Lower Gluteal Liposuction Combined With Upper Gluteal and Infragluteal Region Fat Grafting: A Novel Concept to Improve Gluteal Ptosis.

BACKGROUND: Gluteal ptosis results in a severe disturbance of gluteal aesthetics. Currently, satisfactory procedures for improving gluteal ptosis are lacking. OBJECTIVES: To improve gluteal ptosis, the authors propose a novel concept of combined liposuction of the lower gluteal region and fat grafting to the upper gluteal and infragluteal regions, and verify its efficacy and safety. METHODS: Patients who underwent liposuction of the lower gluteal region combined with fat grafting to the upper gluteal and infragluteal regions between January 2020 and July 2023 were retrospectively reviewed. Postoperative changes in the gluteal ptosis grade, complications, and patient satisfaction were evaluated. RESULTS: A total of 28 patients were enrolled in this study; 21 (75.0%) patients had gluteal ptosis grade 4 and 7 (25.0%) patients had gluteal ptosis grade 5. The median fat removal volume was 210 mL, and the median fat graft injected volume was 355 mL in the gluteal region and 180 mL in the infragluteal region. All patients showed improvement in gluteal ptosis; 16 (57.1%) patients improved by 1 grade and 12 (42.9%) patients showed a 2-grade improvement. All patients were satisfied with their posttreatment outcomes. Only 1 patient showed lateral translocation of the fat graft. No other complications were observed. CONCLUSIONS: Liposuction of the lower gluteal region combined with fat grafting to the upper gluteal and infragluteal regions is effective in improving gluteal ptosis, with a low risk of complications and high patient satisfaction.

Aesthetic Improvement of Body Proportion Through Trunk Liposculpture: A Waistline-based Strategy.

BACKGROUND: Abdominal contouring through liposuction has been practiced for decades. However, few studies have focused on describing the definition and enhancement of the waistline in torso contouring procedures. OBJECTIVES: In the present study, the authors proposed a waistline-based strategy for abdominal liposculpture to achieve a better aesthetic outcome and emphasize high overall patient satisfaction. METHODS: The data of patients who underwent the waistline-based liposculpture procedure from 2020 to 2023 were retrospectively reviewed. Aesthetic improvement of the central trunk contour was evaluated and analyzed by comparing preoperative and postoperative photogrammetric measurements. Satisfaction with the outcome was assessed with a patient satisfaction questionnaire. RESULTS: A total of 70 patients were enrolled in this study. During 6 months of postoperative evaluation, the shape of the central trunk contour improved significantly (both waist concavity and hip convexity increased quantitatively, P < .05), while the position of the waist did not differ significantly postoperatively (P > .05). All patients were satisfied with their postoperative outcomes, including their overall aesthetic appearance, waistline position, and waist-to-hip ratio. There were no intraoperative complications or rare postoperative complications. CONCLUSIONS: Waistline-based liposculpture is a simple and effective procedure to improve the aesthetic outcomes of trunk contouring and has highly satisfactory results after long-term follow-up.

The biological functions of peptide signaling in plant and the advances on its utilization for crop improvement.

As the important signaling molecules in plants, peptides at femtomolar levels are recognized and bound by the corresponding plasma membrane-localized receptor-like kinases. This triggers the peptide-receptor-mediated intercellular signal transduction for regulation of the stem cell growth and proliferation, modulation of the development of plant organs (such as roots, stems, leaves, flowers, and fruits) as well as coordinating plant responses to biotic and abiotic stresses. With the advancement of in-depth research, an increasing number of studies have revealed the crucial role of peptides in regulating agronomic traits of various crops, including rice (Oryza sativa), maize (Zea mays), potato (Solanum tuberosum) and tomato (Solanum lycopersicum). These findings suggest the great potentials of utilizing the peptide signaling for genetic improvement of crops. In this review, we provide a comprehensive overview of the biological function and molecular mechanism of peptide-receptor signaling in plants, and highlight the advances in research of peptides in regulating crop yield, quality and resistance. Then, we discuss the strategies for the application of peptide signaling in crop improvement. Finally, we point out some future directions for peptide research in plant.

