Recent advances in microfluidic technology of arterial thrombosis investigations.

Microfluidic technology has emerged as a powerful tool in studying arterial thrombosis, allowing researchers to construct artificial blood vessels and replicate the hemodynamics of blood flow. This technology has led to significant advancements in understanding thrombosis and platelet adhesion and aggregation. Microfluidic models have various types and functions, and by studying the fabrication methods and working principles of microfluidic chips, applicable methods can be selected according to specific needs. The rapid development of microfluidic integrated system and modular microfluidic system makes arterial thrombosis research more diversified and automated, but its standardization still needs to be solved urgently. One key advantage of microfluidic technology is the ability to precisely control fluid flow in microchannels and to analyze platelet behavior under different shear forces and flow rates. This allows researchers to study the physiological and pathological processes of blood flow, shedding light on the underlying mechanisms of arterial thrombosis. In conclusion, microfluidic technology has revolutionized the study of arterial thrombosis by enabling the construction of artificial blood vessels and accurately reproducing hemodynamics. In the future, microfluidics will place greater emphasis on versatility and automation, holding great promise for advancing antithrombotic therapeutic and prophylactic measures.

What is the context? To study the mechanism of arterial thrombosis, including the platelet adhesion and aggregation behavior and the coagulation process.Microfluidic technology is commonly used to study thrombosis. Microfluidic technology can simulate the real physiological environment on the microscopic scale in vitro, with high throughput, low cost, and fast speed.As an innovative experimental platform, microfluidic technology has made remarkable progress and has found applications in the fields of biology and medicine.What is new? This review summarizes the different fabrication methods of microfluidics and compares the advantages and disadvantages of these methods. Recent developments in microfluidic integrated systems and modular microfluidic systems have led to more diversified and automated microfluidic chips in the future.The different types and functions of microfluidic models are summarized. Platelet adhesion aggregation and coagulation processes, as well as arterial thrombus-related shear force changes and mechanical behaviors, were investigated by constructing artificial blood vessels and reproducing hemodynamics.Microfluidics can provide a basis for the development of personalized thrombosis treatment strategies. By analyzing the mechanism of action of existing drugs, using microfluidic technology for high-throughput screening of drugs and evaluating drug efficacy, more drug therapy possibilities can be developed.What is the impact?This review utilizes microfluidics to further advance the study of arterial thrombosis, and microfluidics is also expected to play a greater role in the biomedical field in the future.

Miniaturized ascorbic acid assay platform based on point discharge atomic emission spectrometry coupling with gold filament enrichment.

BACKGROUND: Miniaturized microplasma-based atomic emission spectrometry (AES) has been extensively used for element analysis in recent years due to the advantages of low power consumption, low gas consumption, relatively low manufacturing and running cost, and the potential for real-time and field analysis. However, few applications in bioassay detection have been reported based on microplasma AES systems because of their relatively low sensitivity and the absence of indirect analytical strategies. It is still a challenge to develop a simple, sensitive, and portable microplasma-based AES bioassay approach. RESULTS: In this work, a portable analytical system was designed based on point discharge chemical vapor generation atomic emission spectrometry (PD-CVG-AES) coupling with gold filament enrichment. The detection of ascorbic acid (AA) was realized indirectly by means of the highly sensitive analysis of Hg2+. The measurement was based on Ag + can decrease the concentration of Hg2+ by forming Ag-Hg amalgam in the presence of the reductant SnCl2, while AA can pre-reduce Ag + to Ag0, leading to the generation of silver nanoparticles (Ag NPs). The pre-reduce procedure can decrease the generation of Ag-Hg amalgam, resulting in the recovery of Hg2+ signal. The dissociative Hg2+ was further detected by PD-CVG-AES combination of gold filament enrichment, which significantly improved the detection sensitivity for both Hg2+ and AA. Under optimal conditions, the limit of detection (LOD) of AA is as low as 19 nM with a relative standard deviation (RSD, n = 5) of 0.7 %. SIGNIFICANCE: The developed novel analytical strategy obviously broadens the application of microplasma-based AES, and it is well demonstrated by the determination of AA in several traditional Chinese medicines (TCMs), offering a higher level of sensitivity compared to current AA detection techniques. It has potential for future application in point-of-care testing (POCT) assays.

