Didymin attenuates doxorubicin-induced cardiotoxicity by inhibiting oxidative stress / 中草药·英文版

Objective: This study was designed to investigate the protective effects of didymin (Did) on doxorubicin (DOX)-induced cardiotoxicity. Methods: After pretreatment with Did (2, 4, 8 mg/kg intraperitoneal i.p.) for 7 d, the male C57 mice were injected with single dose of DOX (20 mg/kg i.p.). The cardioprotective effect of Did was observed on the 7th day after DOX treatment. Results: DOX delayed body growth and caused cardiac tissue injury, oxidative stress, and mitochondrial dysfunction. Similar experiments in H9C2 cardiomyocytes showed that DOX reduced cell viability, increased generation of reactive oxygen species (ROS) and fragmentation of DNA, decreased mitochondrial membrane potential, and induced cardiomyocyte apoptosis. However, all of these adverse effects were suppressed by Did pretreatment. Did increased protein expression of glutamate-L-cysteine ligase catalytic subunit (GCL), heme oxygenase 1 (HO-1), and nuclear factor erythroid 2-related factor 2 (Nrf2). Besides, Did also induced activation of PI3K/AKT. Conclusion: These findings indicated Did prevented DOX-induced cardiac injury and apoptosis via activating PI3K/AKT/Nrf2 signaling pathway.

Protective Effect of Water Extract of Citri Grandis Exocarpium on Alcohol-induced Acute Liver Injury / 中国实验方剂学杂志

ObjectiveTo explore the pharmacodynamic effect of the water extract of Citri Grandis exocarpium （WEC） on mice with alcohol-induced acute liver injury and provide data support for the development of this medicinal for anti-alcoholism and liver protection. MethodThe main components of WEC were determined by high performance liquid chromatography （HPLC）. Sixty Balb/c mice were randomized into 6 groups： control group （equal volume of 0.5% carboxymethyl cellulose sodium solution）， model group （equal volume of 0.5% carboxymethyl cellulose sodium solution）， low-， medium-， and high-dose WEC groups （0.5， 1.0， 2.0 g·kg-1）， and Haiwang Jinzun tablet positive control group （2.0 g·kg-1）. The administration lasted 14 days. One day before the end of the administration， mice were fasted for 12 h with free access to water. The mice， except the control group， were given 56° Chinese liquor （13 mL·kg-1）. After 2 h， blood was taken from eyeballs and the liver was dissected and weighed. Automatic biochemical analyzer was employed to detect the expression of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and alcohol dehydrogenase （ADH）. The pathological changes of liver tissues were observed based on hematoxylin-eosin （HE） staining， and apoptosis of hepatocytes based on TUNEL/DAB staining. The expression of proteins related to apoptosis was detected by Western blot. ResultAccording to the HPLC fingerprint， the main components of WEC were rhoifolin and naringin. Compared with the control group， the model group showed increase in liver/body weight ratio （P<0.01） and the expression of ALT and AST （P<0.05， P<0.01）， decrease in the expression of ADH （P<0.05）， blurred structure of hepatic lobules， pathological changes of liver tissue， loose cytoplasm with edema， severe steatosis， rise of the TUNEL-positive rate （P<0.01）， reduction in expression of Bcl-2 （P<0.01）， and increase in Bax and Caspase-3 （P<0.01）. Compared with the model group， medium-dose WEC lowered liver/body weight ratio （P<0.05）. All doses of WEC depressed the activity of ALT and AST （P<0.05， P<0.01）， up-regulated the expression of ADH （P<0.05）， significantly improved the pathological features of alcohol-induced cytoplasmic porosity， edema， and steatosis， down-regulated the TUNEL-positive rate （P<0.05， P<0.01）， enhanced the expression of Bcl-2 （P<0.05）， and decreased Bax and Caspase-3 （P<0.01）. ConclusionWEC regulates the expression of ALT， AST， and ADH and improves hepatic steatosis and hepatocyte apoptosis to fight against acute liver injury.

