Epidemiological Characterisation of Chronic Diseases Among Civil Servants in Hebei Province, China: A Cross-Sectional Real-World Study of Approximately 50,000 Adults.

Background: The objective of this investigation was to explore the health status and epidemiological features of civil servants working in Hebei Province, China. Methods: Data was collected through a cross-sectional survey that involved 50,039 adult civil servants in Hebei Province. The research was conducted at the Hebei Provincial Medical Examination Centre and included inquiries about demographics, health behaviours, chronic illnesses, and abnormal check-up indicators. Statistical data were used to determine the prevalence of chronic diseases and abnormal health examination indicators. Subgroup analyses by sex were then conducted to calculate the similarities and differences in health status between men and women. Results: The findings of the survey indicate that 14.2% of individuals who work in civil service suffer from obesity. Additionally, a considerable proportion of this group display poor health behaviours, including smoking and alcohol consumption. Hypertension (21.03%), dyslipidaemia (10.88%), and diabetes mellitus (8.56%) were identified as the top three chronic diseases, while cardiovascular diseases were prevalent at 6.27% among civil servants. Ultrasound showed a high prevalence of fatty liver, non-smooth gallbladder and liver cysts (44.61%, 33.24% and 23.26% respectively). The occurrence of pulmonary nodules was alarmingly high at 88.48%, while thyroid nodules were found in as much as 62.65% of patients. Abnormal E/A values≤1, prostate hyperplasia, breast nodules, and carotid plaques were also prevalent, with percentages ranging from 46.76% to 63.04%. In subgroup analyses by gender, the prevalence of chronic diseases and abnormal screening indicators was consistently higher in men than in women, with the exception of thyroid nodules and thyroid surgery. Conclusion: The survey revealed a large proportion of civil servants in Hebei Province, China, suffering from chronic diseases, underscoring the necessity for enhanced attention to chronic disease prevention and management in this group and emphasising the requirement for focused interventions aimed at improving health outcomes.

Effect of Semaglutide and Empagliflozin on Pulmonary Structure and Proteomics in Obese Mice.

Objective: This study utilized proteomics to investigate changes in protein expression associated with lung health in obese mice exposed to semaglutide and empagliflozin through a high-fat diet. Methods: Twenty-eight male C57BL/6JC mice were randomly assigned to two groups: a control diet group (n = 7) and a high-fat diet group (n = 21). The HFD group was further divided into three groups: HFD group (n = 7), Sema group (n = 7), and Empa group (n = 7). Post-treatment, mice underwent assessments including glucose tolerance, lipids, oxidative stress markers, body weight, lung weight, and structure. Proteomics identified differentially expressed proteins (DEPs) in lung tissue, and bioinformatics analyzed the biological processes and functions of these proteins. Results: Semaglutide and empagliflozin significantly attenuated obesity-induced hyperglycemia, abnormal lipid metabolism, oxidative stress response, and can decrease alveolar wall thickness, enlarge alveolar lumen, and reduce collagen content in lung tissue. Both medications also attenuated lung elastic fibre cracking and disintegration. In the HFD/NCD group, there were 66 DEPs, comprising 30 proteins that were increased and 36 that were decreased. Twenty-three DEPs overlapped between Sema/HFD and Empa/HFD, with 11 up-regulated and 12 down-regulated simultaneously. After analysing DEPs in different groups, four proteins - LYVE1, BRAF, RGCC, and CHMP5 - were all downregulated in the HFD group and upregulated by semaglutide and empagliflozin treatment. Conclusion: This study demonstrates that obesity induced by a high-fat diet causes a reduction in the expression of LYVE1, BRAF, RGCC, and CHMP5 proteins, potentially affecting lung function and structure in mice. Significantly, the administration of semaglutide and empagliflozin elevates the levels of these proteins, potentially offering therapeutic benefits against lung injury caused by obesity. Merging semaglutide with empagliflozin may exert a more pronounced impact.

The Relationship Between UA/HDL and Diabetic Peripheral Neuropathy: A Cross-Sectional Analysis.