Molecularly imprinted polymer sheathed mesoporous silica tube as SPME fiber coating for determination of tobacco-specific nitrosamines in water.

Tobacco-specific nitrosamines (TSNAs) are probably carcinogenic disinfection byproducts eliciting health risk concerns. The determination and surveillance of TSNAs in water is still cumbersome due to the lack of advanced sample preparation methods. Herein, we prepared a solid phase microextraction (SPME) fiber coated with the molecularly imprinted polymer (MIP) sheathed mesoporous silica tube (MST) composite material, and developed a highly efficient, selective, and sensitive method for the determination of five TSNAs in water. Benefiting from the TSNAs-specific recognition of MIP and the increased specific surface area derived from MST, the MIP@MST fiber exhibited excellent extraction performance for TSNAs, which was much superior to the commercially available SPME fibers. By coupling to high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), the outstanding analytical merits such as low method detection limits (ranging 0.1-6.7 ng L-1) and good reproducibility (intra-fiber and inter-fiber relative standard deviations ranging 4.1 %-11.6 % and 3.5 %-12.2 %, respectively) were achieved with the consumption of 8 mL water sample and 100 µL methanol solvent in 50 min. The feasibility of the SPME-HPLC-MS/MS method was demonstrated in tap water and chloraminated source water, with relative recoveries for the five TSNAs ranging from 85.2 % to 108.5 %. In result, none of the TSNAs were found in the tap water samples, while 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-Butanol (NNAL) were detected in the chloraminated source water samples. The rapid and convenient SPME-HPLC-MS/MS method developed in this study offers a powerful tool for monitoring TSNAs in water.

Sea-urchin-like covalent organic framework as solid-phase microextraction fiber coating for sensitive detection of trace pyrethroid insecticides in water.

Pyrethroid insecticides residues in water pose a critical threat to the environment from widespread production and overuse. Therefore, it is of major relevance to develop a sensitive and efficient method to detect pyrethroid insecticides in water. In this paper, a covalent organic framework (COF) with NHCO as the structural unit was synthesized using a simple condensation reaction of TTL (NH2) and TDBA (COOH). Various characterization results and density functional theory (DFT) calculations demonstrated that multiple interactions synergistically promoted the adsorption of pyrethroid insecticides on COFTDBA-TTL. Based on the excellent extraction capability of COFTDBA-TTL, efficient detection of 11 pyrethroid insecticides in water was achieved using COFTDBA-TTL-coated SPME fiber and gas chromatography-tandem mass spectrometry (GC-MS). The results showed that the extraction enhancement factors (EFs) of pyrethroid insecticides were as high as 2584-7199, and the extraction efficiencies were 3.28-446 times higher than that of commercial fiber, which reflected its high adsorption property. Meanwhile, the limits of detection (LODs) of the COFTDBA-TTL coated fiber were as low as 0.170-1.68 ng/L under the optimal conditions, and the recoveries of 11 pyrethroid insecticides in the actual water samples were 88.5-108 %. In conclusion, the SPME-GC-MS method based on COFTDBA-TTL coated fiber was simple, rapid, and efficient, and should have a promising application in trace detection of pyrethroid insecticides in the environment.

Validation of the 2018 FIGO Staging System for Predicting the Prognosis of Patients With Stage IIIC Cervical Cancer.

