/L CdCl2) for 14 days. Cd accumulation, liver and intestine histopathology, and intestinal microorganism were investigated in the present study. The results indicated that Cd accumulation in the gill, liver, intestine, and muscle gradually decreased as Cd concentration increased. The gill accumulated higher amounts of Cd than other tissues. The histopathology of liver and intestine underwent changes with different Cd concentrations, including hepatocyte hypertrophy, aggregation of blood cells, sinusoids, lipidosis, necrosis of hepatic tissues, the erosion of villi, necrosis in the mucosal layer, the appearance of vacuoles in the lamina propria, hyperplasia, and swelling of goblet cells. Moreover, the core gut microbiota existed in the intestinal microorganism and did not change as Cd concentration increased. However, the diversity of intestinal microorganism was significantly reduced compared with that of the control sample. The present results indicated that C. a. gibelio exposed to Cd suffered toxicity, and Cd could affect the biodiversity of the intestinal microbiota of C. a. gibelio.

Inducible SHP-2 activation confers resistance to imatinib in drug-tolerant chronic myeloid leukemia cells.

BCR-ABL kinase mutations, accounting for clinical resistance to tyrosine kinase inhibitor (TKI) such as imatinib, frequently occur in acquired resistance or in advanced phases of chronic myeloid leukemia (CML). Emerging evidence implicates a critical role for non-mutational drug resistance mechanisms underlying the survival of residual cancer 'persister' cells. Here, we utilized non-mutational imatinib-resistant K562/G cells to reveal SHP-2 as a resistance modulator of imatinib treatment response during the early phase. SHP-2 phosphorylation was significantly higher in K562/G cells than in sensitive K562 cells. In K562 cells, both short-term and long-term exposure to imatinib induced SHP-2 phosphorylation. Consistently, gain- and loss-of-function mutants in SHP-2 proved its regulation of imatinib resistance. SHP-2 inhibitor and imatinib exhibited a strong antitumor synergy in in vitro and in vivo K562/G models. Mechanistically, dual SHP-2 and BCR-ABL inhibition blocked RAF/MEK/ERK and PI3K/AKT/mTOR pathways, respectively, leading to dramatic apoptotic death of K562/G cells. In conclusion, our results highlight that SHP-2 could be exploited as a biomarker and therapeutic target during the early phase of imatinib resistance development in CML.

Retention of the spacing effect with mental practice in hemiparetic stroke.

Mental practice (MP) is a promising adjuvant to physical practice that involves many of the same mechanisms and takes on many of the same properties as physical practice. This study compared efficacy of a "massed" MP regimen versus a "distributed" MP regimen on upper extremity (UE) motor impairment and functional limitation. Twenty-seven chronic stroke survivors were administered the UE section of the Fugl-Meyer (FM) and Action Research Arm Test (ARAT), followed by standardized physical practice and MP regimens. One group was administered "massed" MP (60 min of MP during a single daily session) and a second group administered distributed MP (20 min of MP occurring three times/day). After intervention, changes in FM and ARAT scores of subjects in the distributed condition were significantly higher than those of subjects in the massed condition (FM 3.65, 95 % CI 0.82-6.49, p value = 0.01; ARAT 3.95, 95 % CI 1.24-6.67, p value = 0.006). Likewise, at POST 3, subjects in the distributed group showed significantly higher change in ARAT scores (ARAT 4.90, 95 % CI 0.57-9.22, p value = 0.03); the change in FM scores at POST 3 was 3.18 points higher among subjects in the distributed condition, but only approached significance (95 % CI -1.27 to 7.63, p value = 0.15). Results suggest that a distributed MP schedule is more efficacious in bringing about paretic UE changes than a massed practice schedule, especially in terms of reducing UE functional limitation.

Polymer Micelles Laden Hydrogel Contact Lenses for Ophthalmic Drug Delivery.