Protective Effect of Water Extract of Citri Grandis Exocarpium on Alcohol-induced Acute Liver Injury / 中国实验方剂学杂志

ObjectiveTo explore the pharmacodynamic effect of the water extract of Citri Grandis exocarpium （WEC） on mice with alcohol-induced acute liver injury and provide data support for the development of this medicinal for anti-alcoholism and liver protection. MethodThe main components of WEC were determined by high performance liquid chromatography （HPLC）. Sixty Balb/c mice were randomized into 6 groups： control group （equal volume of 0.5% carboxymethyl cellulose sodium solution）， model group （equal volume of 0.5% carboxymethyl cellulose sodium solution）， low-， medium-， and high-dose WEC groups （0.5， 1.0， 2.0 g·kg-1）， and Haiwang Jinzun tablet positive control group （2.0 g·kg-1）. The administration lasted 14 days. One day before the end of the administration， mice were fasted for 12 h with free access to water. The mice， except the control group， were given 56° Chinese liquor （13 mL·kg-1）. After 2 h， blood was taken from eyeballs and the liver was dissected and weighed. Automatic biochemical analyzer was employed to detect the expression of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and alcohol dehydrogenase （ADH）. The pathological changes of liver tissues were observed based on hematoxylin-eosin （HE） staining， and apoptosis of hepatocytes based on TUNEL/DAB staining. The expression of proteins related to apoptosis was detected by Western blot. ResultAccording to the HPLC fingerprint， the main components of WEC were rhoifolin and naringin. Compared with the control group， the model group showed increase in liver/body weight ratio （P<0.01） and the expression of ALT and AST （P<0.05， P<0.01）， decrease in the expression of ADH （P<0.05）， blurred structure of hepatic lobules， pathological changes of liver tissue， loose cytoplasm with edema， severe steatosis， rise of the TUNEL-positive rate （P<0.01）， reduction in expression of Bcl-2 （P<0.01）， and increase in Bax and Caspase-3 （P<0.01）. Compared with the model group， medium-dose WEC lowered liver/body weight ratio （P<0.05）. All doses of WEC depressed the activity of ALT and AST （P<0.05， P<0.01）， up-regulated the expression of ADH （P<0.05）， significantly improved the pathological features of alcohol-induced cytoplasmic porosity， edema， and steatosis， down-regulated the TUNEL-positive rate （P<0.05， P<0.01）， enhanced the expression of Bcl-2 （P<0.05）， and decreased Bax and Caspase-3 （P<0.01）. ConclusionWEC regulates the expression of ALT， AST， and ADH and improves hepatic steatosis and hepatocyte apoptosis to fight against acute liver injury.

Clinical Features of Multicenter Autoimmune Glial Fibrillary Acidic Protein Astrocytosis / 罕见病研究

  Objective  To investigate the clinical features of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy.  Methods  We collected and analyzed the clinical and laboratory data and obtained the clinical characteristics of diagnosis and treatment from fifteen patients with positive GFAP antibody tested by cerebrospinal fluid and diagnosed autoimmune GFAP astrocytopathy by the multi-centers.  Results  The mean age of the first onset of autoimmune GFAP astrocytopathy was 39.73 years old (range 4-65 years), with no significant gender difference. In terms of clinical manifestations, we found the whole brain symptoms including abnormal mental behavior, disturbance of consciousness, epileptic attack accounting for more than 50, , meningitis accounting for 66.7%, myelitis (53.3%), limb tremor (53.3%), vision loss (33.3%); systemic symptoms including fever(100%) and fatigue(86.7%). 46.7% of patients were initially diagnosed with tuberculous meningoencephalitis and were treated with diagnostic antituberculous therapy. The MRI showed 46.7% of patients showed brain linear perivascular radial gadolinium enhancement in the white matter perpendicular to the ventricle.  Conclusions  Autoimmune GFAP astrocytopathy are acute or subacute dieases and the main clinical features include encephalitis, meningitis, myelitis and optic neuritis. They are likely to be misdiagnosed as tuberculous meningoencephalitis and can manifest progressive loss of consciousness in early phase, which is even life threatening.

