Association of the metabolic score for insulin resistance with cardiovascular diseases, cardiovascular and all-cause mortality in Chinese hypertensive population

ImportanceLittle is known about the relationship between the metabolic score for insulin resistance (METS-IR) and the prognosis of hypertensive patients in China.ObjectiveTo investigate the association between the novel non–insulin‐based METS-IR index and the cardiovascular composite endpoints and all-cause mortality in Chinese hypertensive participants.Design, setting, and participantsThis cohort study used data from the China H-Type Hypertension Project, a long-term prospective cohort consisting of 14234 hypertensive patients in southern China, with a baseline from March to August 2018. The median follow-up period for participants was 3.94 years, as of 2022. The data analysis period is from July 2023 to September 2023.ExposuresMETS-IR index of participants in the Chinese H-type hypertension project. The calculation formula for METS-IR is (Ln (2 × FPG) +TG) × BMI/Ln (HDL-C).Main outcomes and measuresCardiovascular events and cardiovascular, all-cause mortality were identified by linking the cohort database with the health care system through October, 2023.ResultsA total of 14220 participants were included in this study. The prevalence rates of cardiovascular disease (CVD), cardiovascular death, and all-cause death were 2.59% (369/14220), 2.79% (397/14220), and 5.66% (805/14220), respectively. After adjusting for confounding factors in the multivariate logistic regression analysis models, the METS-IR index was significantly positively correlated with CVD, and cardiovascular, all-cause mortality, whether as a categorical or continuous variable. Layered analysis showed that the METS-IR index of hypertensive participants in different subgroups was positively correlated with the endpoint event.Conclusions and relevanceThis large, prospective cohort study demonstrated that the METS-IR index, a new IR evaluation index, were independently associated with a higher risk of the cardiovascular composite endpoint and all-cause mortality among Chinese hypertensive population. Importantly, our finding provides an independent indicator for evaluating the prognosis of hypertensive patients

Positive correlation between fatty liver index and hyperuricemia in hypertensive Chinese adults: a H-type hypertension registry study

BackgroundFew studies have examined the relationship between fatty liver index (FLI) and hyperuricemia (HUA). This study explores the relationship between FLI and HUA in hypertensive patients.MethodsA total of 13,716 hypertensive subjects were included in the current study. FLI, a simple index calculated from triglycerides (TG), waist circumference (WC), body mass index (BMI), and γ -glutamyltransferase (GGT), was used as a useful predictor of nonalcoholic fatty liver disease (NAFLD) distribution. HUA was defined as serum uric acid ≥ 360 μmol/L for females and ≥ 420 μmol/L for males.ResultsThe mean value of total FLI was 31.8 ± 25.1. Multiple logistic analyses revealed a significant positive correlation between FLI and HUA (OR, 1.78; 95% CI: 1.69–1.87). A subgroup analysis demonstrated that the correlation between FLI (< 30 vs. ≥ 30) and HUA was significant in both sexes (P for interaction = 0.006). Further analyses stratified by sex indicated a positive correlation between FLI and HUA prevalence among male and female subjects. However, the correlation between FLI and HUA was stronger in female subjects than in males (male: OR, 1.70; 95% CI: 1.58–1.83; female: 1.85; 95% CI: 1.73–1.98).ConclusionThis study demonstrates a positive correlation between FLI and HUA in hypertensive adults, but stronger in females than males

Association between serum uric acid levels and peripheral artery disease in Chinese adults with hypertension

BackgroundHigher serum uric acid (SUA) can cause gout, which is principally characterized by arthritis due to monosodium urate crystal deposition in the lower extremities. High levels of SUA have been linked to endothelial dysfunction, oxidative stress, and inflammation, all of which are involved in the pathogenesis of peripheral artery disease(PAD). To date, the relationship between SUA levels and PAD is still poorly understood.MethodAn analysis of 9,839 Chinese adults with essential hypertension from the ongoing China H-type Hypertension Registry Study was conducted in this cross-sectional study. Patients with an ABI ≤0.9 was diagnosed with PAD. Hyperuricemia was defined as SUA levels >420 mol/L in men and >360 mol/L in women. The association between SUA levels and PAD was evaluated using multivariable logistic regression models based on odds ratios (ORs) and their 95% confidence intervals (CIs).ResultsThe enrolled subjects ranged in age from 27 to 93 years, with a mean age of 63.14 ± 8.99 years. The proportion of male patients was 46.22%, and the prevalence of hyperuricemia was 50.72%. In males, hyperuricemia was positively associated with the risk of PAD (adjusted OR per SD increase: 1.72, 95% CI 1.17 to 2.53, P =0.006). Males in the highest SUA tertile were significantly more likely to have PAD (adjusted OR: 2.63, 95% CI 1.42 to 4.86, P = 0.002; P for trend = 0.001). However, this positive relationship was not observed in females (adjusted OR: 1.29, 95% CI 0.77 to 2.17, P = 0.327; P for trend = 0.347).ConclusionAccording to this cross-sectional study, higher SUA levels were positively associated with PAD in male hypertensive patients, while this positive relationship disappeared in female participants

