Clinical study of the effect of 5 kinds of antiepileptic drugs on the postictal state.

OBJECTIVE: To compare the effects of levetiracetam（LEV）, lamotrigine(LTG), oxcarbazepine(OXC), topiramate(TPM) and valproate (VPA) on postictal state (PIS). METHODS: A total of 187 epilepsy patients undergoing monotherapy were enrolled in a long-term follow-up study at the Affiliated Hospital of Yangzhou College. This included 30 patients on levetiracetam, 41 on valproate, 30 on oxcarbazepine, 28 on topiramate, and 31 on lamotrigine. A control group of 28 newly diagnosed or previously untreated epilepsy patients was also included. The Liverpool Seizure Severity Scale 2.0 (LSSS2.0) and the Seizure Severity Questionnaire (SSQ) were utilized to evaluate the patients' condition, with comparison based on the results of the postictal status items. EEG during PIS termination was assessed using the Grand Total EEG score (GTE) as an objective tool to measure the impact of Antiseizure medications (ASMs) on the post-seizure state. RESULTS: The LSSS2.0 score indicated a statistically significant difference in post-seizure status score among the 5 groups (p < 0.05). The difference between the 5 groups and the control group was statistically significant (p < 0.05). Results of the SSQ demonstrated that all 5 drugs significantly reduced the post-seizure status score compared to the control group (p < 0.05). The GTE score revealed that, in the later stage of the seizure, the GTE score of the levetiracetam group, valproate group, oxcarbazepine group, and lamotrigine group significantly decreased compared to the control group (P < 0.05). There was no significant decrease in the GTE score in the topiramate group (P < 0.05). CONCLUSION: Levetiracetam, lamotrigine, oxcarbazepine, topiramate, and valproate demonstrate favorable efficacy in ameliorating the severity of post-seizure condition. Further investigations are warranted to assess the potential of other widely employed anti-seizure medications in enhancing post-seizure status.

Association of endometriosis with asthma: a study of the NHANES database in 1999-2006.

OBJECTIVE: Asthma is a chronic inflammatory disease of the airways with a gender differences in the prevalence after puberty. Recent studies have reported a relationship between asthma and endometriosis, possibly related to the immune response mechanisms, but the evidences are limited and inconsistent. Herein, this research aimed to investigate the association of endometriosis with asthma based on the representative population in the United States (U.S.) to provide some reference for further exploration on mechanism of gender difference in asthma. METHODS: In this cross-sectional study, data of women aged ≥ 20 years old were extracted from the National Health and Nutrition Examination Survey (NHANES) database in 1999-2006. Weighted univariate and multivariate logistic regression analyses were utilized to explore the association of endometriosis with asthma. The multivariate models adjusted for covariates including age, race, education level, marital status, poverty income ratio (PIR), body mass index (BMI), waist circumference, smoking, estrogen and progesterone hormones use, uterine fibroids, at least one ovary removed, and birth control pills intake. The evaluation indexes were odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses of age, race, BMI, and pregnancy history were also performed. RESULTS: Among 5,556 eligible women, 782 had asthma, and 380 had endometriosis. The average age of participants was 37.19 years old, and more than half of them were non-Hispanic White (68.44%). After adjusting for covariates, endometriosis was associated with higher odds of asthma compared with non-endometriosis [OR = 1.48, 95%CI: (1.10-1.99)]. This relationship was also found in 40-49 years old [OR = 2.26, 95%CI: (1.21-4.23)], BMI of 25-29.9 kg/m2 [OR = 2.87, 95%CI: (1.52-5.44)], and pregnancy history [OR = 1.44, 95%CI: (1.01-2.06)] subgroups. CONCLUSION: Endometriosis had a positive association with asthma in adult women. Females aged 40-49 years old, with BMI of 25-29.9 kg/m2 and had a history of pregnancy should take care about monitoring endometriosis to reduce the potential risk of asthma. Further studies are still needed to clarify the causal association between endometriosis and asthma.

Tetramethylpyrazine Attenuates Oxygen-glucose Deprivation-induced Neuronal Damage through Inhibition of the HIF-1α/BNIP3 Pathway: From Network Pharmacological Finding to Experimental Validation.