Long Noncoding RNAs: Novel Important Players in Adipocyte Lipid Metabolism and Derivative Diseases.

Obesity, a global public health issue, is characterized by excessive adiposity and is strongly related to some chronic diseases including cardiovascular diseases and diabetes. Extra energy intake-induced adipogenesis involves various transcription factors and long noncoding RNAs (lncRNAs) that control lipogenic mRNA expression. Currently, lncRNAs draw much attention for their contribution to adipogenesis and adipose tissue function. Increasing evidence also manifests the pivotal role of lncRNAs in modulating white, brown, and beige adipose tissue development and affecting the progression of the diseases induced by adipose dysfunction. The aim of this review is to summarize the roles of lncRNAs in adipose tissue development and obesity-caused diseases to provide novel drug targets for the treatment of obesity and metabolic diseases.

Isolation, identification, and phylogenetic analysis of subgroup III strain of bovine respiratory syncytial virus contributed to outbreak of acute respiratory disease among cattle in Northeast China.

Bovine respiratory syncytial virus (BRSV) is a clinically important causative agent of acute respiratory diseases in postweaning calves and feedlot cattle and causes numerous economic losses to the cattle industry. In June 2018, an outbreak of an acute respiratory disease occurred among 4- to 10-month-old calves on three intensive beef cattle farms in Heilongjiang Province, Northeast China, with a 27.42% morbidity rate (329/1200) and a > 25% mortality rate (85/329). Using next-generation sequencing, we comprehensively analyzed microbial diversity in the lung samples of the diseased cattle and found that the causative agent of this epidemic outbreak is mainly a bovine orthopneumovirus named BRSV strain DQ. We then isolated and confirmed the virus by RT-PCR and an indirect immunofluorescence assay. Phylogenetic analysis of genes G, F, N, NS1, NS2, and SH of BRSV strain DQ showed that this strain shares the highest genetic similarity with strains USII/S1, 15489, V41, and NY487834 belonging to subgroup III of BRSV. This is the first report of subgroup III strain of BRSV presence in China. Heilongjiang Province is a major cattle-breeding province in China; therefore, it is necessary to test for BRSV in the cattle trade and to conduct region-extended epidemiological surveillance for BRSV in China.

Evaluation of drug myocardial toxicity and biological activity by real time xCELLigence analysis: a review / 生物工程学报

Realtime xCELLigence analysis (RTCA) is a new cell detection technology to continuously monitor, record and analyze a variety of information generated by cell activity. In drug research, it plays an important role in assessing myocardial toxicity and cell biological activity. Here, we first introduce the underlying mechanisms and characteristics of RTCA. Then we review the applications of RTCA in the research of myocardial toxicity and cell biological activity, to provides the fundamental baseline for understanding and exploiting RTCA. With the real-time, unlabeled, non-invasive, high throughput, and high accuracy features, RTCA not only promotes drug research and development, but also has a broad and good application prospect in other fields.

Detection of the epidemic of the H3N8 subtype of the equine influenza virus in large-scale donkey farms.

To monitor the occurrence of equine influenza in large-scale donkey farms in Liaocheng City, Shandong Province, serological investigation and sequence analysis of HA/M protein gene of equine influenza virus (EIV) were carried out. Samples (n = 65) of the lung and nasal swab were collected in six different large-scale donkey farms and detected with RT-PCR for HA and M protein gene. The homology and evolution of HA and M genes were analysed with known sequences. Antibody titres of serum samples (n = 120, unvaccinated) level was determined by the HI test. The average seropositive rate was 32.5% (39/120) with great diversity among different populations. The positive rate of EIV HA/M protein gene was 21.5% (14/65) by RT-PCR. The equine influenza H3N8 virus was confirmed by gene sequencing, and the homology of the sequence was 99.77% with isolates from Northeast China (equine/heilongjiang/1/2010), consistent with the input of donkeys. This suggested that EIV has become an important threat to large-scale donkey farms in Liaocheng and threats from the input area must be vigilant.

