The success rate of cannulation of needle-knife precut is superior to continuing wire-guided after difficult biliary cannulation with pancreatic stent placement.

BACKGROUND: Difficult biliary cannulation and unintended pancreatic cannulation exist in biliary interventions during endoscopic retrograde cholangiopancreatography. Wire-guided cannulation over a pancreatic stent (PS-WGC) and needle-knife precut over a pancreatic stent (PS-NKP) may facilitate biliary cannulation. This study aimed to compare the outcomes of PS-NKP and PS-WGC following guidewire passage into the pancreatic duct. METHODS: A total of 304 patients who inserted a pancreatic stent and continued cannulation using wire-guided (PS-WGC) or needle-knife precut (PS-NKP) from October 2018 to November 2021 in three centers were ultimately enrolled in this study. The success rate of cannulation and incidence of complications were compared between the two groups. RESULTS: Results of the success rate of cannulation in the PS-NKP (n = 98) group were significantly higher compared with the PS-WGC (n = 206) group (96.9% vs. 89.8%; P < 0.05). The overall adverse events were 10.2% (31/304), and PS-NKP had lower (PEP) rates compared with the PS-WGC (3.1% vs. 10.7%, P < 0.05). CONCLUSION: The PS-NKP group is superior to the PS-WGC group in terms of the effectiveness and safety of continued cannulation. Using needle-knife precut, especially early use, over the pancreatic stent to continue cannulation reduced PEP compared with PS-WGC.

Characteristics and Evolution of Nitrogen in the Heavy Components of Algae Pyrolysis Bio-Oil.

Algae pyrolytic bio-oil contains a large quantity of N-containing components (NCCs), which can be processed as valuable chemicals, while the harmful gases can also be released during bio-oil upgrading. However, the characteristics of NCCs in the bio-oil, especially the composition of heavy NCCs (molecular weight ≥200 Da), have not been fully studied due to the limitation of advanced analytical methods. In this study, three kinds of algae rich in lipids, proteins, and carbohydrates were rapidly pyrolyzed (10-25 °C/s) at different temperatures (300-700 °C). The bio-oil was analyzed using a Fourier transform ion cyclotron resonance mass spectrometer equipped with electrospray ionization, and the characteristics and evolution of nitrogen in heavy components were first obtained. The results indicated that the molecular weight of most heavy NCCs was distributed in the 200-400 Da range. N1-3 compounds account for over 60% in lipid and protein-rich samples, while N0 and N4 components are prominent in carbohydrate-rich samples. As temperature increases, most NCCs become more aromatic and contain less O due to the strong Maillard and deoxygenation reactions. Moreover, the heavier NCCs were promoted to form lighter compounds with more nitrogen atoms through decomposition (mainly denitrogenation and deoxygenation). Finally, some strategies to deal with the NCCs for high-quality bio-oil production were proposed.

Effects of Moringa oleifera leaf extract on growth performance, physiological and immune response, and related immune gene expression of Macrobrachium rosenbergii with Vibrio anguillarum and ammonia stress.

In order to study the effects of Moringa oleifera leaf extract on Macrobrachium rosenbergii under high ammonia exposure, freshwater prawns were randomly divided into five groups: a control group was fed with basal diet, and four treatment groups fed with basal diet supplemented with 0.25%, 0.5% and 1.0% M. oleifera leaf extract and 0.025% Enrofloxacin for 60 days, respectively. Then, freshwater prawns were exposed to high ammonia stress for 72 h and Vibro anguillarum infection. The growth, antioxidant capabilities, related immune genes as well as resistance to infection by V. anguillarum were determined. The results showed that compared with the control group, the weight gain, specific growth rate and protein efficiency rate, haemolymph catalase (CAT), superoxide dismutase (SOD) and inducible nitric oxide synthase (iNOS) increased while feed conversion ratio, haemolymph aspartate aminotransferase, alanine aminotransferase, nitrogen oxide (NO), hepatopancreas heat shock proteins (HSP70), immune deficiency (IMD) expression levels decreased in the group of 0.5% M. oleifera leaf extract before the stress. After ammonia stress, the group of 0.5% M. oleifera leaf extract also could improve the haemolymph SOD, glutathione peroxidase, NO, iNOS, hepatopancreas HSP70 expression levels and reduce haemolymph CAT, hepatopancreas peroxiredoxin 5 and NF kappa B inhibitor alpha expression level compared with the control group. The rate of mortality of the prawns challenged with V. anguillarum was lower in the supplemented groups in comparison with the control group with the lowest being in the group of 0.5% M. oleifera leaf extract. Antioxidant activities as well as biochemical parameters in the enrofloxacin group (0.025%E) were not significantly enhanced both pre and post challenge in comparison with the M. oleifera leaf extract groups, showing the superiority of the natural herb over the synthetic antibiotic. In summary, this study suggested that at an inclusion rate of 0.5%, M. oleifera leaf extract could increase the growth performance, even has positive effects on physiological and immune function and prevents high ammonia stress in the Freshwater prawn, M.rosenbergii.