Purpose: This study was designed to analyze correlations between the uric acid to high-density lipoprotein cholesterol ratio (UHR) and peripheral nerve conduction velocity (NCV) among type 2 diabetes mellitus (T2DM) patients. Patients and Methods: This was a single-center cross-sectional analysis of 324 T2DM patients. All patients were separated into a group with normal NCV (NCVN) and a group with abnormal NCV (NCVA). Patients were also classified into groups with low and high UHR values based on the median UHR in this study cohort. Neurophysiological data including motor and sensory conduction velocity (MCV and SCV, respectively) were measured for all patients. Results: Relative to patients with low UHR values, those in the high UHR group presented with greater NCVA prevalence (P = 0.002). UHR remained negatively correlated with bilateral superficial peroneal nerve SCV, bilateral common peroneal nerve MCV, bilateral ulnar nerve SCV, and bilateral right median nerve MCV even after adjustment for confounding factors. UHR was identified as an NCVA-related risk factor, with a 1.370-fold increase in NCVA prevalence for every unit rise in UHR (P < 0.001). Conclusion: These results identify UHR as a risk factor associated with NCVA that was independently negatively associated with NCV among T2DM patients.

Correlation Between Glycolipid Metabolism Levels and Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus.

Purpose: We investigate the correlation between glucose and lipid metabolism and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) and its diagnostic and predictive value. Patients and Methods: A retrospective analysis involved 620 patients diagnosed with T2DM, categorized into two groups based on fundus examination results: the non-diabetic retinopathy group (NDR, n=340) and the diabetic retinopathy group (DR, n=280). We collected baseline patient data, calculated the ratio of glycated hemoglobin (HbA1c) to high-density lipoprotein cholesterol (HDL-C), and analyzed its association with Type 2 Diabetic Retinopathy. Results: HbA1c/HDL-C in DR group exhibited significantly higher than the NDR group (P<0.001). Mantel-Haenszel's chi-square trend analysis indicated a notable linear trend (P<0.001) between HbA1c/HDL-C and DR. HbA1c/HDL-C revealed moderate positive correlations with DR, r=0.342, P<0.001. Binary logistic regression analysis showed systolic blood pressure (SBP), diabetes course, fasting blood glucose (FBG) and HbA1c/HDL-C as independent risk factors for DR in T2DM patients. Restrictive cubic spline analysis demonstrated a significant nonlinear relationship between HbA1c/HDL-C and DR (P total trend <0.001, P nonlinear = 0.0196). ROC curve analysis identified that HbA1c/HDL-C had the highest diagnostic accuracy for DR, with an area under the ROC curve (AUC) of 0.711, 53.2% sensitivity, and 78.2% specificity. Conclusion: Our study shows that HbA1c/HDL-C is an independent risk factor for DR in patients with type 2 diabetes. HbA1c/HDL-C has good diagnostic value for DR and can be used as a biological index for early screening of DR.

Effect of Semaglutide on High-Fat-Diet-Induced Liver Cancer in Obese Mice.

This study aims to investigate the impact of semaglutide on the expression of liver cancer proteins in obese mice induced by a high-fat diet. Sixteen obese mice were randomly divided into two groups: the high-fat diet group and the semaglutide group, each consisting of eight mice. Additionally, eight normal male mice were included as the control group. Serum samples were collected, and a differential expression analysis of total proteins in adipose tissue was performed using quantitative tandem mass spectrometry (TMT) in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Significant differential proteins were identified and subjected to a bioinformatics analysis. The findings revealed that these differential proteins, namely, integrin αV (ITGAV), laminin γ1 (LAMC1), fatty acid-binding protein 5 (FABP5), and lipoprotein lipase (LPL), regulate the occurrence and development of liver cancer by participating in the extracellular matrix (ECM) signaling pathway and the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Notably, semaglutide can decelerate the progression of liver cancer by inducing the expression of ITGAV, LAMC1, FABP5, and LPL in the adipose tissue of obese mice.

Sleeve gastrectomy with one anastomosis bipartition versus one anastomosis gastric bypass: A pilot study.

