Sophocarpine attenuates doxorubicin-induced heart injury through inhibition of fibrosis.

BACKGROUND: Doxorubicin (DOX) is a potent anti-cancer medication that is associated with numerous adverse effects, particularly concerning damage to the heart. METHODS: This study aimed to investigate the impact of sophocarpine (SOP) on DOX-induced heart injury through both in vivo and in vitro experiments. The experimental techniques employed encompassed echocardiography, hematoxylin/eosin (H&E) staining, Masson staining, immunohistochemical staining, western blotting, and so on. RESULTS: Echocardiography showed that SOP alleviated DOX-induced cardiac dysfunction, as evidenced by the improvements in both left ventricle ejection fraction and left ventricle fractional shortening. DOX caused upregulations of creatine kinase-MB and lactate dehydrogenase, while SOP decreased these indices. Staining methods such as H&E and Masson showed that SOP reversed the pathological changes induced by DOX. DOX elevated the expression levels of fibrosis-associated proteins such as Collagen I, Collagen III, α-SMA, Fibronectin, MMP-2, and MMP-9. However, SOP reversed these changes. Moreover, the study further revealed that SOP inhibited the TGF-ß1/Smad3 signaling pathway. CONCLUSIONS: These findings imply that SOP has the potential to mitigate DOX-induced heart injury by suppressing fibrosis. The underlying molecular mechanism may involve the inhibition of the TGF-ß1/Smad3 signaling pathway.

Sophocarpine alleviates doxorubicin-induced heart injury by suppressing oxidative stress and apoptosis.

Doxorubicin (DOX) is an effective anti-tumor drug accompanied with many side effects, especially heart injury. To explore what effects of sophocarpine (SOP) on DOX-induced heart injury, this study conducted in vivo experiment and in vitro experiment, and the C57BL/6J mice and the H9C2 cells were used. The experimental methods used included echocardiography, enzyme-linked immunosorbent assay (ELISA), dihydroethidium (DHE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, western blotting and so on. Echocardiography showed that SOP alleviated DOX-induced cardiac dysfunction, as evidenced by the improvements of left ventricle ejection fraction and left ventricle fractional shortening. DOX caused upregulations of creatine kinase (CK), creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), while SOP reduced these indices. The relevant stainings showed that SOP reversed the increases of total superoxide level induced by DOX. DOX also contribute to a higher level of MDA and lower levels of SOD and GSH, but these changes were suppressed by SOP. DOX increased the pro-oxidative protein level of NOX-4 while decreased the anti-oxidative protein level of SOD-2, but SOP reversed these effects. In addition, this study further discovered that SOP inhibited the decreases of Nrf2 and HO-1 levels induced by DOX. The TUNEL staining revealed that SOP reduced the high degree of apoptosis induced by DOX. Besides, pro-apoptosis proteins like Bax, cleaved-caspase-3 and cytochrome-c upregulated while anti-apoptosis protein like Bcl-2 downregulated when challenged by DOX, but them were suppressed by SOP. These findings suggested that SOP could alleviate DOX-induced heart injury by suppressing oxidative stress and apoptosis, with molecular mechanism activating of the Nrf2/HO-1 signaling pathway.

The impact of superselective adrenal artery embolization on renal function in patients with primary aldosteronism: a prospective cohort study.

