Detection rate and shunt grading with synchronous testing of contrast transcranial Doppler and contrast transthoracic echocardiography: Preliminary findings.

Patent foramen ovale, a common congenital atrial septal defect, may lead to cardiac right-to-left shunting (RLS), which has been associated with various diseases. Reliable techniques for detecting RLS are essential for diagnosis and assist with treatment decision-making. Contrast transcranial Doppler (c-TCD), contrast transthoracic echocardiography (c-TTE), and contrast transesophageal echocardiography can be used to detect RLS. However, it is still unclear which ultrasound modalities are the most practical and cost-effective. To evaluate the efficacy of synchronous c-TCD and c-TTE in detecting cardiac RLS. We prospectively designed and continuously recruited 100 patients with cryptogenic stroke, migraines, transient ischemic attack, unexplained syncope, or dizziness admitted at the First Affiliated Hospital of Shenzhen University between February 2020 and August 2020. Ninety-five patients underwent synchronous c-TCD and c-TTE (during a single contrast-enhanced ultrasound session). We compared synchronous test results with the results of c-TCD alone and c-TTE alone. Ninety-five patients successfully underwent synchronous c-TCD and c-TTE, with the data analyzed for each individual. The positive detection rates of Grade I, II, and III shunts with synchronous c-TCD and c-TTE were higher than those with c-TTE or c-TCD alone (P = .047, P = .002, and P = .024, respectively). Overall, the positive detection rates of synchronous tests, c-TCD alone, and c-TTE were 69.5%, 51.6%, and 31.6%, respectively (P = .000, and P = .012). Among the 66 patients who were double-RLS-positive (both c-TTE and c-TCD showed positive results), as detected by the synchronous test, 26 (39.3%) patients who underwent c-TTE alone had higher shunt grades detected than those who underwent c-TCD alone. Conversely, 5 (7.6%) patients who underwent c-TCD alone had higher shunt grades detected than those who underwent c-TTE alone (P = .000). Synchronous c-TCD and c-TTE testing can significantly improve the detection rate, accuracy, and test process efficacy for quantifying RLS, and reduce the testing risk, workload, and medical costs.

Efficacy and safety of intensified antithrombotic therapy followed by stenting in treatment of highly severe stenosis accompanied by thrombosis in carotid atherosclerosis.

OBJECTIVE: This study explored the efficacy and safety of intensified antithrombotic therapy followed by stenting in treatment of highly severe stenosis accompanied by thrombosis in patients with carotid atherosclerosis (CAS). METHODS: This study recruited a total of 24 CAS patients between June 2016 and November 2020 in the research group, who had highly severe stenosis accompanied by in situ thrombosis and were treated with intensified antithrombotic treatment followed by stenting. The control group included 17 patients treated with stent angioplasty immediately after diagnosis with stenosis and thrombosis between January 2012 and May 2016. The efficacy and safety of treatment were compared between these two groups. RESULTS: The thrombus completely disappeared in 22 out of 24 patients (91.67%) in the research group after intensified antithrombotic treatment followed by stenting. Two patients still had the thrombus, but the volume was significantly reduced compared to that pre-treatment. The incidence of clinical events and new infarctions in the research group was significantly lower than that in the control group. In addition, the research group had significantly lower incidence of embolus antedisplacement and blocking the emboshield during the operation than the control group. There were no significant differences in the incidence of long-term complications and mortality between these two groups. The clinical prognosis of patients in the research group was significantly better than that of those in the control group within 3 months after treatment. CONCLUSION: Intensified antithrombotic therapy followed by stenting can effectively reduce the risk of perioperative complications in CAS patients with highly severe stenosis accompanied by thrombosis and improve the long-term clinical prognosis of patients without increasing the risk of bleeding.

Neuron-specific deletion of presenilin enhancer2 causes progressive astrogliosis and age-related neurodegeneration in the cortex independent of the Notch signaling.

INTRODUCTION: Presenilin enhancer2 (Pen-2) is an essential subunit of γ-secretase, which is a key protease responsible for the cleavage of amyloid precursor protein (APP) and Notch. Mutations on Pen-2 cause familial Alzheimer disease (AD). However, it remains unknown whether Pen-2 regulates neuronal survival and neuroinflammation in the adult brain. METHODS: Forebrain neuron-specific Pen-2 conditional knockout (Pen-2 cKO) mice were generated for this study. Pen-2 cKO mice expressing Notch1 intracellular domain (NICD) conditionally in cortical neurons were also generated. RESULTS: Loss of Pen-2 causes astrogliosis followed by age-dependent cortical atrophy and neuronal loss. Loss of Pen-2 results in microgliosis and enhanced inflammatory responses in the cortex. Expression of NICD in Pen-2 cKO cortices ameliorates neither neurodegeneration nor neuroinflammation. CONCLUSIONS: Pen-2 is required for neuronal survival in the adult cerebral cortex. The Notch signaling may not be involved in neurodegeneration caused by loss of Pen-2.

