[Construction of a Predictive Model for Diabetes Mellitus Type 2 in Middle-Aged and Elderly Populations Based on the Medical Checkup Data of National Basic Public Health Service]. / åŸºäºŽå›½å®¶åŸºæœ¬å ¬å ±å«ç”ŸæœåŠ¡ä½“æ£€çš„ä¸­è€å¹´äºº2åž‹ç³–å°¿ç— é£Žé™©é¢„æµ‹æ¨¡åž‹æž„å»º.

Objective: To establish a universally applicable logistic risk prediction model for diabetes mellitus type 2 (T2DM) in the middle-aged and elderly populations based on the results of a Meta-analysis, and to validate and confirm the efficacy of the model using the follow-up data of medical check-ups of National Basic Public Health Service. Methods: Cohort studies evaluating T2DM risks were identified in Chinese and English databases. The logistic model utilized Meta-combined effect values such as the odds ratio (OR) to derive ß, the partial regression coefficient, of the logistic model. The Meta-combined incidence rate of T2DM was used to obtain the parameter α of the logistic model. Validation of the predictive performance of the model was conducted with the follow-up data of medical checkups of National Basic Public Health Service. The follow-up data came from a community health center in Chengdu and were collected between 2017 and 2022 from 7602 individuals who did not have T2DM at their baseline medical checkups done at the community health center. This community health center was located in an urban-rural fringe area with a large population of middle-aged and elderly people. Results: A total of 40 cohort studies were included and 10 items covered in the medical checkups of National Basic Public Health Service were identified in the Meta-analysis as statistically significant risk factors for T2DM, including age, central obesity, smoking, physical inactivity, impaired fasting glucose, a reduced level of high-density lipoprotein cholesterol (HDL-C), hypertension, body mass index (BMI), triglyceride glucose (TYG) index, and a family history of diabetes, with the OR values and 95% confidence interval (CI) being 1.04 (1.03, 1.05), 1.55 (1.29, 1.88), 1.36 (1.11, 1.66), 1.26 (1.07, 1.49), 3.93 (2.94, 5.24), 1.14 (1.06, 1.23), 1.47 (1.34, 1.61), 1.11 (1.05, 1.18), 2.15 (1.75, 2.62), and 1.66 (1.55, 1.78), respectively, and the combined ß values being 0.039, 0.438, 0.307, 0.231, 1.369, 0.131, 0.385, 0.104, 0.765, and 0.507, respectively. A total of 37 studies reported the incidence rate, with the combined incidence being 0.08 (0.07, 0.09) and the parameter α being -2.442 for the logistic model. The logistic risk prediction model constructed based on Meta-analysis was externally validated with the data of 7602 individuals who had medical checkups and were followed up for at least once. External validation results showed that the predictive model had an area under curve (AUC) of 0.794 (0.771, 0.816), accuracy of 74.5%, sensitivity of 71.0%, and specificity of 74.7% in the 7602 individuals. Conclusion: The T2DM risk prediction model based on Meta-analysis has good predictive performance and can be used as a practical tool for T2DM risk prediction in middle-aged and elderly populations.

Comprehensive Analysis of the Function and Prognostic Value of TAS2Rs Family-Related Genes in Colon Cancer.

In the realm of colon carcinoma, significant genetic and epigenetic diversity is observed, underscoring the necessity for tailored prognostic features that can guide personalized therapeutic strategies. In this study, we explored the association between the type 2 bitter taste receptor (TAS2Rs) family-related genes and colon cancer using RNA-sequencing and clinical datasets from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Our preliminary analysis identified seven TAS2Rs genes associated with survival using univariate Cox regression analysis, all of which were observed to be overexpressed in colon cancer. Subsequently, based on these seven TAS2Rs prognostic genes, two colon cancer molecular subtypes (Cluster A and Cluster B) were defined. These subtypes exhibited distinct prognostic and immune characteristics, with Cluster A characterized by low immune cell infiltration and less favorable outcomes, while Cluster B was associated with high immune cell infiltration and better prognosis. Finally, we developed a robust scoring system using a gradient boosting machine (GBM) approach, integrated with the gene-pairing method, to predict the prognosis of colon cancer patients. This machine learning model could improve our predictive accuracy for colon cancer outcomes, underscoring its value in the precision oncology framework.

