Fermented Astragalus membranaceus could promote the liver and intestinal health of juvenile tiger grouper (Epinephelus fuscoguttatus).

In order to understand the effects of fermented Astragalus membranaceus (FAM) on the liver and intestinal health of tiger grouper (Epinephelus fuscoguttatus), this study was conducted. This study evaluates the effects of different levels of FAM on liver and intestinal tissue structure, serum biochemical parameters, intestinal digestive enzyme, and microbiota structure of tiger grouper. Fish were fed with diets (crude protein ≥ 48.0%, crude fat ≥ 10.0%) with five levels of FAM (L1:0.25%, L2: 0.5%, L3: 1%, L4: 2% and L5: 4%) in the experimental groups and a regular diet was used as the control (L0: 0%) for 8 weeks. Compared with AM, the protein content of FAM was significantly changed by 34.70%, indicating that a large amount of bacterial protein was produced after AM fermentation, and its nutritional value was improved. FAM had significant effects on the growth performance of tiger grouper (p < 0.05). The high-density lipoprotein cholesterol (HDL-C) was highest in L4 group, being significantly different from L0 group. The area and diameter of hepatocytes were lowest in L3 and L4, and the density of hepatocyte was highest in L4 group and relatively decreased in L5 group. The mucosal height and muscular thickness were highest in L3 group. The intestinal microbiota structure of tiger grouper was changed under the intervention of FAM. The lower abundance of potential pathogenic bacteria and higher abundance of probiotics colonization in the L4 group showed that the dose of FAM had the best effect on improving the health of intestinal microbiota. This study indicates that the addition of FAM in the feed contributes to liver health, improves intestinal morphology, and regulates the intestinal microbiota of tiger grouper. The addition ratio of 1%-2% is better for intestinal and liver health, and a high addition ratio will cause liver damage. Our work will provide a reference for the addition and management of FAM in the aquaculture industry.

[Quality evaluation and multi-spectral identification of origin herbs of Lonicerae Japonicae Flos based on grey correlation-TOPSIS method].

The grey correlation-TOPSIS method was used to evaluate the quality of the origin herbs of Lonicerae Japonicae Flos, and the Fourier transform near-infrared(NIR) and mid-infrared(MIR) spectroscopy was applied to establish the identification model of origin herbs of Lonicerae Japonicae Flos by combining chemometrics and spectral fusion strategies. The content of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, caffeic acid, secoxyloganin, isoquercitrin, isochlorogenic acid B, isochlorogenic acid A, and isochlorogenic acid C in six origin herbs of Lonicerae Japonicae Flos was determined by high-performance liquid chromatography(HPLC), and their quality was evaluated by the grey correlation-TOPSIS method. The Fourier transform NIR and MIR spectra of six origin herbs of Lonicerae Japonicae Flos(Lonicera japonica, L. macranthoides, L. hypoglauca, L. fulvotomentosa, L. confuse, and L. similis) were collected. At the same time, principal component analysis(PCA), support vector machine(SVM), and spectral data fusion technology were combined to determine the optimal identification method for the origin herbs of Lonicerae Japonicae Flos. There were differences in the quality of the origin herbs of Lonicerae Japonicae Flos. Specifically, there were significant differences between L. japonica and the other five origin herbs(P<0.01). The quality of L. similis was significantly different from that of L. fulvotomentosa, L. macranthoides, and L. hypoglauca(P=0.008, 0.027, 0.01), and there were also significant differences in the quality of L. hypoglauca and L. confuse(P=0.001). The PCA and SVM 2D models based on a single spectrum could not be used for the effective identification of the origin herbs of Lonicerae Japonicae Flos. The data fusion combined with the SVM model further improved the identification accuracy, and the identification accuracy of the mid-level data fusion reached 100%. Therefore, the grey correlation-TOPSIS method can be used to evaluate the quality of the origin herbs of Lonicerae Japonicae Flos. Based on the infrared spectral data fusion strategy and SVM chemometric model, it can accurately identify the origin herbs of Lonicerae Japonicae Flos, which can provide a new method for the origin identification of medicinal materials of Lonicerae Japonicae Flos.

Study on removal of phosphorus and COD in wastewater by sinusoidal AC Fenton oxidation-coagulation.

