Direct Determination of 23 Kinds of Per-and Polyfluoroalkyl Substances in Crude Plant Extracts by Liquid Chromatography-Tandem Mass Spectrometry Coupled with Online Solid Phase Extraction / 分析化学

A new method for simultaneous determination of 23 kinds of per-and polyfluoroalkyl substances(PFASs)(13 kinds of perfluoro carboxylic acids,4 kinds of perfluoro sulfonic acids,and 6 kinds of new substitutes)in plant leaf tissue by ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)using automatic online solid phase extraction(SPE)to remove the matrix interference components in plant crude extracts was developed.The plant leaf samples were extracted twice with 1%formic acid-methanol solution,then evaporated to dry,redissolved with 70%methanol solution,and directly injected for analysis.After 23 kinds of target PFASs were purified automatically by online SPE with a WAX column,the six-way valve was switched to rinse PFASs onto an alkaline mobile phase system-compatible C18 analytical column.Then,the 23 kinds of target PFASs were separated within 16 min by gradient elution using a binary mobile phase system of methanol/water(Containing 0.4%ammonium hydroxide).Tandem mass spectrometry was performed in multiple reaction monitoring(MRM)mode for online detection of various PFASs,and quantification was carried out by internal standard method.The results of the method validation showed that satisfactory average recoveries of 23 kinds of PFASs in plant leaf samples(64.2%-125.5%),precision(relative standard deviations(RSDs)of 0.7%-12.8%),linearity(R2＞0.990),and sensitivity(the detection limits(S/N=3)were in the range of 0.02-0.50 μg/kg)were achieved.Finally,this method was used to detect PFASs in the marine green tide algae(Enteromorpha prolifera)and several tree leaves,and a total of 6 kinds of PFASs were detected,in which PFBA was the main contaminant.Compared with the reported offline SPE methods,the proposed online SPE technique significantly simplified the sample pretreatment process and provided an automatic,simple,and environment-friendly method for the routine monitoring of legacy and emerging PFASs in plant tissues.

Observation on the Therapeutic Effect of Yiqi Huoxue Huazhuo Therapy on Hepatic Fibrosis in Wilson's Disease / 广州中医药大学学报

Objective To assess the clinical effect of the Yiqi Huoxue Huazhuo therapy(the therapy for replenishing qi,activating blood and resolving turbidity)for the treatment of hepatic fibrosis in Wilson's disease(WD,also known as hepatolenticular degeneration).Methods Using retrospective research method,52 patients with liver fibrosis in WD of qi deficiency and blood stasis type were divided into 24 cases in the control group and 28 cases in the treatment group according to the treatment method.The control group was treated with conventional decopper therapy with western medicines,and the treatment group was treated with Chinese herbal decoction based on Yiqi Huoxue Huazhuo therapy together with conventional decopper therapy.Both groups were treated for a total of 4 weeks.Before and after the treatment,the two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome scores,Unified Wilson's Disease Rating Scale(UWDRS)hepatic symptom scores,serum levels of liver fibrosis indicators of pre-collagen typeⅢ(PCⅢ),hyaluronic acid(HA),collagenⅣ(CⅣ),and laminin(LN),C-X-C motif chemokine ligand 10(CXCL10)level,and the point shear-wave elastography(pSWE)values of hepatic ultrasound based on acoustic radiation force impulse imaging(ARFI).After treatment,the clinical efficacy of the two groups was evaluated.Results(1)After 4 weeks of treatment,the total effective rate of the treatment group was 85.71%(24/28),while that of the control group was 54.17%(13/24),and the intergroup comparison(tested by chi-square test)showed that the therapeutic efficacy of the treatment group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the TCM syndrome scores in both groups were decreased compared with those before treatment(P＜0.01),and the decrease of TCM syndrome scores in the treatment group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the UWDRS liver symptom scores in the two groups were decreased compared with those before treatment(P＜0.01),but the difference was not statistically significant when comparing between the two groups after treatment(P＞0.05).(4)After treatment,serum levels of liver fibrosis indicators of HA,LN,CⅣ and PCⅢ in the treatment group were all decreased compared with those before treatment(P＜0.01),while in the control group only serum LN and PCⅢlevels were decreased(P＜0.05).The intergroup comparison showed that the decrease of serum HA,LN,and PCⅢlevels in the treatment group was superior to that in the control group(P＜0.05 or P＜0.01),while the decrease of serum CⅣlevel tended to be superior to that in the control group,but the difference was not statistically significant(P＞0.05).(5)After treatment,the serum chemokine CXCL10 level in the treatment group was significantly decreased compared with that before treatment(P＜0.01),while the level tended to decrease in the control group,but the difference was not statistically significant(P＞0.05).The intergroup comparison showed that the reduction of serum CXCL10 level in the treatment group was significantly superior to that in the control group(P＜0.05).(6)After treatment,the pSWE values of hepatic ultrasound in the two groups were lower than those before treatment(P＜0.01),and the reduction of pSWE values in treatment group was significantly superior to that of the control group(P＜0.01).Conclusion Yiqi Huoxue Huazhuo therapy can effectively reduce the TCM syndrome scores of WD patients,improve the UWDRS hepatic symptom scores,down-regulate the liver fibrosis indicator level and serum CXCL10 expression level,reduce the pSWE values of hepatic ultrasound,and enhance the clinical efficacy.