Dissecting the association between gut microbiota, body mass index and specific depressive symptoms: a mediation Mendelian randomisation study.

Background: Observational studies highlight the association between gut microbiota (GM) composition and depression; however, evidence for the causal relationship between GM and specific depressive symptoms remains lacking. Aims: We aimed to evaluate the causal relationship between GM and specific depressive symptoms as well as the mediating role of body mass index (BMI). Methods: We performed a two-sample Mendelian randomisation (MR) analysis using genetic variants associated with GM and specific depressive symptoms from genome-wide association studies. The mediating role of BMI was subsequently explored using mediation analysis via two-step MR. Results: MR evidence suggested the Bifidobacterium genus (ß=-0.03; 95% CI -0.05 to -0.02; p<0.001 and ß=-0.03; 95% CI -0.05 to -0.02; p<0.001) and Actinobacteria phylum (ß=-0.04; 95% CI -0.06 to -0.02; p<0.001 and ß=-0.03; 95% CI -0.05 to -0.03; p=0.001) had protective effects on both anhedonia and depressed mood. The Actinobacteria phylum also had protective effects on appetite changes (ß=-0.04; 95% CI -0.06 to -0.01; p=0.005), while the Family XI had an antiprotective effect (ß=0.03; 95% CI 0.01 to 0.04; p<0.001). The Bifidobacteriaceae family (ß=-0.01; 95% CI -0.02 to -0.01; p=0.001) and Actinobacteria phylum (ß=-0.02; 95% CI -0.03 to -0.01; p=0.001) showed protective effects against suicidality. The two-step MR analysis revealed that BMI also acted as a mediating moderator between the Actinobacteria phylum and appetite changes (mediated proportion, 34.42%) and that BMI partially mediated the effect of the Bifidobacterium genus (14.14% and 8.05%) and Actinobacteria phylum (13.10% and 8.31%) on both anhedonia and depressed mood. Conclusions: These findings suggest a potential therapeutic effect of Actinobacteria and Bifidobacterium on both depression and obesity. Further studies are required to translate these findings into clinical practice.

From metabolic to epigenetic: Insight into trained macrophages in atherosclerosis (Review).

Atherosclerosis (AS) is a chronic inflammatory disease caused by the deposition of lipoproteins and sequent immune responses. Within the atherosclerotic plaque, macrophages are the most abundant immune cells and play a great part as protagonists and promoters of AS. In the past decade, the concept of 'trained immunity' has emerged, which highlights the memory characteristics of innate immunity, thus opening up a new avenue of research. Evidence suggests that trained immunity may regulate the onset and progression of AS with trained macrophages playing an important and dynamic role in atherogenesis. The present review provided a summary of concepts related to trained immunity and its relationship with AS. Furthermore, different phenotypes of macrophages responding to various stimuli within the atherosclerotic plaque were presented, along with the complex mechanisms of metabolic and epigenetic reprogramming in the cells. Finally, several promising therapeutic approaches for AS cardiovascular disease were discussed, which may shed light on new clinical strategies.

Visible-Light-Promoted and EDA Complex-Driven [4 + 2] Annulation for the Construction of Naphtho[1',2':4,5]imidazo[1,2-a]pyridines.

A green visible-light-promoted and electron donor-acceptor (EDA) complex-driven synthetic strategy for the construction of value-added naphtho[1',2':4,5]imidazo[1,2-a]pyridines from 2-arylimidazo[1,2-a]pyridines with Z-α-bromocinnamaldehydes has been accomplished under photocatalyst- and transition-metal-free conditions. This efficient annulation approach provides a new and straightforward pathway for the annulative π-extension of imidazo[1,2-a]pyridine-based aromatics. Moreover, the sustainable methodology exhibits simple operation, a wide range of substrates, benign conditions, and good functional group compatibility.