Hydrogel contact lens is an attractive drug carrier for the delivery of ophthalmic drugs. But limited drug loading capacity and burst release restricted its application in this field. Polymer micelle laden hydrogel contact lenses were designed for ophthalmic drug delivery in the work. ß-CD/PAA/PEG ternary system was chosen to form polymer micelle. The micelle size could be adjusted by ß-CD content and PAA/PEG concentration. The zeta potential of micelle was irrelevant to ß-CD content, but influenced by PAA/PEG concentration. The absorbed drug concentration in micelle solution depended on both ß-CD content and PAA/PEG concentration. Polymer micelle laden hydrogels were obtained by radical polymerization in situ. The transparency of polymer micelle laden hydrogel declined with PAA/PEG concentration increasing. The equilibrium water content and water loss showed that polymer micelle laden hydrogel with higher PAA/PEG concentration was in a higher swollen state. The dynamic viscoelastic properties howed that all polymer micelle laden hydrogels had some characteristics of crosslinked elastomers. The surface structure of freeze dried composite hydrogels was different from freeze dried pure hydrogel. The drug loading and releasing behaviors were detected to evaluate the drug loading and releasing capacity of hydrogels using orfloxacin and puerarin as model drugs. The results indicated the polymer micelle in hydrogel could hold or help to hold some ophthalmic drugs, and slow down orfloxacin release speed or keep puerarin stably stay for a time in hydrogels. In the end, it was found that the transparency of composite hydrogel became better after the hydrogel had been immersed in PBS for several weeks.

The effect of ginger and garlic addition during cooking on the volatile profile of grass carp (Ctenopharyngodon idella) soup.

Ginger and garlic have long been used in Asian countries to enhance the flavor and to neutralize any unpleasant odors present in fish soup. The purpose of this study was to evaluate the change in the amount of volatile components present in fish soup compared to boiled water solutions of ginger and garlic. The fish soup was prepared by boiling oil-fried grass carp (Ctenopharyngodon idella) with or without ginger and/or garlic. Generally, boiling garlic and ginger in water led to a decrease in the amount of the principal volatile constituents of these spices, together with the formation of some new volatiles such as pentanal, hexanal, and nonanal. The results showed that 16 terpenes present in raw ginger, predominantly camphene, ß-phellandrene, ß-citral, α-zingiberene, and (E)-neral, were detected in fish soup with added ginger and thus remained in the solution even after boiling. Similarly, 2-propen-1-ol and three sulfur compounds (allyl sulfide, diallyl disulfide, and diallyl trisulfide) present in raw garlic, were present in trace amounts in the boiled garlic solution, but were present in considerably larger amounts in the boiled fish solution with garlic or garlic plus ginger. In conclusion, the effect of adding spices on the volatile profile of grass carp soup can be attributed to the dissolution of flavor volatiles mainly derived from raw spices into the solution, with few additional volatiles being formed during boiling. In addition, boiling previously fried grass carp with spices led to enhanced volatile levels compared to boiled spice solutions.

Relationship between family function, self-perceived burden and loneliness in patients with type 2 diabetes mellitus: a cross-lagged analysis.

AIMS: To explore the inter-predictive role and causal relationship between family functioning, self-perceived burden and loneliness in people with type 2 diabetes. METHODS: In this study, patients with type 2 diabetes admitted to two tertiary care hospitals in China were selected for an 8-month follow-up, and the patients' scores on the Family Functioning, Self-perceived Burden, and Loneliness scales were measured repeatedly at three time periods: during hospitalisation (T1), 1 month after discharge (T2), and 3 months after discharge (T3). RESULTS: The results showed that family function at the T1 time point had a negative predictive effect on self-perceived burden at the T2 time point, ß = - 0.43, P = 0.005. Loneliness at the T1 time point had a positive predictive effect on self-perceived burden at the T2 time point, ß = 0.08, P = 0.021. Unlike the pathway at time point T1, family functioning at time point T2 negatively predicted loneliness at time point T3, ß = - 0.32, P = 0.013. Loneliness at time point T2 positively predicted family functioning at time point T3, ß = 0.025, P = 0.013. Loneliness at time point T2 negatively predicted self-perceived burden at time point T3 (P = 0.011). CONCLUSIONS: The results of the cross-lagged analysis show that there is a mutually predictive and moderating relationship between family functioning and loneliness in patients with type 2 diabetes. Loneliness can predict the level of self-perceived burden at the next time point.

Resveratrol Improves Hyperuricemia and Ameliorates Renal Injury by Modulating the Gut Microbiota.

