Self-Assembled Carbon Metal-Organic Framework Oxides Derived from Two Calcination Temperatures as Anode Material for Lithium-Ion Batteries.

Owing to their structural diversity and mesoporous construction, metal-organic frameworks (MOFs) have been used as templates to prepare mesoporous metal oxides, which show excellent performance as anode materials for lithium-ion batteries (LIBs). Co-ZnO/C and Co-Co3O4/C nanohybrids were successfully synthesized based on a precursor of Co-doped MOF-5 by accurately controlling the annealing temperature and atmosphere. Experimental data proved that their electrochemical performance was closely associated with the material phase, especially for Co-ZnO/C, indicating that carbon skeleton materials can maintain a good restoration rate of over 99% after undergoing high-current density cycling. Meanwhile, Co-Co3O4/C nanohybrids showed an exceedingly high reversible capacity of 898 mAh∙g-1 at a current density of 0.1 C after 100 cycles. Their improved coulombic efficiency and superior rate capability contribute to a mesoporous structure, which provides pathways allowing for rapid Li+ diffusion and regulates volume change during charge and discharge processes.

Estimation of pathological subtypes in subsolid lung nodules using artificial intelligence.

Objective: This study aimed to investigate the value of artificial intelligence (AI) for distinguishing pathological subtypes of invasive pulmonary adenocarcinomas in patients with subsolid nodules (SSNs). Materials and methods: This retrospective study included 110 consecutive patients with 120 SSNs. The qualitative and quantitative imaging characteristics of SSNs were extracted automatically using an artificially intelligent assessment system. Then, radiologists had to verify these characteristics again. We split all cases into two groups: non-IA including 11 Atypical adenomatous hyperplasia (AAH) and 25 adenocarcinoma in situ (AIS) or IA including 7 minimally invasive adenocarcinoma (MIA) and 77 invasive adenocarcinoma (IAC). Variables that exhibited statistically significant differences between the non-IA and IA in the univariate analysis were included in the multivariate logistic regression analysis. Receiver operating characteristic (ROC) analyses were conducted to determine the cut-off values and their diagnostic performances. Results: Multivariate logistic regression analysis showed that the major diameter (odds ratio [OR] = 1.38; 95 % confidence interval [CI], 1.02-1.87; P = 0.036) and entropy of three-dimensional(3D) CT value (OR = 3.73, 95 % CI, 1.13-2.33, P = 0.031) were independent risk factors for adenocarcinomas. The cut-off values of the major diameter and the entropy of 3D CT value for the diagnosis of invasive adenocarcinoma were 15.5 mm and 5.17, respectively. To improve the classification performance, we fused the major diameter and the entropy of 3D CT value as a combined model, and the (AUC） of the model was 0.868 (sensitivity = 0.845, specificity = 0.806). Conclusion: The major diameter and entropy of 3D CT value can distinguish non-IA from IA. AI can improve performance in distinguishing pathological subtypes of invasive pulmonary adenocarcinomas in patients with SSNs.

IRX3 promotes adipose tissue browning and inhibits fibrosis in obesity-resistant mice.

Obesity is one of the threats to human health and survival. High fat diet (HFD)-induced obesity leads to adipose tissue fibrosis and a series of metabolic diseases. There are some people still thin under HFD, a phenomenon known as the "obesity resistance (OR) phenotype". It was found that Iroquois homeobox 3 (IRX3) is considered as a regulator in obesity, but the regulatory mechanism between OR and IRX3 is still unclear. In this study, we investigated OR on a HFD and the role of the IRX3 gene. Using mice, we observed that OR mice had lower body weights, reduced liver lipid synthesis, and increased white adipose tissue (WAT) lipolysis compared to obesity-prone (OP) mice. Additionally, OR mice exhibited spontaneous WAT browning and less fibrosis, correlating with higher Irx3 expression. Utilizing 3T3-L1 differentiated adipocytes, our study demonstrated that overexpression of Irx3 promoted thermogenesis-related gene expression and reduced adipocyte fibrosis. Therefore, Irx3 promotes WAT browning and inhibits fibrosis in OR mice. These results provide insight into the differences between obesity and OR, new perspectives on obesity treatment, and guidance for lessening adipose tissue fibrosis.