Mean peak systolic velocity of superior thyroid artery for the differential diagnosis of thyrotoxicosis: a diagnostic meta-analysis.

BACKGROUND: Thyrotoxicosis is often caused by destructive thyroiditis (DT) or Graves' disease (GD), and a prompt and accurate differential diagnosis for thyrotoxicosis is needed as management strategy differs. A meta-analysis of published literature was performed to evaluate the diagnostic accuracy for differentiating GD from DT patients by the measurement of mean peak systolic velocity of superior thyroid artery (STA-PSV) using ultrasonography. METHODS: The databases of Embase, Pubmed, Cochrane, Web of Science, Wanfang, and CNKI were retrieved without time limit to identify eligible studies. The statistical information and scientific quality were assessed and classified. The data were analyzed using Stata12.0 software. RESULTS: A total of 11 studies with 1052 cases only from Asia were included. Meta-analysis results showed the pooled sensitivity and pooled specificity of STA-PSV by ultrasonography were 0.86 (95% CI, 0.80-0.90) and 0.93 (95% CI, 0.86-0.97) in distinguishing GD from DT, respectively, with the AUC of 0.94 (95% CI, 0.92-0.96) . CONCLUSION: STA-PSV by ultrasonography is a useful diagnostic method in differentiating GD from DT. More studies from other countries are needed to further evaluate the accuracy of STA-PSV for the differential diagnosis of thyrotoxicosis.

[Serum anti-Müllerian hormone level for differential diagnosis of obstructive and non-obstructive azoospermia].

OBJECTIVE: To determine whether the serum anti-Müllerian hormone (AMH) level can be used as a serum marker for the differential diagnosis of obstructive azoospermia (OA) and non-obstructive azoospermia (NOA). METHODS: Using chemiluminescence immunoassay, we detected the levels of serum AMH, inhibin B (IhB) and follicle stimulating hormone (FSH) and measured by scrotal ultrasound the testis volume of 43 normal fertile men and 14 OA and 45 NOA male patients, followed by a comparative analysis of the data obtained among the three groups subjects. RESULTS: Compared with the NOA patients, the men in the normal control and OA groups showed significantly higher levels of AMH (ï¼»5.65 ± 3.13ï¼½ vs ï¼»8.13 ± 3.95ï¼½ and ï¼»8.51 ± 4.77ï¼½ ng/ml, P < 0.05) and InH (ï¼»25.98±16.29ï¼½ vs ï¼»127.38 ± 40.5ï¼½ and ï¼»131.25 ± 52.3ï¼½ pg/ml, P < 0.01), but a lower level of FSH (ï¼»19.87 ± 13.09ï¼½ vs ï¼»4.22 ± 3.23ï¼½ and ï¼»4.54 ± 2.09ï¼½ IU/L, P < 0.01), none with statistically significant difference between the latter two groups (P > 0.05). Pearson correlation analysis exhibited that the level of IhB was correlated positively with that of AMH (r = 0.326, P = 0.01) but negatively with that of FSH (r =－0.662, P < 0.01), the FSH level negatively with the AMH level (r = －0.468, P < 0.01), the testis volume positively with the levels of AMH (r = 0.339, P < 0.01) and IhB (r = 0.733, P < 0.01) but negatively with that of FSH (r = 0.597, P < 0.01), the sperm concentration positively with that of IhB (r = 0.522, P < 0.01) but negatively with that of FSH (r = －0.421, P < 0.01), and the testis volume positively with the sperm concentration (r = 0.605, P < 0.01). CONCLUSIONS: AMH can be used as one of the serum markers for testicular spermatogenesis and employed alone or in combination with IhB and FSH for the differential diagnosis of OA and NOA.