MiR-128 suppresses metastatic capacity by targeting metadherin in breast cancer cells

BACKGROUND: Breast cancer, the most common cancer in women worldwide, causes the vast majority of cancer-related deaths. Undoubtedly, tumor metastasis and recurrence are responsible for more than 90 percent of these deaths. MicroRNAs are endogenous noncoding RNAs that have been integrated into almost all the physiological and pathological processes, including metastasis. In the present study, the role of miR-128 in breast cancer was investigated. RESULTS: Compared to the corresponding adjacent normal tissue, the expression of miR-128 was significantly suppressed in human breast cancer specimens. More importantly, its expression level was reversely correlated to histological grade of the cancer. Ectopic expression of miR-128 in the aggressive breast cancer cell line MDA-MB-231 could inhibit cell motility and invasive capacity remarkably. Afterwards, Metadherin (MTDH), also known as AEG-1 (Astrocyte Elevated Gene 1) and Lyric that implicated in various aspects of cancer progression and metastasis, was further identified as a direct target gene of miR-128 and its expression level was up-regulated in clinical samples as expected. Moreover, knockdown of MTDH in MDA-MB-231 cells obviously impaired the migration and invasion capabilities, whereas re-expression of MTDH abrogated the suppressive effect caused by miR-128. CONCLUSIONS: Overall, these findings demonstrate that miR-128 could serve as a novel biomarker for breast cancer metastasis and a potent target for treatment in the future.

Short term effect of total hip arthroplasty through direct anterior approach for the treatment of ankylosing spondylitis with hip flexion deformity / 中国骨伤

OBJECTIVE@#To investigate the short term clinical efficacy of direct anterior approach(DAA) total hip arthroplasty for the treatment of ankylosing spondylitis with hip flexion deformity.@*METHODS@#From September 2014 to June 2017, 15 cases of ankylosing spondylitis with flexion deformity of the hip were treated with total hip arthroplasty through DAA approach including 12 males(17 hips) and 3 females(4 hips) with an average age of 34.4 years old ranging from 21 to 57 years old. Harris score system was used before and after operation to evaluate hip function, total hip activity and visual analogue scale (VAS) were used to evaluate the clinical efficacy.@*RESULTS@#All 15 patients were followed up for an average of 26.2 months. In the operation, 1 case of great trochanter avulsion was given wire binding, and 1 case of linear split of the femur were given by wire binding. There were no hematoma, nerve injury and deep vein thrombosis of lower extremity. No prosthesis loosening and sinking were observed in the follow-up of X-ray film after operation. There was no heterotopic ossification after operation. After operation, 18 hips pain were relieved completely, and 3 hips pain were found when walking, which all satisfied with the daily life self-care requirements. Harris hip score, total hip motion and VAS score at 1 week after operation were significantly different from those before operation(0.05). At the final follow-up, the Harris score was 91.2±5.3, the total hip mobility was (217.1±29.7)°, and the postoperative VAS pain score was 1.2±0.5, which was significantly different from the preoperative score(<0.05).@*CONCLUSIONS@#DAA approach THA has good effect in treating AS hip nonfunctional ankylosis with less trauma, less pain and quick recovery. It has a good short term effect, which can effectively improve the quality of life of patients.

