A case of POEMS syndrome comprising of a complicated diagnostic procedure: Case report.

RATIONALE: This article presents the case of a patient with recurrent chronic diarrhea and cachexia who was misdiagnosed, followed by a literature review to summarize the reasons for misdiagnosis of POEMS syndrome and the treatment strategies. PATIENT CONCERNS: The diagnosis and treatment of this patient suggest that with the improvement of M-protein detection levels, the diagnosis of patients with low M-protein levels, such as those with POEMS syndrome, has been greatly aided. DIAGNOSES: POEMS syndrome requires polyneuropathy and monoclonal plasma cell proliferation as mandatory diagnostic criteria. Therefore, patients presenting with polyneuropathy should routinely undergo M-protein testing and consider the possibility of POEMS syndrome. INTERVENTIONS: The patient, in this case, was treated primarily with relatively conservative immunomodulatory agents. OUTCOMES: During follow-up after treatment, the patient's diarrhea and malnutrition showed significant improvement. LESSONS SUBSECTIONS: POEMS syndrome has low clinical specificity and a high rate of misdiagnosis. However, once a definitive diagnosis is made, the treatment outcome is favorable.

Ultrasound-mediated delivery of Pik3cb shRNA using magnetic nanoparticles for the treatment of in-stent restenosis in a rat balloon-injured model.

The aim of the present work was to examine the effect of polyethylene glycol (PEG)-coated superparamagnetic iron oxide (SPIO) nanoparticles carrying Pik3cb short hairpin RNA (shRNA) in the prevention of restenosis with the aid of ultrasound and a magnetic field. SPIO is a type of contrast agent used in medical imaging to enhance the visibility of specific tissues or organs. It consists of tiny iron oxide nanoparticles that can be targeted to specific areas of interest in the body. PEG-coated SPIO nanoparticles carrying Pik3cb shRNA (SPIO-shPik3cb) were prepared, and the particle size and zeta potential of PEG-coated SPIO nanoparticles with and without Pik3cb shRNA were examined. After a right common artery balloon-injured rat model was established, the rats were randomly divided into four groups, and the injured arteries were transfected with SPIO-shPik3cb, saline, SPIO-shcontrol and naked shRNA Pik3cb. During the treatment, each group was placed under a magnetic field and was transfected with the aid of ultrasound. Rats were sacrificed, and the tissue was harvested for analysis after 14 days. The results suggested that the mean particle size and zeta potential of SPIO-shPik3cbs were 151.45 ± 11 nm and 10 mV, respectively. SPIO-shPik3cb showed higher transfection efficiency and significantly inhibited the intimal thickening compared with naked Pik3cb shRNA in vascular smooth muscle cells (VSMCs) (*P < 0.05). Moreover, SPIO-shPik3cb could also significantly downregulate the expression of pAkt protein compared with naked Pik3cb shRNA. According to the results, SPIO-shPik3cb can remarkably inhibit the intimal thickening under a combination of magnetic field exposure and ultrasound.

Role of dendritic cell­derived exosomes in allergic rhinitis (Review).

Allergic rhinitis (AR) is a common pathological condition in otorhinolaryngology. Its prevalence has been increasing worldwide and is becoming a major burden to the world population. Dendritic cells (DCs) are typically activated and matured after capturing, phagocytosing, and processing allergens during the immunopathogenesis of AR. In addition, the process of DC activation and maturation is accompanied by the production of exosomes, which are cell­derived extracellular vesicles (EVs) that can carry proteins, lipids, nucleic acids, and other cargoes involved in intercellular communication and material transfer. In particular, DC­derived exosomes (Dex) can participate in allergic immune responses, where the biological substances carried by them can have potentially important implications for both the pathogenesis and treatment of AR. Dex can also be exploited to carry anti­allergy agents to effectively treat AR. This provides a novel method to explore the pathogenesis of and treatment strategies for AR further. Therefore, the present review focuses on the origin, composition, function, and biological characteristics of DCs, exosomes, and Dex, in addition to the possible relationship between Dex and AR.