Determination, source analysis and preliminary risk assessment of benzoic acid in rice wine

Objective To analyze the concentration and source of benzoic acid in rice wine and evaluate the health risk of dietary benzoic acid intake from rice wine among adult consumers in China. Methods 231 samples of rice wine and 15 samples of raw materials were collected from five main rice wine production areas in China, including Shandong, Zhejiang, Jiangsu, Fujian and Shanghai; the content of benzoic acid and its precursors were determined by high performance liquid chromatography; the sources of benzoic acid in rice wine were analyzed by the benzaldehyde and phenylalanine simulation test and the real sample acceleration test; the benzoic acid intake among adult consumers was evaluated by simple distribution assessment method. Results In all rice wine samples, the detection rate of benzoic acid was 99.13% (229/231), the concentration range of benzoic acid was ND (not detectable) -37.00 mg/L, and the average was 2.28 mg/L. In 98 end products, the detection rate of benzoic acid was 100.00% (98/98), the concentration range of benzoic acid was ND-1.60 mg/L, and the average was 0.52 mg/L; in 133 base wine samples, the detection rate of benzoic acid was 98.50% (131/133), the content range of benzoic acid was ND-37.00 mg/L, and the average was 3.58 mg/L. The result of source analysis showed that the benzoic acid in rice wine mainly came from raw materials, degradation of phenylalanine and oxidation of benzaldehyde. Exposure assessment result showed that the average exposure of benzoic acid for rice wine consumers in China was 0.001 mg/kg BW, accounting for 0.02% of the acceptable daily intake (ADI); and the 95th percentile was 0.005 mg/kg BW, accounting for 0.1% of the ADI. Conclusion The detection rate of benzoic acid in rice wine was high but the concentration was low. Source analysis result indicated that benzoic acid in rice wine mainly came from raw materials, degradation of phenylalanine and oxidation of benzaldehyde; the health risk of benzoic acid exposure to adult rice wine consumers in China was low

Increased hepcidin in transferrin-treated thalassemic mice correlates with increased liver BMP2 expression and decreased hepatocyte ERK activation

Iron overload results in significant morbidity and mortality in \u3b2-thalassemic patients. Insufficient hepcidin is implicated in parenchymal iron overload in \u3b2-thalassemia and approaches to increase hepcidin have therapeutic potential. We have previously shown that exogenous apo-transferrin markedly ameliorates ineffective erythropoiesis and increases hepcidin expression in Hbbth1/th1 (thalassemic) mice. We utilize in vivo and in vitro systems to investigate effects of exogenous apo-transferrin on Smad and ERK1/2 signaling, pathways that participate in hepcidin regulation. Our results demonstrate that apo-transferrin increases hepcidin expression in vivo despite decreased circulating and parenchymal iron concentrations and unchanged liver Bmp6 mRNA expression in thalassemic mice. Hepatocytes from apo-transferrin treated mice demonstrate decreased ERK1/2 pathway and increased serum BMP2 concentration and hepatocyte BMP2 expression. Furthermore, hepatocyte ERK1/2 phosphorylation is enhanced by neutralizing anti-BMP2/4 antibodies and suppressed by BMP2 in vitro, resulting in converse effects on hepcidin expression, and hepatocytes treated with MEK/ERK1/2 inhibitor U0126 in combination with BMP2 exhibit a more than additive increase in hepcidin expression. Lastly, bone marrow erythroferrone expression is normalized in apo-transferrin treated thalassemic mice but increased in apo-transferrin injected wild type mice. These findings suggest that increased hepcidin expression after exogenous apo-transferrin is in part independent of erythroferrone and support a model in which apo-transferrin treatment in thalassemic mice increases BMP2 expression in the liver and other organs, decreases hepatocellular ERK1/2 activation, and increases nuclear Smad to increase hepcidin expression

Multifunctional magnetic Fe3O4 nanoparticles combined with chemotherapy and hyperthermia to overcome multidrug resistance