Research Progress of Therapeutic Mechanism of Gandou Decoction in Treatment of Wilson's Disease / 中国实验方剂学杂志

Wilson disease (WD) is a treatable neurological inherited disorder characterized by copper metabolism impairment. Metal chelating drugs, such as penicillamine, have been used to treat WD for decades, is exposuring its limitations of effect and utilize sphere. Genetic therapy was considered as the most potential way of curing WD, is still can only be achieved in the laboratory, which have massive problems to solve before its clinical utilization. Based on this, we started to research the curative mechanism of traditional Chinese medicine(TCM) donated by national natural science fund project funding, found that TCM formula Gandou decoction regulate the metabolic disorders caused by liver cells and neurons apoptosis, autophagy, such as programmed cell death,from the molecular pathways of copper metabolism, Wnt/β-catenin pathway and mitogen-activated protein kmase(MAPK) pathways regulating liver damage such as cell signaling pathways, extracellular signal-regulated kinase(ERK) pathway and liver kinase B1(LKB1)/adenosine monophosphate activated protein kinase(AMPK) pathway and the cell signaling pathway of neuronal damage. The above experimental results were verified by TX mice, a reliable WD animal models. This paper aimed to systematically review the research of GDD therapeutic mechanisms from the sight of programmed cell death, including aptosis and autophagy, and provided theoretical for formula optimization. In addition, we elaborated some assumptions and feasible advice for the further research of GDD therapeutic mechanism.

Protective Effect of Gandou Decoction on Cer Signaling Pathway in HT-22 Induced by High Copper / 中国实验方剂学杂志

Objective: To detect ceramide(Cer) signaling pathway-related proteins expression levels in HT-22 with Gandou decoction (GDD), in order to explore its molecular targets and mechanism in regulating Cer signaling pathway. Method: The experiment was divided into normal group (normal HT-22 cultured by 10%blank rabbit serum), model group (HT-22 cells incubated with CuSO4), and GDD group (HT-22 cells incubated with CuSO4, continuously cultured by rabbit serum containing10%, 15%, 20%GDD). HT-22 cells were incubated with different concentrations of CuSO4.The cell growth and proliferation were assessed using methyl thiazolyl tetrazolium(MTT) method; flow cytometry was used to analyze the expression of reactive oxygen species (ROS); Western blot was used to detect relevant protein expression of Cer signaling pathway. Result: The results of MTT showed that CuSO4 inhibited the growth and proliferation of HT-22 cells in a time and concentration-dependent manner; flow cytometry results showed that the model group increased the release of ROS compared with the normal group (PPPPConclusion: High copper can induce oxidative stress and deactivate Cer signaling pathway, which led to hippocampal neuron injury. These findings suggest that GDD reduces neurotoxicity induced by copper overload by increasing the copper excretion that inhibits the expressions of ASM, Cer, p38 MAPK, Cyt C, Caspase-9, Caspase-3.GDD reduces neurotoxicity induced by copper overload by decreasing copper levels in brain and then regulating Cer signaling pathway.

Effect of Gandou Decoction on Autophagy of SH-SY5Y Cell Induced by High Copper and Its Mechanism / 中国实验方剂学杂志