Identification of HOXB9 based on comprehensive bioinformatics analysis for predicting prognosis of head and neck squamous cell carcinoma.

To evaluate the correlation between HOXB9 expression, and the prognosis and immune infiltration in head and neck squamous cell carcinoma (HNSCC). Pan-cancer HOXB9 expression was analyzed through TIMER2.0. The HOXB9 expression data of HNSCC and normal tissues were compared using the gene expression profiling interactive analysis (GEPIA) and the cancer genome atlas (TCGA) databases. The University of Alabama at Birmingham (UALCAN) database was used to analyze the relative expression of HOXB9 in HNSCC subgroups based on clinicopathological features, including cancer stage, tumor grade and lymph node stage. Survival analysis was performed using GEPIA, TCGA-Portal, Kaplan-Meier Plotter, and UALCAN databases. The genes co-expressed with HOXB9 were identified using TCGA data, and functionally annotated by GO and KEGG analyses. Protein-protein interaction network was constructed using the STRING database and Cytoscape 3.7.1. Single-sample gene set enrichment analysis was performed to assess the correlation between HOXB9 and immune infiltration based on TCGA data. TIMER 2.0 database was used to explore the correlation between HOXB9 expression and immune infiltration multiple cancers. HOXB9 mRNA is elevated in multiple cancers, and was upregulated in HNSCC tissues compared to non-paired (P < .05 in GEPIA; P < .0001 in TCGA) as well as paired (P < .0001 in TCGA) normal tissues. In addition, HOXB9 expression was positively correlated with tumor malignancy in the GEPIA and UALCAN databases (P < .05), and negatively with patient prognosis in both databases (P < .05). High HOXB9 expression was associated with increased infiltration of aDCs, NK CD56bright cells, NK cells, and Th2 cells (P < .05), while low HOXB9 expression was associated with an increase in the proportion of DCs, iDCs, mast cells, neutrophils, and Th17 cells (P < .05). HOXB9 likely functions as an oncogene in HNSCC by disrupting the immune landscape, and is a promising prognostic biomarker and therapeutic target.

Identification of galactosamine-(N-acetyl)-6-sulfatase (GALNS) as a novel therapeutic target in progression of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a commonly diagnosed malignancy in southern China and southeast Asia. Previous studies have identified galactosamine-(N-acetyl)-6-sulfatase (GALNS) as a potential biomarker for multiple cancers. However, it is unknown whether GALNS plays a role in NPC development, and the underlying mechanisms remain unclear. In this study, we found that GALNS is overexpressed in NPC cell lines and tissues compared to the normal nasopharyngeal counterparts. Knocking down GALNS expression in the NPC cells significantly decreased their proliferation in vitro, and inhibited xenograft growth in a mouse model. Mechanistically, the anti-proliferative effect of GALNS silencing was the result of autophagy induction via the inhibition of PI3K-AKT-mTOR signaling pathway. Taken together, GALNS drives the progression of NPC via PI3K-AKT-mTOR signaling-mediated autophagy, and is therefore a promising therapeutic target.

Characterizing stenosis severity of coronary heart disease by myocardial work measurement in patients with preserved ejection fraction.