Vascular smooth muscle cells specific deletion of angiopoietin-like protein 8 prevents angiotensin II-promoted hypertension and cardiovascular hypertrophy.

AIMS: Angiopoietin-like protein 8 (ANGPTL8) plays important roles in lipid metabolism, glucose metabolism, inflammation, and cell proliferation and migration. Clinical studies have indicated that circulating ANGPTL8 concentrations are increased in patients with hypertension and positively associated with blood pressure. ANGPTL8 deficiency ameliorates blood pressure in mice treated with chronic intermittent hypoxia. Currently, little is known regarding the pathophysiological role of the vascular smooth muscle cell (VSMC)-derived ANGPTL8 in hypertension and hypertensive cardiovascular remodelling. METHODS AND RESULTS: Circulating ANGPTL8 concentrations, as determined by enzyme-linked immunosorbent assay, were significantly higher in hypertensive patients than in controls (524.51 ± 26.97 vs. 962.92 ± 15.91 pg/mL; P < 0.001). In hypertensive mice [angiotensin II (AngII) treatment for 14 days] and spontaneously hypertensive rats, ANGPTL8 expression was increased and predominantly located in VSMCs. In AngII-treated mice, systolic and diastolic blood pressure in Tagln-Cre-ANGPTL8fl/fl mice were approximately 15-25 mmHg lower than that in ANGPTL8fl/fl mice. AngII-induced vascular remodelling, vascular constriction, and increased expression of cell markers of proliferation (PCNA and Ki67) and migration (MMP-2 and MMP-9) were strikingly attenuated in Tagln-Cre-ANGPTL8fl/fl mice compared with ANGPTL8fl/fl mice. Furthermore, the AngII-induced increase in the heart size, heart weight, heart/body weight ratio, cardiomyocyte cross-sectional area, and collagen deposition was ameliorated in Tagln-Cre-ANGPTL8fl/fl mice compared with ANGPTL8fl/fl mice. In rat artery smooth muscle cells, ANGPTL8-short hairpin RNA decreased intracellular calcium levels and prevented AngII-induced proliferation and migration through the PI3K-Akt pathway, as shown using LY294002 (inhibitor of PI3K) and Akt inhibitor VIII. CONCLUSION: This study suggests that ANGPTL8 in VSMCs plays an important role in AngII-induced hypertension and associated cardiovascular remodelling. ANGPTL8 may be a novel therapeutic target against pathological hypertension and hypertensive cardiovascular hypertrophy.

ANGPTL8 deletion attenuates abdominal aortic aneurysm formation in ApoE-/- mice.

Angiopoietin-like protein 8 (ANGPTL8) plays important roles in lipid metabolism, glucose metabolism, inflammation, and cell proliferation and migration. Clinical studies have indicated that circulating ANGPTL8 levels are increased in patients with thoracic aortic dissection (TAD). TAD shares several risk factors with abdominal aortic aneurysm (AAA). However, the role of ANGPTL8 in AAA pathogenesis has never been investigated. Here, we investigated the effect of ANGPTL8 knockout on AAA in ApoE-/- mice. ApoE-/-ANGPTL8-/- mice were generated by crossing ANGPTL8-/- and ApoE-/- mice. AAA was induced in ApoE-/- using perfusion of angiotensin II (AngII). ANGPTL8 was significantly up-regulated in AAA tissues of human and experimental mice. Knockout of ANGPTL8 significantly reduced AngII-induced AAA formation, elastin breaks, aortic inflammatory cytokines, matrix metalloproteinase expression, and smooth muscle cell apoptosis in ApoE-/- mice. Similarly, ANGPTL8 sh-RNA significantly reduced AngII-induced AAA formation in ApoE-/- mice. ANGPTL8 deficiency inhibited AAA formation, and ANGPTL8 may therefore be a potential therapeutic target for AAA.

The Clinical Efficacy Evaluation of Thigh Liposuction Based on 3-Dimensional Digital Technology: A Quantitative Study.