AIMS: A network pharmacological analysis combined with experimental validation was used to investigate the neuroprotective mechanism of the natural product Tetramethylpyrazine(TMP). BACKGROUND: Protecting neurons is critical for acute ischemic stroke treatment. Tetramethylpyrazine is a bioactive component extracted from Chuanxiong. The neuroprotective potential of TMP has been reported, but a systematic analysis of its mechanism has not been performed. OBJECTIVE: Based on the hints of network pharmacology and bioinformatics analysis, the mechanism by which TMP alleviates oxygen-glucose deprivation-induced neuronal damage through inhibition of the HIF-1α/BNIP3 pathway was verified. METHOD: In this study, we initially used network pharmacology and bioinformatics analyses to elucidate the mechanisms involved in TMP's predictive targets on a system level. The HIF-1α/BNIP3 pathway mediating the cellular response to hypoxia and apoptosis was considered worthy of focus in the bioinformatic analysis. An oxygen-glucose deprivation (OGD)-induced PC12 cell injury model was established for functional and mechanical validation. Cell viability, lactate dehydrogenase leakage, intracellular reactive oxygen species, percentage of apoptotic cells, and Caspase-3 activity were determined to assess the TMP's protective effects. Transfection with siRNA/HIF-1α or pcDNA/HIF-1α plasmids to silence or overexpress hypoxia-inducible factor 1α(HIF-1α). The role of HIF-1α in OGD-injured cells was observed first. After that, TMP's regulation of the HIF-1α/BNIP3 pathway was investigated. The pcDNA3.1/HIF-1α-positive plasmids were applied in rescue experiments. RESULT: The results showed that TMP dose-dependently attenuated OGD-induced cell injury. The expression levels of HIF-1α, BNIP3, and the Bax/Bcl-2 increased significantly with increasing OGD duration. Overexpression of HIF-1α decreased cell viability, increased BNIP3 expression, and Bax/Bcl-2 ratio; siRNA-HIF-1α showed the opposite effect. TMP treatment suppressed HIF-1α, BNIP3 expression, and the Bax/Bcl-2 ratio and was reversed by HIF-1α overexpression. CONCLUSION: Our study shows that TMP protects OGD-damaged PC12 cells by inhibiting the HIF-1α/BNIP3 pathway, which provides new insights into the mechanism of TMP and its neuroprotective potential.

Quality evaluation of Codonopsis Radix and processed products based on the analysis of monosaccharides and oligosaccharides by liquid chromatography coupled with charged aerosol detector.

INTRODUCTION: Codonopsis Radix (CR) is an edible food and traditional Chinese herb medicine that is widely used in China and Southeast Asia. Saccharides, including fructo-oligosaccharides (FOS) and polysaccharides, are among the most important active substances in CR. However, a quality evaluation of CR based on oligosaccharides has not been conducted. OBJECTIVE: This study aimed to establish a high-performance liquid chromatography coupled with charged aerosol detector method (HPLC-CAD) for the quality evaluation of CR and processed products based on analysis of monosaccharides and oligosaccharides. METHOD: A sensitive and rapid HPLC-CAD method for the simultaneous determination of two monosaccharides (D-fructose and D-glucose), sucrose, and FOS (GF2-GF6) was established to evaluate the quality of CR for the first time. In the present study, 65 batches of CR from three species of the genus Codonopsis were analysed using multivariate statistical techniques. Furthermore, the effects of cultivation management measures (plant growth retardants supply, harvesting time, and growth period) and primary process (drying methods) in the production areas on the target compounds were studied by analysing 34 batches of processed samples. RESULTS: Different varieties of CR resulted in considerably different saccharide contents. Cultivation management measures and processing method remarkably affected the quality of CR. Low concentration of plant growth retardants was recommended. The best harvest time is in October after 4 years of growth. Dryer-drying was suggested to meet the requirement for large-scale processing. CONCLUSION: This method would provide an efficient analytical tool for monosaccharides and oligosaccharides of CR and contribute to the improvement of CR quality.

Biotransformation patterns of dictamnine in vitro/in vivo and its relative molecular mechanism of dictamnine-induced acute liver injury in mice.

Dictamnine (DIC), a typical furan-quinoline alkaloid, has a wide range of pharmacological and toxicological effects, such as anti-bacterial, antifungal, anti-cancer, and hepatoxicity. But the molecular mechanism of DIC-induced hepatoxicity in mice remains unclear. This study aimed to clarify the biotransformation patterns of DIC in vitro/in vivo and the relative molecular mechanism of DIC-induced hepatoxicity in mice. All metabolites of DIC were identified by comparing the blank and drug-containing urine, feces, plasma, and liver samples. The structure of epoxide intermediate derived from DIC was confirmed by trapping assay. Oxidative stress injury and inflammation have been confirmed to be involved in the toxicological process of DIC-induced hepatoxicity in mice by detecting the relative biochemical indexes. The results will help to develop a deeper understanding about the biotransformation patterns of DIC, structure of the epoxide intermediate, and the molecular mechanism of DIC-induced hepatoxicity in mice.