Background: The novel echocardiographic parameter of myocardial work incorporates left ventricular pressure into the assessment of left ventricular systolic function and thereby corrects for afterload. We sought to investigate the diagnostic value of myocardial work to identify different grades of stenosis severity in coronary heart disease (CHD) patients with preserved left ventricular ejection fraction and without regional wall motion abnormalities. Methods: One hundred and seventeen consecutive subjects with preserved ejection fraction referred for coronary angiography were randomized and prospectively included in this study. Forty-six in the control group, and 25, 24, and 22 in each of the grade-1, grade-2, and grade-3 CHD groups as classified by the Gensini score. The following indices of myocardial work were assessed with a Vivid E95 Version 203 instrument: global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE). Results: Both GWI (P<0.001) and GCW (P<0.001) decreased significantly in CHD grade-1, increased slightly in CHD grade-2 compared with CHD grade-1, and decreased significantly in CHD grade-3. GWW (P<0.001) increased significantly from CHD grade-1 to CHD grade-3, while GWE (P<0.001) decreased significantly from CHD grade-1 to CHD grade-3. Receiver operating characteristic curves analysis revealed good discrimination between the control group and CHD grade-3 for GWI [area under the curve (AUC): 0.810; 95% confidence interval (CI): 0.691-0.930], GCW (AUC: 0.758; 95% CI: 0.631-0.885), GWW (AUC: 0.754; 95% CI: 0.624-0.885) and GWE (AUC: 0.817; 95% CI: 0.709-0.926). The assessment of intraobserver and interobserver variability in the MW echocardiographic data documented good interclass correlation coefficients (all >0.85). Conclusions: Myocardial work incorporates left ventricular pressure into the assessment of left ventricular systolic function and thereby corrects for afterload. It identifies patients with incipient left ventricular dysfunction caused by chronic ischemia due to CHD. A gradual worsening of myocardial work parameters was observed when comparing patients with higher degrees of stenosis severity. Therefore, adding myocardial work when evaluating patients with suspected CHD may help increase diagnostic accuracy.

TOM40 regulates the progression of nasopharyngeal carcinoma through ROS-mediated AKT/mTOR and p53 signaling.

Nasopharyngeal carcinoma (NPC) is a prevalent cancer in Southern China, North Africa, and Southeast Asia. The translocase of the outer membrane (TOM) 40 is a transporter of mitochondrial proteins, and is involved in ovarian cancer cell growth. However, its role in the progression of NPC is still unclear. We found that TOM40 levels were upregulated in NPC tissues and multiple NPC cell lines. In addition, high TOM40 expression in the tumor tissues was associated with poor overall survival and disease specific survival. TOM40 knockdown in the NPC cell lines inhibited their proliferation in vitro and in vivo. Furthermore, TOM40 silencing also increased intracellular production of reactive oxygen species (ROS) and decreased mitochondrial membrane potential (MMP). Mechanistically, the anti-tumor effects of TOM40 silencing were dependent on the inhibition of AKT/mTOR signaling and activation of p53 signaling. To summarize, TOM40 mediates NPC progression through ROS-mediated AKT/mTOR and p53 signaling. Our findings highlight the potential of TOM40 as a therapeutic target for NPC.

Cytotoxic steroids from the stems of Strophanthus divaricatus.

Phytochemical investigation on the stems of Strophanthus divaricatus led to the isolation of four undescribed cardiac glycosides and one undescribed C21 pregnane, together with eleven known steroids. Their structures were elucidated by a comprehensive analysis of HRESIMS, 1D and 2D NMR spectra. The absolute configuration of 16 was determined by comparison of the experimental and computed ECD spectra. Compounds 1-13 and 15 displayed potent to significant cytotoxicity against human cancer cell lines K562, SGC-7901, A549 and HeLa with IC50 values of 0.02-16.08, 0.04-23.13, 0.06-22.31 and 0.06-15.13 µM, respectively.

Establishment of a canine model of pulmonary arterial hypertension induced by dehydromonocrotaline and ultrasonographic study of right ventricular remodeling.