Acute stress enhances learning and memory by activating acid-sensing ion channels in rats.

Acute stress has been shown to enhance learning and memory ability, predominantly through the action of corticosteroid stress hormones. However, the valuable targets for promoting learning and memory induced by acute stress and the underlying molecular mechanisms remain unclear. Acid-sensing ion channels (ASICs) play an important role in central neuronal systems and involves in depression, synaptic plasticity and learning and memory. In the current study, we used a combination of electrophysiological and behavioral approaches in an effort to explore the effects of acute stress on ASICs. We found that corticosterone (CORT) induced by acute stress caused a potentiation of ASICs current via glucocorticoid receptors (GRs) not mineralocorticoid receptors (MRs). Meanwhile, CORT did not produce an increase of ASICs current by pretreated with GF109203X, an antagonist of protein kinase C (PKC), whereas CORT did result in a markedly enhancement of ASICs current by bryostatin 1, an agonist of PKC, suggesting that potentiation of ASICs function may be depended on PKC activating. More importantly, an antagonist of ASICs, amiloride (10 µM) reduced the performance of learning and memory induced by acute stress, which is further suggesting that ASICs as the key components involves in cognitive processes induced by acute stress. These results indicate that acute stress causes the enhancement of ASICs function by activating PKC signaling pathway, which leads to potentiated learning and memory.

Metabolite profiling of ginsenosides in rat plasma, urine and feces by LC-MS/MS and its application to a pharmacokinetic study after oral administration of Panax ginseng extract.

Panax ginseng is widely consumed as a functional food in the form of tea, powder, capsules, among others, and possesses a range of pharmacological activities including adaptogenic, immune-modulatory, anti-tumor, anti-aging and anti-inflammatory effects. The aim of this study was to identify and quantify the major ginsenosides and their metabolites in rat plasma, urine and feces after administration of P. ginseng extract using LC-MS/MS. We collected rat plasma samples at 0.5, 1, 2, 4, 8, 12, 24 and 48 h, and the amounts of urine and fecal samples accumulated in 24 h. Fourteen major ginsenosides and their metabolites were observed in fecal samples at high levels; however, low levels of 11 ginsenosides were detected in urine samples. The pharmacokinetics of the major ginsenosides and their metabolites was investigated in plasma. The results indicated that the maximum plasma concentration, time to maximum concentration and area under the curve of compound K were significantly greater than those of other ginsenosides. This study thus provides valuable information for drug development and clinical application of P. ginseng.

Histone Modification of Nedd4 Ubiquitin Ligase Controls the Loss of AMPA Receptors and Cognitive Impairment Induced by Repeated Stress.

Stress and the major stress hormone corticosterone induce profound influences in the brain. Altered histone modification and transcriptional dysfunction have been implicated in stress-related mental disorders. We previously found that repeated stress caused an impairment of prefrontal cortex (PFC)-mediated cognitive functions by increasing the ubiquitination and degradation of AMPA-type glutamate receptors via a mechanism depending on the E3 ubiquitin ligase Nedd4. Here, we demonstrated that in PFC of repeatedly stressed rats, active glucocorticoid receptor had the increased binding to the glucocorticoid response element of histone deacetylase 2 (HDAC2) promoter, resulting in the upregulation of HDAC2. Inhibition or knock-down of HDAC2 blocked the stress-induced impairment of synaptic transmission, AMPAR expression, and recognition memory. Furthermore, we found that, in stressed animals, the HDAC2-dependent downregulation of histone methyltransferase Ehmt2 (G9a) led to the loss of repressive histone methylation at the Nedd4-1 promoter and the transcriptional activation of Nedd4. These results have provided an epigenetic mechanism and a potential treatment strategy for the detrimental effects of chronic stress. SIGNIFICANCE STATEMENT: Prolonged stress exposure can induce altered histone modification and transcriptional dysfunction, which may underlie the profound influence of stress in regulating brain functions. We report an important finding about the epigenetic mechanism controlling the detrimental effects of repeated stress on synaptic transmission and cognitive function. First, it has revealed the stress-induced alteration of key epigenetic regulators HDAC2 and Ehmt2, which determines the synaptic and behavioral effects of repeated stress. Second, it has uncovered the stress-induced histone modification of the target gene Nedd4, an E3 ligase that is critically involved in the ubiquitination and degradation of AMPA receptors and cognition. Third, it has provided the epigenetic approach, HDAC2 inhibition or knock-down, to rescue synaptic and cognitive functions in stressed animals.