Identification of Medium-Length Antineurofilament Autoantibodies in Patients with Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Background@#and Purpose: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe central nervous system disorder mediated by NMDAR antibodies that damages neurons. We investigated the correlation between cytoskeletal autoantibodies and the clinical severity in patients with anti-NMDAR encephalitis. @*Methods@#Non-NMDAR autoantibodies were identified by screening matched cerebrospinal fluid (CSF) and the serum samples of 45 consecutive patients with anti-NMDAR encephalitis and 60 healthy individuals against N-methyl-D-aspartate receptor 1-transfected and nontransfected human embryonic kidney 293T cells. Immunocytochemistry was performed to assess antibody binding in rat brain sections and primary cortical neurons. Cell-based assays and Western blotting were applied to identify autoantibodies targeting medium neurofilaments (NFMs). We compared clinical characteristics between patients with NMDAR encephalitis who were positive and negative for anti-NFM-autoantibodies. @*Results@#Anti-NFM autoantibodies were detected in both the serum and CSF in one patient (2%) and in the serum only in six patients (13%). No antibodies were detected in the serum of healthy controls (7/45 vs. 0/60, p=0.0016). Four of the seven patients with anti-NFM autoantibodies in serum were children (57%), and three (43%) had abnormalities in brain magnetic resonance imaging. These patients responded well to immunotherapy, and either no significant or only mild disability was observed at the last follow-up. Anti-NMDAR encephalitis did not differ with the presence of anti-NFM autoantibodies. @*Conclusions@#Anti-NFM autoantibodies may be present in patients with anti-NMDAR encephalitis, indicating underlying neuronal damage. A large cohort study is warranted to investigate the clinical differences between patients with NMDAR encephalitis according to their antiNFM antibody status.

Myelin Oligodendrocyte Glycoprotein-IgG Contributes to Oligodendrocytopathy in the Presence of Complement, Distinct from Astrocytopathy Induced by AQP4-IgG / 神经科学通报·英文版

Immunoglobulin G against myelin oligodendrocyte glycoprotein (MOG-IgG) is detectable in neuromyelitis optica spectrum disorder (NMOSD) without aquaporin-4 IgG (AQP4-IgG), but its pathogenicity remains unclear. In this study, we explored the pathogenic mechanisms of MOG-IgG in vitro and in vivo and compared them with those of AQP4-IgG. MOG-IgG-positive serum induced complement activation and cell death in human embryonic kidney (HEK)-293T cells transfected with human MOG. In C57BL/6 mice and Sprague-Dawley rats, MOG-IgG only caused lesions in the presence of complement. Interestingly, AQP4-IgG induced astroglial damage, while MOG-IgG mainly caused myelin loss. MOG-IgG also induced astrocyte damage in mouse brains in the presence of complement. Importantly, we also observed ultrastructural changes induced by MOG-IgG and AQP4-IgG. These findings suggest that MOG-IgG directly mediates cell death by activating complement in vitro and producing NMOSD-like lesions in vivo. AQP4-IgG directly targets astrocytes, while MOG-IgG mainly damages oligodendrocytes.

A clinical analysis of patients with AQP4-IgG and MOG-IgG seropositive / 中国神经精神疾病杂志