BACKGROUND: One anastomosis gastric bypass (OAGB) is a new recognized metabolic surgery, but the problem that we cannot screen the excluded stomach is a troubling issue in China. The emergence of sleeve gastrectomy plus one anastomosis bipartition (SG + OAB) makes us see a hope to solve this problem. OBJECTIVES: By comparing the efficacy of the two surgical methods, to evaluate whether SG + OAB surgery can solve the dilemma faced by OAGB that the excluded stomach cannot be screened. METHODS: A retrospective study to compare the patients who underwent OAGB and SG + OAB was conducted. The main outcome measures were (1) operation risk, (2) weight loss, and (3) diabetes remission at 6 months. RESULTS: This study was conducted in the bariatric/metabolic surgical center. From November 2021 to February 2022, a total of 30 patients with obesity who received SG + OAB surgery were recruited. Another matched 60 patients undergoing OAGB were recruited as control group. There was no difference in preoperative age (32.15 ± 9.02 vs. 34.47 ± 7.22; p = .224), female ratio (83% vs. 85%; p = .837), and BMI (36.18 ± 5.30 vs. 34.68 ± 5.58; p = .217) between the two groups. OAGB had a shorter mean operation time (121.67 ± 20.41 vs. 143.50 ± 25.07 min; p < .001) and a lower intraoperative blood loss (21.92 ± 12.35 vs. 32.43 ± 22.01 mL; p = .005), but a longer postoperative flatus passage (2.13 ± 0.43 vs. 1.87 ± 0.43 days; p = .007) compared with the SG + OAB group. Two patients (6.7%) developed major surgical complication in SG + OAB group but no major complication developed in OAGB group. At 6 months after surgery, SG + OAB had a higher %total weight loss than OAGB (31.05 ± 3.12 vs. 28.14 ± 5.43%; p = .015), but diabetes remission rate was similarly high in both groups. CONCLUSIONS: SG + OAB operation had a non-inferior or even better weight loss than OAGB, with a similar glycemic control efficacy. However, the high complication rate of SG + OAB is the major drawback that needs attention.

The Combination of Remnant Cholesterol and Waist Circumference Offers Predictive Value for Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study from a Medical Examination Center.

Objective: To explore the association between levels of remnant cholesterol (RC) and the incidence of non-alcoholic fatty liver disease (NAFLD) in the general population, ultimately leading to the assessment of a novel proposed model combining RC and waist circumference (R-W) as a predictor of NAFLD incidence. Methods: A cross-sectional analysis was conducted of 4913 subjects undergoing physical examinations at Hebei General Hospital, with ultrasound findings being used to classify patients into individuals with and without NAFLD. Median RC values were used to separate subjects into those with low and high levels of RC, after which the predictive performance of RC and the novel R-W model when used to assess NAFLD risk was assessed through multifactorial logistic regression analyses and receiver operating characteristic curves. Results: Subjects exhibiting higher RC levels were found to exhibit an elevated risk of NAFLD incidence with or without adjusting for confounding factors. The binary logistic regression analysis-based R-W model may thus offer utility as a tool to gauge the risk of NAFLD in the general population, as it outperformed RC or WC alone, particularly when assessing women or individuals < 45 years of age. The area under the ROC curve for this combined R-W model was 0.813 (0.802, 0.824), with respective sensitivity and specificity values of 83.86% and 63.91%, all of which were significantly higher than corresponding values for RC and WC (P < 0.001). Conclusion: The present supports a strong association between RC levels and NAFLD in the general populace, and the combined R-W model exhibits greater utility as a tool to predict NAFLD incidence relative to RC or WC in isolation, particularly for individuals who are female or <45 years old.

Exploring the Correlation Between the Systemic Immune Inflammation Index (SII), Systemic Inflammatory Response Index (SIRI), and Type 2 Diabetic Retinopathy.