BACKGROUND: There is a lack of convenient and accurate objective methods to evaluate the clinical efficacy of thigh liposuction. METHODS: This retrospective study involved the 3-dimensional images of 19 patients who underwent bilateral thigh liposuction. Data such as volume change and volume change rate before and after surgery, circumference change, and circumference change rate of 3 planes (upper, middle, and lower) were analyzed. The correlation between body mass index and volume change rate and between preoperative circumference and circumference change rate of different planes were determined. RESULTS: There were significant differences between the preoperative and postoperative volume and circumference of 3 planes of 19 patients (38 thighs). The rate of change in total volume (16.90 ± 5.55%) correlated with the circumference change rate at the top of the thigh. There was also a linear relationship between body mass index and volume change rate, but not between preoperative circumference and circumference change rate. CONCLUSIONS: Three-dimensional imaging technology can accurately quantify the volume and circumference change of the thigh to objectively evaluate the clinical efficacy of thigh liposuction.

Efficacy and Safety of Perioral Mound Region Liposuction-A Novel Concept to Improve Perioral Mound Fullness.

BACKGROUND: Fullness of the perioral mound is considered a dissatisfying aspect of premature aging and has become a common complaint of patients seeking facial rejuvenation. OBJECTIVES: The authors propose a novel concept of improving perioral mound fullness by liposuction and verify its safety and efficacy through cadaver and clinical studies. METHODS: A cadaver study was conducted to discover the soft tissue structure of the perioral mound region and identify a vital use for liposuction. For clinical evaluation, 37 patients with perioral mound fullness who underwent liposuction were retrospectively reviewed. RESULTS: The cadaver study results showed moderate fatty tissue in the subcutaneous layer of the perioral mound region. The liposuction manipulation was limited to the subcutaneous fat layer. Among the 37 patients (including 74 perioral mound regions), the median fat removal volume per perioral mound region was 2.0 (1.2, 2.3) mL. After liposuction, the subcutaneous fat thickness significantly decreased (median 5.0 [3.9, 6.6] mm vs 0.7 [0.4, 1.0] mm per perioral mound region, P < .001). All patients were satisfied with their posttreatment outcomes. Two patients (5.4%) had slight skin hyperpigmentation in the liposuction area after treatment and recovered naturally in 3 months without any intervention. No other complications were noted. CONCLUSIONS: Liposuction is effective in improving perioral mound fullness with a low risk of complications.

Knockout of a papain-like cysteine protease gene OCP enhances blast resistance in rice.

Papain-like cysteine proteases (PLCPs) play an important role in the immune response of plants. In Arabidopsis, several homologous genes are known to be involved in defending against pathogens. However, the effects of PLCPs on diseases that afflict rice are largely unknown. In this study, we show that a PLCP, an oryzain alpha chain precursor (OCP), the ortholog of the Arabidopsis protease RD21 (responsive to dehydration 21), participates in regulating resistance to blast disease with a shorter lesion length characterizing the knockout lines (ocp-ko), generated via CRISPR/Cas9 technology. OCP was expressed in all rice tissues and mainly located in the cytoplasm. We prove that OCP, featuring cysteine protease activity, interacts with OsRACK1A (receptor for activated C kinase 1) and OsSNAP32 (synaptosome-associated protein of 32 kD) physically in vitro and in vivo, and they co-locate in the rice cytoplasm but cannot form a ternary complex. Many genes related to plant immunity were enriched in the ocp-ko1 line whose expression levels changed significantly. The expression of jasmonic acid (JA) and ethylene (ET) biosynthesis and regulatory genes were up-regulated, while that of auxin efflux transporters was down-regulated in ocp-ko1. Therefore, OCP negatively regulates blast resistance in rice by interacting with OsRACK1A or OsSNAP32 and influencing the expression profiles of many resistance-related genes. Moreover, OCP might be the cornerstone of blast resistance by suppressing the activation of JA and ET signaling pathways as well as promoting auxin signaling pathways. Our research provides a comprehensive resource of PLCPs for rice plants in defense against pathogens that is also of potential breeding value.