Isolation and genome sequencing of a novel lytic Pseudoalteromonas phage SL20.

Phage SL20, a novel lytic Pseudoalteromonas phage, was isolated from the coastal waters of the Yellow Sea, China. The microbiological characterization demonstrated that phage SL20 was relatively stable from 35 to 55 °C and the optimal pH was approximately 6.0. A latent period of approximately 24 min was indicated by a one-step growth curve. The burst size was approximately 12 ± 3 PFU/cell. The genome had a length of 120,295 bp with a G + C content of 35.84%, and predicted 95 ORFs. The phylogenetic tree based on DNA helicase showed that Pseudoalteromonas phage SL20 was related to the Pseudoalteromonas phage H101 and was a member of the family Shandongvirus. The isolation and genomic analysis of SL20 has improved our understanding of host-phage interactions and the ecology of the marine bacteria Pseudoalteromonas.

Glucose Metabolism Indices and the Development of Chronic Kidney Disease: A Cohort Study of Middle-Aged and Elderly Chinese Persons.

Objective: Chronic kidney disease (CKD) has become a major global health issue, and abnormalities of glucose metabolism are a risk factor responsible for development of CKD. We aimed to investigate associations between glucose metabolism indices and CKD in a Chinese population and determine which index is superior for predicting incident CKD. Methods: We performed a community-based population on 5232 subjects aged ≥40 years without baseline CKD. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g. We examined the associations of glucose metabolism indices, including fasting plasma glucose (FPG), 2-hour (2 h) oral glucose tolerance test (OGTT), hemoglobin A1c (HbA1c), fasting insulin level, homeostasis model assessment of insulin resistance (HOMA-IR), and HOMA-ß and the development of CKD. Results: With an average follow-up of 3.6 years, 6.4% of the subjects developed CKD. Pearson's correlation analysis revealed that FPG, HbA1c, fasting insulin, and HOMA-IR were all significantly correlated with UACR and eGFR. The association persisted in multivariate linear regression analysis adjusted for age and sex. Compared with other glucose indices, HOMA-IR exhibited the strongest associations with CKD in COX multivariate regression analysis (HR = 1.17, 95% CI: 1.04-1.31). Conclusion: HOMA-IR is superior to other routine indices of glucose metabolism for predicting the development of CKD in middle-aged Chinese persons. Screening with HOMA-IR may help prevent the development of CKD in the general population.

Temporal relationships between BMI and obesity-related predictors of cardiometabolic and breast cancer risk in a longitudinal cohort.

Prospective inter-relationships among biomarkers were unexplored, which may provide mechanistic insights into diseases. We investigated the longitudinal associations of BMI change with trajectories of biomarkers related to cardiometabolic or breast cancer risk. A longitudinal study was conducted among 444 healthy women between 2019 to 2021. Cross­lagged path analysis was used to examine the temporal relationships among BMI, cardiometabolic risk score (CRS), and obesity­related proteins score (OPS) of breast cancer. Linear mixed-effect models were applied to investigate associations of time-varying BMI with biomarker-based risk score trajectories. Baseline BMI was associated with subsequent change of breast cancer predictors (P = 0.03), and baseline CRS were positively associated with OPS change (P < 0.001) but not vice versa. After fully adjustment of confounders, we found a 0.058 (95%CI = 0.009-0.107, P = 0.020) units increase of CRS and a 1.021 (95%CI = 0.041-1.995, P = 0.040) units increase of OPS as BMI increased 1 kg/m2 per year in postmenopausal women. OPS increased 0.784 (95%CI = 0.053-1.512, P = 0.035) units as CRS increased 1 unit per year. However, among premenopausal women, BMI only significantly affected CRS (ß = 0.057, 95%CI = 0.007 to 0.107, P = 0.025). No significant change of OPS with time-varying CRS was found. Higher increase rates of BMI were associated with worse trajectories of biomarker-based risk of cardiometabolic and breast cancer. The longitudinal impact of CRS on OPS is unidirectional. Recommendations such as weight control for the reduction of cardiometabolic risk factors may benefit breast cancer prevention, especially in postmenopausal women.