Purpose: Systemic immune inflammation index (SII), systemic inflammatory response index (SIRI) are new inflammation indicators calculated after integrating multiple indicators in blood routine. This study aims to investigate the correlation between the SII, SIRI and type 2 diabetic retinopathy (T2DR) and the diagnostic significance of these indices in T2DR. Patients and Methods: A retrospective analysis involved 500 patients diagnosed with type 2 diabetes (T2DM), categorized into two groups based on fundus examination results: the non-diabetic retinopathy group (NDR, n=256) and the diabetic retinopathy group (DR, n=244). We calculated SII and SIRI, and analyzed their associations with T2DR. Results: The DR group exhibited significantly higher SII and SIRI values compared to the NDR group (P<0.001). Mantel-Haenszel's chi-square trend analysis revealed a notable linear trend (P<0.001) between SII, SIRI, and DR. SII and SIRI exhibited moderate positive correlations with DR, (r=0.354, P<0.001; r=0.469, P<0.001), respectively. Binary logistic regression analysis identified SII and SIRI as independent risk factors for DR. Restrictive cubic spline analysis demonstrated a significant linear relationship between SII and DR (P total trend <0.001, P nonlinear = 0.0657). Stratification by gender indicated that SII is more sensitive to the onset of DR in men. A significant nonlinear relationship was observed between SIRI and DR (P total trend <0.001, P nonlinear = 0.0025), with no gender-related differences in SIRI's association with DR. ROC curve analysis demonstrated that the combined use of SII and SIRI achieved the highest diagnostic accuracy for DR, with an AUC of 0.782, 74.6% sensitivity, and 69.9% specificity. Conclusion: Our findings suggested that SII and SIRI as independent risk factors for DR. The high accuracy of SII combined with SIRI in diagnosing DR underscores their potential as early biological indicators for DR diagnosis.

Correlation Between Fibrinogen/Albumin and Diabetic Peripheral Neuropathy.

Purpose: This study aimed to examine the correlation between fibrinogen/albumin (FAR) and diabetic peripheral neuropathy (DPN). Patients and Methods: A total of 342 patients were included and categorized into either the DPN group or the Non-DPN (NDPN) group based on their DPN status. The FAR index was determined by calculating the ratio of fibrinogen (FIB) to serum albumin (ALB), multiplied by 100. The participants were then divided into a High-FAR group and a Low-FAR group using the median FAR value as the threshold. Neurophysiological data were collected from the participants, which included motor conduction velocity (MCV) and sensory conduction velocity (SCV). Results: The DPN group displayed higher FAR levels [(DPN vs NDPN:6.72 (5.89,7.74) vs 5.94±1.14], in addition to slower SCV and MCV data compared to the NDPN group. The high FAR group had a higher prevalence of DPN (78.9% vs 55.6%) (P<0.05). There was a negative correlation between FAR and NCV, including bilateral median nerve SCV, left ulnar nerve SCV, bilateral median nerve MCV, bilateral common peroneal nerve MCV, bilateral tibial nerve MCV, and left ulnar nerve MCV. FAR was revealed to be an independent risk factor for the development of DPN in patients and demonstrated a greater predictive value for DPN development in Type 2 diabetes mellitus (T2DM) compared with FIB, HbA1c. Conclusion: The results suggest that monitoring FAR levels in patients with T2DM could identify those at higher risk for developing DPN, making the FAR index a valuable predictor of DPN development. Furthermore, since FAR has an inverse relationship with NCV, it stands to reason that high FAR levels may indicate nerve damage and slower conduction velocities. Thus, managing FAR could prove beneficial in both preventing and delaying the onset of DPN in T2DM patients.

The Relationship Between Non-HDL-C /HDL-C Ratio (NHHR) and Vitamin D in Type 2 Diabetes Mellitus.

Purpose: The objective of this research was to examine the relationship between non-HDL cholesterol/HDL cholesterol ratio (NHHR) and vitamin D in type 2 diabetes mellitus (T2DM). Patients and Methods: This study enrolled 617 T2DM participants. Participants were separated into two groups: no vitamin D deficiency and vitamin D deficiency. Participants were split into two categories: individuals who had a high NHHR and those with a low NHHR, with the median NHHR serving as the cut-off. Eventually, the study participants were classified into two groups by gender, which were further classified into vitamin D deficient and non-vitamin D deficient groups. Results: NHHR values were substantially greater in vitamin D deficient group than in the non-deficient group in both male and female T2DM patients (P<0.05). The high NHHR group displayed substantially lower vitamin D levels than the low NHHR group [16.21 (12.55,21.35) vs 19.05 (14.59,24.07), P<0.001]. NHHR was discovered to be negatively and independently associated with vitamin D levels, and there was no sex difference. Conclusion: For the first time, our research revealed a negative relationship between NHHR and vitamin D in patients with T2DM.

Triglyceride-glucose index and cervical vascular function: outpatient-based cohort study.