Comprehensive Metabolomics and Machine Learning Identify Profound Oxidative Stress and Inflammation Signatures in Hypertensive Patients with Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) can aggravate blood pressure and increase the risk of cardiovascular diseases in hypertensive individuals, yet the underlying pathophysiological process is still incompletely understood. More importantly, OSA remains a significantly undiagnosed condition. In this study, a total of 559 hypertensive patients with and without OSA were included. Metabolome and lipidome-wide analyses were performed to explore the pathophysiological processes of hypertension comorbid OSA and derive potential biomarkers for diagnosing OSA in hypertensive subjects. Compared to non-OSA hypertensive patients (discovery set = 120; validation set = 116), patients with OSA (discovery set = 165; validation set = 158) demonstrated a unique sera metabolic phenotype dominated by abnormalities in biological processes of oxidative stress and inflammation. By integrating three machine learning algorithms, six discriminatory metabolites (including 5-hydroxyeicosatetraenoic acid, taurine, histidine, lysophosphatidic acid 16:0, lysophosphatidylcholine 18:0, and dihydrosphingosine) were selected for constructing diagnostic and classified model. Notably, the established multivariate-model could accurately identify OSA subjects. The corresponding area under the curve values and the correct classification rates were 0.995 and 96.8% for discovery sets, 0.997 and 99.1% for validation sets. This work updates the molecular insights of hypertension comorbid OSA and paves the way for the use of metabolomics for the diagnosis of OSA in hypertensive individuals.

ANGPTL3 and Cardiovascular Outcomes in Patients With Acute Coronary Syndrome and Obstructive Sleep Apnea.

Background The aim of this prospective study was to determine the impact of elevated ANGPTL3 (angiopoietin-like protein 3) on cardiovascular events (CVEs) following acute coronary syndrome (ACS) in patients with or without obstructive sleep apnea (OSA). Methods and Results A total of 1174 patients with ACS underwent successful percutaneous coronary intervention were included in this prospective cohort study (NCT03362385). Patients were categorized according to the apnea-hypopnea index (≥15 events/h, OSA) and further classified by ANGPTL3 levels. We analyzed the incidence of CVEs in patients with ACS according to the status of OSA and ANGPTL3. During a median of 3.1 years of follow-up, 217 (18.48%) CVEs occurred. The patients with ACS with OSA had higher ANGPTL3 levels than those without OSA (30.4 [20.9-43.2] versus 27.80 [19.1-41.5] ng/mL; P<0.001). In all patients with ACS, 29≤ANGPTL3<42 mg/dL and ANGPTL3≥42 mg/dL were associated with an increased risk of CVEs with hazard ratios (HRs) of 1.555 (95% CI, 1.010-2.498) and 2.489 (95% CI 1.613-3.840), respectively. When the status of OSA or not was incorporated in stratifying factors, 29≤ANGPTL3<42 mg/dL and ANGPTL3≥42 mg/dL were associated with a significantly higher risk of CVEs in patients with ACS with OSA (HR, 1.916 [95% CI, 1.019-3.601] and HR, 2.692 [95% CI, 1.379-4.503]) but not without OSA. Moreover, adding ANGPTL3 to the Cox model increased C-statistic values by 0.035 and 0.029 in the OSA group and all patients with ACS, respectively, but was not statistically improved in patients with ACS without OSA. Conclusions In conclusion, our study demonstrates a predictive impact of plasma ANGPTL3 on cardiovascular risk in patients with ACS, especially in patients with ACS with OSA. It might be of clinical value in refining risk stratification and tailoring treatment of patients with ACS and OSA. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03362385.

Increasing circulating ESM-1 and adhesion molecules are associated with earlystage atherosclerosis in OSA patients:A cross-sectional study.

