The influence of sleep disorders on perioperative neurocognitive disorders among the elderly: A narrative review.

This review comprehensively assesses the epidemiology, interaction, and impact on patient outcomes of perioperative sleep disorders (SD) and perioperative neurocognitive disorders (PND) in the elderly. The incidence of SD and PND during the perioperative period in older adults is alarmingly high, with SD significantly contributing to the occurrence of postoperative delirium. However, the clinical evidence linking SD to PND remains insufficient, despite substantial preclinical data. Therefore, this study focuses on the underlying mechanisms between SD and PND, underscoring that potential mechanisms driving SD-induced PND include uncontrolled central nervous inflammation, blood-brain barrier disruption, circadian rhythm disturbances, glial cell dysfunction, neuronal and synaptic abnormalities, impaired central metabolic waste clearance, gut microbiome dysbiosis, hippocampal oxidative stress, and altered brain network connectivity. Additionally, the review also evaluates the effectiveness of various sleep interventions, both pharmacological and nonpharmacological, in mitigating PND. Strategies such as earplugs, eye masks, restoring circadian rhythms, physical exercise, noninvasive brain stimulation, dexmedetomidine, and melatonin receptor agonists have shown efficacy in reducing PND incidence. The impact of other sleep-improvement drugs (e.g., orexin receptor antagonists) and methods (e.g., cognitive-behavioral therapy for insomnia) on PND is still unclear. However, certain drugs used for treating SD (e.g., antidepressants and first-generation antihistamines) may potentially aggravate PND. By providing valuable insights and references, this review aimed to enhance the understanding and management of PND in older adults based on SD.

The role of ferroptosis in chronic intermittent hypoxia-induced cognitive impairment.

PURPOSE: Obstructive sleep apnea (OSA) is a sleep disorder that may lead to cognitive impairment. The primary pathophysiological feature of OSA is chronic intermittent hypoxia (CIH), but the underlying mechanisms of CIH are not known. There have been few studies on the role of ferroptosis, a novel form of programmed cell death, during CIH-induced cognitive impairment. Therefore, this paper examined ferroptosis' effect on CIH-mediated cognitive impairment. METHODS: The study randomized twenty-four Sprague-Dawley (SD) male rats to control or CIH group. CIH rats were subjected to intermittent hypoxia for 4 weeks. Rat learning and memory were analyzed by the Morris water maze (MWM) test. Alterations of hippocampal neuronal ultrastructure were observed by transmission electron microscopy (TEM). Malondialdehyde (MDA) and ferrous iron (Fe2+) levels and superoxide dismutase (SOD) and reduced glutathione (GSH) contents were determined. Ferroptosis-associated protein levels were examined by Western blotting. RESULTS: The MWM test indicated that rats in the CIH group exhibited neurocognitive impairment. TEM showed that CIH induced mitochondrial damage. Significant increases in Fe2+ and MDA levels were observed in the CIH group, and GSH and SOD levels were decreased. Expression of Acyl-CoA synthetase long-chain family member 4 (ACSL4) increased, and glutathione peroxidase 4 (GPX4) protein levels were decreased, suggesting that ferroptosis was induced in CIH model rats. The NF-E2-related factor 2 (Nrf2) protein level in the CIH group was decreased. CONCLUSION: Ferroptosis had an essential effect on CIH-mediated cognitive impairment, and it may occur via Nrf2 dysregulation. These findings lay a solid foundation for the subsequent study of OSA-associated cognitive impairment offering potential evidence for the development of therapeutic strategies.

Ascending aortic dilatation rate after transcatheter aortic valve replacement in patients with bicuspid and tricuspid aortic stenosis: A multidetector computed tomography follow-up study.