OBJECTIVE: Pulmonary arterial hypertension (PAH) means high blood pressure in the lungs. We aimed to observe the right ventricular size, wall thickness and characteristic functional changes and their associations with PAH in an established model of beagle dogs, and to explore convenient, reliable and sensitive ultrasound indicators for assessing right ventricular remodeling. METHODS: Twenty healthy beagle dogs (8-10 kg) were randomly divided into control group (N-dimethylformamide, n = 10) and dehydromonocrotaline (DHMCT) group (DHMCT, n = 10). N-dimethylformamide or DHMCT was injected through a catheter into the right atrium, and then right heart catheterization, routine echocardiography and two-dimensional speckle tracking imaging (2D-STI) were performed before modeling (0 weeks) and 8, 14 weeks after modeling. Hemodynamic parameters and right ventricular function-related ultrasound data were acquired. At the end of the experiment, the animals were killed and the lung tissues were taken for HE staining. Left and right ventricular walls were separated and weighed respectively, and right ventricular hypertrophy index (RVHI) was measured. The associations of the routine ultrasound data and 2D-STI data at each time point with hemodynamic parameters and RVHI were analyzed. RESULTS: At 0, 8 and 14 weeks, gradual decreases in the right ventricular global longitudinal strain (RVLS) were found in DHMCT group. RVH occurred in DHMCT group, and DHMCT group had a significantly higher RVHI than that of control group (49.83 ± 4.83% vs. 39.80 ± 1.40%, P < .001) and larger pulmonary artery media thickness. RVLS had significant positive correlations with RVSP (r = 0.74, P < .001), mRVP (r = 0.72, P < .001), PASP (r = 0.75, P < .001), mPAP (r = 0.72, P < .001) and PVR (r = 0.68, P < .001). There was a significant positive correlation between RVLS and RVHI (r = 0.74, P < .001). CONCLUSION: The right ventricular function in PAH can be effectively assessed by echocardiography, and RVLS measured by 2D-STI sensitively reflects right ventricular remodeling following PAH.

Human umbilical cord-derived mesenchymal stem cell transplantation supplemented with curcumin improves the outcomes of ischemic stroke via AKT/GSK-3ß/ß-TrCP/Nrf2 axis.

BACKGROUND: Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) engraftment is a promising therapy for acute ischemic stroke (AIS). However, the harsh ischemic microenvironment limits the therapeutic efficacy of hUC-MSC therapy. Curcumin is an anti-inflammatory agent that could improve inflammatory microenvironment. However, whether it enhances the neuroprotective efficacy of hUC-MSC transplantation is still unknown. In the present study, we investigated the therapeutic efficacy and the possible mechanism of combined curcumin and hUC-MSC treatment in AIS. METHODS: Middle cerebral artery occlusion (MCAO) mice and oxygen glucose deprivation (OGD) microglia were administrated hUC-MSCs with or without curcumin. Neurological deficits assessment, brain water content and TTC were used to assess the therapeutic effects of combined treatment. To elucidate the mechanism, MCAO mice and OGD microglia were treated with AKT inhibitor MK2206, GSK3ß activator sodium nitroprusside (SNP), GSK3ß inhibitor TDZD-8 and Nrf2 gene knockout were used. Immunofluorescence, flow cytometric analysis, WB and RT-PCR were used to evaluate the microglia polarization and the expression of typical oxidative mediators, inflammatory cytokines and the AKT/GSK-3ß/ß-TrCP/Nrf2 pathway protein. RESULTS: Compared with the solo hUC-MSC-grafted or curcumin groups, combined curcumin-hUC-MSC therapy significantly improved the functional performance outcomes, diminished the infarct volumes and the cerebral edema. The combined treatment promoted anti-inflammatory microglia polarization via Nrf2 pathway and decreased the expression of ROS, oxidative mediators and pro-inflammatory cytokines, while elevating the expression of the anti-inflammatory cytokines. Nrf2 knockout abolished the antioxidant stress and anti-inflammation effects mediated with combined treatment. Moreover, the combined treatment enhanced the phosphorylation of AKT and GSK3ß, inhibited the ß-TrCP nucleus translocation, accompanied with Nrf2 activation in the nucleus. AKT inhibitor MK2206 activated GSK3ß and ß-TrCP and suppressed Nrf2 phosphorylation in nucleus, whereas MK2206 with the GSK3ß inhibitor TDZD-8 reversed these phenomena. Furthermore, combined treatment followed by GSK3ß inhibition with TDZD-8 restricted ß-TrCP nucleus accumulation, which facilitated Nrf2 expression. CONCLUSIONS: We have demonstrated that combined curcumin-hUC-MSC therapy exerts anti-inflammation and antioxidant stress efficacy mediated by anti-inflammatory microglia polarization via AKT/GSK-3ß/ß-TrCP/Nrf2 axis and an improved neurological function after AIS.