Objective: To explore the effect of Gandou decoction on autophagy of SH-SY5Y cells induced by high copper and its mechanism, in order to provide new therapeutic targets and research ideas for the prevention and treatment of brain-type Wilson disease (WD) with traditional Chinese medicine. Method: CuSO4 model showed a certain dose-effect and time-effect relationship according to methyl thiazolyl tetrazolium(MTT); lactate dehydrogenase(LDH) leakage rate was detected by LDH release assay; flow cytometry method was used to detect intracellular reactive oxygen species (ROS) content. The fluorescent dye JC-1 was used to detect the mitochondrial membrane potential of the cells. Flow cytometry was used to quantify autophagy. The expressions of liver kinase B1 (LKB1), AMP-activated protein kinase (AMPK), microtubule-associated protein 1 light chain 3 (LC3A/B), mammalian target of rapamycin (mTOR) and UNC-51-like kinase-1 (ULK1), phosphorylation-ULK (p-ULK), phosphorylation-AMPK (p-AMPK) were detected by Western blot. Result: According to MTT results, CuSO4 showed a dose-effect and time-effect relationship with cells (P4, the survival rate of cells showed a downward trend (P4-induced cell death (P4 compared with the normal group (P4-injured cells (P4 significantly increased the production of ROS in cells (P4-induced intracellular ROS production (P4 induced a significant decrease in mitochondrial membrane potential in cells (P4-induced mitochondrial membrane potential in a dose-dependent manner (P1, AMPK, LC3A/B, ULK, p-AMPK in the model group were significantly increased, while the protein expressions of mTOR and p-ULK were significantly decreased (P1, AMPK, LC3A/B, p-AMPK and ULK were significantly decreased, whereas the protein expressions of mTOR and p-ULK were significantly increased in the rabbit serum group containing Gandou decoction (PConclusion: High copper can induce autophagic apoptosis in SH-SY5Y cells by inducing intracellular mitochondrial oxidative stress, up-regulating the expressions of autophagy-related proteins LKB1, AMPK, LC3A/B, ULK, p-AMPK and down-regulating the expressions of mTOR and p-ULK. However, Gandou decoction can inhibit the occurrence of autophagy, and cut off high copper-induced neuronal damage by down-regulating the expressions of autophagy-related proteins LKB1, AMPK, LC3A/B, ULK, p-AMPK, and up-regulating the expression of mTOR and p-ULK, so as to exert a neuroprotective effect.

Regulatory Effect of Gandou Decoction on Wnt/β-catenin Signaling Pathway in Liver of Wilson Model Copper-loaded Rats / 中国实验方剂学杂志

Objective: To investigate the regulatory effect of Gandou decoction (GDD) on Wnt/β-catenin signaling pathway in hepatic tissue of Wilson disease model copper-loaded rats and its potential mechanism. Method: One hundred and fifteen SD rats were randomly divided into the normal group (n=20) and modeling group. Modeling group was given copper sulfate feed (1 g·kg-1·d-1) and 0.185%copper sulfate solution (0.02 mL·g-1·d-1) for 12 weeks after one week's adaptive feeding, so as to build the copper loaded rats model. After modeling, 95 model rats were randomly divided into model group (n=45), which were fed by modeling method for continuously four weeks; GDD group and penicillamine (PCA) group (n=25 per group). GDD group and PCA group were given GDD(0.4 g·kg-1·d-1) and PCA (0.09 g·kg-1·d-1) by gavage for four weeks. The hepatic tissues of rats in each group were removed after final medication for further research:inductively coupled plasma-atomic emission spectrometry(ICP-AES) was used to detect the content of Cu element in rat livers. Htoxylin eosin(HE) staining was used to detect the pathological changes of rat liver. Immunohistochemistry was used to detect expression of oxidative stress. Western blot was used to detect protein expressions in Wnt/β-catenin of rat livers. Result: Compared with model group, content of Cu element in GDD group was less (PPPβ-catenin, p-glycogen synthase kinase-3β(p-GSK3β),cellular myelocytomatosis oncogene (c-Myc) in GDD and PCA group increased, while p-β-catenin, Dishevelled3, GSK3β protein expressions reduced (PConclusion: GDD can relieve liver damage by promoting excessive copper discharge. GDD decoction can promote the compensatory self-healing of the injured liver tissue by activating Wnt/β-catenin signaling pathway in the hepatic tissue of Wilson disease model copper-loaded rats, so as to reduce the therapeutic effect of hepatocellular injury induced by high copper.