Superselective adrenal artery embolization (SAAE) is an effective treatment for patients with primary aldosteronism (PA). However, the impact of SAAE on renal function in the PA population remains uncertain. We investigated the estimated glomerular filtration rate (eGFR) and age, sex, body mass index, and diabetes-specific percentiles of eGFR residuals in 182 PA patients treated with SAAE in a prospective cohort from Nanchang SAAE in treating PA registry study. Data suggest that SAAE caused a significant decrease in eGFR from 91.9 ± 26.1 to 88.7 ± 24.1 ml/min/1.73 m2 (p < 0.05) after a median follow-up of 8 months in PA patients. Patients experienced a significant decrease in eGFR from 110.6 ± 18.9 to 103.8 ± 18.2 ml/min/1.73 m2 (p < 0.001) and a very slight increase from 71.1 ± 14.8 to 71.8 ± 17.8 ml/min/1.73 m2 (p = 0.770) with baseline eGFR ≥90 and <90 ml/min/1.73 m2, respectively. Patients with high eGFR residuals (glomerular hyperfiltration) experienced a significant decrease in their eGFR levels from 123.1 ± 22.6 to 105.0 ± 18.6 ml/min/1.73 m2 (p < 0.001). In contrast, there was no significant impact of SAAE on the eGFR of patients with normal or low eGFR residuals. The very early eGFR changes (24 h after SAAE) best predicted the effect of SAAE on eGFR changes after median of eight months in PA patients. On the whole, SAAE seems to have a beneficial impact on renal function in patients with PA, the results of which vary depending on the patient's baseline eGFR and glomerular hyperfiltration status.

The Correlation Between Aldosterone and Leukocyte-Related Inflammation: A Comparison Between Patients with Primary Aldosteronism and Essential Hypertension.

Background: Hypertension patients with primary aldosteronism (PA) have a higher risk of cardiovascular complications than blood pressure-matched essential hypertension (EH) patients. The cause may be closely related to inflammation. We explored the correlations between leukocyte-related inflammation parameters and plasma aldosterone concentration (PAC) in PA patients and clinical characteristics-matched EH patients. Methods: A total of 346 PA and 346 sex, age and 24-h blood pressure-matched EH patients at the 2nd Affiliated Hospital of Nanchang University from January 2020 to June 2021 were enrolled in this study. The differences and correlations of aldosterone and leukocyte parameters between the two groups were analyzed. Results: Compared with EH patients, the lymphocyte count was significantly lower (P = 0.004), the neutrophil-lymphocyte ratio (NLR) (P = 0.023) and the monocyte-lymphocyte ratio (MLR) (P = 0.037) were significantly higher in PA patients. Linear regression analysis and multivariate regression analysis identified that lymphocyte count, NLR and MLR were significantly and independently correlated with PAC in PA patients, and the correlations were stronger with increasing levels of aldosterone. However, in EH patients, only NLR maintained an independent correlation with PAC. Conclusion: Leukocyte-related inflammation parameters, including lymphocyte count, NLR, and MLR, were significantly and independently correlated with PAC in PA patients. The correlations were stronger with increasing levels of aldosterone. However, the above correlations were not always present in patients with EH matched for clinical characteristics.

The protective effects of sophocarpine on sepsis-induced cardiomyopathy.

This investigation elucidates the impact of sophocarpine treatment on lipopolysaccharide (LPS) stimulated sepsis-induced cardiomyopathy (SIC) via in vivo and in vitro experiments. Echocardiography, ELISA, TUNEL, Western blotting experiments, and Hematoxylin/Eosin, Dihydroethidium, and Immunohistochemistry staining assays, were carried out to identify associated indicators. The echocardiography revealed that sophocarpine treatment alleviated LPS-induced cardiac dysfunction as indicated by fractional shortening shortened and improved ejection fraction. Heart injury biomarkers, such as creatine kinase, lactate dehydrogenase, and creatine kinase-MB, were assessed, and indicated that sophocarpine treatment could alleviate LPS-induced upregulation of these indices. Furthermore, different experimental protocols revealed that sophocarpine treatment inhibits LPS-induced pathological alterations and decreases LPS-stimulated inflammatory cytokines, IL-1ß, monocyte chemoattractant protein-1, IL-6, NOD-like receptor protein-3, and TNF-α, increase. Apoptotic proteins such as cytochrome-c, Bax, and cleaved-caspase-3 were increased, and Bcl-2 was alleviated after LPS stimulation; however, these effects were inhibited by sophocarpine treatment. Decreased antioxidant proteins [superoxide dismutase-1 (SOD-1) and SOD-2] induced by LPS stimulation were upregulated by sophocarpine treatment. LPS upregulated autophagic proteins such as Beclin-1 and the ratio of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I and downregulated sequestosome 1 (SQSTM1, or P62), sophocarpine therapy reversed these effects. Moreover, it was indicated that sophocarpine treatment inhibited the Toll-like receptor-4 (TLR-4)/nuclear transcription factor-kappa B (NF-κB) signaling pathway and activated nuclear factor erythroid 2-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. In conclusion, sophocarpine treatment could alleviate LPS-trigger SIC by repressing oxidative stress, autophagy, inflammation, and apoptosis via TLR-4/NF-κB inhibition and Nrf2/HO-1 signaling pathway activation, implicating the potential of sophocarpine as a new therapeutic approach against SIC.