Myocardial Work Measurement With Functional Capacity Evaluation in Primary Systemic Hypertension Patients: Comparison Between Left Ventricle With and Without Hypertrophy.

OBJECTIVE: Noninvasive measurement of myocardial work (MW) incorporates left ventricular (LV) pressure, and, therefore, allows correction of global longitudinal strain for changing afterload conditions. We sought to investigate MW as a tool to detect early signs of LV dysfunction in primary systemic hypertension patients, particularly with different predictive indices. METHODS AND RESULTS: None left ventricular hypertrophy (NLVH) and left ventricular hypertrophy (LVH) patients established were all primary systemic hypertension with preserved ejection fraction. Forty in NLVH and forty in LVH according to left ventricular end-diastolic mass index (LVEDmassI) were prospectively enrolled. The following indices of MW were assessed: global work index, global constructive work, global wasted work (GWW), and global work efficiency (GWE). Both global work index (P=0.348) and global constructive work (P=0.225) were increased in NLVH and decreased in LVH, and GWW (P<0.001) was increased significantly in NLVH and increased more in LVH, while GWE (P<0.001) was decreased significantly in NLVH and decreased more in LVH. The clinical utility of GWW (95% CI: 0.802-0.951) and GWE (95% CI: 0.811-0.950) were verified by receiver-operating characteristic curve analysis showing larger net benefits as evaluated with LVH and control comparisons. In multivariate linear regression analysis, 4-dimenaional LVEDmassI was independently associated with GWE (P=0.018) in systemic hypertension patients. Assessment of intraobserver and interobserver variability in the MW echocardiographic data documented good interclass correlation coefficients (all >0.85). CONCLUSION: GWW and GWE derived from MW are more accurate, sensitive, and reproducible predictors to detect early LV dysfunction in primary systemic hypertension patients, especially in distinguishing the potential functional abnormality of NLVH and LVH, even though the ejection fraction is preserved.

Research Advances in the Treatment of Allergic Rhinitis by Probiotics.

Allergic rhinitis (AR) impairs the quality of life of patients and reduces the efficiency of social work, it is an increasingly serious public medical and economic problem in the world. Conventional anti-allergic drugs for the treatment of allergic rhinitis (AR) can cause certain side effects, which limit the quality of life of patients. Therefore, it makes sense to look for other forms of treatment. Several studies in recent years have shown that probiotics have shown anti-allergic effects in various mouse and human studies. For example, the application of certain probiotic strains can effectively relieve the typical nasal and ocular symptoms of allergic rhinitis in children and adults, thereby improving the quality of life and work efficiency. At the same time, previous studies in humans and mice have found that probiotics can produce multiple effects, such as reduction of Th2 cell inflammatory factors and/or increase of Th1 cell inflammatory factors, changes in allergy-related immunoglobulins and cell migration, regulate Th1/Th2 balance or restore intestinal microbiota disturbance. For patients with limited activity or allergic rhinitis with more attacks and longer attack duration, oral probiotics have positive effects. The efficacy of probiotics in the prevention and treatment of allergic rhinitis is remarkable, but its specific mechanism needs further study. This review summarizes the research progress of probiotics in the treatment of allergic rhinitis in recent years.

[Effect of Butyl Xanthate on Pb2+ and Cd2+ Adsorption by Soil Around a Dressing Plant].