Trends in diabetic ketoacidosis- and hyperosmolar hyperglycemic state-related mortality during the COVID-19 pandemic in the United States: A population-based study.

BACKGROUND: During the pandemic, a notable increase in diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS), conditions that warrant emergent management, was reported. We aimed to investigate the trend of DKA- and HHS-related mortality and excess deaths during the pandemic. METHODS: Annual age-standardized mortality rates related to DKA and HHS between 2006 and 2021 were estimated using a nationwide database. Forecast analyses based on prepandemic data were conducted to predict the mortality rates during the pandemic. Excess mortality rates were calculated by comparing the observed versus predicted mortality rates. Subgroup analyses of demographic factors were performed. RESULTS: There were 71 575 DKA-related deaths and 8618 HHS-related deaths documented during 2006-2021. DKA, which showed a steady increase before the pandemic, demonstrated a pronounced excess mortality during the pandemic (36.91% in 2020 and 46.58% in 2021) with an annual percentage change (APC) of 29.4% (95% CI: 16.0%-44.0%). Although HHS incurred a downward trend during 2006-2019, the excess deaths in 2020 (40.60%) and 2021 (56.64%) were profound. Pediatric decedents exhibited the highest excess mortality. More than half of the excess deaths due to DKA were coronavirus disease 2019 (COVID-19) related (51.3% in 2020 and 63.4% in 2021), whereas only less than a quarter of excess deaths due to HHS were COVID-19 related. A widened racial/ethnic disparity was observed, and females exhibited higher excess mortality than males. CONCLUSIONS: The DKA- and HHS-related excess mortality during the pandemic and relevant disparities emphasize the urgent need for targeted strategies to mitigate the escalated risk in these populations during public health crises.

Combination of Epicardial Adipose Tissue and Left Atrial Low-Voltage Areas Predicting Atrial Fibrillation Recurrence after Radiofrequency Ablation.

INTRODUCTION: Atrial fibrillation (AF) is a common arrhythmia, with radiofrequency catheter ablation (RFCA) being first-line therapy. However, the high rate of post-ablation recurrence necessitates the identification of predictors for recurrence risk. Left atrial low-voltage areas (LA-LVASs), reflecting atrial fibrosis, have been confirmed to be related to recurrence of AF. Recently, epicardial adipose tissue (EAT) has been studied due to its role in initiating and maintaining AF. In this study, we try to evaluate the significance of the combined use of left atrial epicardial adipose tissue (LA-EAT) and percentage of LA-LVAs (LA-LVAs%) for predicting the recurrence of AF. METHODS: A total of 387 patients with AF who had undergone RFCA for the first time were followed up for 1, 3, 6, and 12 months. They were divided into two groups: the recurrence group (n = 90) and the non-recurrence group (n = 297). Before the ablation, all patients underwent computed tomography angiography examination of the left atrium, and the LA-EAT was measured using medical software (Advantage Workstation 4.6, GE, USA). After circumferential pulmonary vein isolation, a three-dimensional mapping system was used to map the LA endocardium and evaluate the LA-LVAs in sinus rhythm. RESULTS: After a median follow-up of 10.2 months, 90 patients developed AF recurrence after RFCA. Compared to patients without recurrence, the volume of LA-EAT (33.45 ± 13.65 vs. 26.27 ± 11.38; p < 0.001) and the LA-LVAs% (1.60% [0%, 9.99%] vs. 0.00% [0%, 2.46%]; p < 0.001) was significantly higher. Multivariate analysis indicated that PersAF, LA-EAT volume, and LA-LVAs% were independent predictors. Compared to PersAF (AUC 0.628; specificity 0.646; sensitivity 0.609), LA-EAT volume (AUC 0.655; specificity 0.675; sensitivity 0.586), or LA-LVAs% (AUC 0.659; specificity 0.836; sensitivity 0.437), the combined use of LA-EAT volume and LA-LVAs% offers higher accuracy for predicting AF recurrence after ablation (AUC 0.738; specificity 0.761; sensitivity 0.621). CONCLUSION: The combined LA-EAT and LA-LVAs% can effectively predict the risk of AF recurrence after radiofrequency ablation.