U-shaped association between serum IGF2BP3 and T2DM: A cross-sectional study in Chinese population.

OBJECTIVE: To clarify the expression of N6-methyladenosine (m6 A) modulators involved in the pathogenesis of type 2 diabetes mellitus (T2DM). We further explored the association of serum insulin-like growth factor 2 mRNA-binding proteins 3 (IGF2BP3) levels and odds of T2DM in a high-risk population. METHODS: The gene expression data set GSE25724 was obtained from the Gene Expression Omnibus, and a cluster heatmap was generated by using the R package ComplexHeatmap. Differential expression analysis for 13 m6 A RNA methylation regulators between nondiabetic controls and T2DM subjects was performed using an unpaired t test. A cross-sectional design, including 393 subjects (131 patients with newly diagnosed T2DM, 131 age- and sex-matched subjects with prediabetes, and 131 healthy controls), was carried out. The associations between serum IGF2BP3 concentrations and T2DM were modeled by restricted cubic spline and logistic regression models. RESULTS: Two upregulated (IGF2BP2 and IGF2BP3) and 5 downregulated (methyltransferase-like 3 [METTL3], alkylation repair homolog protein 1 [ALKBH1], YTH domain family 2 [YTHDF2], YTHDF3, and heterogeneous nuclear ribonucleoprotein [HNRNPC]) m6 A-related genes were found in islet samples of T2DM patients. A U-shaped association existed between serum IGF2BP3 levels and odds of T2DM according to cubic natural spline analysis models, after adjustment for body mass index, waist circumference, diastolic blood pressure, total cholesterol, and triglyeride. Multivariate logistic regression showed that progressively higher odds of T2DM were observed when serum IGF2BP3 levels were below 0.62 ng/mL (odds ratio 3.03 [95% confidence interval 1.23-7.47]) in model 4. CONCLUSION: Seven significantly altered m6 A RNA methylation genes were identified in T2DM. There was a U-shaped association between serum IGF2BP3 levels and odds of T2DM in the general Chinese adult population. This study provides important evidence for further examination of the role of m6 A RNA methylation, especially serum IGF2BP3 in T2DM risk assessment.

Structural, optical and photocatalytic properties of magnetic recoverable Mn0.6Zn0.4Fe2O4@Zn0.9Mn0.1O heterojunction prepared from waste Mn-Zn batteries.

Green, simple and high value-adding technology is crucial for realizing waste batteries recycling. In this work, the magnetically recyclable Mn0.6Zn0.4Fe2O4@Zn0.9Mn0.1O (MZFO@ZMO) heterojunctions are prepared from waste Mn-Zn batteries via a green bioleaching and sample co-precipitation method. The as-prepared catalysts with different Zn0.9Mn0.1O weight percentage (25%, 50% and 75%) have been comprehensively characterized in structure, optics, photoelectrochemistry and photocatalytic activity. Characterization results indicate that MZFO@ZMO heterojunctions with the core-shell structure, demonstrates excellent absorption intensity in the visible light region, outperforming that of individual ZnO and Zn0.9Mn0.1O. Especially, the staggered bandgap alignment of Mn0.6Zn0.4Fe2O4 and Zn0.9Mn0.1O greatly enhances electron transfer and charge separation in the binary heterojunction system. The optimized MZFO@50%-ZMO shows the highest photodegradation performance toward methylene blue (MB) under the visible light irradiation, with a 99.7% of photodegradation efficiency of 20 mg L-1 of MB within 90 min, and its reactive kinetic constants is about 7.2, 10.8 and 21.7 times higher than that of Zn0.9Mn0.1O, P25 TiO2 and Mn0.6Zn0.4Fe2O4, respectively. The MB photocatalytic mechanism is investigated in the scavenger and 5,5-dimethylpyrroline-N-oxide (DMPO) spin-trapping electron spin resonance (ESR) experiments, and h+ and *O2- are identified as the major active species for MB degradation. In addition, MZFO@50%-ZMO also exhibits a good reusability and high magnetic separation properties after six successive cycles. This new material indicates the advantages of low costs, simple reuse and great potential in application.