Background: Risk stratification of patients with cervical cancer accompanied by positive lymph nodes (stage IIIC) (the 2018 International Federation of Gynecology and Obstetrics [FIGO] new staging system) yields a clinically heterogeneous group. In this study, we investigated the prognostic performance of the 2018 FIGO staging system for stage IIIC cervical cancer. Methods: The study included patients with stage III cervical cancer based on the 2018 FIGO staging system, who visited Chongqing University Cancer Hospital between January 2011 and December 2014. Kaplan-Meier curves were generated to evaluate overall survival (OS), which was compared using the log-rank test. The Cox proportional hazard regression model was used for multivariable analysis. Results: A total of 418 patients were eligible for analysis. The 5-year OS was 54.1% for stage IIIC1, 43.3% for stage IIIA, 40.6% for stage IIIB, and 23.1% for stage IIIC2 (P < .001). Multivariable analysis revealed that compared with stages IIIA (hazard ratio [HR] 1.432, 95% confidence interval [CI] 0.867-2.366, P = .161) and IIIB (HR 1.261, 95% CI 0.871-1.827, P = .219), stage IIIC1 cancer was not significantly associated with an increased mortality risk. Stage IIIC2 was independently associated with an increased mortality risk compared with stages IIIA (HR 2.958, 95% CI 1.757-4.983, P < .001) and IIIB (HR 2.606, 95% CI 1.752-3.877, P < .001). We stratified patients with stage IIIC1 based on the T stage. The 5-year OS was significantly longer in patients with stage IIIC1 (T1) than in those with stage IIIA (P = .004) or IIIB (P < .001). Analysis of multiple factors revealed that the mortality risk was 2.75-fold higher in patients with stage IIIC1pN>2 than in patients with stage IIIC1pN1-2 (HR 2.753, 95% CI 1.527-4.965, P = .001). Conclusions: Patients with stage IIIC1 cervical cancer showed heterogeneous clinical characteristics that reflected variable prognoses, depending on the T stage and the extent of pelvic lymph node metastases.

Three new coumarins and a new coumarin glycoside from Micromelum integerrimum.

Three new coumarins, integmarins A-C (1-3), and a new coumarin glycoside, integmaside A (4) were isolated from the leaves and stems of Micromelum integerrimum. Their structures were elucidated on the basis of 1D and 2D NMR and MS data, and their absolute configurations were assigned according to the ECD data of the in situ formed transition metal complexes and comparison of experimental and calculated ECD data. Compounds 1 and 2 are two rare coumarins with butyl and propyl moieties at the C-6 position; compound 3 is a novel coumarin with a highly oxidized prenyl group, and compound 4 is a rare bisdihydrofuranocoumarin glycoside.

miR-30a-5p targets Becn1 to ameliorate high-glucose-induced glomerular podocyte injury in immortalized rat podocyte cell line.

OBJECTIVE: Diabetic nephropathy (DN) is a serious kidney-based complication of diabetes, wherein podocyte injury is deemed crucial in the development of early stage. Various miRNAs, as report goes, is involved in the pathogenesis of varieties of kidney diseases including DN. In this study, we found a target relationship between miR-30a-5p and Becn1, of which there are few studies about the role in podocyte injury. We therefore used immortalized rat podocyte cell line to explore the role and molecular mechanism of miR-30a-5p targeting Becn1 gene in high-glucose-induced glomerular podocyte injury. METHODS: The mRNA and protein expressions of miR-30a-5p and Becn1 were detected respectively by quantitative reverse transcriptase PCR and western blotting. The proliferation, apoptosis, and the levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were detected by MTT assay, flow cytometry, and enzyme-linked immuno sorbent assay, respectively. Intracellular reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were also determined. RESULTS: Compared with normal group, miR-30a-5p in model groups were down-regulated, while Becn1 expression was significantly up-regulated, with slower proliferation, higher apoptosis rate, lower SOD level, and significantly higher ROS, MDA, IL-6, and TNF-α levels (all P<0.05). Overexpression of miR-30a-5p or Becn1 knock-out could lower Becn1 expression, apoptosis rate, promote proliferation, with relatively higher SOD level and lower ROS, MDA, Il-6, and TNF-α levels of model cells (all P<0.05). CONCLUSION: Up-regulation of miR-30a-5p can suppress the expression of Becn1 to increase the growth and inhibit the apoptosis of immortalized rat podocyte cell line, therefore ameliorating podocyte injury induced by high glucose in vitro.

A new prenylated coumarin diglycoside with insulin-release promoting activity from Clausena dunniana.