Predictors of improvement in left ventricular systolic function after catheter ablation in patients with persistent atrial fibrillation complicated with heart failure.

AIMS: The current management of patients with atrial fibrillation (AF) and concomitant heart failure (HF) remains a significant challenge. Catheter ablation (CA) has been shown to improve left ventricular ejection fraction (LVEF) in these patients, but which patients can benefit from CA is still poorly understood. The aim of our study was to determine the predictors of improved ejection fraction in patients with persistent atrial fibrillation (PeAF) complicated with HF undergoing CA. METHODS AND RESULTS: A total of 435 patients with persistent AF underwent an initial CA between January 2019 and March 2023 in our hospital. We investigated consecutive patients with left ventricular systolic dysfunction (LVEF < 50%) measured by transthoracic echocardiography (TTE) within one month before CA. According to the LVEF changes at 6 months, these patients were divided into an improved group (fulfilling the '2021 Universal Definition of HF' criteria for LVEF recovery) and a nonimproved group. Eighty patients were analyzed, and the improvement group consisted of 60 patients (75.0%). In the univariate analysis, left ventricular end-diastolic diameter (P = 0.005) and low voltage zones in the left atrium (P = 0.043) were associated with improvement of LVEF. A receiver operating characteristic analysis determined that the suitable cutoff value for left ventricular end-diastolic diameter (LVDd) was 59 mm (sensitivity: 85.0%, specificity: 55.0%, area under curve: 0.709). A multivariate analysis showed that LVDd (OR = 0.85; 95% CI: 0.76-0.95, P = 0.005) and low voltage zones (LVZs) (OR = 0.26; 95% CI: 0.07-0.96, P = 0.043) were significantly independently associated with the improvement of LVEF. Additionally, parameters were significantly improved regarding the left atrial diameter, LVDd and ventricular rate after radiofrequency catheter ablation (all p < 0.05). CONCLUSIONS: The improvement of left ventricular ejection fraction (LVEF) occurred in 75.0% of patients. Our study provides additional evidence that LVDd < 59 mm and no low voltage zones in the left atrium can be used to jointly predict the improvement of LVEF after atrial fibrillation ablation.

The effect of icotinib or apatinib on the pharmacokinetic profile of oxycodone in rats and the underlying mechanism.

This study aimed to investigate the interactions between icotinib/apatinib and oxycodone in rats and to unveil the underlying mechanism. An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to determine oxycodone and its demethylated metabolite simultaneously. In vivo, Sprague-Dawley (SD) male rats were administered oxycodone with or without icotinib or apatinib. Blood samples were collected and subjected to UPLC-MS/MS analysis. An enzyme incubation assay was performed to investigate the mechanism of drug-drug interaction using both rat and human liver microsomes (RLM and HLM). The results showed that icotinib markedly increased the AUC(0-t) and AUC(0-∞) of oxycodone but decreased the CLz/F. The Cmax of oxycodone increased significantly upon co-administration of apatinib. In vitro, the Km value of oxycodone metabolism was 101.7 ± 5.40 µM and 529.6 ± 19.60 µM in RLMs and HLMs, respectively. Icotinib and apatinib inhibited the disposition of oxycodone, with a mixed mechanism in RLM (IC50 = 3.29 ± 0.090 µM and 0.95 ± 0.88 µM, respectively) and a competitive and mixed mechanism in HLM (IC50 = 22.34 ± 0.81 µM and 0.48 ± 0.05 µM, respectively). In conclusion, both icotinib and apatinib inhibit the metabolism of oxycodone in vitro and in vivo. Therefore, the dose of oxycodone should be reconsidered when co-administered with icotinib or apatinib.

Mangiferin alleviates renal inflammatory injury in spontaneously hypertensive rats by inhibiting MCP-1/CCR2 signaling pathway.