In order to treat domestic wastewater containing phosphorus and chemical oxygen demand (COD), the new technology of Sinusoidal Alternating Current (AC) Fenton Oxidation-Coagulation (SACFOC) was used to improve the removal efficiency (Re) and reduce energy consumption (EEC). The morphology, elemental composition, crystal structure and functional groups of the sludge were characterised by Scanning Electron Microscope (SEM), Energy-dispersive X-ray Spectroscopy (EDS), X-ray diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FTIR). The results show that total phosphorus removal efficiency {Re(TP)} and removal efficiency of organic matter {Re(COD)} can reach 97.56% and 87.77%, respectively, but EEC is only 0.09 kWh·m-3 under the optimum conditions of pH0 = 3, current density (j) = 0.5 A·m-2, c0(TP) = 18 mg·dm-3, c0(COD) = 300 mg·dm-3, c0(H2O2) = 0.06 mol·dm-3, t = 45 min. As compared with direct current (DC) Fenton Oxidation-Coagulation (DCFOC), the COD removal efficiency of SACFOC treatment was improved by 37%, but the energy consumption was reduced by 45%. The degradation process of total phosphorus and COD by SACFOC abides by the quasi-first-order kinetic model. The process of SACFOC includes double effects of electrocoagulation of iron sol by electrolysis and degrade COD by oxidation of formed hydroxyl radicals (·OH) in wastewater, which improves removal efficiency of total phosphorus and COD in wastewater. Our research findings will provide technical guidance and a theoretical basis for the simultaneous treatment of wastewater containing phosphorus and COD applying SACFOC process.

Quality evaluation and multi-spectral identification of origin herbs of Lonicerae Japonicae Flos based on grey correlation-TOPSIS method / 中国中药杂志

The grey correlation-TOPSIS method was used to evaluate the quality of the origin herbs of Lonicerae Japonicae Flos, and the Fourier transform near-infrared(NIR) and mid-infrared(MIR) spectroscopy was applied to establish the identification model of origin herbs of Lonicerae Japonicae Flos by combining chemometrics and spectral fusion strategies. The content of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, caffeic acid, secoxyloganin, isoquercitrin, isochlorogenic acid B, isochlorogenic acid A, and isochlorogenic acid C in six origin herbs of Lonicerae Japonicae Flos was determined by high-performance liquid chromatography(HPLC), and their quality was evaluated by the grey correlation-TOPSIS method. The Fourier transform NIR and MIR spectra of six origin herbs of Lonicerae Japonicae Flos(Lonicera japonica, L. macranthoides, L. hypoglauca, L. fulvotomentosa, L. confuse, and L. similis) were collected. At the same time, principal component analysis(PCA), support vector machine(SVM), and spectral data fusion technology were combined to determine the optimal identification method for the origin herbs of Lonicerae Japonicae Flos. There were differences in the quality of the origin herbs of Lonicerae Japonicae Flos. Specifically, there were significant differences between L. japonica and the other five origin herbs(P<0.01). The quality of L. similis was significantly different from that of L. fulvotomentosa, L. macranthoides, and L. hypoglauca(P=0.008, 0.027, 0.01), and there were also significant differences in the quality of L. hypoglauca and L. confuse(P=0.001). The PCA and SVM 2D models based on a single spectrum could not be used for the effective identification of the origin herbs of Lonicerae Japonicae Flos. The data fusion combined with the SVM model further improved the identification accuracy, and the identification accuracy of the mid-level data fusion reached 100%. Therefore, the grey correlation-TOPSIS method can be used to evaluate the quality of the origin herbs of Lonicerae Japonicae Flos. Based on the infrared spectral data fusion strategy and SVM chemometric model, it can accurately identify the origin herbs of Lonicerae Japonicae Flos, which can provide a new method for the origin identification of medicinal materials of Lonicerae Japonicae Flos.

The potential mechanism of Bupleurum against anxiety was predicted by network pharmacology study and molecular docking.

Bupleurum chinense DC. (Chaihu) is a traditional Chinese medicine (TCM) used in the treatment of anxiety. But the anxiolytic mechanisms of bupleurum are still unclear. Therefore, this unknown is predicted by network pharmacology study with molecular docking in the present study. The components of bupleurum were obtained from the databases. Genes associated with components and disease were also provided by databases. Overlapping genes between components and disease were analyzed. The network of medicine-components-targets-disease was constructed, visualized, and analyzed. Protein-protein interaction (PPI), gene ontology (GO), pathway enrichment (KEGG) and molecular docking were conducted to predict the potential mechanisms of bupleurum on anxiety. A total of 9 bioactive components derived from bupleurum with 80 target genes were involved in anxiety. Neurotransmitter receptor activity, G protein-coupled amine receptor activity, regulation of blood circulation, neuroactive ligand-receptor interaction, calcium signaling pathway and salivary secretion may play significant roles in the anxiolytic of bupleurum. Molecular docking implicated that ACHE and MAOA showed high affinity for stigmasterol. Based on network pharmacology study with molecular docking, multi-component-multi-target-multi-pathway action mode of bupleurum on anxiety was elaborated. Stigmasterol might be the core bioactive component, while ACHE and MAOA might be the core target genes in the pharmacological profile of bupleurum on anxiety.