A new prenylated coumarin diglycoside, 6-prenylcoumarin-7-O-ß-D-apiofuranosyl-(1→6)-ß-D-glucopyranoside (1) and five known flavonoid glycosides (2-6) were isolated from the leaves and stems of Clausena dunniana. The structures of these isolates were elucidated based on comprehensive MS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature. Compounds 2-6 are obtained from the title plant for the first time. All these isolates were evaluated for their insulin-release promoting effects, and compounds 1, 2, and 4 exhibited significant activities (2.0 to 3.3-fold higher in comparison with the control, p < 0.01) at 40 µM.[Formula: see text].

Isolation and structure characterization of cytotoxic alkaloids from Micromelum integerrimum.

Ten undescribed alkaloids, named integerrines A-J, including one racemic heterodimer of carbazole and indole, two racemic, two scalemic, and one enantiomerically enriched biscarbazoles, two aldoximes, and one racemic pyrrolone, were isolated from the dried leaves and stems of Micromelum integerrimum. The racemic or scalemic compounds were resolved using chiral-phase HPLC and their configurations were determined by comparison of experimental and calculated ECD data. Four compounds exhibited moderate to weak cytotoxicities against HepG2, HTC-116, HeLa, and PANC-1 cell lines, with IC50 values of 14.1-67.5 µM.

CO2 Capture With Absorbents of Tertiary Amine Functionalized Nano-SiO2.

To improve CO2 adsorption performance of nanoparticle absorbents, a novel tertiary amine functionalized nano-SiO2 (NS-NR2) was synthesized based on the 3-aminopropyltrimethoxysilane (KH540) modified nano-SiO2 (NS-NH2) via methylation. The chemical structure and performances of the NS-NR2 were characterized through a series of experiments, which revealed that NS-NR2 can react with CO2 in water and nanofluid with low viscosity revealed better CO2 capture. The CO2 capture mechanism of NS-NR2 was studied by kinetic models. From the correlation coefficient, the pseudo second order model was found to fit well with the experiment data. The influencing factors were investigated, including temperature, dispersants, and cycling numbers. Results has shown the additional surfactant to greatly promote the CO2 adsorption performance of NS-NR2 because of the better dispersity of nanoparticles. This work proved that NS-NR2 yields low viscosity, high capacity for CO2 capture, and good regenerability in water. NS-NR2 with high CO2 capture will play a role in storing CO2 to enhanced oil recovery in CO2 flooding.

Anti-inflammatory and cytotoxic carbazole alkaloids from Murraya kwangsiensis.

Chemical investigation of the traditional Chinese medicine, Murraya kwangsiensis, led to the isolation of 16 undescribed biscarbazole alkaloids, kwangsines A-M, two undescribed natural products, (+/-)-bispyrayafoline C, and 19 known monomeric analogues. (±)-Bispyrayafoline C and (±)-kwangsines A-C are four pairs of biscarbazole atropisomers, and they were separated by chiral HPLC to obtain the optically pure compounds. The structures of the undescribed compounds were elucidated on the basis of HRESIMS and NMR data analysis. Their absolute configurations were assigned via comparison of the specific rotation, ECD exciton coupling method, as well as comparison of experimental and calculated ECD data. A compound showed significant inhibition on NO production in lipopolysaccharide-stimulated BV-2 microglial cells, and four compounds exhibited moderate cytotoxicities against HepG2 cells, with IC50 values less than 20 µM.

[Famous veteran traditional Chinese medicine doctors' medication rules in treating spermatorrhea].