Inhibition of HBV Release by BST-2 / 病毒学报

Bone marrow stromal antigen 2 (BST-2) is a kind of host restriction factor. Since it was discovered to be responsible for the defect in virion release of HIV-1 mutants lacking the accessory gene vpu in 2008, it was thought to mainly restrict the viruses by directly tethering viral particles at the plasma membrane. Recent reports suggest that BST-2 also can inhibit the the release of HBV particles, which are budding in the intracellular vesicles, expanding the antiviral spectrum of BST-2. Futhermore, the machanism that BST-2 used to restrict HBV release in multivesicular bodies (MVBs) is similar to that used to restrict HIV at the plasma membrane. However, HBV have evolved strategies to antagonize the antiviral action of BST-2. There are two different opinions about the antagonist. One is HBV inactivated BST-2 by HBx requiring a hepatocyte-specific environment. Another thought envelope protein HBs counteract the antiviral action of BST-2. In this review, we focus on the current advances in the anti-HBV activity of BST-2.

The Correlation between Blood Uric Acid and Goldstein Grading in Hepatolenticular Degeneration Patients with Different Chinese Medical Syndrome Types / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe blood uric acid levels and Goldstein grading, as well as their correlation in Wilson's disease (WD) patients with different Chinese medical syndrome types.</p><p><b>METHODS</b>Totally 906 WD patients in line with inclusive criteria were assigned to 6 groups, i.e., the heart spirit confused by phlegm group (HSCP, 26 cases), the phlegm-fire disturbing heart group (PFDH, 90 cases), the retention of damp-heat group (RDH, 113 cases), deficiency of qi and blood group (DQB, 168 cases), the deficiency of Gan-yin and Shen-yin group (DGYSY, 327 cases), the deficiency of Gan and Shen group (DGS, 182 cases) due to different Chinese medical syndrome types. Recruited were another 160 healthy subjects having similar ages and diet structures, who came for medical examinations, as the healthy control group. Venous blood was collected from the medial cubital vein of each-patient on an empty stomach in early mornings to detect blood uric acid levels. Results Blood uric acid levels were lower in each syndrome type group than in the healthy control group (146.08 +/- 67.24 micromol/L in the HSCP group; 157.08 +/- 69.77 micromol/L in the PFDH group; 162.58 +/- 97.72 micromol/L in the RDH group; 156.20 +/- 62.63 micromol/L in the DQB group; 161.83 +/- 111.23 micromol/L in the DGYSY group; 194.41 +/- 90.01 micromol/L in the DGS group; 242.39 +/- 87.55 micromol/L in the healthy control group, P < 0.01). Blood uric acid levels were higher in the DGYSY group than in the other 5 syndrome groups (P < 0.01). Correlation analyses between Goldstein grading and blood uric acid showed that, along with increased Goldstein grade (that was aggravating disease conditions), WD patients' blood uric acid levels decreased (P < 0.01).</p><p><b>CONCLUSIONS</b>WD patient's blood uric acid levels decreased more. Blood uric acid levels and Goldstein grading were different in various Chinese medical syndrome types. Blood uric acid levels had certain value in assessing the severity of WD.</p>

Assessment on depressive status and the therapeutic effects of highly active antiretroviral therapy among anti-HIV-1(+) population / 中华流行病学杂志

<p><b>OBJECTIVE</b>To assess the depressive status and its influence on Chinese HIV-1(+) population, and how it was influenced by highly active antiretroviral therapy (HAART) and the CD4(+) T cell count.</p><p><b>METHODS</b>Anti-HIV-1(+) patients (age between 18 and 65 years old) who had met the criteria to commence the anti-HIV treatment but had not yet started, were selected from the Beijing Ditan Hospital between March 2011 and June 2012. BDI-II (Beck Depression Inventory) and a self-designed questionnaire were used to evaluate the baseline and the status of 48 weeks post the HAART treatment. Statistically, t test and the Wilcoxon rank sum test were used to compare the BDI scores under different conditions and before/after the HAART.</p><p><b>RESULTS</b>(1) Of 100 subjects: male to female ratio was 99:1; the average age was 31.37 ± 5.58 years; the average education background was of 13.13 ± 3.51 years; the unemployed percentage was 4%; time before being identified as anti-HIV-1(+) was 5.0 (1.0 - 21.0) months; the percentage being infected through homosexual contact was 83%. The baseline BDI score was 6.0 (3 - 10.25). (2) There was no significant difference (P > 0.05) in BDI score between those subjects having had education less or more than 12 years; the BDI score of patients whose anti-HIV-1(+) was significantly higher (P < 0.05) among those discovered within the past 6 months than those more than 6 months. The BDI score of patients whose baseline CD4(+) T cell count below 200 cells/µl was significantly higher (P < 0.05) than those with baseline CD4(+) T cell count greater than 200 cells/µl. The CD4(+) T cell count was significantly high (P < 0.001) after 48 weeks of anti-viral treatment, but the BDI score was not significantly different (P > 0.05). There was no significant change (P > 0.05) in the proportion of patients with different degrees of BDI score before and after 48 weeks of antiviral treatment.</p><p><b>CONCLUSION</b>Depression in HIV patients was most overt in the first six months when they were aware of the infection. The degree of depression was more severe in patients with baseline CD4(+) T cell count less than 200 cells/µl with improvement of immunity after the HAART did not alleviate the level of depression.</p>