Tissue-specific inhibition of urokinase-type plasminogen activator expression in the testes of mice by inducible lentiviral RNA interference causes male infertility.

Urokinase-type plasminogen activator (uPA) is involved in many physiological processes, including male infertility. To explore the effects of uPA in male reproduction, we constructed an inducible uPA short hairpin RNA (shRNA) system expressed by lentiviral vectors. After proving inhibition of uPA expression in the mouse Sertoli cell line TM4 by 1µgmL-1 doxycycline (Dox), two lentivirus (pLenti4-shRNA and pLenti6/TR) were co-microinjected into mouse testes to produce TetR&shuPA mice model. Though oral gavage by 0.75mgmL-1 Dox each day for 1 week, the Plau mRNA expression, uPA protein level and uPA enzyme activity in mice testis decreased significantly in TetR&shuPA mice model. After Dox induction of 1 week, the TetR&shuPA mice mated with female mice. Our results show that the pregnancy rate was reduced by approximately 40% and the sperm motility also decreased significantly. These data indicated that downregulation of uPA could decrease the fertility of male mice, which may be caused by a reduction in sperm motility. To investigate the reversible effect and safety of the inducible uPA shRNA system, we withdraw Dox and found the mating rate and sperm motility gradually recovered after 2 weeks. The histopathology structure of the testis, epididymis, and main organs was not altered significantly. The results of the present study indicating that uPA may be regarded as a novel target for the regulation of male fertility.

Inhibitory effects of capsaicin on voltage-gated potassium channels by TRPV1-independent pathway.

Previously we observed that capsaicin, a transient receptor potential vanilloid 1 (TRPV1) receptor activator, inhibited transient potassium current (IA) in capsaicin-sensitive and capsaicin-insensitive trigeminal ganglion (TG) neurons from rats. It suggested that the inhibitory effects of capsaicin on IA have two different mechanisms: TRPV1-dependent and TRPV1-independent pathways. The main purpose of this study is to further investigate the TRPV1-independent effects of capsaicin on voltage-gated potassium channels (VGPCs). Whole cell patch-clamp technique was used to record IA and sustained potassium current (IK) in cultured TG neurons from trpv1 knockout (TRPV1(-/-)) mice. We found that capsaicin reversibly inhibited IA and IK in a dose-dependent manner. Capsaicin (30 µM) did not alter the activation curve of IA and IK but shifted the inactivation-voltage curve to hyperpolarizing direction, thereby increasing the number of inactivated VGPCs at the resting potential. Administrations of high concentrations capsaicin, no use-dependent block, and delay of recovery time course were found on IK and IA. Moreover, forskolin, an adenylate cyclase agonist, selectively decreased the inhibitory effects of IK by capsaicin, whereas none influenced the inhibitions of IA. These results suggest that capsaicin inhibits the VGPCs through TRPV1-independent and PKA-dependent mechanisms, which may contribute to the capsaicin-induced nociception.

Water extract of the fungi from Fuzhuan brick tea improves the beneficial function on inhibiting fat deposition.

Fuzhuan brick tea (FBT) is traditionally consumed by the ethnic group in the border region of northwest China. The unique yellow fungal (Eurotium cristatum) growth phase is considered to be the key process point in the manufacture of the brick tea. The fungi from FBT are not only strongly correlated to the quality of brick tea, but also have the potential function of preventing obesity. The water extract of fungi (100 µg/mL) can significantly inhibit fat deposition in 3T3-L1 adipocyte and Caenorhabditis elegans. Furthermore, the inhibition of 3T3-L1 adipocyte formation was not due to the suppression on cell viability.

n-Butanol extract of Rhynchosia volubilis Lour: a potent spermicidal agent In Vitro.