Yanyan Ren1,2,*, Haijun Zhang1,2,*, Baoan Chen1, Jian Cheng1, Xiaohui Cai1, Ran Liu1, Guohua Xia1, Weiwei Wu1, Shuai Wang1, Jiahua Ding1, Chong Gao1, Jun Wang1, Wen Bao1, Lei Wang1, Liang Tian1, Huihui Song1, Xuemei Wang1,2 1Department of Hematology and Oncology, Key Medical Discipline, Jiangsu Province, Zhongda Hospital, and Faculty of Oncology, Medical School, Nanjing, 2State Key Laboratory of Bioelectronics, Southeast University, Nanjing, People's Republic of China*These authors contributed equally to this workBackground: Multidrug resistance in cancer is a major obstacle for clinical therapeutics, and is the reason for 90% of treatment failures. This study investigated the efficiency of novel multifunctional Fe3O4 magnetic nanoparticles (Fe3O4-MNP) combined with chemotherapy and hyperthermia for overcoming multidrug resistance in an in vivo model of leukemia.Methods: Nude mice with tumor xenografts were randomly divided into a control group, and the treatment groups were allocated to receive daunorubicin, 5-bromotetrandrine (5-BrTet) and daunorubicin, Fe3O4-MNP, and Fe3O4-MNP coloaded with daunorubicin and 5-bromotetrandrine (Fe3O4-MNP-DNR-5-BrTet), with hyperthermia in an alternating magnetic field. We investigated tumor volume and pathology, as well as P-glycoprotein, Bcl-2, Bax, and caspase-3 protein expression to elucidate the effect of multimodal treatment on overcoming multidrug resistance.Results: Fe3O4-MNP played a role in increasing tumor temperature during hyperthermia. Tumors became significantly smaller, and apoptosis of cells was observed in both the Fe3O4-MNP and Fe3O4-MNP-DNR-5-BrTet groups, especially in the Fe3O4-MNP-DNR-5-BrTet group, while tumor volumes in the other groups had increased after treatment for 12 days. Furthermore, Fe3O4-MNP-DNR-5-BrTet with hyperthermia noticeably decreased P-glycoprotein and Bcl-2 expression, and markedly increased Bax and caspase-3 expression.Conclusion: Fe3O4-MNP-DNR-5-BrTet with hyperthermia may be a potential approach for reversal of multidrug resistance in the treatment of leukemia.Keywords: magnetic nanoparticles, daunorubicin, 5-bromotetrandrine, multidrug resistance, hyperthermi

Mature cystic extragonadal teratoma in Douglas’ pouch: Case report and literature review

Teratomas often occur in the gonads, while Extragonadal mature cystic teratomas are reported occasionally, with the most common site being the omentum. Teratoma in the Douglas sac is extremely rare. we report a rare case of mature cystic Teratoma in the Douglas sac in a 71-year-old woman who underwent laparoscopic surgery. A cyst with a diameter of approximately 6 cm from Douglas was found during surgery, and the mass was separated from both ovaries. Microscopically, the cyst was a mature cystic teratoma that did not originate from the ovary

Decreasing TfR1 expression reverses anemia and hepcidin suppression in β-thalassemic mice

Iron availability for erythropoiesis and its dysregulation in β-thalassemia are incompletely understood. We previously demonstrated that exogenous apotransferrin leads to more effective erythropoiesis, decreasing erythroferrone (ERFE) and derepressing hepcidin in β-thalassemic mice. Transferrin-bound iron binding to transferrin receptor 1 (TfR1) is essential for cellular iron delivery during erythropoiesis. We hypothesize that apotransferrin's effect is mediated via decreased TfR1 expression and evaluate TfR1 expression in β-thalassemic mice in vivo and in vitro with and without added apotransferrin. Our findings demonstrate that β-thalassemic erythroid precursors overexpress TfR1, an effect that can be reversed by the administration of exogenous apotransferrin. In vitro experiments demonstrate that apotransferrin inhibits TfR1 expression independent of erythropoietin- and iron-related signaling, decreases TfR1 partitioning to reticulocytes during enucleation, and enhances enucleation of defective β-thalassemic erythroid precursors. These findings strongly suggest that overexpressed TfR1 may play a regulatory role contributing to iron overload and anemia in β-thalassemic mice. To evaluate further, we crossed TfR1+/- mice, themselves exhibiting iron-restricted erythropoiesis with increased hepcidin, with β-thalassemic mice. Resultant double-heterozygote mice demonstrate long-term improvement in ineffective erythropoiesis, hepcidin derepression, and increased erythroid enucleation in relation to β-thalassemic mice. Our data demonstrate for the first time that TfR1+/- haploinsufficiency reverses iron overload specifically in β-thalassemic erythroid precursors. Taken together, decreasing TfR1 expression during β-thalassemic erythropoiesis, either directly via induced haploinsufficiency or via exogenous apotransferrin, decreases ineffective erythropoiesis and provides an endogenous mechanism to upregulate hepcidin, leading to sustained iron-restricted erythropoiesis and preventing systemic iron overload in β-thalassemic mice