Lipid Parameters and the Development of Chronic Kidney Disease: A Prospective Cohort Study in Middle-Aged and Elderly Chinese Individuals.

Epidemiological evidence suggests that lipid parameters are related to the progression of chronic kidney disease (CKD). Nevertheless, prospective studies that comprehensively assess the effect of routinely available lipid measures on the development of CKD are lacking. The aim of this study was to longitudinally assess the influence of lipid metabolism indicators on the presence of CKD in a large community-based population. We conducted a prospective cohort study at Sun Yat-sen Memorial Hospital, China, with 5345 patients of 40 years or older. Cox regression models were conducted, and hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess lipid parameters and their relationship with the incidence of CKD. During the follow-up period, 340 (6.4%) subjects developed CKD. The incidence of CKD increased progressively with quartile values of triglyceride (TG), the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (non-HDL-C/HDL-C) and the ratio of TG to HDL-C, but decreased with HDL-C quartiles (p < 0.0001 for all trends). Pearson's correlation analysis and multiple regression analyses indicated that these parameters were also associated with various indicators of kidney function. Moreover, we found that among all the lipid parameters, TG/HDL-C emerged as the most effective predictor of CKD. In conclusion, our findings suggest that TG/HDL-C better predicts the incidence of CKD in middle-aged and elderly Chinese individuals than other lipid parameters tested in the study.

Association between uric acid lowering and renal function progression: a longitudinal study.

BACKGROUND: This study aimed to explore the association between uric acid lowering and renal function. MATERIALS AND METHODS: We conducted a population-based cohort study with 1,534 subjects for 4 years from 2012 to 2016. The population was divided into four groups according to the interquartile range of changes in serum uric acid with quartile 1 representing lower quarter. Renal function decline was defined as eGFR decreased more than 10% from baseline in 2016. Renal function improvement was defined as eGFR increased more than 10% from baseline in 2016. Cox regression analysis was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: In the adjusted Cox regression models, compared to quartile 4, quartile 1 (HR = 0.64, 95% CI [0.49-0.85]), quartile 2 (HR = 0.65, 95% CI [0.50-0.84]) and quartile 3 (HR = 0.75, 95% CI [0.58-0.96]) have reduced risk of renal function decline. An increasing hazard ratio of renal function improvement was shown in quartile 1 (HR = 2.27, 95% CI [1.45-3.57]) and quartile 2 (HR = 1.78, 95% CI [1.17-2.69]) compared with quartile 4. CONCLUSIONS: Uric acid lowering is associated with changes in renal function. The management of serum uric acid should receive attention in clinical practice and is supposed to be part of the treatment of chronic kidney disease.

Association of metabolic syndrome with the incidence of low-grade albuminuria: a cohort study in middle-aged and elderly Chinese adults.