OBJECTIVES: The purpose of this study was to investigate the correlation between triglyceride-glucose (TyG) index and cervical vascular function parameters in the general population without cerebrovascular disease. MATERIALS AND METHODS: This was a cross-sectional study that recruited a total of 1996 participants without cerebrovascular disease. TyG index was calculated based on fasting triglycerides and glucose. All patients were divided into two groups based on the median TyG index: the high TyG group and the low TyG group. The differences in basic clinical characteristics and neck vascular function parameters between the two groups of participants were compared, and then the correlation between TyG index and neck vascular function parameters was investigated. RESULTS: Participants with a high TyG index had lower systolic, diastolic, and mean flow velocities in the basilar, vertebral, and internal carotid arteries compared with those with a low TyG index. Participants with a high TyG index had higher pulsatility index in the left vertebral artery and right internal carotid artery, but this difference was not observed in the basilar artery. In addition, TyG index was significantly negatively correlated with systolic, diastolic, and mean flow velocities in the basilar, vertebral, and internal carotid arteries, and the correlation remained after adjusting for confounding factors. CONCLUSION: In the general population, there was a well-defined correlation between TyG index and cervical vascular function parameters, and increased TyG index was independently associated with reduced cervical vascular blood flow velocity.

Peptide immunization against the C-terminal of alpha-synuclein reduces locomotor activity in mice overexpressing alpha-synuclein.

Abnormal accumulation of alpha-synuclein (αSyn) in the remaining nigra dopaminergic neurons is a common neuropathological feature found in patients with Parkinson's disease (PD). Antibody-based immunotherapy has been considered a potential approach for PD treatment. This study aims to investigate the effectiveness of active immunization against αSyn in a mouse model of PD. Adult mice were immunized with or without a synthetic peptide containing the C-terminal residues of human αSyn and activation epitopes, followed by an intranigral injection of adeno-associated virus vectors for overexpressing human αSyn. Upon the peptide injection, αSyn-specific antibodies were raised, accompanied by degeneration of dopaminergic neurons and motor deficits. Furthermore, the induction of neuroinflammation was postulated by the elevation of astroglial and microglial markers in the immunized mice. Instead of lessening αSyn toxicity, this peptide vaccine caused an increase in the pathogenic species of αSyn. Our data demonstrated the potential adverse effects of active immunization to raise antibodies against the C-terminal fragment of αSyn. This drawback highlights the need for further investigation to weigh the pros and cons of immunotherapy in PD. Applying the αSyn C-terminal peptide vaccine for PD treatment should be cautiously exercised. This study provides valuable insights into the intricate interplay among immune intervention, αSyn accumulation, and neurodegeneration.

Metabolic and Hepatic Effects of Empagliflozin on Nonalcoholic Fatty Liver Mice.

Purpose: Among chronic liver diseases, non-alcoholic fatty liver disease (NAFLD) is one of the commonest. Although empagliflozin has several therapeutic uses in treating cardiovascular and renal disorders, its impacts and mechanisms on NAFLD are poorly understood. This research aimed to examine the metabolic regulatory mechanism through which empagliflozin protects against NAFLD. Methods: Equal grouping of twenty-seven male C57BL/6J mice into those fed a normal diet (NCD), those fed a high-fat diet (HFD), and those fed an HFD with empagliflozin (Empa) was approached. HE, oil red O staining, and Masson staining were utilized for evaluating the pathological damage to the liver and the mice's liver and body weights. Lipids, blood glucose, and inflammation index were compared across the three groups. Liquid chromatography/mass spectrometry (LC-MS) has been employed for identifying liver metabolomics. Results: The findings suggested that empagliflozin mitigated the inflammatory and oxidative stress response associated with the buildup of lipids caused by HFD. Differentially expressed metabolites (DEMs) were identified by metabonomics analysis as present in both the HFD/NCD and Empa/HFD groups. These DEMs were primarily found in lipids and organic acids like lysophosphatidylcholine (lysoPC), lecithin (PC), triglyceride (TG), palmitic acid, and L-isoleucine. Among the enriched pathways that were shown to be important were those involved in the metabolism of histidine, arachidonic acid, the control of lipolysis in adipocytes, and insulin resistance. There was a strong correlation between inflammation and oxidative stress in most of the metabolites. The inflammation and oxidative stress unbalance were ameliorated by empagliflozin. Conclusion: NAFLD mice model showed considerable improvement in metabolic abnormalities and liver protection after treatment with empagliflozin. The process may include the overexpression of L-isoleucine and the downregulation of lysoPC, PC, TG, and palmitic acid to reduce liver harm caused by lipotoxicity.