Flotation agents can enter the soil and water environment around mining areas through beneficiation wastewater discharge and overflow from tailings ponds. The adsorption of Pb2+ and Cd2+ on soil around a lead-zinc dressing plant was investigated in the presence of potassium butyl xanthate (PBX). Batch experiments were conducted with different initial pH, PBX, Pb2+, and Cd2+solution concentrations. The fractions of lead and cadmium were altered after treatment with different concentrations of PBX. The results showed that adsorption of Pb2+and Cd2+ on soil was seriously inhibited by PBX. When PBX concentration was 40 mg·L-1, the adsorption capacity of Pb2+ and Cd2+ decreased from 3540 mg·kg-1 and 387 mg·kg-1 to 3085 mg·kg-1 and 100 mg·kg-1, respectively. The Pb2+ and Cd2+ adsorption kinetic process was best fitted by the quasi-second-order kinetic model, which indicated that the adsorption process of Pb2+ and Cd2+ on soil was mainly chemical adsorption. The formation of a hydrophobic and insoluble complex and competitive adsorption between PBX, Pb2+, and Cd2+ on the soil surface was the main reason for reducing the adsorption capacity. The results showed that PBX could increase the mobility of Pb2+ and Cd2+ on soil. The degree of impact improved with increasing initial concentration of PBX and pH but decreased with increasing initial concentration of Pb2+ and Cd2+, and the adsorption isotherms conformed to the Freundlich isotherm. Under low PBX content (100 mg·kg-1), exchangeable and reducible cadmium contents in the soil increased, which could lead to the activation of cadmium in soil. However, the addition of PBX to the treated soil could reduce the content of exchangeable and reducible lead. As the concentration of PBX increased, the reduction effect also increased, which was related to the stronger complex stability of Pb(C4H9OCS2)2 than that of Cd(C4H9OCS2)2. The results showed that residual flotation reagents in beneficiation wastewater may increase the potential ecological risk of heavy metals such as Pb and Cd in soil, and the prevention and control of the potential ecological risk should be strengthened.

Four-dimensional quantification on left atrial volume-strain in coronary heart disease patients without regional wall motion abnormalities: Correlation with the severity of coronary stenosis.

OBJECTIVE: Echocardiography is a time and cost-effective imaging modality, providing evidence of myocardial ischemia by detecting the regional wall motion abnormalities (RWMA). However, quite a few coronary heart disease (CHD) patients do not present RWMA. The left atrium (LA) plays an irreplaceable role in determining the prognosis and risk stratification of cardiovascular disease including CHD. In this present study, we intend to explore the myocardial mechanics changes of LA mainly using four-dimensional (4D) LA quantitative volume-strain in CHD patients without RWMA at rest but were confirmed by coronary angiography (CAG) and to figure out several variables of the LA that could contribute to the identification of those patients. METHODS: We prospectively enrolled 76 patients who underwent two-dimensional echocardiography (2DE), four-dimensional echocardiography (4DE), and CAG for suspected CHD but without echocardiographic visible RWMA at rest. Patients diagnosed with CHD by CAG were furtherly divided into three groups according to the extent of coronary stenosis accessed by Gensini score (GS) as the mild, moderate, and severe CHD group. Twenty-four subjects with negative CAG results served as the control group. LA end-systolic anteroposterior diameter (LAAPD) and biplane LV ejection fraction (Biplane LVEF) were measured by 2DE; LA maximum volume (LAVmax), LA minimum volume (LAVmin), LA volume at the onset of atrial contraction (LAVpreA), LAVmax index (LAVmaxI), LA ejection volume (LAEV), LA ejection fraction (LAEF) accompanied by LA longitudinal strain during reservoir phase (LASr), conduit phase (LAScd), contraction phase (LASct) and LA circumferential strain during reservoir phase (LASr_c), conduit phase (LAScd_c), contraction phase (LASct_c) were measured by 4DE automatically. We compared these parameters between groups, explored how they change and whether they are related to the CHD severity. RESULTS: LAEF, LASr_c, and LASct_c was lower in CHD group compared with the control group (p = .031, .002, .004, respectively). Pearson correlation analysis showed that LASr, LASct, LASr_c, and LASct_c negatively correlated with the GS. Additionally, LASr of patients in the severe CHD group decreased significantly compared with those in the mild CHD group, moderate CHD group, and control group, demonstrating the highest area under the receiver operating characteristic (ROC) curve (AUC) (AUC = .736 [p = .003, 95% CI .589-.884], sensitivity 67.8%, specificity 70.6%) with the cut-off value of 17.5% for predicting severe CHD patients. CONCLUSION: Four-dimensional LA strain may provide new insight into identification and management for CHD patients and correlate with CHD severity. LASr showed good sensitivity (67.8%) and specificity (70.6%) for diagnosing severe CHD individuals.