Exploring the Potential Antidepressant Mechanisms of Pinellia by Using the Network Pharmacology and Molecular Docking.

About 350 million people worldwide suffered from depression, but less than half of the patients received effective and regular treatments. Traditional Chinese Medicine (TCM) such as pinellia has been proven effective for antidepressant treatment with fewer side effects. However, the exact mechanisms remain unclear. Herein, we use the methods of network pharmacology and molecular docking to analyze the effective monomer components of pinellia and reveal the involved signaling pathways to produce antidepressant effects. TCMSP, BATMAN-TCM, and TCMID databases were utilized to analyze the bioactive ingredients and target genes derived from pinellia via the screening the molecular weight (MW), oral bioavailability (OB), blood-brain barrier (BBB) and drug similarity (DL). OMIM, TTD, DisGeNET, GeneCards and DrugBank databases were used to obtain key genes of depression. Then, the networks of protein-protein interaction (PPI) and "medicine-ingredients-targets-pathways" were built. The target signaling pathways were enriched by GO and KEGG by using R language. Furthermore, bioactive ingredients binding of the targets were verified by molecular docking. Nine active monomer ingredients and 96 pivotal gene targets were selected from pinellia. 10,124 disease genes and 87 drug-disease intersecting genes were verified. GO analysis proposed that the receptor activity of neurotransmitter, postsynaptic neurotransmitter, G protein-coupled neurotransmitter, and acetylcholine through the postsynaptic membrane could be modulated by pinellia. KEGG pathway analysis revealed that pinellia influenced depression-related neural tissue interaction, cholinergic synapse, serotonin activated synapse and calcium signaling pathway. Besides, the reliability and accuracy of results obtained from the indirect network pharmacology were validated by molecular docking. The bioactive components of pinellia made significant antidepressant effects by regulating the key target genes/proteins in the pathophysiology of depression.

Efficacy of hyaluronic acid on the prevention of intrauterine adhesion and the improvement of fertility: A meta-analysis of randomized trials.

BACKGROUND: and purpose:Intrauterine adhesion (IUA) and re-adhesion were common problems in women of childbearing age. The aim of our research was to evaluate the efficacy of hyaluronic acid gel on preventing IUA and improving the fertility. METHODS: A systematic search for randomized controlled trial (RCT) articles that tested the effectiveness of using hyaluronic acid gel during intrauterine surgery in prevention of IUA and improvement of fertility was performed in PubMed, Medline, Embase, the Cochrane Library and clinicaltrials.gov until December 2020. Data were extracted independently and analyzed using RevMan statistical software version 5.3. RESULTS: Twelve articles (11 studies) were deemed eligible for inclusion. There was a significantly reduced proportion of IUA after using hyaluronic acid gel during intrauterine operation (OR 0.39, 95% CI 0.29 to 0.52). It has significantly reduced the incidence of moderate-to-severe IUA after using hyaluronic acid gel, but no effect on the mild IUA. In addition, our analysis showed that the hyaluronic acid gel group was associated with a significant increased incidence of pregnancy (OR 1.64, 95% CI 1.08 to 2.50). CONCLUSION: Our analysis confirmed that using hyaluronic acid gel during intrauterine operation seemed to be more helpful for patients with high risk of IUA. However, larger and well-designed studies would be desired in the future to confirm its efficacy and safety in protecting fertility.

Application of a nomogram to radiomics labels in the treatment prediction scheme for lumbar disc herniation.