Antifatigue and antihypoxia activities of oligosaccharides and polysaccharides from Codonopsis pilosula in mice.

Codonopsis pilosula is a traditional Chinese medicine and food supplement that is widely used in China. This study aimed to investigate the antifatigue and antihypoxia activities of different extracts and fractions from C. pilosula, including ethanol extract (ETH), water extract (WAT), polysaccharides (POL), inulin (INU) and oligosaccharides (OLI). Different extracts and fractions were orally administered to mice at the doses of 0.25, 0.5 and 1.0 g kg-1 once a day for 21 days. Antifatigue activity was assessed through the weight-loaded swimming test on the 21st day, and antihypoxia activity was evaluated through the normobarie hypoxia test on the following day. Finally, biochemical parameters, such as liver glycogen (LG), muscle glycogen (MG), blood urea nitrogen (BUN), lactic dehydrogenase (LDH), malondialdehyde (MDA), and glutathione (GSH) levels, were determined. The results showed that, compared with the control treatment, only POL treatment significantly prolonged the swimming time of the mice. POL groups had the strongest hypoxia tolerance, followed by the OLI and WAT groups. The levels of LG and MG were significantly increased by treatment with POL at the doses of 0.5 and 1.0 g kg-1, whereas BUN and LDH levels in POL groups were significantly lower than those in the control group. MDA under POL and OLI treatment was significantly lower than that under the control treatment. In addition, treatments with POL and OLI, except for treatment with a low dose of OLI, significantly increased GSH levels. In conclusion, POL could efficiently enhance antifatigue and antihypoxia abilities by increasing energy resources, decreasing detrimental metabolite accumulation, and enhancing antioxidant activity. OLI could improve antihypoxia activity by preventing lipid peroxidation and enhancing antioxidant activity.

Hypoxia downregulates the angiogenesis in human placenta via Notch1 signaling pathway.

Placentation, which is critical for maternal-fetal exchange of nutrients and gases, is a complicated process comprising stepwise vasculogenesis and angiogenesis. Hypoxia caused by impaired trophoblast invasion may cause various angiogenic abnormalities in human placenta. The Notch1 signaling pathway plays an important role in the regulation of angiogenesis. The angiogenesis of human umbilical vein endothelial cells (HUVECs) under normal/hypoxic conditions and the mRNA/protein level of Notch1/Dell4/Jagged1 were investigated in this study. The effects of DAPT/JAG-1 on the migration of HUVECs were also assessed by cell wound healing assay, so as to discover the possible role of notch1 signaling pathway in the angiogenesis of human placenta. The results showed that angiogenic ability of HUVECs was seriously reduced under hypoxic conditions. The mRNA and protein levels of Notch1/Dell4/Jagged1 were decreased in the hypoxic group compared to the control one. In addition, the migration capability of HUVECs was significantly obstructed when treated with DAPT and under hopoxic condition, but promoted when treated with JAG-1. The above results demonstrate that hypoxia downregulates the angiogenesis in human placenta via Notch1 signaling pathway.

Hypoxia Downregulates the Angiogenesis in Human Placenta via Notch1Signaling Pathway / 华中科技大学学报（医学）（英德文版）

Placentation,which is critical for maternal-fetal exchange of nutrients and gases,is a complicated process comprising stepwise vasculogenesis and angiogenesis.Hypoxia caused by impairedtrophoblast invasion may cause various angiogenic abnormalities in human placenta.The Notchl signaling pathway plays an important role in the regulation of angiogenesis.The angiogenesis of human umbilical vein endothelial cells (HUVECs) under normal/hypoxic conditions and the mRNA/protein level of Notchl/Dell4/Jaggedl were investigated in this study.The effects of DAPT/JAG-1 on the migration of HUVECs were also assessed by cell wound healing assay,so as to discover the possible role of notchl signaling pathway in the angiogenesis of human placenta.The results showed that angiogenic ability of HUVECs was seriously reduced under hypoxic conditions.The mRNA and protein levels of Notchl/Dell4/Jaggedl were decreased in the hypoxic group compared to the control one.In addition,the migration capability of HUVECs was significantly obstructed when treated with DAPT and under hopoxic condition,but promoted when treated with JAG-1.The above results demonstrate that hypoxia downregulates the angiogenesis in human placenta via Notch 1 signaling pathway.