BACKGROUND: Individuals with metabolic syndrome have elevated risks of micro- and macro-albuminuria as well as chronic kidney disease (CKD). OBJECTIVE: To assess the influence of metabolic abnormalities on the presence of low-grade albuminuria (below the threshold for microalbuminuria). Design, participants, and main outcome measures: This community-based cohort study included 3,935 eligible individuals aged 40 years or older. The presence of low-grade albuminuria was detected in those without micro- or macro-albuminuria and analyzed according to the highest quartile of the baseline urinary albumin-to-creatinine ratio (ACR ≥11.13 mg/g). CKD was defined by an estimated glomerular filtration rate <60 mL/min/1.73 m2 or the new presence of albuminuria (ACR ≥30 mg/g). RESULTS: Overall, 577 (14.7%) participants developed low-grade albuminuria and 164 (4.2%) participants developed CKD during a mean follow-up period of 3.6 years. Compared with participants without metabolic syndrome, those with metabolic syndrome had greater risks of low-grade albuminuria [adjusted odd ratio (OR) and 95% confidence interval (95% CI): 1.30 (1.05-1.61)] and CKD [1.71 (1.20-2.44)]. Moreover, the incidence rates of low-grade albuminuria and CKD increased as the number of metabolic syndrome components increased (P for trend <0.0001). CONCLUSIONS: The presence of metabolic syndrome is associated with increased incidence rates of low-grade albuminuria and CKD the middle-aged and elderly Chinese populations.

LncRNA TUG1 promotes esophageal cancer development through regulating PLK1 expression by sponging miR-1294.

OBJECTIVES: Esophageal cancer is one of the malignant tumor with poor survival. The 5-year survival rate of esophageal cancer patients remains poor due to limited therapeutic options and the development of drug-resistance. Recent evidence suggests that long non-coding RNAs (lncRNAs) are involved in occurrence and development of tumor, however, the molecular mechanisms of lncRNA taurine-upregulated gene 1 (TUG1) in esophageal cancer remain unknown. RESULTS: TUG1 was overexpressed in esophageal cancer tissues and cells. The knockdown of TUG1 repressed proliferation and invasion, while promoted apoptosis of esophageal cancer cells by negatively regulating miR-1294 expression. Furthermore, PLK1 was a target mRNA of miR-1294 in esophageal cancer cells. Therefore, the effects of PLK1 silencing on proliferation, apoptosis, and invasion of esophageal cancer cells could be overturned by silencing miR-1294. Additionally, TUG1 silencing inhibited growth of tumor cells in vivo. CONCLUSIONS: TUG1 was found as oncogenic gene in esophageal cancer. Mechanically, TUG1 attributed to esophageal cancer process by regulating miR-1294/ PLK1 axis.

pH/redox sequentially responsive nanoparticles with size shrinkage properties achieve deep tumor penetration and reversal of multidrug resistance.

Multidrug resistance (MDR) remains a serious impediment to successful tumor chemotherapy. Despite considerable efforts to address MDR, limited approaches have been successful in the clinic to date. Here, we have developed pH/redox cascade-sensitive multiscale nanoparticles (DMA-NPs) with size- and charge-changeable properties for the efficient delivery of a non-P-glycoprotein substrate anticancer drug (podophyllotoxin, PPT) to combat MDR. DMA-NPs are composed of a charge-reversible polymer (PEG-PAH-DMA) shell and a redox-sensitive small-sized dendrimeric PPT-prodrug (PAMAM-ss-PPT) core. The PEG-PAH-DMA polymer shell on DMA-NPs maintains a negative charge in a normal environment, which reverts to a positive charge in a mildly acidic tumor environment (pH 6.5), leading to the release of positive PAMAM-ss-PPT via electrostatic repulsion. PAMAM-ss-PPT completely releases PPT under elevated intracellular glutathione (GSH) conditions in tumors. Several properties facilitate the hierarchical transport of DMA-NPs across multiple drug resistance pathological obstacles, including long blood circulation times, significant accumulation in tumors, deep tumor permeation, cancer cell internalization, and rapid and complete drug release. Experimental evaluations, both in vitro and in vivo, collectively indicate that nanomedicines can effectively penetrate xenografted A549 paclitaxel-resistant lung cancer cells and inhibit tumor proliferation with negligible toxicity. The current study presents a novel nanoparticle-based therapeutic strategy aimed at overcoming MDR.