Research on the correlation between Chinese medical syndrome types and objective indices of Wilson's disease / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the correlation between Chinese medical syndrome types of Wilson's disease (WD) and clinical materials as well as physical and chemical indices.</p><p><b>METHODS</b>Totally 116 WD patients were typed by Chinese medical syndrome. The correlation between Chinese medical syndrome types and clinical materials as well as physical and chemical indices were analyzed using binary stepwise Logistic regression by SPSS 19.0 Software, taking the common Chinese medical syndrome types as the dependent variable and clinical materials as well as physical and chemical indices as the independent variables.</p><p><b>RESULTS</b>Gan-Galibladder dampness-heat syndrome (GGDHS, 35.3%). Gan-stagnation and Pi-deficiency syndrome (GSPDS, 13.8%), Gan-Shen yin deficiency syndrome (GSYDS, 13.8%), and phlegm-dampness retention syndrome (PDRS, 12.1%) were most often seen. GGDHS was positively correlated with grade of K-F ring, total bilirubin (TBIL), alanine transaminase (ALT), laminin (LN) (P < 0.01). GSYDS was positively correlated with TBIL (P < 0.01). PDRS was positively correlated with clinical types, ceruloplasmin (CP), aspartate aminotransferase (AST), and total protein (TP) (P < 0.01, P < 0.05). Qi blood deficiency syndrome was positively correlated with disease course, blood ammonia, blood urea nitrogen (BUN), and LN (P < 0.01, P < 0.05).</p><p><b>CONCLUSIONS</b>Chinese medical syndrome types were correlated with clinical materials, physical and chemical indices in WD patients, which could provide experimental reference for Chinese medical syndrome typing. GGDHS, GSPDS, GSYDS, and PDRS were most often seen.</p>

Research progresses of pharmacokinetics of traditional Chinese medicine / 药学学报

With the deepening of modernization of traditional Chinese medicine (TCM) and continuing emergence of new theories, methods and techniques, a very rapid and significant development has been achieved in the pharmacokinetics (PK) of TCM. This paper reviews the main research progresses of PK of TCM, including integrated PK of multiple effective components of TCM, fingerprint PK of TCM, novel dosage form PK of TCM, polysaccharide PK of TCM and drug interactions of TCM; and further sets up the prospects.

Multiple pharmacological actions of Yiqi Huatan Decoction in a model of depression in rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the influence of Yiqi Huatan Decoction (, YHD) on a model of depression in rats under different pathological conditions.</p><p><b>METHODS</b>Thirty-two male SD rats were randomly divided into 4 groups of 8: normal, model, YHD, and maprotiline. The model group, YHD group and maprotiline group used separate feeding and rats were exposed to chronic and unpredictable stress to build the depression model. From day 2, the YHD group and maprotiline group were respectively given YHD (7 g/kg) and maprotiline (10 mg/kg) by gastrogavage once daily. The normal and model groups were given the same volume of drinking water. The medication duration were 21 days. At the end of the experiment, the serum levels of copper and zinc were determined by atomic absorption spectroscopy, plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol (COR) were detected by radioimmunoassay, and levels of norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine (5-HT) in the hypothalamus were analysed by high performance liquid chromatography-eletricochemistry.</p><p><b>RESULTS</b>Compared with the content of copper and zinc in the serum of rats in the normal group, serum copper levels in model rats were significantly increased and zinc content was significantly reduced (both P<0.05). Plasma concentrations of ACTH and COR in the model group were significantly increased compared with those in the normal group (P<0.05, P<0.01). The contents of NE, DA, and 5-HT in the hypothalamus of rats in the model group were significantly reduced compared with those of the normal group (P<0.05 or P<0.01). Compared with those in the model group, the serum copper content and plasma concentrations of ACTH and COR were significantly decreased (all P<0.05); meanwhile, serum zinc content and hypothalamic contents of NE, DA, and 5-HT were significantly increased in rats of the YHD group (all P<0.05). The same effects were also shown in the maprotiline group except for 5-HT (all P<0.05)</p><p><b>CONCLUSION</b>The pharmacological actions of YHD for depression might be related to improving trace-element anomalies, reversing endocrine dysfunction, and modulating the disorders of monoaminergic neurotransmitters.</p>