Objective To study the seropositive ratio of the antibody to aquporin 4 (AQP4-IgG) and myelin oligodendrocytes glycoprotein antibody(MOG-IgG)in patients with autoimmune-associated central nervous system (CNS) diseases. Meanwhile, epidemiology and clinical manifestation and diagnosis,laboratory examination and magnetic resonance imaging(MRI)of AQP4-IgG seropositive and MOG-IgG seropositive patients are described. Methods 2068 patients serum samples were collected and enrolled in the multi-center research. The methodology of cell-mediated immunofluorescence staining was used to detect serum AQP4-IgG and MOG-IgG. Clinic medical records were collected and characteristics of epidemiology and manifestation were compared. Results 681 patients were AQP4-IgG seropositive and 110 patients were MOG-IgG seropositive. The female/male ratio and age of onset of patients with AQP4-IgG seropositive(616 female and 65 male,female:male=9.50:1.00;Age of onset=41.7±14.9)were significantly higher than that of patients with MOG-IgG (57 female and 53 male, female:male=1.08:1.00, P<0.0001; Age of onset=27.0 ±17.7, P<0.0001). The optic neuritis was significantly higher in patients with AQP4-IgG seropositive and patients with MOG-IgG seropositive (38.4% vs.53.5%, P<0.05).Among patients with AQP4-IgG seropositive, 42.14% conformed the diagnostic criteria of neuromyelitis optica (NMO),which was higher than that of patients with MOG-IgG seropositive (13.64%, P<0.0001). Laboratory examination showed that there was no significant difference in cerebrospinal fluid protein levels between patients with AQP4-IgG seropositive and those with MOG-IgG seropositive.MRI imaging suggested that AQP4-IgG positive patients were more common in cervical thoracic spinal cord lesions, while MOG-IgG positive patients were more involved in thoracolumbar spinal cord. The study also found that these two groups of patients could be comorbid with other autoimmune antibodies. Conclusions This multi-center research has revealed that patients with AQP4-IgG seropositive and those with MOG-IgG seropositive display differences in epidemiology,clinic manifestations and diagnosis,laboratory examination and MRI imaging. AQP4-IgG and MOG IgG auto-antibody detection are necessary for clinic diagnosis and differential diagnosis.

Longitudinal electroencephalographic(EEG) finding in anti-N-methyl-D-aspartate(Anti-NMDA) receptor encephalitis / 中国神经精神疾病杂志

Objective To investigate electroencephalographic (EEG) characteristics of anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis during different courses of the disease. Methods This study enrolled 30 cases of anti-NMDA receptor encephalitis patients. A total of 58 EEG monitoring reports and their clinical data were retrospectively analyzed based on different disease courses and severity of disease. According to the clinical stages, EEG data was divided into 4 phases: the initial stage (4), the peak stage (23), the improvement stage (16) and the recovery stage(15). Based on severity of disease during the peak stage, patients were divided into mild group(10 cases) and severe group (13 cases). Results Occipital background activity of the EEG was presented in all patients (100%) in the initial stage and in the recovery stage, in 39.1%(9/23)in the peak stage and in 13/16 (81.2%)in the improvement stage. Generalized rhythmic delta activity (GRDA) pattern could only be detected in the peak stage and the improvement stage. In the peak stage, the main presentation of abnormal EEG was diffuse slow-wave (9 cases, 90%) in mild group. GRDA and extreme delta brush(EDB) were more common in severe group than in mild group(P<0.05). Three focal epilepsy including one status epilepticus were detected in three patients in the peak stage. Focal epileptiform discharges in EEG existed in the whole course. Conclusion Occipital background activity and GRDA pattern are evolved and gradually recovered during the course of the disease. The EEG patterns of GRDA and EDB are common in severe anti- NMDA receptor encephalitis patients in the peak stage. Focal epileptiform discharges in EEG can be detected during the whole course.

Clinical efficacy of cutting edge needle for treating KOA and its effect on biomechanical indexes / 重庆医学

Objective To investigate the clinical effect of cutting edge needle for treating knee osteoarthritis(KOA) and its effect on biomechanical indexes.Methods Thirty-eight patients with KOA diagnosed in the Ganzhou Municipal Hospital of Traditional Chinese Medicine from March 2016 to December 2016 were selected and divided into the acupuncture group(using traditional acupuncture method) and sham-acupuncture group(using round cutting edge needle method),19 cases in each group.The patient' s pain situation of each group during the treatment process,knee joint function,inflammatory effects and biomechanical indicators after 3-week treatment were observed.Results The total effective rate of the sham-acupuncture group was 94.74％,which was higher than 68.42％ in the acupuncture group,the difference between the two groups was statistically significant(P＜0.05).The visual analog scale(VAS) and Tegner scores before treatment had no statistical difference between the two groups(P＞0.05).The VAS and Tegner scores after treatment had statistical difference between the two groups(P＜0.05).After treatment,the differences of femoral angle(F),joint space angle(JS) and femoral condyle height(H)/width(W) between the two groups were statistically significant(P＜0.05),while the tibial angle(T) and femoral tibial angle(FT) had no statistically significant difference(P＞0.05).Conclusion The clinical efficacy of cutting edge needle in the treatment of KOA is prominent,and the VAS score,Tegner score and biomechanical indexes are significantly improved,which is worthy of clinical promotion.