Objective: Hypertension is a low-grade inflammation state of the disease and was easily complicated by kidneys' inflammatory response. Mangiferin (MGF), a pharmacologically active compound in various plants including Mangifera indica, has a strong anti-inflammatory activity. However, the effects of MGF on renal inflammatory injury in spontaneously hypertensive rats (SHRs) remain unclear. The purpose of this study was to investigate the protective effects and mechanisms of MGF on renal inflammatory injury in SHRs. Methods: MGF was used in SHRs at the doses of 10, 20, 40 mg/kg/d for 8 weeks consecutively. The blood and urine were collected for assessment of renal function. Renal tissues were collected for histological, immunohistochemistry, ELISA, Western blot and real time reverse transcription PCR (RT-PCR) analysis. Results: The results showed that the levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and recombinant chemokine C-C-Motif receptor 2 (CCR2) were increased in SHRs, meanwhile, the level of IL-10 was decreased in SHR. Treatment of MGF inhibited the expression of IL-6, TNF-α, MCP-1 and CCR2, and promoted the expression of IL-10. Furthermore, the content of blood urea nitrogen (BUN) and serum uric acid (SUA) was significantly increased in the model group, and treatment of MGF had no obvious effects on these parameters at all dose levels. Conclusion: Our study proved that the kidneys of SHRs had significant inflammatory injury, and MGF had the protective effects on renal inflammatory injury in SHRs; The protective mechanism may be mediated partly by the MCP-1/CCR2 signaling pathway. Thus, it is a potential new drug for the treatment of hypertension.

Establishment and Validation of the Nomogram Model and the Probability of Silent Cerebral Infarction After Ablation Atrial Fibrillation.

BACKGROUND: The objective of this study is to establish and validate a nomogram model for predicting the probability of silent cerebral infarction following ablation of atrial fibrillation. METHODS AND RESULTS: A retrospective observational study was conducted on the data of 238 patients with atrial fibrillation who underwent radiofrequency ablation in our hospital from October 2019 to December 2022. LASSO regression and multivariate logistics regression analysis were used to assess the independent risk factors for silent cerebral infarction after ablation. The AUC of the predictive model was 0.733 (95% CI, 0.649-0.816) and the internal validation (bootstrap = 1000) of the bootstrap method was 0.733 (95% CI 0.646-0.813). The Hosmer-Lemeshow test yields an insignificant p-value of X-squared = 10.212 and p-value = 0.2504, thus indicating an insignificant difference between predicted and observed values and good calibration results. The clinical impact curve (CIC) and clinical decision curve also prove that this graph is useful in the clinical setting. CONCLUSION: We developed an easy-to-use nomogram model to predict the probability of silent cerebral infarction following radiofrequency ablation of atrial fibrillation. This model can provide a valid assessment of the probability of postoperative silent cerebral infarction in patients undergoing radiofrequency ablation of atrial fibrillation.

Exploring temporal trends and influencing factors for thyroid cancer in Guangzhou, China: 2004-2018.

PURPOSE: Describe and analyze the trends of thyroid cancer incidence and mortality in Guangzhou, explore the potential influencing factors, and provide evidence for the government to formulate prevention and treatment measures. METHODS: Incident and death cases of thyroid cancer were retrieved from the Guangzhou cancer registry. The joinpoint regression models were used to estimate the incidence and mortality trends. Age-period-cohort models were used to estimate the age, period, and cohort effects on the time trends. Grey correlation analysis was performed to explore possible connections between thyroid cancer and social factors. RESULTS: A total of 15,955 new cases of thyroid cancer were registered in Guangzhou during 2004-2018, the age-standardized incidence rate (ASIR) of thyroid cancer increased from 4.29/105 in 2004 to 22.36/105 in 2018, with the average annual percentage change (AAPC) of 13.40%. The overall increase can be attributed to the increase in the incidence of papillary thyroid carcinoma (PTC), which was dominated by tumors <2 cm. The ASIR was higher in women (16.12/105) compared to men (5.46/105), and young and middle-aged individuals had higher incidence rates than older people. The number of thyroid cancer deaths registered between 2010 and 2018 was 356, and the age-standardized mortality rates (ASMRs) were stable (approximately 0.42/105). Men's ASMR (0.34/105) and women's (0.49/105) were similar, and those 60 and older had greater mortality. The period and cohort relative risks showed an overall increasing trend. Furthermore, there was a strong positive correlation between the ASIRs and social determinants. CONCLUSIONS: During the study period, the incidence rate of thyroid cancer among young and middle-aged people in Guangzhou showed a rapidly increasing trend, and the mortality was relatively stable. In the future, more effective preventive measures should be taken for this age group to reduce the burden of disease and avoid overdiagnosis.