Integrated pharmacokinetic study of multiple effective components of tea polyphenols and its correlation with anti-free radical pharmacodynamics in rats / 药学学报

LC-MS/MS method was used to simultaneously determine anti-oxidative active catechins EGCG, ECG, EGC and EC in plasma of rats treated with tea polyphenols (TP). The integrated plasma concentration (C') of TP was calculated by means of self-defined weighing coefficient based on percent AUC of individual components, thereby assessing integrated pharmacokinetic (PK) parameters of TP via log C'-T curve. The anti-free radical effects of TP were estimated using inhibitory rate of drug-containing serum collected at different times from rats against in vitro lipid peroxidation of mouse liver homogenate. The obtained E-T curves were used to calculate anti-free radical pharmacodynamic (PD) parameters of TP. E-logC and E-log C' plots and linear regression were carried out in order to obtain the correlation coefficient (R2). The results indicated that the log C'-T curves of TP, which could be best described by three-compartment model, corresponded to elimination rule of iv administration of drugs. The integrated PK parameters showed that TP was distributed in body rapidly and widely, and eliminated from deep compartment slowly. From comparison of R2 values and consistence of C'-T course and E-T course, it was evident that TP integrated PK behaviors correlated much better with its PD behaviors than individual active components, and thus demonstrated that integrated PK parameters could characterize to maximal extent holistic disposition of Chinese herbal drugs and reflect residence properties of holistic effective substances in biological body.

Application of mesenchymal stem cells as a vehicle to deliver replication-competent adenovirus for treating malignant glioma / 癌症

Although gene therapy was regarded as a promising approach for glioma treatment, its therapeutic efficacy was often disappointing because of the lack of efficient drug delivery systems. Mesenchymal stem cells(MSCs) have been reported to have a tropism for brain tumors and thus could be used as delivery vehicles for glioma therapy. Therefore, in this study, we attempted to treat glioma by using MSCs as a vehicle for delivering replication-competent adenovirus. We firstly compared the infectivity of type 3, type 5, and type 35 fiber-modified adenoviruses in MSCs. We also determined suitable adenovirus titer in vitro and then used this titer to analyze the ability of MSCs to deliver replication-competent adenovirus into glioma in vivo. Our results indicated that type 35 fiber-modified adenovirus showed higher infectivity than did naked type 3 or type 5 fiber-modified adenovirus. MSCs carrying replication-competent adenovirus significantly inhibited tumor growth in vivo compared with other control groups. In conclusion, MSCs are an effective vehicle that can successfully transport replication-competent adenovirus into glioma, making it a potential therapeutic strategy for treating malignant glioma.

Pharmacokinetics and metabolic disposition of exogenous phosphocreatine in rats / 药学学报