BACKGROUND: There are increasing evidences for a direct relationship between the vascular system and obstructive sleep apnea (OSA). The aim of this study was to investigate the relationship between circulating endothelial cell specific molecule-1 (ESM-1), adhesion molecules and subclinical atherosclerosis in patients with OSA. METHODS: This was a cross-sectional study in which 161 patients with OSA and 56 controls were recruited. Demographic data, biochemical and polysomnography parameters were collected. We used a powerful high-throughput Multiplex Immunobead Assay technique to simultaneously test plasm levels of ESM-1, P-selectin, E-selectin, L-selectin, inter-cellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). Carotid intima-media thickness (CIMT) were measured as parameters of vascular endothelial dysfunction and early atherosclerosis. RESULTS: Increasing circulating levels of ESM-1, P-selectin, E-selectin, L-selectin, ICAM-1 and VCAM-1 were found increased in patients with OSA (all P < 0.001). Furthermore, OSA patients exhibited increased CIMT than controls (P < 0.05). Multivariate linear analysis indicated that elevated ESM-1, P-Selectin, E-selectin, and L-selectin levels were associated with AHI (all P < 0.05). Moreover, multivariate analysis showed that increasing ESM-1, VCAM-1, P-Selectin, and L-selectin were significantly associated with thick CIMT in OSA patients (all P < 0.05). CONCLUSIONS: Increased circulating ESM-1 and adhesion molecules associated with thick CIMT in OSA, which is a marker of subclinical atherosclerosis. Strict attention to monitor circulating ESM-1 and adhesion molecules is necessary for early detection of subclinical atherosclerosis in OSA patients.

Circumferential Liposuction of the Thigh with Concomitant Fat Transplantation to the Infragluteal Region: A Promising Option for Preventing Postliposuction Gluteal Ptosis.

BACKGROUND: Gluteal ptosis is a common complication of circumferential liposuction of the thigh. The authors propose a novel concept of combining circumferential liposuction of the thigh with concomitant fat transplantation to the infragluteal/posterior thigh junction region to prevent postliposuction gluteal ptosis. METHODS: Patients underwent circumferential liposuction of the thigh with or without concomitant fat transplantation from 2015 to 2020 and were retrospectively reviewed. The postoperative changes in the grade of gluteal ptosis, length of hospitalization, time to recovery, postoperative complications, and patient satisfaction were evaluated. RESULTS: A total of 109 patients were enrolled in this study, including 46 patients in the liposuction-only group and 63 patients in the liposuction plus fat transplantation group. There was no significant difference in fat removal volume between the liposuction-only group and the liposuction plus fat transplantation group ( p = 0.152). Aggravation of gluteal ptosis occurred in 43 patients (93.5 percent) in the liposuction-only group and four patients (6.3 percent) in the liposuction plus fat transplantation group ( p < 0.001). The length of hospitalization and time to recovery was not significantly different between the two groups ( p = 0.402 and p = 0.423, respectively). Complications were rare in both groups. With a minimum evaluation time of 6 months, patients in the liposuction plus fat transplantation group showed significantly higher satisfaction ( p < 0.001). CONCLUSION: Concomitant fat transplantation to the infragluteal/posterior thigh junction region during circumferential liposuction of the thigh is effective in preventing postliposuction gluteal ptosis and improving patient satisfaction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Combined Association Between ADIPOQ, PPARG, and TNF Genes Variants and Obstructive Sleep Apnea in Chinese Han Population.

Purpose: Obstructive sleep apnea (OSA) is a common chronic polygenic disease. Multiple genetic markers associated with OSA have been identified by genome-wide association studies. Here, we aimed to construct a polygenic risk score (PRS) and examine the association with the presence of OSA in a Chinese Han Population. Patients and Methods: This study included 1057 individuals who were genotyped for nine susceptibility loci from three genes (ADIPOQ, PPARG, and TNF), from which each individual's PRS was calculated by summing the number of risk alleles. The associations between PRS and OSA were determined by logistic regression analyses. Model discrimination was assessed by a receiver operating characteristic (ROC) curve using bootstrapping with 1000 resamples. Results: The subjects included 874 with OSA and 183 controls. A higher PRS was associated with an increased apnea-hypopnea index (AHI). The PRS was an important risk factor for the development of OSA (OR = 1.237 per SD, P = 0.030). Subjects with higher PRS had a 2.88-fold (95% CI: 1.393-5.955, P = 0.004) and 5.402-fold (95% CI: 2.311-12.624, P<0.001) greater risk for having OSA and moderate-to-severe OSA, respectively, compared with those with lower genetic risk. More importantly, compared with determination of risk based solely on clinical factors, addition of the PRS increased discriminatory accuracy for both OSA (AUC from 0.75 to 0.78, P = 0.02) and moderate-to-severe OSA (AUC from 0.80 to 0.83, P = 0.02). Conclusion: Our study suggests that the PRS is independently associated with AHI and OSA. Combining PRS with conventional risk factors could improve the discrimination of OSA.