Development and Validation of a Nomogram Model Affecting the ACT Targeting Rate During Radiofrequency Ablation of Atrial Fibrillation in China.

CONTEXT: A nomogram model affecting the activated clotting time (ACT) targeting rate during radiofrequency ablation of atrial fibrillation (RFCA) in China. PURPOSE: The aim of this study is to develop and validate a nomogram model for predicting the activated clotting time targeting rate after the initial bolus heparin dosages during the radiofrequency catheter ablation of atrial fibrillation in China. METHODS AND RESULTS: A retrospective observational study was conducted on the data of 465 patients with atrial fibrillation who underwent radiofrequency catheter ablation (RFCA) from October 2019 to June 2022. All patients were randomized into a training cohort (70%; n = 325) and a validation cohort (30%; n = 140). Independent risk factors were identified using univariate and multifactorial logistic regression analysis. The predictive nomogram model was established using R software. The nomogram was developed and evaluated based on differentiation, calibration, and clinical efficacy using concordance statistic (C-statistic), calibration plots, and decision curve analysis (DCA), respectively. The nomogram was established using three variables, including sex (OR 1.01, 95% CI 0.29-1.76, P = 0.007), heparin dose (OR 0.04; 95%CI 0.02-0.05, P < 0.001), and the baseline ACT (OR 0.03; 95%CI 0.02-0.04, P < 0.001). The C-statistic of the nomogram was 0.736 (95%CI 0.675-0.732) in the training cohort and 0.700 (95%CI 0.622-0.721) in the validation cohort. The calibration plots showed good agreement between the predictions and observations in the training and validation cohorts. The clinical decision curve also proves that the map is useful in clinical settings. CONCLUSION: The nomogram model has good discrimination and accuracy, which can screen attainment groups intuitively and individually, and has a certain predictive value for the probability of ACT reaching the target after the adequate dosage of initial heparin in Chinese patients with atrial fibrillation.

Evaluation of retinal microcirculation alterations using OCTA in hyperopic ametropic amblyopia patients before and after treatment.

PURPOSE: We aimed to compare retinal microcirculation in hyperopic ametropic amblyopia patients before and after treatment and in healthy children using optical coherence tomography angiography (OCTA), and to explore the pathogenesis of hyperopic ametropic amblyopia. METHODS: Eighteen patients with hyperopic ametropic amblyopia aged 4-8 years were selected as the patient group, and 18 age-matched healthy children were randomly selected as controls. The foveal avascular zone (FAZ) area, perimeter and circularity, vessel density (VD) and perfusion density (PD) of macular superficial retinal capillary plexus, macular thickness, peripapillary retinal nerve fiber layer thickness, and ganglion cell-inner plexiform layer thickness were compared between both groups. After 6 months of amblyopia treatment, the same parameters were measured again. RESULTS: The VD and PD in the central, inner, inner nasal, and inner inferior regions in hyperopic ametropic amblyopia were lower than in the control group after adjustment for axial length. After 6 months of treatment, the VD increased significantly, except in the outer nasal and outer inferior regions. The PD in the central (p < 0.001), inner superior (p = 0.001), inner inferior (p = 0.011) and inner temporal (p = 0.026) regions increased. The FAZ perimeter and circularity significantly differed between the groups. After 6 months of treatment, the FAZ area and perimeter decreased, but circularity increased. CONCLUSION: Hyperopic ametropic amblyopia eyes showed a significant decrease in vessel and perfusion densities. After amblyopia treatment, the vessel and perfusion densities of patients with hyperopic ametropic amblyopia increased, suggesting that abnormalities in the microvascular system are a pathogenic factor of amblyopia.