This article is report the study of the pharmacokinetics and metabolic disposition of exogenous phosphocreatine (PCr) in rats by means of an ion-pair HPLC-UV assay. PCr and its metabolite creatine (Cr) and related-ATP in rat plasma and red blood cell (RBC) were simultaneously determined. A blank plasma and RBC were initially run for baseline subtraction. Plasma and RBC samples were deproteinized with 6% PCA prior to HPLC. Following i.v. administration of PCr 500 mg x kg(-1) and 1 000 mg x kg(-1) the C-T curve could be described by the two-compartment model with t1/2beta 22.5-23.3 min, V(d) 0.956 4-0.978 6 L x kg(-1), CL 0.029 L. kg(-1) x min(-1). The Cr as PCr degraded product appeared as early as 2 min post i.v. dosing with t(max) 20 min, t1/2kappa (m) 40.6-42.7 min and f(m) 60%-76%. After po administration of PCr, the parent drug in plasma was undetectable, but the metabolite Cr was detected with t(max) 65-95 min, t1/2kappa (m) 56.0-57.7 min, metabolite-based bioavailability F(m) 55.02%-62.31%. PCr i.v. administration resulted in significant elevation of ATP level in RBC but not in plasma, the related-ATP in RBC was characterized by t(max) 68-83 min, t1/2kappa 49-52 min. In RBC no exogenous PCr was found but Cr was detected following i.v. administration of PCr, with the t(max) 120 min and t1/2k (m) 70 min for Cr. The above results indicate that PCr eliminates and bio-transforms in body very rapidly; K > K(m) confers ERL, instead of FRL, type upon the metabolic disposition of Cr. Following po administration of PCr, the degraded product Cr is absorbed but not the parent drug PCr. The formed Cr can be accounted for by most of i.v. and po PCr. Intravenous dosing leads apparently increased and sustained Cr and related-ATP concentration in RBC.

Synthesis and activity of some new histone deacetylases inhibitors / 药学学报

To explore novel histone deacetylase (HDAC) inhibitors with anti-tumor activity, twelve target compounds were synthesized, and their structures were confirmed by 1H NMR, MS and elemental analyses. Evaluation results in vitro showed that compound Ia exhibited potent inhibition against HDAC and is worth for further investigation. And compounds IIa, IIb, IIIa-IIIi possessed moderate HDAC inhibitory activity.

Application of anatomical measurement and canine lumbar spine models in anterior fusion / 中国组织工程研究

BACKGROUND: Primate is the best animal to establish a model of spinal implants. However, ethics and cost limit its application. Mixed-breed dogs have similar anatomic structures as human. Moreover, it is easy to obtain with low cost, so it may replace primate to serve as models.OBJECTIVE: To determine the feasibility of canine lumbar spine to establish the anterior interfixation model following measurements of related anatomic data.METHODS: A total of 9 adult healthy dogs were selected. The transversal diameter, sagittal diameter and height of vertebral body and disc were measured, and the artificial vertebral body replacement was performed. Bone graft fusion was observed. RESULTS AND CONCLUSION: The transversal diameter, sagittal diameter and height of vertebral body and disc increasedgradually from L_(1) to L_(7), and the height was greatly exceeded its sagittal diameter. All dogs survived, but one was paraplegia. Allthe others stood and acted in 12 h to 72 h after operation. The fusion effect was proved to be good by imageology and histology. The establishment of models was simple and cost-effective, and the biocompatibility of bone tissues and implants, as well as thebone tissue ingrowth can be observed. The lumbar spine of dog can be used as an anterior interfixation model in vitro test.

Executive dysfunction in patients with hepatolenticular degeneration / 中华神经医学杂志

Objective To assess the characteristics of executive dysfunction in patients with hepatolenticular degeneration (HLD) through neuropsychological tests and explore its mechanism. Methods One hundred and two patients with HLD were chosen and divided into CT/MRI positive (n=70) and CT/MRI negative (n=32) groups in accordance with cerebral imaging and the other 30 healthy subjects were selected as normal control group. These three groups were recorded the results of such imaging data as Raven's standard progressive matrices (R'SPM) test, Stroop color-word test (CWT), trail making test (TMT). Results Imaging data indicated a statistical change of frontal-striatal loops in patients with HLD. Significant differences of the total scores, perception discrimination, serial relationship and abstract reasoning of R'SPM test were showed in the three groups and the word interference time of CWT, B items time-consuming and interference effects of TMT in these groups were statistically different (P<0.05). Conclusion Executive dysfunction appears commonly in patients with HLD. The CT/MRI positive group showed a more serious degree and area of the damage as compared to that in the CT/MRI negative group. Damages of frontal-striatal loops may be one of the important mechanisms of executive dysfunction in patients with HLD.