Circulating motilin, ghrelin, and GLP-1 and their correlations with gastric slow waves in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) commonly complain upper gastrointestinal (GI) symptoms, especially anorexia. Hemodialysis (HD) has been noted to improve GI symptoms; however, the underlying mechanisms are unclear. This study was designed 1) to study effects of HD on GI symptoms and gastric slow waves; and 2) to investigate possible roles of ghrelin and glucagon-like peptide-1 (GLP-1): the study recruited 13 healthy controls, 20 CKD patients without HD (CKD group), and 18 CKD patients with HD (HD group). Dyspeptic symptoms, autonomic functions, gastric slow waves, and plasma level of ghrelin and GLP-1 were analyzed. First, the CKD patients with HD showed markedly lower scores of anorexia (0.6 ± 0.2 vs. 3.2 ± 0.4, P < 0.001) compared with patients without HD. Second, the CKD group but not HD group showed a significant reduction (25.6%) in the percentage of normal gastric slow waves, compared with controls. Third, the CKD group exhibited a significantly lower ghrelin level compared with the HD group (26.8 ± 0.9 vs. 34.1 ± 2.3 ng/l, P < 0.02) and a higher GLP-1 level (29.4 ± 2.8 vs. 20.0 ± 2.1 pmol/l, P < 0.05) compared with controls. Moreover, the percentage of normal slow waves was positively correlated with ghrelin (r = 0.385, P = 0.019) but negatively correlated with GLP-1 (r = -0.558, P < 0.001) in all CKD patients. Hemodialysis improves upper GI symptoms and gastric slow waves in CKD patients. An increase in ghrelin and a decrease in GLP-1 might be involved in the HD-induced improvement in gastric slow waves.

Assessment of the key aroma compounds in rose-based products.

In this study, headspace solid phase microextraction-gas chromatography-mass spectrometry and GC-olfactometry were used to analyze the key aroma compounds in three types of rose-based products, including low-temperature extracts (LTEs), high-temperature extracts (HTEs), and rose drinks (RDs). In combination with the Guadagni theory, it was confirmed that the key aroma components of LTE were ß-phenyl ethyl alcohol, citronellol, geraniol, and eugenol. The main aroma compounds in HTE were ß-phenyl ethyl alcohol, citronellol, geraniol, eugenol, linalool, and rose oxide. The four key aroma compounds in RDs were ß-phenyl ethyl alcohol, eugenol, geraniol, and linalool.

Monoterpenes from Paeonia albiflora and their inhibitory activity on nitric oxide production by lipopolysaccharide-activated microglia.

Eleven new monoterpenes, paeonidangenin (1), paeonidanin A (2), paeonidanin B (3), paeonidanin C (4), paeonidanin D (5), paeonidanin E (6), paeoniflorone (7), 4-O-methylbenzoylpaeoniflorin (8), 4-O-methylgalloylpaeoniflorin (9), 4-O-methyldebenzoylpaeoniflorin (10), and 4-O-methylalbiflorin (11), were isolated from the 60% ethanol extract of the roots of Paeonia albiflora. Their structures were determined primarily on the basis of 1D and 2D NMR techniques and MS studies. Paeonidanins D (5) and E (6) are unprecedented examples of "cage-like" monoterpene dimers. The inhibitory effects of the isolated compounds on nitric oxide production by lipopolysaccharide (LPS)-activated N9 microglia were evaluated.

Comparison of inhibitory potency of three different curcuminoid pigments on nitric oxide and tumor necrosis factor production of rat primary microglia induced by lipopolysaccharide.

Microglia are the resident innate immune cells in the central nervous system. Evidence supports that the unregulated activation of microglia results in the production of pro-inflammatory cytokines and chemokines that propagate neuronal injury and finally cause neurodegenerative diseases. Curcuminn (Cur), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) are curcuminoid pigments extracted from turmeric (Curcuma longa L.). Cur has been reported to suppress the activation of microglia by reducing toxic factors production, but little is known about whether the two natural demethoxy derivatives of Cur, DMC and BDMC, have the similar effects as Cur. In the present study, we found that all of the three curcuminoid pigments significantly suppressed nitric oxide (NO) production by LPS-activated microglia and the relative potency was DMC>BDMC>Cur. This result was verified by RT-PCR analysis of iNOS mRNA. The NO-scavenging abilities of three curcuminoid pigments are very weak, which suggested that the indirect effect may not be critical in inhibiting NO production by LPS-activated microglia. Moreover, these three curcuminoid pigments attenuated the expression of mRNA and proteins of tumor necrosis factor-alpha (TNF-alpha) in a concentration-dependent manner and the relative potency was also DMC>BDMC>Cur. In conclusion, Cur, DMC and BDMC were found as potent microglia-activation inhibitors, and DMC exhibited the strongest inhibitory activity on NO and TNF-alpha production. These results provided an interesting clue for designing new compounds which could have better potential therapeutic implications for various neurodegenerative diseases.