miR-203 affects esophageal cancer cell proliferation, apoptosis and invasion by targeting MAP3K1.

miR-203 has been indicated to be a tumor suppressor in esophageal cancer, however, the underlying molecular mechanisms by which it functions are not fully understood. The present study aimed to investigate the molecular mechanisms underlying the regulatory activities of microRNA (miR)-203 in esophageal cancer. The miR-203 mimic/inhibitor, Mitogen-Activated Protein Kinase Kinase Kinase 1 (MAP3K1) overexpression plasmid and MAP3K1 small interfering (si)RNA were transfected into TE-1 cells. miR-203 and MAP3K1 mRNA expression were detected via reverse transcription-quantitative PCR analysis, while MAP3K1 protein expression was detected via western blot analysis. Dual-luciferase reporter assay was used to determine whether MAP3K1 was a direct target of miR-203. Cell proliferation and invasion abilities were assessed via MTT and Matrigel assays, respectively. Cell apoptosis was analyzed via flow cytometry, Caspase 8/3 Assay kits and western blot analysis. The results demonstrated that MAP3K1 was a direct target of miR-203. Overexpression of MAP3K1 reversed the suppressed cell proliferation and invasion abilities induced by miR-203 mimic, as well as the inhibitory effect of miR-203 mimic on cell apoptosis. Furthermore, MAP3K1 siRNA weakened the effect of miR-203 inhibitor on cell proliferation, apoptosis and invasion.

Parity is associated with albuminuria and chronic kidney disease: a population-based study.

BACKGROUND AND AIMS: Epidemiological studies have shown that increasing parity is associated with risk of hypertension and diabetes in parous women. However, the relationship between the parity degree with chronic kidney disease (CKD) is still unknown. RESULTS: Parous women with higher parity had increased age, body mass index, waist circumference, systolic blood pressure, fasting plasma glucose, fasting insulin and decreased high-density lipoprotein cholesterol, eGFR and education levels. Compared with women with one-child birth, those with more than two-child births had greater prevalence of increased urinary albumin excretion (odds ratios [ORs] 1.53, 95% confidence intervals [CI], 1.03 - 2.28) and CKD (ORs 1.79, 95% CI, 1.24 - 2.58) after multiple adjustments. In dose-response analysis, a nonlinear relationship of parity degree with albuminuria and CKD was detected. CONCLUSION: Parity is associated with higher prevalence of albuminuria and CKD in middle-aged and elderly Chinese women. METHODS: We conducted a community-based study in 6,946 women to investigate the association of parity with albuminuria and CKD. Increased urinary albumin excretion was defined as albumin-to-creatinine ratio (ACR) greater or equal than 30 mg/g. CKD was defined as estimated glomerular filtration rate (eGFR) less than 60 mL/min per 1.73 m² or presence of albuminuria.

Number of parity is associated with low-grade albuminuria in middle-aged and elderly Chinese women.

BACKGROUND: Women with a higher number of pregnancies have a higher risk of developing cardiovascular diseases. Subtle fluctuations in albumin excretion could be related to pathophysiologic changes in the vascular system. We aimed to investigate the possible association of parity with low-grade albuminuria. METHODS: We conducted a community-based study in 6495 women aged 40 years or older. Low-grade albuminuria was defined according to the highest quartile of urine albumin-to-creatinine ratio in participants free of micro- or macro-albuminuria. RESULTS: Parous women with a higher number of pregnancies had increased age, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), fasting plasma glucose (FPG), and fasting insulin, as well as decreased high-density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate (eGFR) levels, and proportion of menopause. The prevalence of low-grade albuminuria in parous women gradually increased with parity number. Compared with women with one childbirth, those with more than two childbirths were independently associated with a higher prevalent low-grade albuminuria (odds ratios [ORs] 1.41, 95% confidence interval [CI], 1.09-1.81) after multiple adjustments. In subgroup analysis after multiple adjustments, significant relation between parity number and prevalent low-grade albuminuria was detected in subjects age 55 years or older. CONCLUSION: Number of parity is associated with prevalent low-grade albuminuria in middle-aged and elderly Chinese women without micro- or macro-albuminuria.