Superselective adrenal arterial embolization for primary aldosteronism without lateralized aldosterone secretion: an efficacy and safety, proof-of-principle study.

Superselective adrenal arterial embolization (SAAE) appears to be beneficial in primary aldosteronism (PA) patients with lateralized aldosterone secretion (unilateral PA). As confirmed by adrenal vein sampling (AVS), nearly 40% of PA patients would be PA without lateralized aldosterone secretion (bilateral PA). We aimed to investigate the efficacy and safety of SAAE on bilateral PA. We identified 171 bilateral PA patients from 503 PA patients who completed AVS. Thirty-eight bilateral PA patients received SAAE, and 31 completed a median 12-month clinical follow-up. The blood pressure and biochemical improvements of these patients were carefully analyzed. 34% of patients were identified as bilateral PA. Plasma aldosterone concentration, plasma renin activity, and aldosterone/renin ratio (ARR) were significantly improved 24-h after SAAE. SAAE was associated with 38.7% and 58.6% of complete/partial clinical and biochemical success within a median 12-month follow-up. A significant reduction in left ventricular hypertrophy was shown in patients who obtained complete biochemical success compared with partial/absent biochemical success. SAAE was associated with a more apparent nighttime blood pressure reduction than daytime blood pressure reduction in patients with complete biochemical success. No major adverse safety events related to SAAE were reported during the intraoperative, postoperative, and follow-up periods. SAAE was associated with blood pressure and biochemical improvements in part of bilateral PA and appeared safe. The biochemistry success was accompanied by improved cardiac remodeling and a more prominent decrease in nocturnal blood pressure. This study was part of a trial registered with the Chinese Clinical Trial Registry, number ChiCTR2100047689.

Interactions Between Body Mass Index and Glomerular Filtration Rate Increase the Identification Ability of Obstructive Sleep Apnea in Patients with Hypertrophic Cardiomyopathy.

Purpose: Obstructive sleep apnea (OSA) is common in hypertrophic cardiomyopathy (HCM) patients and is related to worse adverse prognosis in HCM patients. However, there are no acknowledged warning characteristics to help to identify OSA in HCM patients. Methods: Seventy-one HCM patients and forty-nine hypertensive (HTN) patients as control group underwent polysomnography (PSG) examination at the Second Affiliated Hospital of Nanchang University from January 2015 to December 2019 patients were consecutively enrolled. The characteristics were analyzed and compared between HCM patients with OSA and without OSA. Results: A total of 37 (52%) HCM patients and 25 (51%) HTN patients were diagnosed with OSA. High body mass index (BMI) (OR = 1.228, 95% CI: 1.032,1.461, P = 0.020) and low estimated glomerular filtration rate (eGFR) (OR = 0.959, 95% CI: 0.931,0.989, P = 0.007) independently correlated with the occurrence of OSA in HCM patients, respectively. Multiplicative interaction was shown between high BMI and low eGFR on the risk of OSA in HCM patients (OR: 6.050, 95% CI: 1.598, 22.905, P = 0.008). The additive interaction analysis further suggested that 70.1% of HCM patients developed OSA due to the additive interaction between BMI and eGFR. The identification ability of OSA in HCM patients was significantly enhanced by using both BMI and eGFR (area under receiver-operating characteristic analysis curve 0.785; P = 0.000038) as compared with BMI (area under curve 0.683, P = 0.008) or eGFR (area under curve 0.700, P = 0.004), respectively. Conclusion: High BMI or low eGFR independently related to the occurrence of OSA in HCM patients, and the multiplicative and additive interactions between BMI and eGFR increased the identification ability of OSA in HCM patients.