Evaluation of retinal microcirculation alterations using optical coherence tomography angiography in patients with hyperopia ametropic amblyopia: A case-control study.

Given that there are controversial findings regarding vessel density in amblyopia, we quantified retinal microcirculation using optical coherence tomography angiography and compared it between hyperopic ametropic amblyopia eyes and age-matched control eyes. This case-control study was conducted from March 2021 to March 2022 at the Affiliated Eye Hospital of Nanchang University, Nanchang, China. Both groups included 72 eyes. Foveal avascular zone area, circularity and perimeter, perfusion density and vessel density of macular superficial retinal capillary plexus, macular thickness, macular volume, peripapillary retinal nerve fiber layer thickness, and ganglion cell-inner plexiform layer thickness were compared between hyperopia ametropic amblyopia eyes and age-matched control eyes. Additionally, best-corrected visual acuity, maximum corneal curvature, minimum corneal curvature, and anterior chamber depth were measured. In the hyperopia ametropic amblyopia eyes and control eyes, vessel density was 7.51 ± 2.13 and 9.91 ± 2.71 mm-1 in the central, 17.20 ± 1.38 and 18.25 ± 1.37 mm-1 in the inner, and 17.90 ± 0.88 and 18.43 ± 0.97 mm-1 in the full regions, respectively. The perfusion densities were 0.17 ± 0.06 and 0.23 ± 0.07 in the central, 0.41 ± 0.05 and 0.44 ± 0.03 in the inner, and 0.44 ± 0.03 and 0.46 ± 0.02 in the full regions, respectively. The central macular thicknesses of hyperopia ametropic amblyopia and control eyes were 240.04 ± 20.11 and 235.08 ± 24.41 µm, respectively. Foveal avascular zone perimeter and circularity (P < .043 and P = .001) significantly differed between the 2 groups. Hyperopia ametropic amblyopia eyes showed lower appreciably in vessel and perfusion densities, which could be one of the major pathophysiological mechanisms of hyperopia ametropic amblyopia and provide a new direction for the diagnosis and treatment of amblyopia.

Robust optimization for casualty scheduling considering injury deterioration and point-edge mixed failures in early stage of post-earthquake relief.

Objective: Scientifically organizing emergency rescue activities to reduce mortality in the early stage of earthquakes. Methods: A robust casualty scheduling problem to reduce the total expected death probability of the casualties is studied by considering scenarios of disrupted medical points and routes. The problem is described as a 0-1 mixed integer nonlinear programming model. An improved particle swarm optimization (PSO) algorithm is introduced to solve the model. A case study of the Lushan earthquake in China is conducted to verify the feasibility and effectiveness of the model and algorithm. Results: The results show that the proposed PSO algorithm is superior to the compared genetic algorithm, immune optimization algorithm, and differential evolution algorithm. The optimization results are still robust and reliable even if some medical points fail and routes are disrupted in affected areas when considering point-edge mixed failure scenarios. Conclusion: Decision makers can balance casualty treatment and system reliability based on the degree of risk preference considering the uncertainty of casualties, to achieve the optimal casualty scheduling effect.

The predictive value of left atrium epicardial adipose tissue on recurrence after catheter ablation in patients with different types of atrial fibrillation.