Content Determination and Cluster Analysis of 3 Lignans from Cortex Magnoliae Officinalis in Different Regions / 世界科学技术-中医药现代化

Objective: To establish the method of simultaneous determination of contents of honokiol, magnolol and piperitylmagnolol in Cortex Magnoliae Officinalis from different regions, which could provide evidence for the quality control evaluation of Cortex Magnoliae Officinalis. Methods: The quantitative analysis was performed with a column of Waters Acquity UPLC BEH-Cl8 (2.1 mm×50 mm, 1.7 μm) by UPLC-PDA, and eluted with a mobile phase of 0.2％formic acid solution (A)-methanol (B) in a gradient mode (0-2 min, 65％-65％ B; 2-3 min, 65％-75％ B; 3-5 min, 75％-84％ B; 5-9 min, 84％-90％ B) under a flow rate of 0.5 mL·min-1. The column temperature was set at 35℃, and the detection wavelength was 294 nm and the injection volume was 1 μL. Results: The 3 lignan components were completely separated and could be separated well from other components. The honokiol, magnolol and piperitylmagnolol showed a good linear relationship with chromatographic peak area in range of 20.3-406.0, 15.2-304.0, 5.6-112.0 ng, respectively.The average recoveries were 91.75％, 93.86％, 95.15％ with the RSDs were 1.75％, 1.88％, 1.91％ (n = 9), respectively.Conclusion: Contents of the 3 constituents from different place were significantly different and this method is simple and effective, which can be used to quality control of Cortex Magnoliae Officinalis.

The Development Strategy and Mode of Co-construction and Sharing Base to Improve the Chinese Herbal Medicine Quality / 世界科学技术-中医药现代化

Chinese medicinal materials occupy an important position in China's health industry. However, its overall quality needs to be improved and it is in urgent need of regulation. Exploring the formation of effective organizational mechanisms and industry models has become an urgent need of the industry. In this context, the alliance of coconstruction and sharing Chinese herbal medicine base came into being. The alliance is based on the pursuit of the quality of Chinese herbal medicines and continues to promote the construction of Chinese herbal medicines. The Alliance provides a platform for economic and scientific cooperation in the industry. Its purpose is to guide the promotion of the standardization of local varieties and the construction of modern Chinese medicine agricultural enterprises based on the development needs of Chinese herbal medicine resources and the common interests of all members. As an important content, we will strive to expand the new pattern of coordinated development of traditional Chinese medicine agriculture and industry, explore the establishment of a new organizational system for modern Chinese medicine agricultural production with controllable quality, output and price under the link of production and demand. For the sustainable, stable and healthy development of the Chinese medicine industry, it will serve 1.3 billion people and serve humanity, provide high-quality sustainable Chinese herbal medicine resources. Since its establishment six years ago, the alliance has carried out work on key aspects such as standardized production of Chinese herbal medicines, plant protection, decoction processing, supply and demand docking, medicinal materials standards, poverty alleviation, breeding, and provided technical support to enterprises. During this period, the alliance also proposed the concept of"three-no and one- all"requires the members to take the lead in achieving the standards of"sulfur- free processing, no aflatoxin pollution, pollution-free, traceable throughout the whole", setting a benchmark for the industry.