To explore famous veteran traditional Chinese medicine( TCM) doctors' medication rules in treating spermatorrhea based on the medical cases about spermatorrhea collected from Hundred TCM Clinical Doctors of Hundred Years in China and Proven Cases and National Medical Master Test Case. Researchers extracted such data as medicinal and therapies from these cases according to the inclusion and exclusion criteria. Then,Excle 2010,SPSS Clementine 12. 0 and SPSS 22. 0 were adopted respectively for frequency analysis,association rules analysis,cluster analysis and factor analysis. Cluster analysis was carried out by Ochiai algorithm of binary variable data,one of the systematic clustering methods. And principal component analysis was used for factor analysis. Finally,27 medical cases and 41 prescriptions were included in total. The frequency analysis showed that the most common therapy was the astringent therapy( n = 28),which was followed by the tonifying method,tranquilizing method,heat-clearing method,damp-dispelling method and Qiregulating method. The top three kinds of high-frequency traditional Chinese medicines were Poria,Ostreae Concha and Dioscoreae Rhizoma. The association rules analysis found out 11 association rules of medicine pairs,23 association rules of medicine combinations of the three kinds of herbs and 6 association rules of medicine combinations of five kinds of herbs. Among them,the representatives were Rubi Fructus→Fossilia Ossis Mastodi,Rehmanniae Radix Praeparata + Corni Fructus→Dioscoreae Rhizoma,and Pinelliae Rhizoma→Citri Reticulatae Pericarpium,which showed the therapeutic characteristics of astringing,tonifying the kidney and replenishing essence,fortifying the spleen and dispelling dampness. Moreover,7 medicine groups with relevance were extracted from the tree map generated by cluster analysis,including " Phellodendri Chinensis Cortex and Anemarrhenae Rhizoma" and " Angelicae Sinensis Radix,Rehmanniae Radix,Bupleuri Radix and Glycyrrhizae Radix et Rhizoma",which demonstrated the effects of nourishing Yin and purging fire,tonifying and soothing the liver. Besides,totally 12 common factors were obtained according to factor analysis,including 14 drug combinations,like " Amomi Fructus,Anemarrhenae Rhizoma and Phellodendri Chinensis Cortex" and " Nelumbinis Stamen,Moutan Cortex,Poria and Scrophulariae Radix",which indicated the compatibility characteristics of tonifying the spleen and purging fire,dispelling dampness and clearing heat. In conclusion,data mining techniques( including frequency analysis,association rules analysis,cluster analysis and factor analysis) were used to comprehensively analyze the famous veteran TCM doctors' medication rules in treating spermatorrhea,which was helpful for guiding the clinical practice of treating spermatorrhea in TCM.

Nitric oxide inhibitory coumarins from the roots and rhizomes of Notopterygium incisum.

Phytochemical study on the roots and rhizomes of Notopterygium incisum resulted in the isolation of six new coumarins, notoptetherins A - F (1-6), and 20 known analogues (7-26). Their structures were elucidated on the basis of extensive analyses of NMR and HRMS data, and the absolute configurations of 5 and 6 were established by Mo2(AcO)4-induced CD and exciton chirality, respectively. Moreover, a biomimetic synthesis of 6 from 21 was employed to confirm its absolute configuration. In a subsequent activity screening, compounds 12 and 17 exhibited potent inhibition against LPS-induced nitric oxide production in RAW 264.7 cells with IC50 values of 12.7 and 10.2 µM, respectively.

Bioactive carbazole and quinoline alkaloids from Clausena dunniana.

Nine undescribed carbazole and quinoline alkaloids, named dunnines A-E, and 14 known analogues were isolated from the leaves and stems of Clausena dunniana. Their structures were elucidated on the basis of comprehensive analysis of NMR and HRMS spectroscopic data, and the absolute configurations were assigned via comparison of their specific rotations and calculated and experimental ECD data. (±)-Dunnines A-C and (±)-clausenawalline A are four pairs of biscarbazole atropisomers and (±)-dunnine D is a pair of dihydropyranocarbazole enantiomers. They were separated by chiral HPLC to obtain the optically pure compounds. Three compounds showed weak inhibitory effects on nitric oxide production stimulated by lipopolysaccharide in BV-2 microglial cells (IC50 > 50 µM); five compounds could significantly promote insulin secretion in HIT-T15 cell line (1.9-3.1-fold of the control, p < 0.01) at 40 µM, and nine compounds could inhibit the apoptosis of PC12 cell induced by 6-hydroxydopamine with IC50 values in the range of 10.9-47.2 µM.

Development of diagnostic criteria and a prognostic score for hepatitis B virus-related acute-on-chronic liver failure.