Rhynchosia volubilis Lour has been a major drug in a folk prescription for contraception in China, whereas its mechanism remains unknown. Its antifertility effects on male mice and antimicrobial activities on sexually transmitted infection (STI) pathogens were previously reported. This study was undertaken to develop the n-Butanol extract of Rhynchosia volubilis Lour (BERVL) as a spermicidal agent with STI prevention. The spermicidal activities of BERVL with different doses were assessed using selected high-motile sperms of normal human semen samples, and their inhibitory effects on Lactobacillus acidophilus were determined. The mechanism of the spermicidal activity was explored by aqueous Eosin Y and Hoechst 33342/PI staining. The results showed spermicidal activities and inhibitory effects of BERVL on Lactobacillus acidophilus were dose-dependent. Dose of 90 mg/mL BERVL terminated all progressive sperm motility within 2 min, and had slight inhibitory effect on Lactobacillus acidophilus, suggesting it was an effective and safe dose for contraception use. About 80% sperms exposed to BERVL displayed changes consistent with high permeability of head membrane. It is concluded that BERVL as spermicide has advantages over N-9 with strong ability to instantaneously kill human sperm and possesses light inhibitory effect on Lactobacillus acidophilus.

The influence of resistance exercise and aerobic exercise on type 2 diabetes: a meta-analysis.

INTRODUCTION: Diabetes is a worldwide chronic disease. The incidence rate of this disease is high, and it is a common disease in clinics. At present, the incidence rate of diabetes patients is increasing year by year due to the increasing work pressure, the accelerated pace of life, the change of diet, the reduction of labor, and the acceleration of aging. EVIDENCE ACQUISITION: The computer retrieves four databases to obtain random controlled trials on the influence of resistance exercise and aerobic exercise on type 2 diabetes. After a rigorous literature quality evaluation, data analysis was performed using RevMan 5.3 software. EVIDENCE SYNTHESIS: Ten studies were ultimately included in this meta-analysis. 10 studies reported the HbA1c of the test group and the control group, which was no significant statistical significance (SMD: -0.01; 95% CI: -0.20,0.19; P=0.959) than the control group, HOMA-IR (SMD: 0.02; 95% CI: -0.65,0.69; P=0.954), SBP (SMD: 3.92; 95% CI: -0.92,8.75; P=0.112), DBP (SMD: 0.67; 95% CI: -3.66,5.01; P=0.761), HDL (SMD: -0.08; 95% CI: -2.79,2.64; P=0.955), TG (SMD: -7.51; 95% CI: -21.25,6.22; P=0.284) and TC (SMD: 9.10; 95% CI: -13.43,31.62; P=0.428). CONCLUSIONS: The results of this study suggest that both resistance exercise and aerobic exercise may be effective on patients with type 2 diabetes, as evidenced by HbA1c, HOMA-IR, SBP, DBP, HDL, TG and TC. There is no significant difference in their impact on type 2 diabetes patients, and the above conclusions need to be verified by more high-quality studies.

Mechanistic insights into the anti-depressant effect of curcumin based on network pharmacology and experimental validation.

Curcumin (CUR) exhibits a definite curative effect in the treatment of depression. To identify potential antidepressant targets and mechanisms of action of CUR. This study used network pharmacology to explore the signaling pathways and CUR-related targets in depression. C57BL/6 J mice (male,12-14 weeks old) were randomly divided into four groups (n = 8): saline-treated (control mice), lipopolysaccharide (LPS, 2 mg/kg/day, intraperitoneally), LPS + CUR (50 mg/kg/day, intragastrically), and LPS + CUR + LY294002 (7.5 mg/kg/day, intraperitoneally). After 1 week, behavioral tests were performed. Then, neuronal damage in the prefrontal cortex of mice was evaluated by hematoxylin-eosin (HE) staining. We uncovered the main active mechanism of CUR against depression using Western blotting and enzyme-linked immunosorbent assay (ELISA). Gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that the most significantly enriched pathway in CUR against depression was the PI3K-Akt pathway. Moreover, 52 targets were significantly correlated with the PI3K-Akt signaling pathway and CUR-related targets. In addition, among the top 50 targets ranked by degree in the protein-protein interaction (PPI) network, there were 23 targets involved in the 52 intersection targets. Administration of LPS alone extended immobility time in the open field test (OFT) and tail suspension test (TST) and decreased sucrose consumption in the sucrose preference test (SPT). Pretreatment with CUR relieved LPS-induced changes in the behavioral tests, activity of the PI3K-Akt signaling pathway, neuronal damage in the prefrontal cortex (PFC), and inflammatory response. Moreover, inhibition of the PI3K-Akt signaling pathway by LY294002 blocked the therapeutic effects of CUR. Our study indicates that CUR may be an effective antidepressant agent in an LPS-induced mouse model, partly because of its anti-inflammatory action through the PI3K-Akt signaling pathway.