Difficulty of Severe Post-liposuction Infragluteal Deformity Correction With Autologous Fat Transplantation: A Case Report.

Overaggressive liposuction of the infragluteal region can lead to iatrogenic infragluteal fold deformity and result in esthetic defects in the gluteal contour. We report a case of using autologous fat transplantation to correct severe post-liposuction infragluteal fold deformity. In the process of reconstruction, the patient experienced fat graft overabsorption, fat graft translocation, and gluteal ptosis aggravation. Despite multiple operations, the effect of fat transplantation was limited. In conclusion, severe post-liposuction infragluteal deformity is very difficult to correct. The infragluteal region should be preserved during liposuction to avoid deformity.

Liposuction of the Zygomatic Arch Area: A Novel Concept to Improve the Midface Contour.

BACKGROUND: An ovoid, slender face with a smooth contour is preferred in oriental esthetics. We developed a novel concept to achieve a slimmer and harmonious midface contour by liposuction of the projection area of the zygomatic arch. METHODS: A cadaver study including anatomical dissection and histologic examination were conducted to better understand the soft tissue structure of the projection area of the zygomatic arch and the vital technique for liposuction. For the clinical evaluation, 49 patients with midface hypertrophy who underwent liposuction of the zygomatic arch area from January 2016 to June 2021 were retrospectively reviewed. RESULTS: Cadaver study showed that abundant fatty tissue existed in the subcutaneous layer of the zygomatic arch area. The liposuction manipulation was precisely limited to the subcutaneous fat layer, and nerve branches were observed in the deeper loose areolar tissue plane. Of the 49 patients enrolled in this study (including 98 zygomatic arch areas), the median fat removal volume per zygomatic arch area was 3.0 (2.0, 5.0) mL. The subcutaneous fat thickness was significantly decreased postoperatively [median 9 (6, 10) mm vs. 1 (1, 2) mm per zygomatic arch area, P < 0.001]. All patients were satisfied with their postoperative outcomes. Only three patients underwent slight depression of the liposuction area during making facial expression after surgery and subsequently recovered. CONCLUSIONS: Liposuction of the zygomatic arch area is effective in improving midface hypertrophy and achieving a harmonious facial contour with a low risk of complications. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Differences in olfactory habituation between orthonasal and retronasal pathways.

The odorant arrives at nasal olfactory epithelium ortho- and retronasally. This experiment aimed to study the potential different olfactory habituation in orthonasal and retronasal pathways. 68 subjects were stimulated by constant airflow with an odor (50% phenethyl alcohol, PEA or 5% n-butyl acetate, BA) presented ortho- or retronasally. Participants rated the perceived odor intensity (0-10 points) per minute until the odor sensation disappeared. We also investigated the cross-habituation: when the subjects achieved full habituation, continue to rate odor intensity in a different pathway after instantly switching the odor stimulation pathway. The olfactory habituation curve was drawn. The differences of ratings between the orthonasal and retronasal olfaction at different time points and between male and female subjects were analyzed. The two odor intensity ratings decreased as the time extended, share the same "fast followed by slow" type. The ratings of orthonasal olfaction decreased faster than that of retronasal. The intensity rating of PEA of male retronasal approach was lower than that of female at the 5th min (p = 0.018). When orthonasal full habituation achieved, there was significant difference between the intensity ratings and the initial ratings of the retronasal stimulation pathway (p < 0.0001), and vice versa. We found obvious habituation as well as cross-habituation in both orthonasal and retronasal olfaction. The habituation of orthonasal olfaction was faster than that of retronasal olfaction. These different habituations were related to the gender.