Inhibition of semaphorin-3a alleviates lipopolysaccharide-induced vascular injury.

Alleviating vascular injury improves the prognosis of atherosclerosis. Semaphorin-3a (Sema3A) is a special membrane-associated secreted protein with various biological properties, like pro-inflammation, anti-tumor and et al. This study aims to investigate the effects of inhibition of Sema3A on lipopolysaccharide (LPS)-induced vascular injury in mice. The mice were randomized into three groups: control, LPS, and LPS + siRNA. Mice in the combined group were given siRNA through fast tail vein injection, then LPS was injected intraperitoneally 7 days later, finally the mice were euthanized 24 h later. Vascular function and structure were assessed by vascular injury biomarkers and relevant stainings. LPS-induced vascular dysfunction and pathological injury were substantially improved by inhibition of Sema3A. Western blot and quantitative real-time polymerase chain reaction assays were used for investigating molecular pathways. The relevant proteins of vascular endothelial cells activation, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), increased after LPS stimulation, while these effects were reversed by inhibition of Sema3A. The levels of inflammatory cytokines (IL-1ß, IL-6 and NLRP3) were upregulated after LPS stimulation, however, inhibition of Sema3A reversed it through NF-κB and MAPKs signaling pathways involvement. Moreover, inhibition of Sema3A alleviated LPS-induced oxidative stress, evidenced by a decrease in total reactive oxygen species and an increase in antioxidant protein of SOD-1. The results showed that inhibition of Sema3A protects against LPS-induced vascular injury by suppressing vascular endothelial cells activation, vascular inflammation, and vascular oxidative stress, implying that inhibition of Sema3A might be used as a therapeutic strategy for septic vascular injury or atherosclerosis.

A Clinical-Radiomic Nomogram Based on Unenhanced Computed Tomography for Predicting the Risk of Aldosterone-Producing Adenoma.

PURPOSE: To develop and validate a clinical-radiomic nomogram for the preoperative prediction of the aldosterone-producing adenoma (APA) risk in patients with unilateral adrenal adenoma. PATIENTS AND METHODS: Ninety consecutive primary aldosteronism (PA) patients with unilateral adrenal adenoma who underwent adrenal venous sampling (AVS) were randomly separated into training (n = 62) and validation cohorts (n = 28) (7:3 ratio) by a computer algorithm. Data were collected from October 2017 to June 2020. The prediction model was developed in the training cohort. Radiomic features were extracted from unenhanced computed tomography (CT) images of unilateral adrenal adenoma. The least absolute shrinkage and selection operator (LASSO) regression model was used to reduce data dimensions, select features, and establish a radiomic signature. Multivariable logistic regression analysis was used for the predictive model development, the radiomic signature and clinical risk factors integration, and the model was displayed as a clinical-radiomic nomogram. The nomogram performance was evaluated by its calibration, discrimination, and clinical practicability. Internal validation was performed. RESULTS: Six potential predictors were selected from 358 texture features by using the LASSO regression model. These features were included in the Radscore. The predictors included in the individualized prediction nomogram were the Radscore, age, sex, serum potassium level, and aldosterone-to-renin ratio (ARR). The model showed good discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.900 [95% confidence interval (CI), 0.807 to 0.993], and good calibration. The nomogram still showed good discrimination [AUC, 0.912 (95% CI, 0.761 to 1.000)] and good calibration in the validation cohort. Decision curve analysis presented that the nomogram was useful in clinical practice. CONCLUSIONS: A clinical-radiomic nomogram was constructed by integrating a radiomic signature and clinical factors. The nomogram facilitated accurate prediction of the probability of APA in patients with unilateral adrenal nodules and could be helpful for clinical decision making.