Exploring the Relevance of Disulfidptosis to the Pathophysiology of Ulcerative Colitis by Bioinformatics Analysis.

Background: Ulcerative colitis (UC) is a nonspecific inflammatory disease confined to the intestinal mucosa and submucosa, and its prevalence significantly increases each year. Disulfidptosis is a recently discovered new form of cell death that has been suggested to be involved in multiple diseases. The aim of this study was to explore the relevance of disulfidptosis in UC. Methods: First, the UC datasets were downloaded from the Gene Expression Omnibus (GEO) database, and UC samples were typed based on upregulated disulfidptosis-related genes (DRGs). Then, weighted gene co-expression network analysis (WGCNA) was performed on the datasets and molecular subtypes of UC, respectively, to obtain candidate signature genes. After validation of the validation set and qRT-PCR, we constructed a nomogram model by signature genes to predict the risk of UC. Finally, single-cell sequencing analysis was used to study the heterogeneity of UC and to demonstrate the expression of DRGs and signature genes at the single-cell level. Results: A total of 7 DRGs were significantly upregulated in the expression profiles of UC, and 180 UC samples were divided into two subtypes based on these DRGs. Five candidate signature genes were obtained by intersecting two key gene modules selected by WGCNA. After evaluation, four signature genes with diagnostic relevance (COL4A1, PRRX1, NNMT, and PECAM1) were eventually identified. The nomogram model showed excellent prediction ability. Finally, in the single-cell analysis, there were eight cell types (including B cells, T cells, monocyte, smooth muscle cells, epithelial cells, neutrophil, endothelial cells and NK cells) were identified. The signature genes were significantly expressed mainly in endothelial cells and smooth muscle cells. Conclusion: In this study, subtypes related to disulfidptosis were identified, and single-cell analysis was performed to understand the pathogenesis of UC from a new perspective. Four signature genes were screened and a prediction model with high accuracy was established. This provides novel insights for early diagnosis and therapeutic targets in UC.

Digestion and absorption characteristics of iron-chelating silver carp scale collagen peptide and insights into their chelation mechanism.

Iron deficiency is widespread throughout the world, supplementing sufficient iron or improving the bioavailability of iron is the fundamental strategy to solve the problem of iron scarcity. Herein, we explored a new form of iron supplement, iron chelates of silver carp scales (SCSCP-Fe) were prepared from collagen peptide of silver carp scales (SCSCP) and FeCl2·4H2O, the effects of external environment and simulated gastrointestinal digestive environment on the stability of SCSCP-Fe and the structural changes of peptide iron chelates during digestion were investigated. The results of in vitro iron absorption promotion showed that the iron bioavailability of SCSCP-Fe was higher than that of FeSO4. Two potential high iron chelating peptides DTSGGYDEY (DY) and LQGSNEIEIR (LR) were screened and synthesized from the SCSCP sequence by molecular dynamics and LC-MS/MS techniques. The FTIR results displayed that the binding sites of DY and LR for Fe2+ were the carboxyl group, the amino group, and the nitrogen atom on the amide group on the peptide. ITC results indicated that the chelation reactions of DY and LR with Fe2+ were mainly dominated by electrostatic interactions, forming chelates in stoichiometric ratios of 1:2 and 1:1, respectively. Both DY and LR had a certain ability to promote iron absorption. The transport of DY-Fe chelate may be a combination of the three pathways: PepT1 vector pathway, cell bypass, and endocytosis, while LR-Fe chelate was dominated by bivalent metal ion transporters. This study is expected to provide theoretical reference and technical support for the high-value utilization of silver carp scales and the development of novel iron supplements.

Revealing the pharmacological mechanisms of nao-an dropping pill in preventing and treating ischemic stroke via the PI3K/Akt/eNOS and Nrf2/HO-1 pathways.