OBJECTIVE: To investigate and verify the efficiency and effectiveness of a nomogram based on radiomics labels in predicting the treatment of lumbar disc herniation (LDH). METHODS: By reviewing medical records that were analysed over the past three years, clinical and imaging data of 200 lumbar disc patients at the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine were obtained. The collected cases were randomly divided into a training group (n = 140) and a testing group (n = 60) at a ratio of 7:3. Two radiologists with experience in reading orthopaedics images independently segmented the ROIs. The whole intervertebral disc with the most obvious protrusion in the sagittal plane T2WI lumbar MRI as a mask (ROI) is sketched. The LASSO (Least Absolute Shrinkage And Selection Operator) algorithm was used to filter the features after extracting the radiomics features. The multivariate logistic regression model was used to construct a quantitative imaging Rad­Score for the selected features with nonzero coefficients. The radiomics labels and nomogram were evaluated using the receiver operating characteristic curve (ROC) and the area under the curve (AUC). The calibration curve was used to evaluate the consistency between the nomogram prediction and the actual treatment plan. The DCA decision curve was used to evaluate the clinical applicability of the nomogram. RESULT: Following feature extraction, 11 radiomics features were used to construct the radiomics label for predicting the treatment plan of LDH. A nomogram was then constructed. The AUC was 0.93 (95% CI: 0.90-0.97), with a sensitivity of 89%, a specificity of 91%, a positive predictive value of 92.7%, a negative predictive value of 89.4%, and an accuracy of 91%. The calibration curve showed that there was good consistency between the prediction and the actual observation. The DCA decision curve analysis showed that the nomogram of the imaging group has great potential for clinical application when the risk threshold is between 5 and 72%. CONCLUSION: A nomogram based on radiomics labels has good predictive value for the treatment of LDH and can be used as a reference for clinical decision-making.

Removal of phosphorus in wastewater by sinusoidal alternating current coagulation: performance and mechanism.

The effects of initial total phosphorus (TP) concentration, current density, conductivity and initial pH value on the removal rate of TP and energy consumption, as well as the behaviour and mechanism of phosphorus removal, were investigated by sinusoidal alternating current coagulation (SACC). The flocs produced by SACC were characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy FTIR and X-ray photo electron spectroscopy. The thermodynamic and kinetic behaviours of phosphorus removal by iron sol adsorption were also studied in detail. In a self-made SACC reactor equipped with five sets of parallel iron electrodes spacing 10 mm, the removal rate of TP reached 90.9% for a pH 7.0 wastewater with 5 mg dm-3 TP (κ = 800 µS cm-1) after being treated for 60 min by applying 2.12 mA cm-2 sinusoidal alternating current. Compared with direct current coagulation (DCC), SACC exhibits a higher removal efficiency of phosphorus due to the stronger adsorption of the produced flocs. It was found that the adsorption in the SACC process follows pseudo-second-order kinetic with the involvement of the intra-particle model. The adsorption of iron sol to phosphorus was an endothermic and spontaneous process, and its adsorption behaviour can be characterized with Langmuir and Redlich-Peterson isothermal adsorption models. SACC may be employed for the treatment of more complex wastewater combined with biological and/or electrochemical techniques.

Effects of early-life zinc deficiency on learning and memory in offspring and the changes in DNA methylation patterns.

OBJECTIVE: To investigate the effect of maternal zinc deficiency on learning and memory in offspring and the changes in DNA methylation patterns. METHODS: Pregnant rats were divided into zinc adequate (ZA), zinc deficient (ZD), and paired fed (PF) groups. Serum zinc contents and AKP activity in mother rats and offspring at P21 (end of lactation) and P60 (weaned, adult) were detected. Cognitive ability of offspring at P21 and P60 were determined by Morris water maze. The expression of proteins including DNMT3a, DNMT1, GADD45ß, MeCP2 and BDNF in the offspring hippocampus were detected by Western-blot. The methylation status of BDNF promoter region in hippocampus of offspring rats was detected by MS-qPCR. RESULTS: Compared with the ZA and PF groups, pups in the ZD group had lower zinc levels and AKP activity in the serum, spent more time finding the platform and spent less time going through the platform area. Protein expression of DNMT1 and GADD45b were downregulated in the ZD group during P0 and P21 but not P60 compared with the ZA and PF group, these results were consistent with a reduction in BDNF protein at P0 (neonate), P21. However, when pups of rats in the ZD group were supplemented with zinc ion from P21 to P60, MeCP2 and GADD45b expression were significantly downregulated compared with the ZA and PF group. CONCLUSION: Post-weaning zinc supplementation may improve cognitive impairment induced by early life zinc deficiency, whereas it may not completely reverse the abnormal expression of particular genes that are involved in DNA methylation, binding to methylated DNA and neurogenesis.