Oxymatrine relieves high-fructose/fat-induced obesity via reprogramming the activity of lipid metabolism-related enhancer.

Introduction: Emerging evidence demonstrates that the high-fructose and high-fat diet (HFHF) induced obesity and fatty liver disease has become one of the most common metabolic disorders worldwide. Therefore, innovative investigations on compounds targeting obesity and fatty liver diseases are urgently needed. Methods: The high-throughput natural compounds screen was performed to screen the important compounds. A rat HFHF model was constructed, the regulatory function of Oxymatrine in HFHF-induced obesity was further explored. Results: We identified Oxymatrine, a natural compound extracted from Sophora flavescens, showed a potential compacity in high-fat diet-induced fatty liver disease. We found that oxymatrine significantly inhibited HFHF-induced obesity using a rat HFHF model. Additionally, we found that oxymatrine altered the enhancer landscape of subcutaneous adipose tissues by ChIP-seq analysis using antibodies against the H3K27ac histone modification. Motif enrichment analysis showed the Smad motif was significantly enriched in enhancers altered post-oxymatrine treatment. Further chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) analysis and luciferase reporter assays showed oxymatrine alters the binding of Smad3 on the enhancer regions of B-cell lymphoma 2 (Bcl2) and the enhancer activity of Bcl2. Discussion: Together, our study highlighted oxymatrine could suppress high-fructose and high-fat diet-induced obesity by inhibiting the suppressor of mothers against decapentaplegic 3 (Smad3) binding on obesity-related enhancers.

Roux-en-Y and One-Anastomosis Gastric Bypass Surgery Are Superior to Sleeve Gastrectomy in Lowering Glucose and Cholesterol Levels Independent of Weight Loss: a Propensity-Score Weighting Analysis.

BACKGROUND: The superior effects of gastric bypass surgery in preventing cardiovascular diseases compared with sleeve gastrectomy are well-established. However, whether these effects are independent of weight loss is not known. METHODS: In this retrospective cohort study, we compared the change in cardiometabolic risks of 1073 diabetic patients undergoing Roux-en-Y gastric bypass (RYGB) (n = 265), one-anastomosis gastric bypass (OAGB) (n = 619), and sleeve gastrectomy (SG) (n = 189) with equivalent weight loss from the Min-Shen General Hospital. Propensity score-weighting, multivariate regression, and matching were performed to adjust for baseline differences. RESULTS: After 12 months, OAGB and, to a lesser extent, RYGB exhibited superior effects on glycemic control compared with SG in patients with equivalent weight loss. The effect was significant in patients with mild-to-modest BMI reduction but diminished in patients with severe BMI reduction. RYGB and OAGB had significantly greater effects in lowering total and low-density lipoprotein cholesterol than SG, regardless of weight loss. The results of matching patients with equivalent weight loss yielded similar results. The longer length of bypassed biliopancreatic (BP) limbs was correlated with a greater decrease in glycemic levels, insulin resistance index, lipids, C-reactive protein (CRP) levels, and creatinine levels in patients receiving RYBG. It was correlated with greater decreases in BMI, fasting insulin, insulin resistance index, and C-reactive protein levels in patients receiving OAGB. CONCLUSION: Diabetic patients receiving OAGB and RYGB had lower glucose and cholesterol levels compared with SG independent of weight loss. Our results suggest diabetic patients with cardiovascular risk factors such as hypercholesterolemia to receive bypass surgery.

Mechanisms of Small Intestine Involvement in Obesity-Induced Atherosclerosis.