Salidroside Ameliorated Intermittent Hypoxia-Aggravated Endothelial Barrier Disruption and Atherosclerosis via the cAMP/PKA/RhoA Signaling Pathway.

Background: Endothelial barrier dysfunction plays a key role in atherosclerosis progression. The primary pathology of obstructive sleep apnea-hypopnea syndrome is chronic intermittent hypoxia (IH), which induces reactive oxygen species (ROS) overproduction, endothelial barrier injury, and atherosclerosis. Salidroside, a typical pharmacological constituent of Rhodiola genus, has documented antioxidative, and cardiovascular protective effects. However, whether salidroside can improve IH-aggravated endothelial barrier dysfunction and atherosclerosis has not been elucidated. Methods and results: In normal chow diet-fed ApoE-/- mice, salidroside (100 mg/kg/d, p. o.) significantly ameliorated the formation of atherosclerotic lesions and barrier injury aggravated by 7-weeks IH (21%-5%-21%, 120 s/cycle). In human umbilical vein endothelial cells (HUVECs), exposure to IH (21%-5%-21%, 40 min/cycle, 72 cycles) decreased transendothelial electrical resistance and protein expression of vascular endothelial cadherin (VE-cadherin) and zonula occludens 1. In addition, IH promoted ROS production and activated ras homolog gene family member A (RhoA)/Rho-associated protein kinase (ROCK) pathway. All of these effects of IH were reversed by salidroside. Similar to salidroside, ROCK-selective inhibitors Y26732, and Fasudil protected HUVECs from IH-induced ROS overproduction and endothelial barrier disruption. Furthermore, salidroside increased intracellular cAMP levels, while the PKA-selective inhibitor H-89 attenuated the effects of salidroside on IH-induced RhoA/ROCK suppression, ROS scavenging, and barrier protection. Conclusion: Our findings demonstrate that salidroside effectively ameliorated IH-aggravated endothelial barrier injury and atherosclerosis, largely through the cAMP/PKA/RhoA signaling pathway.

Increased levels of VCAM-1 is associated with higher occurrence of coronary artery disease in adults with moderate to severe obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) leads to important vascular abnormalities, including the endothelial dysfunction and the production of endothelial cell adhesion molecules. The adhesion molecules play an important role in the process of endothelial dysfunction in the pathogenesis of atherosclerosis. We assess the relationship between the levels of adhesion molecules and the presence of coronary artery disease (CAD) in Chinese adults with moderate to severe OSA. METHODS: The cross-sectional study included a total of 189 Chinese adults: 90 patients with moderate to severe OSA (apnea-hypopnea index≥15 events/h) alone, 40 patients with moderate to severe OSA and CAD, and 59 controls without OSA or with mild OSA and without CAD. We used high-throughput Multiplex Immunobead Assay technology to simultaneously test plasma levels of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1). The associations between the levels of circulating adhesion molecules and CAD in moderate to severe OSA patients were evaluated by multivariate logistic regression analysis. RESULTS: The circulating VCAM-1 levels were significantly elevated in patients suffering from moderate to severe OSA combined CAD compared with patients having moderate to severe OSA alone [853.28 (564.26) vs. 416.61 (301.69) ng/mL, P < 0.001]. Furthermore, circulating VCAM-1 levels were independently associated with CAD (odds ration = 2.113, 95%CI 1.400-2.766, P < 0.001) and showed higher discriminatory accuracy in assessing the presence of CAD (AUC: 0.899, 95%CI 0.849-0.950, P < 0.001) in moderate to severe OSA patients. However, no significant association was found between circulating ICAM-1 levels and CAD in moderate to severe OSA patients. CONCLUSIONS: The circulating VCAM-1 levels were significantly correlated with the presence of CAD in Chinese adults with moderate to severe OSA. The circulating VCAM-1 may function as a novel biomarker for monitoring the development and progression of CAD in patients with moderate to severe OSA.

Angiopoietin-like proteins 8 knockout reduces intermittent hypoxia-induced vascular remodeling in a murine model of obstructive sleep apnea.