BACKGROUND: A growing body of evidence supports that the left atrium epicardial adipose tissue (LA-EAT) is related to the occurrence and recurrence of atrial fibrillation (AF). The relationship between LA-EAT and the recurrence after radiofrequency catheter ablation (RFCA) in patients with different types of AF is still unclear. This study aims to evaluate the predictive value of LA-EAT on the recurrence of AF after RFCA in patients with different types of AF. METHODS: 301 AF patients who underwent RFCA for the first time were divided into the paroxysmal atrial fibrillation (PAF) group (n = 181) and the persistent atrial fibrillation (PersAF) group(n = 120), which were followed up at 3, 6, and 12 months. All patients underwent left atrial computed tomography angiography (CTA) examination before the operation, and LA-EAT was measured using software (Advantage Workstation4.6, GE, USA). RESULTS: After a median follow-up of 10.7 months, 73/301 patients (24.25%) had a recurrence of AF, including 43 /120(35.83%) patients with PersAF and 30/181(16.57%) patients with PAF. In multivariable Cox regression analysis, LA-EAT volume (OR = 1.053;95%CI: 1.024-1.083, p < 0.001), attenuation (OR = 0.949;95%CI:0.911-0.988, p = 0.012) and left atrial diameter (LAD) (OR = 1.063;95%CI:1.002-1.127，p = 0.043) were independent risk factors for recurrence in patients with PersAF but not in patients with PAF. CONCLUSION: LA-EAT volume and attenuation are independent risk factors for recurrence after RFCA in patients with PersAF.

CYP2D6 gene polymorphism and apatinib affect the metabolic profile of fluvoxamine.

This study aimed 1) to investigate the influence of CYP2D6 variants on the catalyzing of fluvoxamine, and 2) to study the interaction between fluvoxamine and apatinib. An enzymatic reaction system was setup and the kinetic profile of CYP2D6 in metabolizing fluvoxamine was determined. In vivo, drug-drug interaction was investigated using Sprague-Dawley (SD) rats. Fluvoxamine was given gavage with or without apatinib. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine the concentrations of fluvoxamine and desmethyl-fluvoxamine. The results demonstrated that the relative clearance rates of CYP2D6.A5V, V104A, D337G, F164L, V342M, R440C and R497C increased significantly compared with CYP2D6.1, ranging from 153.626% ± 6.718% to 394.310% ± 33.268%. The activities of other variants reduced to different extent, or even lost function, but there was no statistical difference. The IC50 of apatinib against fluvoxamine disposition was determined, which is 0.190 µM in RLM and 6.419 µM in HLM, respectively. In vivo, apatinib can enhance the plasma exposure of fluvoxamine remarkably characterized by increased AUC, Tmax and Cmax. Meanwhile, the produce of desmethyl fluvoxamine was dramatically inhibited, both AUC and Cmax decreased significantly. Mechanistically, apatinib inhibit the generation of fluvoxamine metabolite with a mixed manner both in RLM and HLM. Furthermore, there were differences in the potency of apatinib in suppressing fluvoxamine metabolism among CYP2D6.1, 2 and 10. In conclusion, CYP2D6 gene polymorphisms and drug-drug interaction can remarkably affect the plasma exposure of fluvoxamine. The present study provides basis data for guiding individual application of fluvoxamine.

Saponins from Panax japonicus alleviate adipose tissue fibrosis and metabolic dysfunction in high-fat-diet-induced obese mice.

INTRODUCTION: Adipose tissue fibrosis is a typical feature of adipose tissue dysfunction in obese individuals, which is closely related to metabolic diseases. OBJECTIVE: To explore the effect and mechanism of Saponins from Panax japonicus (SPJ) on adipose tissue fibrosis in obese mice induced by high fat diet (HFD). MATERIALS AND METHODS: We established a HFD induced obese mice model. Then the obese mice were treated with 90 mg/kg SPJ by oral gavage for 10 weeks. The levels of adipose tissue fibrosis and molecules related to signalling pathways were measured. Then the effects of SPJ on TGFß1-induced fibrosis in 3T3-L1 differentiated adipocytes were evaluated. RESULTS: SPJ reduced body weight, fat accumulation, and improved glucose and lipid metabolism in obese mice. SPJ decreased collagen deposition and expressions of fibrotic genes in epididymal white adipose tissue (eWAT) of obese mice. SPJ decreased the levels of TGFß1 protein and pSmad2, and increased the expression of PPARγ and PGC1α, thus alleviating oxidative stress in eWAT. Consistently, SPJ inhibited TGFß1-induced fibrosis in 3T3-L1 differentiated adipocytes. CONCLUSIONS: SPJ may alleviate adipose tissue fibrosis and improve obesity by inhibiting TGFß1/Smad2 and activating PPARγ/PGC1α pathway. SPJ is expected to become an efficient medicine for treatment of obesity.