Competitive fragmentation pathways of acetic acid dimer explored by synchrotron VUV photoionization mass spectrometry and electronic structure calculations.

In present study, photoionization and dissociation of acetic acid dimers have been studied with the synchrotron vacuum ultraviolet photoionization mass spectrometry and theoretical calculations. Besides the intense signal corresponding to protonated cluster ions (CH(3)COOH)(n)·H(+), the feature related to the fragment ions (CH(3)COOH)H(+)·COO (105 amu) via ß-carbon-carbon bond cleavage is observed. By scanning photoionization efficiency spectra, appearance energies of the fragments (CH(3)COOH)·H(+) and (CH(3)COOH)H(+)·COO are obtained. With the aid of theoretical calculations, seven fragmentation channels of acetic acid dimer cations were discussed, where five cation isomers of acetic acid dimer are involved. While four of them are found to generate the protonated species, only one of them can dissociate into a C-C bond cleavage product (CH(3)COOH)H(+)·COO. After surmounting the methyl hydrogen-transfer barrier 10.84 ± 0.05 eV, the opening of dissociative channel to produce ions (CH(3)COOH)(+) becomes the most competitive path. When photon energy increases to 12.4 eV, we also found dimer cations can be fragmented and generate new cations (CH(3)COOH)·CH(3)CO(+). Kinetics, thermodynamics, and entropy factors for these competitive dissociation pathways are discussed. The present report provides a clear picture of the photoionization and dissociation processes of the acetic acid dimer in the range of the photon energy 9-15 eV.

Photoionization study of L-valine in the gas phase by vacuum ultraviolet synchrotron radiation.

The photoionization and photodissociation of L-valine are studied by tunable synchrotron vacuum ultraviolet photoionization mass spectrometry at the photon energy of 13 eV. The ionization energy of L-valine and the appearance energies of major fragments are measured by the photoionization efficiency spectrum in the photon energy range of 8-11 eV. Possible formation pathways of the major fragments, NH(2)CHC(OH)(2)(+) (m/z=75), NH(2)(CH(3))(2)(CH)(2)(+) (m/z=72) and NH(2)CHCO(+) (m/z=57), are discussed in detail with the theoretical calculations at the B3LYP/6-31++G (d, p) level. Hydrogen migration is considered as the key way for the formation of NH(2)CHC(OH)(2)(+) (m/z=75) and NH(2)CHCO(+) (m/z=57). Furthermore, other fragments, NH(2)CHCOOH(+) (m/z=74), (CH(3))(2)(CH)(2)(+) (m/z=56), C(4)H(7)(+) (m/z=55), NH(2)CHOH(+) (m/z=46), NH(2)CH(2)(+) (m/z=30) and m/z=18, species are also briefly described.

[Biodiversity and enzyme screening of actinomycetes from Hami lake].

OBJECTIVE: In order to study the biodiversity of actinomycetes isolated from salt lakes in Hami, Xinjiang, and the characteristics of enzymes thereof. METHODS: Soil samples in salt lakes Hami were isolated with 4 isolation media containing 5% and 10% NaCl (w/v) by dilution-plate method. The activities of lipase, galactosidase, amylase, esterase and cellulose from isolated strains were qualitatively detected by using five selective media. Based on morphological characteristics, test of salt tolerance, antibacterial activitity, enzymatic characters and sequencing of 16S rRNA gene, strains were selected for phylogenetic analysis. RESULTS: A total of 63 actinomycetes were isolated from salt lake in Hami, of which 47 strains were halophilic actinomycetes. The antibacterial activity results showed that 23 strains had antibacterial activity toward Bacillus subtilis and other pathogens. Three strains produced proteinase, 46 strains produced amylase, 14 strains produced esterase, 34 strains produced galactosidase, and 5 strains produced cellulase. Analysis of 16S rRNA gene sequence indicated relatively rich genotypic diversity among these actinomycetes. CONCLUSION: There were abundant actinomycetes resources in the salt lakes in Hami, Xinjiang. The strains had very promising enzyme activities.

Saccharopolyspora qijiaojingensis sp. nov., a halophilic actinomycete isolated from a salt lake.