OBJECTIVE: The definition of acute-on-chronic liver failure (ACLF) based on cirrhosis, irrespective of aetiology, remains controversial. This study aimed to clarify the clinicopathological characteristics of patients with hepatitis B virus-related ACLF (HBV-ACLF) in a prospective study and develop new diagnostic criteria and a prognostic score for such patients. DESIGN: The clinical data from 1322 hospitalised patients with acute decompensation of cirrhosis or severe liver injury due to chronic hepatitis B (CHB) at 13 liver centres in China were used to develop new diagnostic and prognostic criteria. RESULTS: Of the patients assessed using the Chronic Liver Failure Consortium criteria with the exception of cirrhosis, 391 patients with ACLF were identified: 92 with non-cirrhotic HBV-ACLF, 271 with cirrhotic HBV-ACLF and 28 with ACLF with cirrhosis caused by non-HBV aetiologies (non-HBV-ACLF). The short-term (28/90 days) mortality of the patients with HBV-ACLF were significantly higher than those of the patients with non-HBV-ACLF. Total bilirubin (TB) ≥12 mg/dL and an international normalised ratio (INR) ≥1.5 was proposed as an additional diagnostic indicator of HBV-ACLF, and 19.3% of patients with an HBV aetiology were additionally diagnosed with ACLF. The new prognostic score (0.741×INR+0.523×HBV-SOFA+0.026×age+0.003×TB) for short-term mortality was superior to five other scores based on both discovery and external validation studies. CONCLUSIONS: Regardless of the presence of cirrhosis, patients with CHB, TB ≥12 mg/dL and INR ≥1.5 should be diagnosed with ACLF. The new criteria diagnosed nearly 20% more patients with an HBV aetiology with ACLF, thus increasing their opportunity to receive timely intensive management.

[Chemical constituents from Murraya euchrestifolia].

The open silica gel, ODS, and Sephadex LH-20 column chromatography, along with the semi-preparative HPLC was used to isolate and purify the chemical constituents from Murraya euchrestifolia. The structures of the isolates were elucidated by their physiochemical properties, NMR, and MS spectroscopic data, as well as comparison with literature data. Eighteen compounds were isolated from the CH2Cl2 fraction of the 95% aqueous EtOH extract of M. euchrestifolia, and their structures were identified as sakuranetin (1), eriodictyol-7,4'-dimethyl ether (2), isosakuranetin (3), 5-hydroxy-7,4'-dimethoxyflavanone (4), eriodictyol-7-methyl ether (5), lichexanthon (6), 5,6,7-trimethoxycoumarin (7), 5-hydroxy-6,8-dimethoxycoumarin (8), 8-hydroxy-6-methoxy-3-n-pentylisocoumarin (9), ethyl caffeate (10), 4-hydroxy-3,5- dimethoxycinnamic acid ethyl ester (11), methyl 3-(5'-hydroxyprenyl)-coumarate (12), (E)-coniferol (13), ß-hydroxypropiovanillone (14), 3-hydroxy-7,8-didehydro-ß-ionone (15), 3ß-hydroxy-5α, 6α-epoxy-7-megastigmen-9-one (16), grasshopper ketone (17), and 4-hydroxy-3,5-dimethoxybenzaldehyde (18). Compounds 1-15 and 18 were first obtained from the plants of Murraya genus, and compounds 16 and 17 were isolated from M. euchrestifolia for the first time.

Serum C-reactive protein predicts early mortality in hospitalized patients with HBV-related decompensated cirrhosis.

The serum C-reactive protein (CRP) is an inflammatory marker. The aim of the present study was to elucidate whether CRP could serve as a potential surrogate marker for 30-day mortality in hospitalized patients with HBV-related decompensated cirrhosis (HBV-DeCi).This was a retrospective cohort study that included 140 patients with HBV-DeCi. All patients were followed up for 1-month. A panel of clinical and biochemical variables were analyzed for potential associations with outcomes using multiple regression models.The serum CRP was significantly higher in nonsurviving patients than in surviving patients. Multivariate analysis demonstrated that CRP levels (odds ratio: 1.047, P = 0.002) and the model for end-stage liver disease score (odds ratio: 1.370, P = 0.001) were independent predictors for mortality.Serum CRP is a simple marker that may serve as an additional predictor of 1-month mortality in hospitalized patients with HBV-DeCi.