Study on the Effect and Mechanism of Xuezhiping Capsule on Blood Lipid Levels of High Blood Lipid Model Golden Hamsters / 中国药房

OBJECTIVE:To study the effect and its possible mechanism of Xuezhiping capsule on blood lipid levels of high blood lipid model golden hamsters. METHODS:Golden hamsters were randomly divided into normal control group,model group, atorvastatin group (3 mg/kg),combination group (Xuezhiping capsule 1.3 g/kg+atorvastatin 1.5 mg/kg),Xuezhiping capsule low-dose,medium-dose,high-dose groups(Xuezhiping capsule 1.3,2.6,5.2 g/kg),10 in each group. Hamsters in normal control group received normal diet,the other groups were given high-fat diet to establish high blood lipid model. Then relevant drugs were intragastrically given 2 weeks later. Normal control group and model group were intragastrically given equal volume of distilled wa-ter,once a day,for 4 weeks. After last administration,blood lipid indexes(TG,TC,HDL-C,LDL-C,FFA),mRNA and protein expressions of lipid metabolism related genes (PPAR-α,CYP7A1,ACOX,SREBP-1c,ACC1) were detected. RESULTS:Com-pared with normal control group,serum contents of TC,TG,LDL-C,FFA in model group increased,HDL-C content decreased;PPAR-α,CYP7A1,ACOX mRNA and protein expressions were weakened,SREBP-1c,ACC1 mRNA and protein expressions were enhanced(P<0.05). Compared with model group,above-mentioned indexes were obviously improved in Xuezhiping capsule high-dose group,atorvastatin group and combination group (except for HDL-C in Xuezhiping capsule high-dose group)(P<0.05);TC,TG,FFA contents,and PPAR-α,CYP7A1,ACOX,ACC1 mRNA,and CYP7A1,SREBP-1c,ACC1 protein were obviously improved in Xuezhiping capsule medium-dose group(P<0.05);TC,TG contents,and PPAR-α mRNA,and CYP7A1, SREBP-1c protein were obviously improved in Xuezhiping capsule low-dose group (P<0.05). CONCLUSIONS:Xuezhiping cap-sule has a promising effect of lowering blood lipid,the mechanism may be related to activating PPAR-α and inhibiting SREBP-lc signaling pathway.

Pharmacokinetics studies on caffeine,dextromethorphan,omeprazole, midazolam and their metabolites in rat plasma by LC-MS/MS / 中国药理学通报

Aim To develop a sensitive,rapid and ac-curate LC-MS /MS method for the simultaneous deter-mination of cytochrome P450 probe substrates,inclu-ding caffeine and its metabolite paraxanthine for CYP1 A2,omeprazole and its metabolite 5-hydroxyome-prazole for CYP2C1 9,dextromethorphan and its metab-olite dextrorphan for CYP2D6,midazolam and its me-tabolite 1 ′-hydroxymidazolam for CYP3A4.Methods Probe drugs with the IS diazepam were extracted using ethyl acetate.Gradient elution was performed on an Agilent Eclipse Plus-C1 8 column (50 mm ×2.1 mm, 3.5 μm).The mobile phase consisted of 0.01 % for-mic acid(1 mmol·L -1 ammonium formate)and aceto-nitrile.The flow rate was 0.3 mL·min -1 ,and the in-jection volume was 1 0 μL.The analyte was detected u-sing electrospray ionization(ESI)in positive multiple reaction monitoring(MRM+)mode.The reaction se-lected ions were 1 95.0 /1 38.1 m /z for caffeine, 1 81 .1 /1 24.1 m /z for paraxanthine,346.1 /1 98.1 m /z for omeprazole,362.1 /21 4.1 m /z for 5-hydroxyome-prazole, 272.2 /1 47.1 m /z for dextromethorphan, 258.1 /1 57.1 m /z for dextrorphan,326.1 /291 .1 m /z for midazolam,342.1 /324.1 m /z for 1 ′-hydroxymid-azolam and 285.1 /1 54.0 m /z for diazepam as internal standard.Results The linear ranges of caffeine,pa-raxanthine,omeprazole,5-hydroxyomeprazole,dextro-methorphan, dextrophan, midazolam and 1 ′-hydroxymidazolam were 1 .95 ~2 000,0.98 ~250, 0.48 ~2 000,0.98 ~250,0.98 ~2 000,0.48 ~1 25,1 .95 ~2 000 and 1 .95 ~250 μg·L -1 respec-tively.The RSD of all probe drugs was less than 1 5%and matrix effects in plasma on the ionization of probe drugs were negligible.Conclusion This sensitive and rapid LC-MS /MS method is suitable for determination of the drug/metabolite concentrations in plasma,so as to study the metabolism of CYP1 A2, CYP2C1 9, CYP2D6 and CYP3A4 in depth.