Purpose: Studies have shown that atherosclerotic plaques are associated with changes in the microbial composition of the intestinal flora and obesity, and that the small intestine plays an irreplaceable role in regulating intestinal flora homeostasis, but the role of the small intestine in the development of obesity-related atherosclerosis remains understudied. Therefore, this study explores the role of the small intestine in obesity-induced atherosclerosis and its molecular mechanisms. Methods: In the GSE59054 data, small intestine tissue samples from 3 normal and 3 obese mice were analyzed using bioinformatics methods. Screening for differentially expressed genes (DEGs) using the GEO2R tool. The DEGs were next processed for bioinformatics analysis. We constructed an obese mouse model and measured aortic arch pulse wave velocity (PWV). Aortic and small intestine tissues were stained with hematoxylin-eosin (HE) to observe pathological changes. Finally, immunohistochemistry was performed to verify the expression of small intestinal proteins. Results: We identified a total of 122 DEGs. Pathway analysis revealed that BMP4, CDH5, IL1A, NQO1, GSTM1, GSTA3, CAV1 and MGST2 were mainly enriched in the Fluid shear stress and atherosclerosis pathway. In addition, BMP4, NQO1 and GSTM1 are closely related to atherosclerosis. Ultrasound and pathological findings suggest the presence of obesity atherosclerosis. Immunohistochemistry verified high expression of BMP4 and low expression of NQO1 and GSTM1 in obese small intestine tissues. Conclusion: The altered expression of BMP4, NQO1 and GSTM1 in small intestine tissues during obesity may be related to atherosclerosis, and Fluid shear stress and atherosclerosis pathway may be the molecular mechanism of their role.

The Ratio of Fibrinogen to Albumin is Related to the Occurrence of Retinopathy in Type 2 Diabetic Patients.

Purpose: Type 2 diabetic retinopathy is a long-term chronic inflammatory disease. The aim of this study was to investigate the relationship between fibrinogen to albumin ratio (FAR) and retinopathy in type 2 diabetic patients. Methods: This was a retrospective study that included 500 patients with type 2 diabetes mellitus (T2DM), and were divided into non-diabetic retinopathy group (NDR, n=297) and diabetic retinopathy group (DR, n=203) according to fundus examination findings, and the DR group was further divided into non-proliferative retinopathy group (NPDR, n=182) and proliferative retinopathy group (PDR, n=21). Baseline data of patients were collected, and the fibrinogen to albumin ratio (FAR) and neutrophil to lymphocyte ratio (NLR) were calculated to analyze the correlation between FAR and NLR and type 2 diabetic retinopathy. Results: The FAR and NLR were significantly higher in the DR group compared with the NDR group (both P < 0.001). Spearman correlation analysis showed that FAR was positively correlated with NLR and DR (P < 0.05). As the FAR quartile increased, the prevalence of DR increased (14.8%, 16.7%, 25.1%, and 43.30%, respectively; P < 0.05). Multifactorial logistic regression analysis showed that FAR, diabetic course, systolic blood pressure (SBP) and diabetic peripheral neuropathy (DPN) were risk factors for the development of DR in patients with T2DM. The area under the ROC curve for FAR to predict DR progression was 0.708, with an optimal critical value of 7.04, and the area under the ROC curve for diabetes duration and SBP to predict DR was 0.705 and 0.588, respectively. Conclusion: Our findings show for the first time that FAR is an independent risk factor for assessing DR in patients with type 2 diabetes.

The effects of daily dose and treatment duration of metformin on the prevalence of vitamin B12 deficiency and peripheral neuropathy in Chinese patients with type 2 diabetes mellitus: A multicenter cross-sectional study.

AIMS: To evaluate the prevalence of vitamin B12 deficiency in Chinese patients with type 2 diabetes mellitus receiving metformin treatment and to investigate the effects of metformin daily dose and treatment duration on the prevalence of vitamin B12 deficiency and peripheral neuropathy (PN). MATERIALS AND METHODS: In this multicenter cross-sectional study, 1027 Chinese patients who had been taking ≥1000 mg/day metformin for ≥1 year were enrolled using proportionate stratified random sampling based on daily dose and treatment duration. Primary measures included the prevalence of vitamin B12 deficiency (<148 pmol/L), borderline B12 deficiency (148 pmol/L-211 pmol/L), and PN. RESULTS: The prevalence of vitamin B12 deficiency, borderline deficiency, and PN were 2.15%, 13.66%, and 11.59%, respectively. Patients receiving ≥1500 mg/day metformin had significantly higher prevalence of borderline vitamin B12 deficiency (16.76% vs. 9.91%, p = .0015) and serum B12 ≤221 pmol/L (19.25% vs. 11.64%, p < .001) than patients receiving <1500 mg/day metformin. No difference was found in prevalence of borderline vitamin B12 deficiency (12.58% vs. 15.49%, p = .1902) and serum B12 ≤221 pmol/L (14.91% vs. 17.32%, p = .3055) between patients receiving metformin for ≥3 and <3 years. Patients with vitamin B12 deficiency had numerically higher PN prevalence (18.18% vs. 11.27%, p = .3192) than patients without it. Multiple logistic analyses revealed that HbA1c and metformin daily dose were associated with the prevalence of borderline B12 deficiency and B12 ≤221 pmol/L. CONCLUSIONS: High daily dosage (≥1500 mg/day) played an important role in metformin-associated vitamin B12 deficiency while not contributing to the risk of PN.