The traditional uses, phytochemistry, and pharmacological properties of Paris L. (Liliaceae): A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Paris L. (Liliaceae) consisted of 33 species, of which the study focused on Paris polyphylla Smith, P. polyphylla var. chinensis (Franch.) Hara, and P. polyphylla Smith var. yunnanensis (Franch.) Hand. -Mazz. Due of course to the good effects of analgesia and hemostasis, it was traditionally used to treat trauma by folk herbalists. AIM OF THIS REVIEW: This study summarized the traditional uses, distributions, phytochemical components, pharmacological properties, and toxicity evaluation of the genus Paris, and reviewed the economic value of cultivate P. polyphylla. This aim was that of providing a new and comprehensive recognition of these medicinal plants for the further utilization of Paris plants. MATERIALS AND METHODS: The literature about traditional and folk uses of genus Paris was obtained from Duxiu Search, and China National Knowledge Infrastructure (CNKI). The other literature about genus Paris was searched online on Web of Science, PubMed, Google Scholar, Baidu Scholar, Scifinder database, and Springer research. The Scientific Database of China Plant Species (DCP) (http://db.kib.ac.cn/Default.aspx) databases were used to check the scientific names and provide species, varieties, and distribution of genus Paris. The botany studies information of genus Paris was available online from Plant Plus of China (www.iplant.cn). All the molecular structures of chemical compounds displayed in the text were produced by ChemBioDraw Ultra 14.0. RESULTS: The plants of genus Paris, containing about 33 species and 15 varieties, are mainly distributed in Southwest China (Yunnan, Sichuan, and Guizhou provinces). More than 320 chemical components have been isolated from genus Paris since 2020, including steroidal saponins, C-21 steroids, phytosterols, insect hormones, pentacyclic triterpenes, flavonoids, and other compounds. Arrays of pharmacological investigations revealed that compounds and extracts of Paris species possess a wide spectrum of pharmacological effects, such as antitumor, cytotoxic, antimicrobial, antifungal, hemostatic, and anti-inflammatory activities. The studies about toxicity evaluation suggested that Rhizome Paridis had slight liver toxicity. CONCLUSIONS: The dried rhizomes of P. polyphylla, P. polyphylla var. chinensis, and P. polyphylla var. yunnanensis were used to treat wound, bleeding, and stomachache, etc. in folk medicine. Phytochemistry researches showed that different species had pretty similarities especially in terms of chemical constituents. Pharmacological studies witnessed that Rhizome Paridis has various activities. Among these activities, steroidal saponins were the main active ingredients. Furthermore, an important aspect responsible for increasing interest in genus Paris is the use of antifertility-nonhormonal contraceptives by women. Also, the development of TCM (Traditional Chinese medicine) planting industry can improve the income of ethnic minorities and promote economic development.

Traditional Chinese medicine shenhuang granule in patients with severe/critical COVID-19: A randomized controlled multicenter trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is still a pandemic, with a high mortality rate in severe/critical cases. Therapies based on the Shenghuang Granule have proved helpful in viral infection and septic shock. HYPOTHESIS/PURPOSE: The objective of the current study was to compare the efficacy and safety of the traditional Chinese medicine, Shenhuang Granule, with standard care in hospitalized patients with severe/critical COVID-19. STUDY DESIGN AND METHODS: This was an open-label, multicenter, randomized, controlled clinical trial. At 4 medical centers, a total of 111 severe/critical patients were randomly assigned to receive Shenhuang Granule (SHG group) twice a day for 14 days, in addition to standard care, or to receive standard care alone (Control group). The maximal follow up time was 75 days. The clinical endpoint was clinical improvement and mortality. RESULTS: 54 patients were assigned to the control group and 57 to the SHG group. The overall mortality was 75.9% (41/54) in the control group, and 38.6% (22/57) in the SHG group (p < 0.01 vs. control). The post hoc analysis showed that in the severe category, the mortality of the control group vs. the SHG group was 58.8% (10/17) vs. 5.3% (1/19) (p < 0.01); while in the critical category, it was 83.8% (31/37) vs. 55.3% (21/38) (p < 0.05). In the severe category, the mortality of patients who eventually received an invasive ventilator in the control vs. the SHG group was 58.8% (10/17) vs. 0 (0/19) (p < 0.01). Administration of SHG was associated with increased lymphocytes and decreased adverse events. CONCLUSION: Shenhuang Granule is a promising integrative therapy for severe and critical COVID-19.

Clinical Effect of Traditional Chinese Medicine Shenhuang Granule in Critically Ill Patients with COVID-19: A Single-Centered, Retrospective, Observational Study.