Nao-an Dropping Pill (NADP) is a Chinese patent medicine which commonly used in clinic for ischemic stroke (IS). However, the material basis and mechanism of its prevention or treatment of IS are unclear, then we carried out this study. 52 incoming blood components were resolved by UHPLC-MS/MS from rat serum, including 45 prototype components. The potential active prototype components hydroxysafflor yellow A, ginsenoside F1, quercetin, ferulic acid and caffeic acid screened by network pharmacology showed strongly binding ability with PIK3CA, AKT1, NOS3, NFE2L2 and HMOX1 by molecular docking. In vitro oxygen-glucose deprivation/reperfusion (OGD/R) experimental results showed that NADP protected HA1800 cells from OGD/R-induced apoptosis by affecting the release of LDH, production of NO, and content of SOD and MDA. Meanwhile, NADP could improve behavioral of middle cerebral artery occlusion/reperfusion (MCAO/R) rats, reduce ischemic area of cerebral cortex, decrease brain water and glutamate (Glu) content, and improve oxidative stress response. Immunohistochemical results showed that NADP significantly regulated the expression of PI3K, Akt, p-Akt, eNOS, p-eNOS, Nrf2 and HO-1 in cerebral ischemic tissues. The results suggested that NADP protects brain tissues and ameliorates oxidative stress damage to brain tissues from IS by regulating PI3K/Akt/eNOS and Nrf2/HO-1 signaling pathways.

A rapid facilitation of acid-sensing ion channels current by corticosterone in cultured hippocampal neurons.

Acid-sensing ion channels (ASIC) play an important role in the central neuronal system and excessive activation of ASICs induces neuronal damage. Recent studies show that ASIC1a, a subunit of ASIC, is involved in stress processes but the mechanisms by which ASIC1a is regulated by corticosterone (CORT), a stress-induced hormone, are as yet unelucidated. In the present study, to explore the effects of CORT on ASIC1a in cultured hippocampal neurons, the whole-cell patch clamp technique was used. We present data showing that extracellular application of 1 and 10 µM CORT increase the inward current when solution of pH 6.0 is applied to the exterior of the cell. Moreover, extracellular application of membrane-impermeable CORT-BSA (1 µM) maintains current elevation induced by the action of ASIC1a. However, intracellular application of CORT (1 µM) did not increase ASIC1a current. Subsequent extracellular application of CORT enhanced the amplitude of ASIC1a current. Also, RU38486 (10 µM), an antagonist of nuclear glucocorticoids receptor, did not block an increase of ASIC1a current induced by CORT. In addition, CORT application further resulted in a significant enhancement of ASIC1a current in the presence of phorbol 12-myristate 13-acetate (0.5 µM) or bryostatin1 (1 µM), which are both protein kinase C (PKC) agonists. On the contrary, after pretreatment with GF109203X (3 µM), an antagonist of PKC, CORT did not elevate ASIC1a current. These data indicate that the rapid increase of ASIC1a current induced by CORT may be caused by the activation of corticosteroid receptors found on the cell membranes of hippocampal neurons and it may involve a PKC-dependent mechanism.

2L polyethylene glycol combined with castor oil versus 4L polyethylene glycol for bowel preparation before colonoscopy among inpatients.

Inpatients are more likely to have inadequate bowel preparation compared to outpatients. Although experts recommend 4L split polyethylene glycol (PEG) preparation, bowel preparation with castor oil (CaO) was recently found to reduce the volume of solution required. The aim of the study was to evaluate the cleansing effect and safety of 2L-PEG with Cao in bowel preparation among inpatients. Our study retrospectively analyzed the medical records and colonoscopy reports of inpatients (n = 1251) who underwent colonoscopy in the Affiliated Changzhou No.2 People Hospital of Nanjing Medical University, and the inpatients were divided into 2L-PEG-CaO and 4L-PEG group according to different bowel preparation protocols. Boston Bowel Preparation Scale (BBPS) is used to assess bowel preparation efficacy before colonoscopy. Furthermore, we also calculated other outcomes, such as polyp or adenoma detection rates and adverse events. A total of 1251 patients undergoing colonoscopy were included in this study, 738 were taken 4L-PEG and 513 2L-PEG-CaO. Both inpatients groups were matched for baseline characteristics. The 2L-PEG-CaO group was significantly higher than the 4L-PEG group on both BBPS (7.26 ± 1.75 vs 7.06 ± 1.58, P = .043) and adequate bowel cleansing rates (83.2% vs 77.4%, P = .011). Regarding adverse events, the 4L-PEG group was significantly higher than the 2L-PEG-CaO group on the incidence of abdominal fullness (6.4% vs 9.6%, P = .045) and adverse events (33.7% vs 28.5%, P = .048). The 2L split PEG with CaO preparation increased quality of bowel cleansing and improved tolerance in inpatients. Bowel preparation with 2L-PEG-CaO is suitable alternative to traditional 4L split PEG bowel preparation for colonoscopy of inpatients.