Assessment of adiposity distribution and its association with diabetes and insulin resistance: a population-based study.

BACKGROUND: Rational measures in estimating adiposity distribution in diabetic patients has yet to be validated. This study aims to provide insight about the possible links between routinely available body adiposity parameters and the development of both diabetes and insulin resistance. METHODS: We performed a population-based cross-sectional study in 9496 subjects aged 40 years or older. All of the body adiposity measures including body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), waist-height ratio (WHtR), visceral adiposity index (VAI), body adiposity index (BAI) and lipid accumulation product index (LAP) were separately evaluated according to standard measurement methods. Diabetes was diagnosed according to the American Diabetes Association 2010 criteria. RESULTS: All tested body adiposity measurements were significantly associated with fasting plasma glucose (FPG), oral glucose tolerance test (OGTT) 2 h glucose, HbA1c and fasting insulin. Compared with other adiposity phenotypes, LAP have shown the relatively strongest while BAI have shown the relatively weakest association with increased odds of both diabetes and insulin resistance across all logistic regression models. Additionally, LAP provided the best discrimination accuracy for diabetes [area under the curve (AUC): 0.658 95% confidence intervals (CI) 0.645-0.671] and insulin resistance (AUC: 0.781 95% CI 0.771-0.792) when compared with other body adiposity parameters. CONCLUSIONS: The LAP index seems to be a better indicator than other adiposity measures tested in the study to evaluate the association of visceral fat mass with diabetes and insulin resistance, which should be given more consideration in the clinical practice.

EPHA5 mediates trastuzumab resistance in HER2-positive breast cancers through regulating cancer stem cell-like properties.

Trastuzumab is a successful, rationally designed therapy that provides significant clinical benefit for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients. However, about half of individuals with HER2-positive breast cancer do not respond to trastuzumab treatment because of various resistance mechanisms, including but not limited to: 1) shedding of the HER2 extracellular domain, 2) steric hindrance ( e.g., MUC4 and MUC1), 3) parallel pathway activation (this is the general mechanism cited in the quote above), 4) perturbation of downstream signaling events ( e.g., PTEN loss or PIK3CA mutation), and 5) immunologic mechanisms (such as FcR polymorphisms). EPHA5, a receptor tyrosine kinase, has been demonstrated to act as an anticancer agent in several cancer cell types. In this study, deletion of EPHA5 can significantly increase the resistance of HER2-positive breast cancer patients to trastuzumab. To investigate how EPHA5 deficiency induces trastuzumab resistance, clustered regularly interspaced short palindromic repeat technology was used to create EPHA5-deficient variants of breast cancer cells. EPHA5 deficiency effectively increases breast cancer stem cell (BCSC)-like properties, including NANOG, CD133+, E-cadherin expression, and the CD44+/CD24-/low phenotype, concomitantly enhancing mammosphere-forming ability. EPHA5 deficiency also caused significant aggrandized tumor malignancy in trastuzumab-sensitive xenografts, coinciding with the up-regulation of BCSC-related markers and intracellular Notch1 and PTEN/AKT signaling pathway activation. These findings highlight that EPHA5 is a potential prognostic marker for the activity of Notch1 and better sensitivity to trastuzumab in HER2-positive breast cancer. Moreover, patients with HER2-positive breast cancers expressing high Notch1 activation and low EPHA5 expression could be the best candidates for anti-Notch1 therapy.-Li, Y., Chu, J., Feng, W., Yang, M., Zhang, Y., Zhang, Y., Qin, Y., Xu, J., Li, J., Vasilatos, S. N., Fu, Z., Huang, Y., Yin, Y. EPHA5 mediates trastuzumab resistance in HER2-positive breast cancers through regulating cancer stem cell-like properties.