BACKGROUND: Current data is lacking about the progression of ascending aortic dilatation after transcatheter aortic valve replacement (TAVR) in aortic stenosis (AS) patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). This study aims to assess the ascending aortic dilatation rate (mm/year) after TAVR in patients with BAV versus TAV using a multidetector computed tomography (MDCT) follow-up and to determine the predictors of ascending aortic dilatation rate. METHODS: Severe AS patients undergoing TAVR from March 2013 to March 2018 at our center with MDCT follow-ups were included. BAV and TAV were identified using baseline MDCT. Baseline and follow-up MDCT images were analyzed, and the diameters of ascending aorta were measured. Study end point is ascending aortic dilatation rate (mm/year). Furthermore, factors predicting ascending aortic dilatation rate were also investigated. RESULTS: Two hundred and eight patients were included, comprised of 86 BAV and 122 TAV patients. Five, 4, 3, 2, and 1-year MDCT follow-ups were achieved in 7, 9, 30, 46, and 116 patients. The ascending aortic diameter was significantly increased after TAVR in both BAV group (43.7±4.4 mm vs. 44.0±4.5 mm; P<0.001) and TAV group (39.1±4.8 mm vs. 39.7±5.1 mm; P<0.001). However, no difference of ascending aortic dilatation rate was found between BAV and TAV group (0.2±0.8 mm/year vs. 0.3±0.8 mm/year, P=0.592). Multivariate linear regression revealed paravalvular leakage (PVL) grade was independently associated with ascending aortic dilatation rate in the whole population and BAV group, but not TAV group. No aortic events occurred during follow-ups. CONCLUSION: Ascending aortic size continues to grow after TAVR in BAV patients, but the dilatation rate is mild and comparable to that of TAV patients. PVL grade is associated with ascending aortic dilatation rate in BAV patients post-TAVR.

First-in-man implantation of the retrievable and repositionable VenusA-Plus valve.

BACKGROUND: No retrievable and repositionable second generation transcatheter aortic valve is available in China. Here, we report the first-in-man implantation of the retrievable and repositionable VenusA-Plus valve. METHODS: A 76-year-old patient with symptomatic severe aortic stenosis and high surgical risk (STS 13.8%) was recommended for transcatheter aortic valve replacement (TAVR) by heart valve team. Type 0 bicuspid aortic valve with asymmetric calcification was identified by dual source computed tomography, and the unfavorable anatomies increased the possibility of malposition and paravalvular leakage during TAVR. Therefore, we used the retrievable and repositionable VenusA-Plus valve for the patient. RESULTS: Transfemoral TAVR was performed under local anesthesia with sedation, and a 26mm VenusA-Plus valve was successfully implanted. No transvalvular pressure gradient and trace paravalvular leakage were found. CONCLUSION: The successful first-in-man implantation indicates the retrievable and repositionable VenusA-Plus valve is feasible in complicated TAVR cases such as bicuspid aortic valve.

[Relationship among the Oxygen Concentration, Reactive Oxygen Species and the Biological Characteristics of Mouse Bone Marrow Hematopoietic Stem Cells].

OBJECTIVE: To investigate the effects of oxygen concentration and reactive oxygen species (ROS) on the biological characteristics of hematopoietic stem cells (HSC) and to analyzed the relationship among the oxygen concentration, ROS and the biological characteristics of mouse HSC through simulation of oxygen environment experienced by PB HSC during transplantation. METHODS: The detection of reactive oxygen species (ROS), in vitro amplification, directional differentiation (BFU-E, CFU-GM, CFU-Mix), homing of adhesion molecules (CXCR4, CD44, VLA4, VLA5, P-selectin), migration rate, CFU-S of NOD/SCID mice irradiated with sublethal dose were performed to study the effect of oxgen concentration and reactive oxygen species on the biological characteristics of mouse BM-HSC and the relationship among them. RESULTS: The oxygen concentrations lower than normal oxygen concentration (especially hypoxic oxygen environment) could reduce ROS level and amplify more Lin(-) c-kit(+) Sca-1(+) BM HSC, which was more helpful to the growth of various colonies (BFU-E, CFU-GM, CFU-Mix) and to maintain the migratory ability of HSC, thus promoting CFU-S growth significantly after the transplantation of HSC in NOD/SCID mice irradiated by a sublethal dose. BM HSC exposed to oxygen environments of normal, inconstant oxygen level and strenuously thanging of oxygen concentration could result in higher level of ROS, at the same time, the above-mentioned features and functional indicators were relatively lower. CONCLUSION: The ROS levels of BM HSC in PB HSCT are closely related to the concentrations and stability of oxygen surrounding the cells. High oxygen concentration results in an high level of ROS, which is not helpful to maintain the biological characteristics of BM HSC. Before transplantation and in vitro amplification, the application of antioxidancs and constant oxygen level environments may be beneficial for transplantation of BMMSC.