Resveratrol (RES) has been reported to prevent hyperuricemia (HUA); however, its effect on intestinal uric acid metabolism remains unclear. This study evaluated the impact of RES on intestinal uric acid metabolism in mice with HUA induced by a high-fat diet (HFD). Moreover, we revealed the underlying mechanism through metagenomics, fecal microbiota transplantation (FMT), and 16S ribosomal RNA analysis. We demonstrated that RES reduced the serum uric acid, creatinine, urea nitrogen, and urinary protein levels, and improved the glomerular atrophy, unclear renal tubule structure, fibrosis, and renal inflammation. The results also showed that RES increased intestinal uric acid degradation. RES significantly changed the intestinal flora composition of HFD-fed mice by enriching the beneficial bacteria that degrade uric acid, reducing harmful bacteria that promote inflammation, and improving microbial function via the upregulation of purine metabolism. The FMT results further showed that the intestinal microbiota is essential for the effect of RES on HUA, and that Lactobacillus may play a key role in this process. The present study demonstrated that RES alleviates HFD-induced HUA and renal injury by regulating the gut microbiota composition and the metabolism of uric acid.

Solvent-responsive wettability of self-assembled monolayers of dithiooctanoic acid derivatives bearing N,N-disubstituted amide groups.

We have designed and synthesized two dithiooctanoic acid derivatives bearing N,N-disubstituted amide groups and used them to fabricate self-assembled monolayers (SAMs) on gold surface. These films showed a reversible changes in wettability, one of which was indicated by surface contact angle switching between 40° and 59° upon alternating treatment with ethanol and cyclohexane. NMR experimental results of a model molecule suggest that the solvent-responsive wettability of the SAMs could be related with the changes in the relative populations of two stereoisomers of amide. The solvent responsivity of SAMs fabricated from other two amides was also studied, and the results confirmed that N,N-disubstitution was essential for an amide-containing SAM to have stimuli responsivity. Thus, introduction of a functional group exhibiting controlled isomerization of conformation could be an effective strategy for designing new stimuli-responsive materials.

Multidimensional master equation and its Monte-Carlo simulation.

We derive an integral form of multidimensional master equation for a markovian process, in which the transition function is obtained in terms of a set of discrete Langevin equations. The solution of master equation, namely, the probability density function is calculated by using the Monte-Carlo composite sampling method. In comparison with the usual Langevin-trajectory simulation, the present approach decreases effectively coarse-grained error. We apply the master equation to investigate time-dependent barrier escape rate of a particle from a two-dimensional metastable potential and show the advantage of this approach in the calculations of quantities that depend on the probability density function.

Association of MAFLD with end-stage kidney disease: a prospective study of 337,783 UK Biobank participants.

INTRODUCTION: Metabolic dysfunction-associated fatty liver (MAFLD) has been found to be associated with the prevalence of chronic kidney disease (CKD). However, it is unknown whether MAFLD is associated with CKD development and the incidence of end-stage kidney disease (ESKD). We aimed to clarify the association between MAFLD and incident ESKD in the prospective UK Biobank cohort. METHODS: We analyzed the data of 337,783 UK Biobank participants and relative risks for the ESKD were calculated by using the Cox regression analysis. RESULTS: Among 337,783 participants over a median duration of 12.8 years follow-up, a total of 618 ESKD cases were diagnosed. Participants with MAFLD were twice likely to develop ESKD (hazard ratio [HR] 2.03, 95% confidence interval [CI] 1.68-2.46, p < 0.001). The association of MAFLD with ESKD risk remained significant in both non-CKD and CKD participants. Our results also showed that there were graded associations between liver fibrosis scores and the risk of ESKD in MAFLD cases. Compared to non-MAFLD individuals, the adjusted HRs for incident ESKD in MAFLD patients with increasing levels of NAFLD fibrosis score were 1.23 (95% CI 0.96-1.58), 2.45 (1.98-3.03) and 7.67 (5.48-10.73), respectively. Furthermore, the risking alleles of PNPLA3 rs738409, TM6SF2 rs58542926, GCKR rs1260326 and MBOAT7 rs641738 amplified the MAFLD effect on ESKD risk. In conclusion, MAFLD is associated with incident ESKD. CONCLUSION: MAFLD may help identify the subjects at high risk of ESKD development and MAFLD interventions should be encouraged to slow down CKD progression.

The impact of spouse health on social participation of older adults in China: Evidence from the CLHLS.