The coronavirus disease 2019 (COVID-19) pandemic has become a public health emergency of global concern. In China, traditional Chinese medicine has been widely administered to COVID-19 patients without sufficient evidence. To evaluate the efficacy of Shenhuang Granule (SHG) for treating critically ill patients with COVID-19, we included in this study 118 patients who were admitted to the ICU of Tongji Hospital between January 28, 2020 and March 28, 2020. Among these patients, 33 (27.9%) received standard care plus SHG (treatment group) and 85 (72.1%) received standard care alone (control group). Enrolled patients had a median (IQR) age of 68 (57-75) years, and most (79 [67.1%]) were men. At end point of this study, 83 (70.3%) had died in ICU, 29 (24.5%) had been discharged from ICU, and 6 patients (5.2%) were still in ICU. Compared with control group, mortality was significantly lower in treatment group (45.4% vs. 80%, p < .001). Patients in treatment group were less likely to develop acute respiratory distress syndrome (ARDS) (12 [36.3%] vs. 54 [63.5%], p = 0.012) and cardiac injury (5 [15.1%] vs. 32 [37.6%], p = 0.026), and less likely to receive mechanical ventilation (22 [66.7%] vs. 72 [84.7%], p = 0.028) than those in control group. The median time from ICU admission to discharge was shorter in treatment group (32 [20-73] days vs. 76 [63-79] days, p = 0.0074). These findings suggest that SHG treatment as a complementary therapy might be effective for critically ill adults with COVID-19 and warrant further clinical trials.

Antitumor Effects of Baicalein and Its Mechanism via TGFß Pathway in Cervical Cancer HeLa Cells.

BACKGROUND: Due to dual-regulating carcinogenesis, the TGFß pathway is an ideal and alternative tumor target. Natural flavonoids possess the similar structures to estrogen and could exert an important benefit to cervical cancer. The present study aimed to screen the inhibitor of TGFß pathway from natural flavonoids and evaluate the function and mechanism of the TGFß pathway inhibitor on cervical cancer. MATERIALS AND METHODS: The cervical cancer HeLa cells were firstly treated with different flavonoids and probed by western blot for screening the inhibitor of TGFß pathway. And then, the effect of the identified inhibitor on cell proliferation was studied by CCK-8 and clone formation assay. Then, RT-PCR and western blot assay were performed to evaluate the effect of identified inhibitor on mTOR/p70S6K pathway, and the cell migration and EMT pathway were also examined using scratching analysis and western blot assay. Finally, the role of TGFß was assessed via the classic inhibitor of TGFß/SMAD pathway. RESULTS: Screening data by western blot assay showed that baicalein displayed the best inhibitor effect on TGFß expression. CCK-8 and clone formation assay showed that baicalein inhibited the cell proliferation and clone cell number. RT-PCR and western bolt for probing mTOR, p70S6K, and 4EBP1 revealed that baicalein could suppress their expression and phosphorylation. The scratching analysis and western blot assay displayed that baicalein inhibited the cell migration and EMT progression in HeLa. The use of SB431542, a TGFß inhibitor, revealed that TGFß was crucial to baicalein-regulating cell proliferation and migration in HeLa cells. CONCLUSION: Baicalein, a medicine agent screened from natural flavonoids targeting TGFß pathway, could suppress mTOR/p70S6K pathway-mediated cell proliferation and EMT pathway-related migration via TGFß pathway in cervical cancer HeLa cells.

A large dose of methamphetamine inhibits drug­evoked synaptic plasticity via ER stress in the hippocampus.

Drug addiction is a chronic and recurrent disease associated with learning and memory. Shaped by drug use and cues from the environment, drug memory serves a key role in drug­seeking behaviour. Methamphetamine (MA), a globally abused drug, causes cognitive impairment, and endoplasmic reticulum (ER) stress is one of the mechanisms via which this occurs. In the current study, it was hypothesized that ER stress may serve a role in the disturbance of drug memory. The present study demonstrated that 5 mg/kg MA inhibited conditioned place preference behaviour via ER stress, which caused a disruption in long­term potentiation in the hippocampus. When mice were pre­treated with the ER stress inhibitors 4­phenyl butyric acid or tauroursodeoxycholic acid, drug­evoked synaptic plasticity was induced. Western blotting results indicated that treatment with 5 mg/kg MA enhanced the expression of cyclin­dependent kinase­5 and decreased the expression of Ca2+/calmodulin­dependent protein kinase II α via ER stress. Collectively, the present results suggested that a large dose of MA inhibited drug­evoked synaptic plasticity and disrupted drug memory by inducing ER stress.