Polymorphisms of adiponectin gene and gene-lipid interaction with hypertension risk in Chinese coal miners: A matched case-control study.

OBJECTIVE: Low serum adiponectin level can predict hypertension development, and adiponectin gene (ADIPOQ) polymorphisms have been reported to be linked with hypertension risk. Whereas, the interaction between ADIPOQ polymorphisms and environmental factors on the susceptibility of hypertension remained unclear. The purpose of this study was to explore the relationship of ADIPOQ polymorphisms with hypertension risk and their interaction with lipid levels in coal miners. METHODS: A matched case-control study with 296 case-control pairs was performed in a large coal mining group located in North China. The participants were questioned by trained interviewers, and their ADIPOQ genotype and lipid levels were determined. Logistic regression, stratified analysis, and crossover analysis were applied to evaluate the effects of rs2241766, rs1501299, and rs266729 genotypes and gene-lipid interaction on hypertension risk. RESULTS: In this matched case-control study, the genotypes of rs2241766 TG+GG, rs1501299 GT+TT, and rs266729 CG+GG were marginally related to hypertension risk. Individuals with high total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) level were susceptible to hypertension (TC: odds ratio [OR] = 1.807, 95% confidence intervals [95%CI] = 1.266-2.581; LDL-C: OR = 1.981, 95%CI = 1.400-2.803; HDL-C: OR = 1.559, 95%CI = 1.093-2.223). Antagonistic interactions were detected between rs2241766 and TC, rs1501299 and TC, rs2241766 and LDL-C, and rs1501299 and HDL-C (rs2241766 and TC: OR = 0.393, 95%CI = 0.191-0.806; rs1501299 and TC: OR = 0.445, 95%CI = 0.216-0.918; rs2241766 and LDL-C: OR = 0.440, 95%CI = 0.221-0.877; rs1501299 and HDL-C: OR = 0.479, 95%CI = 0.237-0.967). Stratified analysis showed that hypertension risk was high for the subjects with rs2241766 TG+GG or rs1501299 GG under the low lipid level but low for those under the high lipid level. In the case group, the TC and LDL-C levels for rs2241766 TG+GG were lower than those for rs2241766 GG, and the TC and HDL-C levels for rs1501299 GT+TT were higher than those for rs1501299 GG. CONCLUSIONS: Although the effects of ADIPOQ polymorphisms alone were not remarkable, an antagonistic interaction was observed between ADIPOQ polymorphisms and lipid levels.

Development of a Lateral Flow Strip with a Positive Readout for the On-Site Detection of Aflatoxin B1.

Aflatoxin B1 is one of the contamination indicators for food safety monitoring. The rapid and effective assessment and determination of AFB1 in food is of great importance to dietary safety. The lateral flow assay shows advantages in its simplicity, and rapidity, and provides a visual readout, while the available lateral flow assay for AFB1 requires a competitive format that produces readings inversely proportional to the AFB1 concentration, which is counterintuitive and may lead to a potential misinterpretation of the results. Herein, we developed a positive readout aptamer-based lateral flow strip (Apt-strip) for the detection of AFB1. This Apt-strip relies on the competition between AFB1 and fluorescein-labeled complementary DNA strands (FAM-cDNA) for affinity binding to limited aptamers against AFB1 (AFB1-Apt). In the absence of AFB1, AFB1-Apt hybridizes with FAM-cDNA. No signal at the T-line of the Apt-strip was observed. In contrast, AFB1-Apt binds to AFB1 in the sample, and then a part of the FAM-cDNA is hybridized with the free AFB1-Apt, at which time the other unreacted FAM-cDNA is captured by A35-Apt on the T-line. The signal was observed. This method achieved fast detection of AFB1 with a detection limit (DL) of 0.1 ng/mL, positive readout, and increased sensitivity.