OBJECTIVE: Obstructive sleep apnea (OSA) is a major risk factor for cardiovascular mortality. Apnea-induced chronic intermittent hypoxia (CIH) is a primary pathophysiological manifestation of OSA that promotes various cardiovascular alterations, such as aortic vascular remodeling. In this study, we investigated the association between angiopoietin-like proteins 8 (ANGPTL8) and CIH-induced aortic vascular remodeling in mice. METHODS: C57BL/6J male mice were divided into four groups: Normoxia group, ANGPTL8-/- group, CIH group, CIH + ANGPTL8-/- group. Mice in the normoxia group and ANGPTL8-/- group received no treatment, while mice in the CIH and CIH + ANGPTL8-/- group were subjected to CIH (21%-5% O2, 180 s/cycle, 10 h/day) for 6 weeks. At the end of the experiments, intima-media thickness (IMT), elastin disorganization, and aortic wall collagen abundance were assessed in vivo. Immunohistochemistry and Western-blot were used to detect endoplasmic reticulum stress (ERS) and aortic vascular smooth muscle cell proliferation. ANGPTL8 shRNA and ANGPL8 overexpression were used in aortic vascular smooth muscle cells to investigate the mechanism of ANGPTL8 in CIH. RESULTS: Compared to the control group, CIH exposure significantly increased intima-media thickness (IMT), elastic fibers disorganization, and aortic wall collagen abundance. CIH also significantly increased blood pressure, induced hyperlipidemia, as well as the expression of ERS protein activating transcription factor-6 (ATF6) and aortic vascular smooth muscle cell proliferation. Contrary, ANGPTL8-/- significantly mitigated the CIH-induced vascular remodeling; ANGPTL8-/- decreased CIH-induced hypertension and hyperlipidemia, inhibited the protein expression of ATF6, and aortic vascular smooth muscle cell proliferation. Moreover, our in vitro study suggested that CIH could induce ANGPTL8 expression via hypoxia-inducible factor (HIF-1α); ANGPTL8 induced proliferation of aortic vascular smooth muscle cells via the ERS pathway. CONCLUSION: ANGPTL8-/- can prevent CIH-induced aortic vascular remodeling, probably through the inhibition of the ERS pathway. Therefore, ANGPTL8 might be a potential target in CIH-induced aortic vascular remodeling.

Upper Lip Reconstruction Utilizing a Two-Stage Approach with Nanofat Grafting After Hemangioma Treatment.

Importance: Lip deformities that occur after treatment of vascular anomalies treatment are often followed by serious local cicatricial adhesion and mucosa atrophy that can complicate reconstruction methods involving simple fat grafting or local flap transfer. Objective: To develop a novel technique that combines flap transfer with nanofat grafting that can be used to reconstruct the upper lip after treatment of vascular anomalies. Design, Setting, and Participants: A retrospective study of a consecutive series of 24 patients with upper lip deformities (13 female and 11 male) aged between 7 and 24 years old was conducted. Of these, 15 patients were treated with nanofat grafting alone and 9 cases were treated with nanofat grafting combined with flap transfer (6 inferior- and 3 superior-based flaps). Main Outcomes and Measures: The appearance, symmetry, and smooth of upper lips with deformities before and after surgery were compared as the main outcome. Results: Among the patients examined, 15 achieved satisfactory results after undergoing multiple nanofat grafting treatments. The remaining nine patients who had serious deformities of the upper lip were treated using a combination of nanofat grafting and flap transfer. For these nine patients, postoperative results showed that the final appearance of the lips was generally symmetrical and smooth. Functional problems such as whistling defects were effectively corrected and no significant complications occurred. The aesthetic symmetry was higher for inferior flaps than for superior flaps and the incision scar for superior flaps was more obvious than for inferior flaps. Conclusion and Relevance: The technique combining nanofat autografting with local flap transfer for upper lip reconstruction was demonstrated to be effective, safe, and simple to perform. These findings suggest that this combined technique can be easily performed to achieve good results with only mild undercorrection.