Semaglutide ameliorates obesity-induced cardiac inflammation and oxidative stress mediated via reduction of neutrophil Cxcl2, S100a8, and S100a9 expression.

Obesity, which is driven by inflammation and oxidative stress, is a risk factor for cardiovascular disease. Semaglutide, a glucagon-like peptide-1 receptor agonist, is an antidiabetic drug with major effects on weight loss. In this study, single-cell transcriptomics was used to examine non-cardiomyocytes to uncover the mechanism of obesity-induced myocardial damage and the cardioprotective impact of semaglutide. We constructed obese mouse models and measured Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), Reactive Oxygen Species (ROS), and Malonic dialdehyde (MDA) levels in serum and heart tissue to determine the levels of inflammation and oxidative stress in obesity and the effect of semaglutide on these levels. Then, utilizing single-cell transcriptomes to screen for key cell populations and differentially expressed genes (DEGs), we assessed the effects of obesity and semaglutide on non-cardiac cells. Finally, a DEG localization analysis was performed to explore DEGs as well as cell types associated with inflammation and oxidative stress. Semaglutide reduced increased TNF-α, IL-6, ROS, and MDA levels in serum and cardiac tissues in obese mouse. Several genes are closely associated with inflammation and oxidative stress. Chemokine (C-X-C motif) ligand 2 (Cxcl2), S100 calcium binding protein A8 (S100a8), and S100 calcium binding protein A9 (S100a9), which were elevated in obesity but decreased following semaglutide treatment, were also expressed particularly in neutrophils. Finally, by decreasing neutrophil Cxcl2, S100a8, and S100a9 expressions, semaglutide may help to reduce cardiac inflammation and oxidative stress. Semaglutide significantly reduced body weight in obese mice as well as exerted anti-inflammatory and antioxidant effects possibly by inhibiting the expression of S100a8, S100a9, and Cxcl2 in neutrophils. These discoveries are expected to reveal new molecular mechanisms underlying obesity-related heart damage and semaglutide's cardioprotective properties.

Retinal Microvascular Diameters are Associated with Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus.

Objective: To investigate the association between retinal microvascular diameters and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 690 patients with T2DM were included in this retrospective study. Patients were divided into DKD and non-DKD groups according to urine microalbumin/creatinine ratio and estimated glomerular filtration rate. Retinal microvascular diameters were measured by the automated retinal image analysis system. Multivariate logistic regression analysis and restricted cubic splines were used to assess the relationships between the retinal microvascular diameters and DKD in patients with T2DM. Results: Multivariate logistic regression showed that widened diameters of retinal venules and narrowed diameters of retinal arterioles were associated with DKD after adjusting for potential confounding variables. There was a significant linear trend between the diameters of superior temporal retinal venula (P for trend < 0.001, P for non-linearity = 0.080), inferior temporal retinal venula (P for trend < 0.001, P for non-linearity = 0.111) and central retinal venular equivalent (CRVE) (P for trend < 0.001, P for non-linearity = 0.392) and risk of DKD in patients with T2DM. The restricted cubic splines showed that narrowed retinal arteriolar diameters, superior and inferior nasal retinal venulas were associated with the risk of DKD in a non-linear fashion (all P for non-linearity < 0.001). Conclusion: Wider retinal venular diameters and narrower retinal arteriolar diameters were associated with an increased risk of DKD in patients with T2DM. Widened retinal venular diameters, especially CRVE, superior and inferior temporal retinal venula, were positively associated with an increased risk of DKD in a linear fashion. In contrast, narrowed retinal arteriolar diameters were associated with the risk of DKD in a non-linear fashion.