High-Dose Benzodiazepines Positively Modulate GABAA Receptors via a Flumazenil-Insensitive Mechanism.

Benzodiazepines (BZDs) produce versatile pharmacological actions through positive modulation of GABAA receptors (GABAARs). A previous study has demonstrated that high concentrations of diazepam potentiate GABA currents on the α1ß2γ2 and α1ß2 GABAARs in a flumazenil-insensitive manner. In this study, the high-concentration effects of BZDs and their sensitivity to flumazenil were determined on synaptic (α1ß2γ2, α2ß2γ2, α5ß2γ2) and extra-synaptic (α4ß2δ) GABAARs using the voltage-clamp electrophysiology technique. The in vivo evaluation of flumazenil-insensitive BZD effects was conducted in mice via the loss of righting reflex (LORR) test. Diazepam induced biphasic potentiation on the α1ß2γ2, α2ß2γ2 and α5ß2γ2 GABAARs, but did not affect the α4ß2δ receptor. In contrast to the nanomolar component of potentiation, the second potentiation elicited by micromolar diazepam was insensitive to flumazenil. Midazolam, clonazepam, and lorazepam at 200 µM exhibited similar flumazenil-insensitive effects on the α1ß2γ2, α2ß2γ2 and α5ß2γ2 receptors, whereas the potentiation induced by 200 µM zolpidem or triazolam was abolished by flumazenil. Both the GABAAR antagonist pentylenetetrazol and Fa173, a proposed transmembrane site antagonist, abolished the potentiation induced by 200 µM diazepam. Consistent with the in vitro results, flumazenil antagonized the zolpidem-induced LORR, but not that induced by diazepam or midazolam. Pentylenetetrazol and Fa173 antagonized the diazepam-induced LORR. These findings support the existence of non-classical BZD binding sites on certain GABAAR subtypes and indicate that the flumazenil-insensitive effects depend on the chemical structures of BZD ligands.

[Effect of transcutaneous electrical acupoint stimulation on catheter related bladder discomfort after ureteroscopic lithotripsy].

OBJECTIVE: To verify the efficacy of transcutaneous electrical acupoint stimulation (TEAS) on catheter related bladder discomfort after ureteroscopic lithotripsy. METHODS: Sixty male patients with selective ureteroscopic lithotripsy under general anesthesia were randomly divided into a TEAS group (30 cases, one case dropped off) and a sham TEAS group (30 cases, 2 cases dropped off). Before anesthesia induction, the patients in the TEAS group were treated with TEAS at Guanyuan (CV 4), Zhongji (CV 3), Zusanli (ST 36) and Sanyinjiao (SP 6) for 30 min, with disperse-dense wave, frequency of 2 Hz/ 15 Hz and current intensity of 6 to 10 mA. The patients in the sham TEAS group were treated with the same TEAS device at the same acupoints, but no electrical stimulation was given. After 30 min, anesthesia induction started. The total dosages of propofol and remifentanil in the two groups were recorded, and the time of operation and anesthesia, the time of wake-up and the time of stay in postanesthesia care unit (PACU) were recorded. The postoperative recovery was evaluated 5 min (T1) after wake-up, 1 h (T2), 2 h (T3) and 6 h (T4) after the operation, including the severity of urinary tract irritation and visual analogue scale (VAS) score. The occurrence of adverse reactions was observed, such as nausea and vomiting, dizziness and headache. RESULTS: The dosage of remifentanil in the TEAS group was significantly lower than that in the sham TEAS group (P<0.05); but the dosage of propofol had no significant difference between the two groups (P>0.05). Compared with the sham TEAS group, the incidence of more-than-moderate urinary tract irritation symptoms in the TEAS group was reduced (P<0.05), and the VAS scores 1 and 2 h after operation were reduced (P<0.05). CONCLUSION: The 30-min TEAS at Guanyuan (CV 4), Zhongji (CV 3), Zusanli (ST 36) and Sanyinjiao (SP 6) before anesthesia induction could significantly control the severity of postoperative urinary tract irritation in patients with ureteroscopic lithotripsy, reduce the dosage of anesthetic drugs and relieve postoperative pain.

Bismuth chelate as a contrast agent for X-ray computed tomography.