BACKGROUND: China is dealing with a serious aging issue. Social participation is essential for active aging. The health status of spouses is intertwined with the trajectory of the social function of the elderly. OBJECTIVES: This study examined the association between spouse health and social participation among older Chinese adults. The study also explored the mediating role of loneliness and anxiety between spousal health and social participation. METHODS: The analytic sample included 6125 adults aged 60 years and above. Prospective data were obtained from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). First, we described basic socio-demographic information about the sample. Secondly, Spearman's correlation analysis was used to determine whether correlations existed between spousal health, loneliness, anxiety, and social participation. Finally, mediation analysis was run using the SPSS macro PROCESS program. RESULTS: Spousal health, loneliness, anxiety, and social participation were significantly correlated (P < 0.01). Spousal health could not only have a direct positive impact on social participation in older adults (ß = 0.239, 95 % CI: 0.120, 0.359), but also indirectly on social participation through three pathways: an independent mediating effect of loneliness (ß = 0.020, 95 % CI: 0.009, 0.034), an independent mediating effect of anxiety (ß = 0.018, 95%CI: 0.009, 0.032), and a chain mediating effect of loneliness and anxiety (ß = 0.004, 95%CI: 0.002, 0.007). CONCLUSION: This study suggests paying more attention to elderly couples and decreasing the negative consequences of changes in spousal health.

Associations of Macronutrients Intake With MRI-determined Hepatic Fat Content, Hepatic Fibroinflammation, and NAFLD.

CONTEXT: A healthy lifestyle is the cornerstone of management in nonalcoholic fatty liver disease (NAFLD). However, the associations between dietary macronutrient composition and different aspects of NAFLD pathology are unclear and dietary recommendations for NAFLD are lacking. OBJECTIVE: This work aimed to evaluate the associations of dietary macronutrient composition with hepatic steatosis, hepatic fibroinflammation, and NAFLD. METHODS: In this cross-sectional study, a total of 12 620 UK Biobank participants who completed both the dietary questionnaire and magnetic resonance imaging (MRI) examination were included in this study. Dietary consumption of macronutrient was self-reported and calculated. MRI-determined hepatic fat content, fibroinflammation, and NAFLD were estimated. RESULTS: First, we found that saturated fatty acid (SFA) intake was associated with higher hepatic steatosis, fibroinflammation, and NAFLD prevalence. In contrast, higher fiber or protein intake was reversely correlated with hepatic steatosis and fibroinflammation. Interestingly, starch or sugar intake was significantly associated with hepatic fibroinflammation, whereas monounsaturated fatty acid (MUFA) intake was negatively correlated with hepatic fibroinflammation. Isocaloric analysis revealed that replacing SFA with sugar, fiber, or protein was significantly associated with a reduction in hepatic steatosis, while replacing starch, sugar, or SFA with protein or MUFA was significantly correlated with a decrease in hepatic fibroinflammation. CONCLUSION: Overall, our results demonstrate that specific macronutrients are associated with different aspects of NAFLD, and specific dietary compositions should be recommended for distinct NAFLD-risk populations.

Identification of factors associated with fear of hypoglycemia using the capability, opportunity, motivation and behavior model in people with type 2 diabetes mellitus: a cross-sectional study.

AIMS: To examined the relationship between fear of hypoglycemia and certain variables in people with type 2 diabetes mellitus (T2DM) based on the Capability, Opportunity, Motivation, and Behavior model, combined with the context unique to people with diabetes to provide a basis for developing targeted nursing interventions. METHODS: In this cross-sectional study, 212 people with T2DM were recruited from February 2021 to July 2021. Data were collected using the Hypoglycaemia Fear Survey, Gold score, Patient Assessment of Chronic Illness Care (PACIC) scale and Diabetic Self-Management Attitudes Scale. Multiple linear regression analysis was performed to determine the predictors of fear of hypoglycemia using SPSS 26.0. RESULTS: The mean fear of hypoglycemia score was 74.88 ± 18.28 (range: 37.00-132.00). In people with T2DM, the frequency of blood glucose monitoring, the frequency of hypoglycemia in the past half-year, degree of understanding of hypoglycemia, impaired awareness of hypoglycemia, PACIC, and self-management attitude of diabetes were the influencing factors of fear of hypoglycemia (adjusted R2 = 0.560, F[21,190] = 13.800, P < 0.001). These variables explained 56.0% of the variance in the fear of hypoglycemia. CONCLUSIONS: The level of fear of hypoglycemia in people with T2DM was relatively high. In addition to paying attention to the disease characteristics of people with T2DM, medical staff should also pay attention to patients' own perception and handling ability of disease and hypoglycemia, attitude toward self-management behavior and external environment support, all of which have a positive effect on improving the fear of hypoglycemia in people with T2DM, optimizing the self-management level and improving quality of life.