Evaluation of the safety and efficacy of transcatheter aortic valve implantation in patients with a severe stenotic bicuspid aortic valve in a Chinese population.

OBJECTIVE: The purpose of this study is to evaluate the safety and efficacy of transcatheter aortic valve implantation (TAVI) in patients with a severe stenotic bicuspid aortic valve (BAV) in a Chinese population. While several groups have reported the feasibility, efficacy, and safety of TAVI for patients with a BAV, worldwide experience of the technique is still limited, especially in China. METHODS: From March 2013 to November 2014, high surgical risk or inoperable patients with symptomatic severe aortic stenosis (AS) who had undergone TAVI at our institution were selected for inclusion in our study. RESULTS were compared between a BAV group and a tricuspid aortic valve (TAV) group. RESULTS: Forty patients were included in this study, 15 (37.5%) of whom were identified as having a BAV. In the BAV group, the aortic valve area was smaller ((0.47±0.13) vs. (0.59±0.14) cm(2)), the ascending aortic diameter was larger ((40.4±4.4) vs. (36.4±4.3) mm), and the concomitant aortic regurgitation was lower. No significant differences were found between the groups in the other baseline characteristics. No differences were observed either in the choice of access or valve size. The procedural success achieved in this study was 100%. There were no differences between groups in device success (86.7% vs. 88.0%), 30-d mortality (6.7% vs. 8.0%), or 30-d combined end point (13.3% vs. 12.0%). The incidences of new pacemaker implantation, paravalvular regurgitation and other complications, recovery of left ventricle ejection fraction and heart function were similar in both groups. CONCLUSIONS: Patients with a severely stenotic BAV can be treated with TAVI, and their condition after treatment should be similar to that of people with a TAV.

[Prescription screening of total coumarins of Angelica dahurica var. formosana extended action tablets based on artificial neural network].

OBJECTIVE: To analyze the screening of prescription for the total coumarins of Angelica dahurica var. formosana sustained release tablets, and to preliminarily discuss the releasing mechanism. METHODS: On the basis of orthogonal test data, the prescriptions were screened and optimized by adopting the artificial neural network technology and by taking the in vitro release rate at the setting time as the evaluation indicator. RESULTS: The in vitro release performance of sustained release tablets prepared by the screened optimal technology was good, and the drugs released continuously for 12 h. The drug release process was fitted by adopting the Ritger-Peppas equation. The release of these tablets in artificial gastric juice could be described as the combined action of diffusion and skeleton dissolution. CONCLUSIONS: Artificial neural network technology can be used to design the pharmacy prescription, optimize the process, solve nonlinear problems with multiple factors and multiple levels, and reduce the experimental workload. So it has broad application prospect.

Cytotoxic triterpenesaponins from Ilex pubescens.

Two new triterpenesaponins, ilexsaponins G and H (1 and 2), together with six known triterpenesaponins (3-8), were isolated from the roots of Ilex pubescens. Their structures were elucidated on the basis of spectroscopic evidence and hydrolysis products. Those compounds showed inhibitory activities against two human colorectal cancer cell lines HCT 116 and HT-29.

The study of absorption kinetics of berberine based on portal vein in rat, and the influence of verapamil and borneol to its absorption ability by UHPLC method.

This paper aims to investigate the portal-vein absorption kinetics of berberine in rat, and the influence of P-gp inhibitors such as verapamil and borneol, to its absorption ability. In the paper, a validated UHPLC method was established to determine the berberine in plasma, and the portal-vein absorption model was applied to conduct the pharmacokinetic study. Animals were divided into four groups as follow: group berberine group (BG); group verapamil + berberine group (VBG); group borneol + berberine group (BBG) and group long-term use of borneol + berberine group (LBBG). Plasma samples were obtained at regular time intervals after administration and separated on Agilent 1290 Infinity UHPLC instrument. The method showed good linearity (r = 0.9988) over wide dynamic ranges (4.08-163.20 ng/mL). Variations within- and between-batch never exceeded 7.58 and 2.21 %, respectively. The extraction recovery rates ranged from 85.34 to 111.62 %. We discovered that the AUC of four group exhibited no significant differences (P > 0.05), and co-administration of berberine with borneol of group BBG and group LBBG in advance could both reduce the T max and C max as compared to group BG (P < 0.05), while co-administration of verapamil seems to have had little influence to berberine's absorption ability.