Lymphocyte-monocyte ratio at admission predicts possible outcomes in patients with acute-on-chronic liver failure.

BACKGROUND: The lymphocyte-monocyte ratio (LMR) in the peripheral blood is suggested to be a potential biomarker for predicting the clinical outcomes of several diseases. We aimed to evaluate the relative efficiency of LMR for predicting 3-month mortality in patients with acute-on-chronic liver failure (AoCLF). PATIENTS AND METHODS: In this study, 74 chronic hepatitis B patients, 90 AoCLF patients, and 70 healthy controls were followed up for 4 months. The primary endpoint was 3-month in-hospital mortality. Hematological and virological parameters as well as liver biochemistry were determined using blood samples ordered upon admission. A panel of clinical and biochemical variables were analyzed for potential associations with outcomes using Cox proportional hazards and multiple regression models. RESULTS: A significantly lower LMR was detected in AoCLF patients than in healthy controls and chronic hepatitis B groups (both P=0.001). The LMR inversely correlated with model for end-stage liver disease scores, and a lower LMR was associated with increased 3-month mortality. Multivariate analysis suggested that both LMR and model for end-stage liver disease scores were independent predictors of 3-month mortality (P<0.01). CONCLUSION: A low LMR measured at admission is predictive of a poor prognosis in AoCLF patients.

Tenuifolin, a saponin derived from Radix Polygalae, exhibits sleep-enhancing effects in mice.

BACKGROUND: Radix Polygalae, the dried root of Polygala tenuifolia, has been extensively used as a traditional Chinese medicine for promoting intelligence and tranquilization. Polygalasaponins extracted from the root of P. tenuifolia possess evident anxiolytic and sedative-hypnotic activities. Previous studies have reported that tenuifolin was a major constituent of polygalasaponins. PURPOSE: The currently study aims to investigate the hypnotic effect and possible mechanism of tenuifolin in freely moving mice. DESIGN/METHODS: The hypnotic effects of tenuifolin (20, 40 and 80mg/kg, p.o.) were assessed by electroencephalographic (EEG) and electromyographic (EMG) analysis. Double-staining immunohistochemistry test was performed to evaluate the neuronal activity of sleep-wake regulating brain areas. High performance liquid chromatograph- electrochemical detection (HPLC-ECD) and ultrafast liquid chromatography-mass spectrometry (UFLC-MS) were used for the detection of neurotransmitters. Locomotor activity was measured by Open-field Test. RESULTS: Tenuifolin at doses of 40 and 80mg/kg (p.o.) significantly prolonged the total sleep time by increasing the amount of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, associated with the significant increase in the bouts of episodes respectively. After administration of tenuifolin, the cortical EEG power spectral densities during NREM and REM sleep were similar to that of natural sleep (vehicle) and thus compatible with physiological sleep. Double-immunohistochemistry staining test showed that tenuifolin increased the c-Fos positive ratios of GABAergic NREM sleep-promoting neurons in ventrolateral preoptic area (VLPO), cholinergic REM sleep-promoting neurons in laterodorsal tegmental area (LDT) and pontomesencephalic tegmental area (PPT) and decreased the c-Fos positive ratios in wake-promoting neurons (locus coeruleus (LC) and perifornical area (Pef)). Neurotransmitter detections revealed that tenuifolin significantly reduced the noradrenaline (NA) levels in LC, VLPO, PPT and LDT, elevated the GABA levels in VLPO, LC and Pef and increased the acetylcholine (Ach) levels in LDT and PPT. In addition, tenuifolin did not cause any change to locomotor activity. CONCLUSION: Taken together, these results provide the first experimental evidence of the significant sleep-enhancing effect of tenuifolin in mice. This effect appears to be mediated, at least in part, by the activation of GABAergic systems and/or by the inhibition of noradrenergic systems. Moreover, this study adds new scientific evidence and highlights the therapeutic potential of the medicinal plant P. tenuifolia in the development of phytomedicines with hypnotic properties.