Early Passive Leg Movement Prevents Against the Development of Heart Failure With Preserved Ejection Fraction in Rats.

Exercising was reported by several studies to bring great benefits to heart failure with preserved ejection fraction (HFpEF), which reduced the hospitalization and the mortality of heart failure. However, the underlying mechanism of exercising on HFpEF remains unclear. In the present study, we designed and constructed a device that can perform early passive leg movement (ePLM) in rats and further observed whether treatment of ePLM exerts protective effects on HFpEF of rats. Rats were fed with high salt feed to establish an animal model of pre-clinical diastolic dysfunction (PDD), which would eventually develop into HFpEF, and then treated rats with ePLM. We conducted several experiments to evaluate the conditions of heart and blood vessel. The results show that diastolic functions of heart and blood vessel in rats were significantly improved by treatment of ePLM. We also found that pathological injuries of heart and blood vessel were ameliorated after treatment of ePLM. Moreover, treatment of ePLM decreased the protein levels of Collagen type I, Collagen type III, MMP2, and MMP9 in heart and blood vessel, indicating that cardiac and vascular fibrosis were reduced apparently by treatment of ePLM. Further investigation suggested that treatment of ePLM probably inhibit the activation of TGF-ß1/Smad3 signaling pathway as well as promote the activation of Akt/eNOS signaling pathway in high salt diet induced HFpEF. In conclusion, treatment of ePLM alleviated high salt diet induced HFpEF by inhibiting fibrosis via suppressing TGF-ß1/Smad3 signaling pathway as well as activating Akt/eNOS signaling pathway, implicating treatment of ePLM as a promising novel non-pharmacological approach for HFpEF.

Association Between Intermittent Hypoxia and Left Ventricular Remodeling in Patients With Obstructive Sleep Apnea-Hypopnea Syndrome.

The present study was undertaken to examine the association between intermittent hypoxia and left ventricular (LV) remodeling and explore which parameter of intermittent hypoxia is most relevant to LV remodeling in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). Two hundred eighty six patients underwent polysomnographic examination were enrolled. Based on apnea-hypoxia index (AHI), patients were divided into no, mild, moderate and severe OSAHS groups. Between-group differences in LV remodeling and the association between parameters of intermittent hypoxia and LV remodeling was evaluated. Patients with severe OSAHS were more likely to have hypertension, and higher values of LV mass (LVM) and LVM index (LVMI). In univariate regression analysis, male, body mass index (BMI), systolic and diastolic blood pressure (BP), statins, antihypertensive drugs, creatinine, and parameters of intermittent hypoxia (AHI, obstructive apnea index [OAI], lowest oxygen saturation [LSpO2], oxygen desaturation index [ODI], time spent below oxygen saturation of 90% [TS90%], and mean nocturnal oxygen saturation [MSpO2]) were associated with LVMI. After multivariate regression analyses, only male gender, BMI, systolic BP, creatinine, and ODI remained significantly associated with LVMI. Compared to those without LV hypertrophy (LVH), patients with LVH had higher ODI. Compared to patients with normal LV, concentric remodeling and eccentric LVH, those with concentric LVH had higher ODI. In conclusion, intermittent hypoxia was significantly associated with left ventricular remodeling; and among various parameters of intermittent hypoxia, ODI was the most relevant to LV remodeling.

Sacubitril/Valsartan Reduces Fibrosis and Alleviates High-Salt Diet-Induced HFpEF in Rats.