Epigenetic modulation of Drp1-mediated mitochondrial fission by inhibition of S-adenosylhomocysteine hydrolase promotes vascular senescence and atherosclerosis.

AIMS: Vascular senescence, which is closely related to epigenetic regulation, is an early pathological condition in cardiovascular diseases including atherosclerosis. Inhibition of S-adenosylhomocysteine hydrolase (SAHH) and the consequent increase of S-adenosylhomocysteine (SAH), a potent inhibitor of DNA methyltransferase, has been associated with an elevated risk of cardiovascular diseases. This study aimed to investigate whether the inhibition of SAHH accelerates vascular senescence and the development of atherosclerosis. METHODS AND RESULTS: The case-control study related to vascular aging showed that increased levels of plasma SAH were positively associated with the risk of vascular aging, with an odds ratio (OR) of 3.90 (95% CI, 1.17-13.02). Elevated pulse wave velocity, impaired endothelium-dependent relaxation response, and increased senescence-associated ß-galactosidase staining were observed in the artery of SAHH+/- mice at 32 weeks of age. Additionally, elevated expression of p16, p21, and p53, fission morphology of mitochondria, and over-upregulated expression of Drp1 were observed in vascular endothelial cells with SAHH inhibition in vitro and in vivo. Further downregulation of Drp1 using siRNA or its specific inhibitor, mdivi-1, restored the abnormal mitochondrial morphology and rescued the phenotypes of vascular senescence. Furthermore, inhibition of SAHH in APOE-/- mice promoted vascular senescence and atherosclerosis progression, which was attenuated by mdivi-1 treatment. Mechanistically, hypomethylation over the promoter region of DRP1 and downregulation of DNMT1 were demonstrated with SAHH inhibition in HUVECs. CONCLUSIONS: SAHH inhibition epigenetically upregulates Drp1 expression through repressing DNA methylation in endothelial cells, leading to vascular senescence and atherosclerosis. These results identify SAHH or SAH as a potential therapeutic target for vascular senescence and cardiovascular diseases.

A Randomized Trial on Resveratrol Supplement Affecting Lipid Profile and Other Metabolic Markers in Subjects with Dyslipidemia.

Resveratrol is a polyphenol with a well-established beneficial effect on dyslipidemia and hyperuricemia in preclinical experiments. Nonetheless, its efficacy and dose-response relationship in clinical trials remains unclear. This study examined whether resveratrol supplement improves the serum lipid profile and other metabolic markers in a dose-response manner in individuals with dyslipidemia. A total of 168 subjects were randomly assigned to placebo (n = 43) and resveratrol treatment groups of 100 mg/d (n = 41), 300 mg/d (n = 43), and 600 mg/d (n = 41). Anthropometric and biochemical parameters were analyzed at baseline and 4 and 8 weeks. Resveratrol supplementation for 8 weeks did not significantly change the lipid profile compared with the placebo. However, a significant decrease of serum uric acid was observed at 8 weeks in 300 mg/d (-23.60 ± 61.53 µmol/L, p < 0.05) and 600 mg/d resveratrol groups (-24.37 ± 64.24 µmol/L, p < 0.01) compared to placebo (8.19 ± 44.60 µmol/L). Furthermore, xanthine oxidase (XO) activity decreased significantly in the 600 mg/d resveratrol group (-0.09 ± 0.29 U/mL, p < 0.05) compared with placebo (0.03 ± 0.20 U/mL) after 8 weeks. The reduction of uric acid and XO activity exhibited a dose-response relationship (p for trend, <0.05). Furthermore, a marked correlation was found between the changes in uric acid and XO activity in the resveratrol groups (r = 0.254, p < 0.01). Resveratrol (10 µmol/L) treatment to HepG2 cells significantly reduced the uric acid levels and intracellular XO activity. Nevertheless, we failed to detect significant differences in glucose, insulin, or oxidative stress biomarkers between the resveratrol groups and placebo. In conclusion, resveratrol supplementation for 8 weeks had no significant effect on lipid profile but decreased uric acid in a dose-response manner, possibly due to XO inhibition in subjects with dyslipidemia. The trial was registered on ClinicalTrials.gov (NCT04886297).