Corrigendum: Adenosine A2A Receptor Suppressed Astrocyte-Mediated Inflammation through the Inhibition of STAT3/YKL-40 Axis in Mice with Chronic Cerebral Hypoperfusion-Induced White Matter Lesions.

[This corrects the article DOI: 10.3389/fimmu.2022.841290.].

Adenosine A2A Receptor Suppressed Astrocyte-Mediated Inflammation Through the Inhibition of STAT3/YKL-40 Axis in Mice With Chronic Cerebral Hypoperfusion-induced White Matter Lesions.

White matter lesions are an important pathological manifestation of cerebral small vessel disease, with inflammation playing a pivotal role in their development. The adenosine A2a receptor (ADORA2A) is known to inhibit the inflammation mediated by microglia, but its effect on astrocytes is unknown. Additionally, although the level of YKL-40 (expressed mainly in astrocytes) has been shown to be elevated in the model of white matter lesions induced by chronic cerebral hypoperfusion, the specific regulatory mechanism involved is not clear. In this study, we established in vivo and in vitro chronic cerebral hypoperfusion models to explore whether the ADORA2A regulated astrocyte-mediated inflammation through STAT3/YKL-40 axis and using immunohistochemical, western blotting, ELISA, PCR, and other techniques to verify the effect of astrocytes ADORA2A on the white matter injury. The in vivo experiments showed that activation of the ADORA2A decreased the expression of both STAT3 and YKL-40 in the astrocytes and alleviated the white matter injury, whereas its inhibition had the opposite effects. Similarly, ADORA2A inhibition significantly increased the expression of STAT3 and YKL-40 in astrocytes in vitro, with more proinflammatory cytokines being released by astrocytes. STAT3 inhibition enhanced the inhibitory effect of ADORA2A on YKL-40 synthesis, whereas its activation reversed the phenomenon. These results suggest that the activation of ADORA2A in astrocytes can inhibit the inflammation mediated by the STAT3/YKL-40 axis and thereby reduce white matter injury in cerebral small vessel disease.

Quantitative Differentiation of Left Atrial Performance in Hypertrophic Cardiomyopathy: Comparison Between Nonobstruction and Occult Obstruction With 4-dimensional Volume-strain.

OBJECTIVE: The objective of this study was to describe the different components of left atrial (LA) dysfunction predictors in nonobstructive and occult obstructive hypertrophy cardiomyopathy (HCM) patients especially with preserved left ventricular (LV) ejection fraction, particularly using LA 4-dimensional (D) longitudinal and circumferential strains. METHODS: Twenty-eight nonobstructive HCM patients and 30 occult obstructive HCM patients according to LV outflow tract gradient at rest and after exercise were prospectively enrolled. 4D echocardiographic evaluation was performed in 58 HCM patients, both nonobstructive and occult obstructive, and 38 control subjects. LA reservoir, conduit, contractile functions were performed by 4D volume-strain with volumes and longitudinal, circumferential strains. RESULTS: Optimal correlation coefficients obtained between LV 4D mass (index) and LA 4D longitudinal/circumferential strain (r=-0.860 to 0.518, all P<0.001). Both nonobstructive and occult obstructive HCM patients had increased volumes and significantly decreased longitudinal, circumferential strain values with lower reservoir, conduit, contractile functions than the controls (all P<0.001). Occult obstructive HCM patients presented incremented volumes compared with nonobstructive ones (P<0.001 to 0.003). Lower conduit function and higher contractile function indicated with lower reservoir function revealed by circumferential strain in occult obstructive HCM patients than nonobstructive ones (P<0.001 to 0.017). Interclass correlation coefficients of intraobserver and interobserver in the LV and LA 4D value evaluations were >0.75 and >0.85, respectively. CONCLUSIONS: LA volumes were significantly increased and LA reservoir, conduit, and contractile functions were significantly impaired in HCM patients. Furthermore, different performances of LA functional analyses in nonobstruction and occult obstruction patients with 4D volume-strain echocardiography may facilitate the recognition of subtle LA dysfunctional differentiation in HCM patients.