Previous studies have confirmed the clinical efficacy of sacubitril/valsartan (Sac/Val) for the treatment of heart failure with reduced ejection fraction (HFrEF). However, the role of Sac/Val in heart failure with preserved ejection fraction (HFpEF) remains unclear. Sac/Val is a combination therapeutic medicine comprising sacubitril and valsartan that acts as a first angiotensin receptor blocker and neprilysin inhibitor (angiotensin-receptor neprilysin inhibitor (ARNI)). Here, we investigated the role of Sac/Val in high-salt diet-induced HFpEF coupled with vascular injury as well as the underlying mechanism. Rats were fed with high-salt feed, followed by intragastric administration of Sac/Val (68 mg/kg; i.g.). The results of functional tests revealed that a high-salt diet caused pathological injuries in the heart and vascular endothelium, which were significantly reversed by treatment with Sac/Val. Moreover, Sac/Val significantly decreased the levels of fibrotic factors, including type I collagen and type Ⅲ collagen, thus, reducing the ratio of MMP2/TIMP2 while increasing Smad7 levels. Further investigation suggested that Sac/Val probably reversed the effects of high-salt diet-induced HFpEF by inhibiting the activation of the TGF-ß1/Smad3 signaling pathway. Thus, treatment with Sac/Val effectively alleviated the symptoms of high-salt diet-induced HFpEF, probably by inhibiting fibrosis via the TGF-ß1/Smad3 signaling pathway, supporting the therapeutic potential of Sac/Val for the treatment of HFpEF.

Forest characteristics and population structure of Glyptostrobus pensilis, a globally endangered relict species of southeastern China.

The Chinese water pine Glyptostrobus pensilis is the sole surviving species of the genus Glyptostrobus. It is endemic to southern China, central Vietnam, and eastern Laos, and today it is nearly extinct in the wild. Forest community characteristics and population structure of G. pensilis in China have remained unknown up to now. We investigated six swamp forest stands and analyzed their forest community characteristics (i.e. vertical stratification, species composition, and diversity) and population structure, including the frequency distribution of DBH (diameter at breast height) and age-classes as found in Fujian Province, southeastern China. The vertical stratifications of all the forest stands were rather simple. The remaining wild specimens ranged from roughly 15 to some 357 years for an average of ca. 85 years, with only a few individuals less than 20 years old. Compared with the stands and populations of G. pensilis in Vietnam, the taxonomic compositions of the stands in the two regions were different, except for the dominant species-G. pensilis. The Shannon-Wiener index showed the overstory of each stand had much lower diversity (0.26 on average) in Fujian Province than that (1.97 on average) in Vietnam, whereas the diversity indices were about the same (around 2.41) for the understories in the two regions. Furthermore, we discovered 18 G. pensilis seedlings at the study sites in Fujian Province. This discovery demonstrates that G. pensilis regeneration is extremely poor and its populations are declining, although these populations are relatively healthier than those in Vietnam.

Treatment of Post-traumatic Pediatric Ankle Varus Deformity with Physeal Bar Resection and Hemi-Epiphysiodesis.

Children presenting with partial physeal arrest and significant remaining growth may benefit from physeal bar resection, although the operation is a technique demanding procedure. This study evaluates the treatment of post-traumatic pediatric ankle varus deformity using physeal bar resection and hemi-epiphysiodesis with the assistance of two operative methods. Forty-five patients presenting with a distal tibial medial physeal bridge as well as ankle varus deformity following traumatic ankle physeal injury between 2009 and 2017 were followed. These patients were treated with physeal bar resection and hemi-epiphysiodesis, with the assistance of either fluoroscopy (10 cases) or intraoperative three-dimensional navigation (35 cases). Of the 45 cases, the median age was 9.0 years (range: 3-14 years) with 28 male and 17 female patients. The median of pre-operation ankle varus angle was 20 degrees (IQR 15-25) and 5 degrees (IQR 0-20) at the time of final follow up, representing a statistically significant difference (P<0.05). No differences were observed with regards to age, gender, and surgical history between effective group and ineffective group (P>0.05). The median of pre-operative ankle varus angles of the navigation and fluoroscopy groups were both 20 degrees (P>0.05). The median correction angle of the navigation and fluoroscopy groups was 10 and 15 degrees, respectively (P>0.05). Our results indicate that physeal bar resection and hemiepiphysiodesis are effective treatments for correcting ankle varus deformity due to traumatic medial physeal arrest of the distal tibia. We observe no difference in outcome between fluoroscopy group and three-dimensional navigation group during the procedures.