Study on intestinal absorption and pharmacokinetic characterization of diester diterpenoid alkaloids in precipitation derived from fuzi-gancao herb-pair decoction for its potential interaction mechanism investigation.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum carmichaelii Debx. (Fuzi in Chinese) has been widely clinically used to treat heart failure and rheumatism. Whereas its serious toxicity, Radix et Rhizoma Glycyrrhizae (Gancao in Chinese) was combined with it as traditional Chinese medicine (TCM) herb-pair for toxicity reduction and pharmacological effect improvement. Though some previous viewpoints about that has been reported, the underlying interaction mechanism of two herbs remain unknown and definitely worthy of investigating. AIM OF STUDY: In present study, we focus on Fuzi-Gancao herb-pair precipitation (FGP), considering it related to the compatibility mechanism of Fuzi-Gancao herb-pair. The intestinal absorption and pharmacokinetic characters of 3 diester diterpenoid alkaloids in the precipitation were investigated. MATERIALS AND METHODS: Both everted gut sac model and in situ single-pass intestinal perfusion model were used to investigate rat small intestinal permeability and transport mechanism of aconitine, hypaconitine and mesaconitine. Moreover, by means of determination of the plasma concentration, the pharmacokinetic characters of 3 alkaloid compounds in rats have been developed. RESULTS: In everted gut sac permeability experiment, the permeability of hypaconitine appeared best in ileum. Furthermore, their uptakes were increased in the presence of P-glycoprotein (P-gp) inhibitors. In situ single-pass intestinal perfusion uptake experiment, results revealed that the transport mechanism may fit the active transport mechanism. And 3 alkaloids in FPG could be absorbed well in rats, fitting 2-compartment model with 1(st) order absorption and lag time. CONCLUSIONS: Our results in present study indicated that 3 diester diterpenoid alkaloids in FGP could be dissolved out in gastrointestinal tract firstly and then absorbed in blood after oral administration, which could result in prolonging their mean residence time and adding their absorbed doses, avoiding dose dumping. The current study has significant enlightenments for further investigation on the interaction mechanisms of other acid-base herb-pairs as well as Fuzi-Gancao herb-pair.

Three new triterpenoid saponins from Ilex pubescens.

Three new triterpene saponins, ilexsaponins D-F (1-3), were isolated from the roots of Ilex pubescens. Their structures were elucidated as 3-O-ß-D-glucopyranosyl(1 → 3)-α-L-arabinopyranosyl urs-12,18-diene-24,28-dioic acid 28-O-ß-D-glucopyranoside (1), 3-O-ß-D-glucopyranosyl(1 → 3)-α-L-arabinopyranosyl urs-12,18-diene-24,28-dioic acid (2), and 3-O-ß-D-glucopyranosyl(1 → 3)-α-L-arabinoyranosyl-30-hydroxyurs-12,19-diene-24,28-dioic acid 28-O-ß-D-glucopyranoside (3) on the basis of the chemical and spectroscopic evidence.

[Effect of different oxygen concentrations on biological properties of bone marrow hematopoietic stem cells of mice].