A halophilic actinomycete strain, designated YIM 91168T, was isolated from a salt lake in Xinjiang province, north-west China. The isolate grew at 20-40 degrees C, pH 5-8 and 6-22% (w/v) NaCl; there was no growth in the absence of NaCl. The whole-cell hydrolysate contained meso-diaminopimelic acid, galactose and arabinose. The major fatty acids were iso-C15:0, iso-C16:0 and iso-C17:0. MK-9(H4) was the predominant menaquinone and the genomic DNA G+C content was 70.1 mol%. These chemotaxonomic data, together with its morphological properties, were consistent with the assignment of strain YIM 91168T to the genus Saccharopolyspora. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain YIM 91168T had highest sequence similarity (95.4%) with Saccharopolyspora gregorii NCIB 12823T, and showed lower 16S rRNA gene sequence similarity (93.0-95.1%) with the other species of the genus Saccharopolyspora. On the basis of evidence from this polyphasic study, the novel species Saccharopolyspora qijiaojingensis sp. nov. is proposed. The type strain is YIM 91168T (=DSM 45088T=KCTC 19235T).

Zhihengliuella alba sp. nov., and emended description of the genus Zhihengliuella.

A Gram-positive, non-motile, white-pigmented, short rod actinobacterium, designated YIM 90734T, was isolated from a saline soil sample collected from Ganjiahu Suosuo Forest National Nature Reserve in Xinjiang province, north-west China, and its taxonomic position was investigated by using a polyphasic approach. Strain YIM 90734T grew optimally at 28-37 degrees C and pH 6.0-8.0 and in 5% (w/v) NaCl. The peptidoglycan type was A4alpha, L-Lys-L-Ala-L-Glu and tyvelose and mannose were the major cell-wall sugars. The predominant menaquinones were MK-10 and MK-9. Major cellular fatty acids (>10% of total) were anteiso-C15:0 and anteiso-C17:0. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, one unknown phospholipid and two unknown glycolipids. The DNA G+C content was 70.3 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain YIM 90734T belonged to the genus Zhihengliuella. The 16S rRNA gene sequence similarity between strain YIM 90734T and the type strain of the only recognized Zhihengliuella species, Zhihengliuella halotolerans, was 97.7%. However, the level of DNA-DNA relatedness of the two strains was 41.4%. The DNA-DNA relatedness data and differential phenotypic properties, together with the phylogenetic distinctiveness, demonstrated that strain YIM 90734T could be differentiated from Z. halotolerans. On the basis of the data presented, strain YIM 90734T is considered to represent a novel species of the genus Zhihengliuella, for which the name Zhihengliuella alba sp. nov. is proposed. The type strain is YIM 90734T (=KCTC 19375T=DSM 21143T). The description of the genus Zhihengliuella has also been emended.

Marinococcus luteus sp. nov., a halotolerant bacterium isolated from a salt lake, and emended description of the genus Marinococcus.

A Gram-positive, aerobic, motile, coccoid, orange-pigmented bacterium, designated strain YIM 91094(T), was isolated from a salt lake sample collected from Barkol Lake in Xinjiang Province, north-west China. The strain was able to grow at pH 6.0-8.0 (optimal growth at pH 7.0), at 10-37 degrees C (optimal growth at 28 degrees C) and in the presence of 0-25 % (w/v) NaCl [optimal growth in the presence of 10-15 % (w/v) NaCl]. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain YIM 91094(T) was affiliated with the genus Marinococcus and exhibited levels of sequence similarity of 99.2 % to Marinococcus halotolerans YIM 70157(T) and 99.7 % to Marinococcus halophilus DSM 20408(T). However, it showed moderately low levels of DNA-DNA relatedness with the above type strains (56.0 and 57.5 %, respectively). The peptidoglycan type of strain YIM 91094(T) was A1gamma, with meso-diaminopimelic acid as the diagnostic diamino acid. MK-7 was the predominant menaquinone and anteiso-C(15 : 0) (49.9 % of the total) and anteiso-C(17 : 0) (29.6 %) were the major cellular fatty acids. The DNA G+C content was 48.7 mol%. Strain YIM 91094(T) possessed chemotaxonomic markers that were consistent with its classification in the genus Marinococcus. On the basis of the data presented, strain YIM 91094(T) is considered to represent a novel species of the genus Marinococcus, for which the name Marinococcus luteus sp. nov. is proposed. The type strain is YIM 91094(T) (=KCTC 13214(T)=CCTCC AA 208014(T)). An emended description of the genus Marinococcus is provided.