Author Correction: Identifying long-term stable refugia for relict plant species in East Asia.

In the original version of this Article, an incorrect sample size was provided for the number of relict species (443 instead of 442) and the number of relict forests (423 instead of 422). These errors have been corrected in both the PDF and HTML versions of the Article.

Identifying long-term stable refugia for relict plant species in East Asia.

Today East Asia harbors many "relict" plant species whose ranges were much larger during the Paleogene-Neogene and earlier. The ecological and climatic conditions suitable for these relict species have not been identified. Here, we map the abundance and distribution patterns of relict species, showing high abundance in the humid subtropical/warm-temperate forest regions. We further use Ecological Niche Modeling to show that these patterns align with maps of climate refugia, and we predict species' chances of persistence given the future climatic changes expected for East Asia. By 2070, potentially suitable areas with high richness of relict species will decrease, although the areas as a whole will probably expand. We identify areas in southwestern China and northern Vietnam as long-term climatically stable refugia likely to preserve ancient lineages, highlighting areas that could be prioritized for conservation of such species.

Significant interaction of hypertension and homocysteine on neurological severity in first-ever ischemic stroke patients.

It is not known whether combination of hypertension and high homocysteine (HHcy) impacts on stroke-related neurological severity. Our aim was to determine whether there is an interaction of hypertension and HHcy on neurological severity in first-ever ischemic stroke patients. We analyzed neurological severity among 189 consecutive first-ever ischemic stroke patients with or without hypertension or HHcy. Hypertension (odds ratio [OR]: 8.086, 95% confidence interval [CI]: 3.596-18.181, P < .001) and total homocysteine (OR: 1.403, 95% CI: 1.247-1.579, P < .001) were independently associated with neurological severity. In receiver-operating characteristic analysis, total homocysteine was a significant predictor of neurological severity (area under curve: 0.794; P < .001). A multiplicative interaction of hypertension and HHcy on more severe neurological severity was revealed by binary logistic regression (OR: 13.154, 95% CI: 5.293-32.691, P < .001). Analysis further identified a more than multiplicative interaction of hypertension and HHcy on neurological severity compared with patients without each condition (OR: 50.600, 95% CI: 14.775-173.285, P < .001). Interaction effect measured on an additive scale showed that 76.4% patients with moderate/severe neurological severity were attributed to interaction of hypertension and HHcy. Significant interaction of hypertension and HHcy on neurological severity was found on multiplicative and additive scale in first-ever Chinese ischemic stroke patients.

Aerobic exercise improves endothelial function and serum adropin levels in obese adolescents independent of body weight loss.

Adropin is a secreted protein that regulates endothelial function. However, adropin levels in obese adolescent patients are currently uncertain. Therefore, we evaluated the association between plasma adropin levels and vascular endothelial function and investigated the effect of aerobic exercise in obese adolescents. A total of 45 obese adolescents and 20 controls (age 16-19 years) were included in our study. The obese adolescents received 12 weeks of aerobic exercise training. Serum adropin was detected using enzyme-linked immunosorbent assay. Vascular reactive hyperemia indexes (RHIs) were obtained using Endo-PAT2000. Adropin levels and RHI were significantly lower in obese adolescents than in normal-weight adolescents. Adropin levels and RHI increased significantly independently of changes in body weight after an exercise intervention (P < 0.01). Pearson correlation analysis revealed that adropin levels positively correlated with HDL-C levels (r = 0.389, P < 0.01) and RHI (r = 0.32, P < 0.01). Multiple linear stepwise regression analysis showed that the insulin resistance index (t = -3.301, P < 0.01) and HDL-C level (t = 2.620, P = 0.011) were independent risk factors of adropin levels. In addition, Δadropin (t = 3.261, P < 0.01) was an independent influencing factor of ΔRHI. Our findings suggest that adropin plays an important role in vascular endothelial function in obese adolescents.