Bilateral periareolar hyperpigmentation after augmentation mammoplasty: a case report and literature review

Complications arising from breast augmentation procedures are broadly categorized as either surgery-related or prosthesis-related. Many reports have described complications associated with breast augmentation. However, to date, periareolar post-inflammatory hyperpigmentation (PIH) after breast augmentation has not been reported. Herein, we report a case of PIH after augmentation mammoplasty using a silicone implant through the periareolar approach. A 35-year-old woman, who underwent bilateral breast augmentation using a periareolar approach, presented with bilateral periareolar tissue changes, with dark brown, irregular macules appearing 6 weeks postoperatively. Based on clinical symptoms and histological examination, the lesion was diagnosed as PIH. Topical hydroquinone and retinoic acid were applied for 8 weeks after the pigmentation appeared. After 6 months of observation, the pigmentation faded. To summarize, we report a case of pigmentation around the bilateral nipples after periareolar breast augmentation along with a literature review.

Targeted Treatment of Ischemic Stroke by Bioactive Nanoparticle-Derived Reactive Oxygen Species Responsive and Inflammation-Resolving Nanotherapies.

Stroke is a primary cause of death and disability worldwide, while effective and safe drugs remain to be developed for its clinical treatment. Herein, we report bioactive nanoparticle-derived multifunctional nanotherapies for ischemic stroke, which are engineered from a pharmacologically active oligosaccharide material (termed as TPCD) prepared by covalently conjugating a radical-scavenging compound (Tempol) and a hydrogen-peroxide-eliminating moiety of phenylboronic acid pinacol ester (PBAP) on ß-cyclodextrin. Of note, combined functional moieties of Tempol and PBAP on ß-cyclodextrin contribute to antioxidative and anti-inflammatory activities of TPCD. Cellularly, TPCD nanoparticles (i.e., TPCD NPs) reduced oxygen-glucose deprivation-induced overproduction of oxidative mediators, increased antioxidant enzyme expression, and suppressed microglial-mediated inflammation, thereby inhibiting neuronal apoptosis. After intravenous (i.v.) delivery, TPCD NPs could efficiently accumulate at the cerebral ischemic injury site of mice with middle cerebral artery occlusion (MCAO), showing considerable distribution in cells relevant to the pathogenesis of stroke. Therapeutically, TPCD NPs significantly decreased infarct volume and accelerated recovery of neurological function in MCAO mice. Mechanistically, efficacy of TPCD NPs is achieved by its antioxidative, anti-inflammatory, and antiapoptotic effects. Furthermore, TPCD NPs can function as a reactive oxygen species labile nanovehicle to efficiently load and triggerably release an inflammation-resolving peptide Ac2-26, giving rise to an inflammation-resolving nanotherapy (i.e., ATPCD NP). Compared to TPCD NP, ATPCD NP demonstrated notably enhanced in vivo efficacies, largely resulting from its additional inflammation-resolving activity. Consequently, TPCD NP-derived nanomedicines can be further developed as promising targeted therapies for stroke and other inflammation-associated cerebrovascular diseases.