This study purposed to investigate the effects of different oxygen concentrations and reactive oxygen species (ROS) on the biological characteristics of hematopoietic stem cells (HSC) and their possible mechanisms through simulating oxygen environment to which the peripheral blood HSC are subjected in peripheral blood HSCT. The proliferation ability, cell cycle, directed differentiation ability, ROS level and hematopoietic reconstitution ability of Lin(-)c-kit(+)Sca-1(+) BMHSC were detected by using in vitro amplification test, directional differentiation test, cell cycle analysis, ROS assay and transplantation of Lin(-)c-kit(+)Sca-1(+) HSC from sublethally irradiated mice respectively. The results showed that oxygen concentrations lower than normal oxygen concentration, especially in hypoxic oxygen environment, could reduce ROS generation and amplify more primitive CD34(+)AC133(+) HSC and active CD34(+) HSC, and maintain more stem cells in the G(0)/G(1) phase, which is more helpful to the growth of CFU-S and viability of mice. At the same time, BMHSC exposed to normal oxygen level or inconstant and greatly changed oxygen concentrations could produce a high level of ROS, and the above-mentioned features and functional indicators are relatively low. It is concluded that ROS levels of HSC in BMHSCT are closely related with the oxygen concentration surrounding the cells and its stability. Low oxygen concentration and antioxidant intervention are helpful to transplantation of BMHSC.

N-Cyclo-hexyl-4-[(2-nitro-anilino)-meth-yl]thio-phene-2-sulfonamide.

In the title compound, C(17)H(21)N(3)O(4)S(2), an intra-molecular N-H⋯O hydrogen bond involving the proximate amine and nitro groups is observed. In the crystal, inter-molecular N-H⋯O hydrogen bonds involving the amine and SO(2) groups occur. One of the notro O atoms is disordered over two conformations with occupancies of 0.578 (12) and 0.422 (12).

Cytotoxic triterpene saponins from Clematis mandshurica.

Two new triterpene saponins, mandshunosides A and B (1 and 2), were isolated from the roots and rhizomes of Clematis mandshurica. Their structures were elucidated on the basis of spectroscopic evidence and hydrolysis products. Compounds 1 and 2 showed inhibitory activities against two colorectal human cancer cells HCT 116 (IC50 2.1 µM for 1 and 2.5 µM for 2) and HT-29 (IC50 3.7 µM for 1 and 3.3 µM for 2).

5-(1H-Indol-3-yl-methyl-idene)-2,2-di-methyl-1,3-dioxane-4,6-dione.

In the title compound, C(15)H(13)NO(4), the conjugated double-bond system between the two rings adopts a cis configuration and there is an intra-molecular indole-ketone C-H⋯O inter-action. The indole N-H group forms an inter-molecular hydrogen bond with a ketone O-atom acceptor, giving a chain structure along the ab direction. The O-heterocyclic ring adopts a boat conformation and makes a dihedral angle of 16.72 (6)° with the indole ring system.

2,2-Dimethyl-5-[(2-nitro-anilino)methyl-idene]-1,3-dioxane-4,6-dione.

The crystal of the title compound, C(13)H(12)N(2)O(6), contains a bifurcated intra-molecular hydrogen bond between the N-H group and one of the O atoms from both the nitro group and the dioxane-4,6-dione moiety. In addition, mol-ecules are linked by a series of inter-molecular C-H⋯O secondary inter-actions. The dihedral angles between the benzene ring and the nitro group and the conjugated part of the dioxane-4,6-dione moiety are 19.1 (2) and 17.89 (7)°, respectively.

[Studies on the chemical constituents of the flowers of Bupleurum chinese].

OBJECTIVE: To study the chemical constituents of the flowers of Bupleurum chinese. METHODS: The compounds were separated by column chromatography with silica gel. Their structures were identified by spectral methods and chemical analysis. RESULTS: Five compounds were isolated and identified as 8-(3',6'-dimethoxy)-4,5-cyclohexadiene-(delta11,12-dioxide-methylene) -dense-dihydrogen-isocoumarin(I), quercetin(II), rutin(III), calcifenol (IV), isorhamnetin (V). CONCLUSION: Compounds I and IV are obtained from the genus for the first time. Compound I is a new compound.

Tris(4-tert-butyl-phen-yl)phosphine oxide.

In the title compound, C(30)H(39)OP, the P=O bond length is 1.4866 (12) Šand the P-C bond lengths range from 1.804 (2) to 1.808 (13) Å. The molecle is located on a crystallographic mirror plane. The methyl groups of one tert-butyl group are disordered over two sites in a 0.776 (4):0.224 (4) ratio.