BACKGROUNDS: Due to the unexpected side effects of the iodinated contrast agents, novel contrast agents for X-ray computed tomography (CT) imaging are urgently needed. Nanoparticles made by heavy metal elements are often employed, such as gold and bismuth. These nanoparticles have the advantages of long in vivo circulation time and tumor targeted ability. However, due to the long residence time in vivo, these nanoparticles may bring unexpected toxicity and, the preparation methods of these nanoparticles are complicated and time-consuming. METHODS: In this investigation, a small molecular bismuth chelate using diethylenetriaminepentaacetic acid (DPTA) as the chelating agent was proposed to be an ideal CT contrast agent. RESULTS: The preparation method is easy and cost-effective. Moreover, the bismuth agent show better CT imaging for kidney than iohexol in the aspect of improved CT values. Up to 500 µM, the bismuth agent show negligible toxicity to L02 cells and negligible hemolysis. And, the bismuth agent did not induce detectable morphology changes to the main organs of the mice after intravenously repeated administration at a high dose of 250 mg/kg. The pharmacokinetics of the bismuth agent follows the first-order elimination kinetics and, it has a short half-life time of 0.602 h. The rapid clearance from the body promised its excellent biocompatibility. CONCLUSIONS: This bismuth agent may serve as a potential candidate for developing novel contrast agent for CT imaging in clinical applications.

[Research progress on mechanism of gastrodin and p-hydroxybenzyl alcohol on central nervous system].

Gastrodin(GAS) and p-hydroxybenzyl alcohol(HBA) are extracts of dried tubers of Gastrodia elata, which is the material basis for its efficacy and belongs to phenolic compounds. Modern pharmacology studies have shown that they have significant effects on central nervous system diseases, such as insomnia, convulsions, depression, ischemic stroke, anxiety, and cognitive impairment, and these diseases are closely related to neurotransmitters and cytokines. This paper described various mechanisms of GAS and HBA monomer components on the central nervous system. They alleviate hippocampal neuronal toxicity mainly by regulating a variety of neurotransmitters, such as acetylcholine, glutamic acid(GLU), γ-aminobutyric acid(GABA), serotonin(5-HT), dopamine(DA), norepinephrine(NE), 5-indoleacetic acid(5-HIAA), high vanillic acid(HVA) and dihydroxyphenylacetic acid(DOPAC), pro-inflammatory cell growth factors, such as IL-1ß, IL-6 and TNF-α and relevant receptor functions, and exert neuropharmacological effects by effectively increasing mRNA expressions of brain neurotrophic factors, such as BDNF and GDNF, and further inhibiting the apoptosis of damaged neurons. This paper summarized various mechanisms on the central nervous system, which provides a scientific basis for the further research of the neuropharmacological mechanism of GAS and HBA and the development of new drugs and functional food.

A Head-to-Head Comparison of Percutaneous Mastoid Electrical Stimulator and Supraorbital Transcutaneous Stimulator in the Prevention of Migraine: A Prospective, Randomized Controlled Study.

INTRODUCTION: This prospective, randomized, multicenter head-to-head outcome study was performed to compare the efficacy and safety of Percutaneous Mastoid Electrical Stimulator (PMES) and Supraorbital Transcutaneous Stimulator (STS) in migraine prevention. METHODS: This was a prospective, randomized, head-to-head outcome study that involved three medical centers. After a one-month run-in, episodic patients with at least two migraine attacks/month were randomized to receive PMES daily for 45 min or STS daily for 20 min for three months. The primary outcomes were change in monthly migraine days and the 50% response rate. RESULTS: A total of 90 patients were included in this study. We observed statistically significant reduction of migraine days in the third month treatment both in the PMES group and STS group. The difference between the two groups was not significant (60.5% vs. 53.8%, p = 0.88). Of note, 77.8% patients in the PMES group and 62.2% patients in the STS group had a ≥50% reduction of migraine days in the third month (p = 0.070). The change in monthly migraine days, monthly migraine attacks, severity of migraine days, accompanying symptoms during migraine and monthly acute anti-migraine drug intake were not significantly different between the two groups. The change of Headache Impact Test-6 (HIT-6) from run-in to the third-month treatment in the STS group was more remarkable than that in the PMES group (36.5% vs. 25.6%, p = 0.041). The occurrence of discomfort paresthesia was higher in the STS group (13.3% vs. 0%, p = 0.026). CONCLUSION: PMES and STS treatment were both effective in migraine prevention. The safety and efficacy of PMES and STS were comparable.