Multiple Autoantibodies and Neuromyelitis Optica Spectrum Disorders.

OBJECTIVE: To investigate the relationship between neuromyelitis optica spectrum disorder (NMOSD) and autoantibodies. METHODS: Blood samples of 108 NMOSD patients and 38 controls were collected from January 2012 to August 2014. Immunological parameters, including anti-aquaporin 4, antinuclear, anti-ribonucleoprotein, anti-SM, anti-SSA/Ro, anti-SSB/La and anti-ribosomal P-protein autoantibodies were examined. RESULTS: The NMOSD group exhibited a significantly higher percentage of anti-aquaporin 4 antibodies compared with the control group (76.9 vs. 0.0%, p = 0). The positive rates for antinuclear and anti-SSA antibodies in the NMOSD group were also higher than in the control group (35.2 vs. 11.8%, p = 0.001; 13.0 vs. 0.0%, p = 0.044). In total, 36.1% of the patients in the NMOSD group were seropositive for autoantibodies but only 8.3% were diagnosed with definite systemic autoimmune disorders. CONCLUSIONS: NMOSD is closely associated with elevated autoantibodies, particularly antinuclear and anti-SSA/Ro antibodies. NMOSD rarely coexists with organ-specific autoimmune diseases.

Protective effect of Panax Notoginseng Saponins of Nrf2 signaling pathway on apoptosis of PC12 cells induced by Aβ25-35 / 中国药理学通报

Aim To investigate the protective effect of Panax Notoginseng Saponins ( PNS ) on Aβ25-35-in-duced apoptosis in PC12 cells and molecular mecha-nism. Methods The cell viability of PC12 cells was detected by MTT assay. The levels of LDH leakage, ROS,MDA,Caspase-3 activity and antioxidant enzyme activities of SOD, CAT, and GSH-Px activity were de-termined by respective kits. The apoptosis of cells was decteced by Western blot. Results PNS could signifi-cantly inhibit the decrease of cell viability and LDH leakage, reduce the production of MDA and ROS( P<0. 01), increase the activity of SOD,CAT and GSH-Px ( P <0. 01 ) , and the mitochondrial membrane poten-tial, inhibit the activation of caspase-3 ( P <0. 01 ) in PC12 cells which were induced by Aβ25-35 . PNS could incrase nuclear Nrf2 and up-regulate HO-1 . The neu-roprotective of PNS could be inhibited by HO-1 inhibi-tor ZnPP. Conclusion PNS may inhibit Aβ25-35-in-duced oxidative stress and apoptosis in PC12 cells by activating Nrf2/HO-1 signaling pathway.

Research progress of JAK/STAT signal transduction pathway and traditional Chinese medicine intervention in the treatment of ischemic stroke / 中国药理学通报

Ischemic stroke, gravely affecting human health with its increasing incidence rate , is a common disease of old age . JAK/STAT way , a recently discovered signaling pathway , is not only widely involved in processes of cell growth ,differentiation, and apoptosis ,but also closely related to the pathophysiology of stroke.However,the pathway function and mechanism in ische-mic cerebral stroke has not yet been fully elucidated .We will review the role and mechanism of JAK/STAT signal transduction pathway in ischemic stroke ,and scientifically draw network chart between various related signal molecules in the process of ische-mic stroke neuropathy combining both domestic and foreign re-search reported in this paper , in order to better understand the pathological mechanism process of brain stroke , find new drugs for the treatment of cerebral ischemic diseases ,then provide more systematic scientific literature support .