OBJECTIVETo analyze and identify the chemical constituents in rat brain tissues after oral administration of Chuanxiong Rhizoma extracts.

METHODThe dosed and blank rat brain tissues were analyzed by UPLC-Q-TOF-MS. Different peaks were observed in total ion chromatograms and then identified according to their retention time, accurate mass weight, MS and MS/MS data.

RESULTAfter oral administration of Chuanxiong Rhizoma extracts, 3 compounds were absorbed into rat brain tissues through BBB. They were identified as senkyunolide I, senkyunolide A and ligustilide.

CONCLUSIONThe study is helpful for interpreting effective substance of Ligusticum chuanxiong.

Animals ; Brain ; drug effects ; metabolism ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; administration & dosage ; analysis ; pharmacokinetics ; Female ; Humans ; Ligusticum ; chemistry ; Mass Spectrometry ; methods ; Rats ; Rats, Sprague-Dawley ; Rhizome ; chemistry

Ligustilide is contained highly or around 1% in such umbelliferous plants as Angelica sinensis and Ligusticum chuanxiong, is one of main bioactive constituents. It shows many pharmacological activities related to their efficacy. At present, ligustilide has attracted extensive attention and more and more studies have been reported, indicating that it is a promising compound. This essay summarizes the progress of pharmacological effects of ligustilide on neuroprotection, vasodilatation, anti-caner and anti-tumor, analgesia and anti-inflammation, and pharmacokinetics including absorption, distribution, metabolism and excretion, providing basis for further studies and development of ligustilide.
4-Butyrolactone ; analogs & derivatives ; pharmacokinetics ; pharmacology ; Angelica sinensis ; chemistry ; Animals ; Drugs, Chinese Herbal ; pharmacokinetics ; pharmacology ; Humans ; Ligusticum ; chemistry

Z-Ligustilide, a major phthalide isolated from a widely used traditional Chinese medicine Ligusticum chuanxiong, possesses various pharmacological activities including neuroprotective, anti-inflammatory, antiproliferative and vasorelaxing effects. However, it is unstable and inclined to degrade in natural conditions, which limits its study and application greatly. In this study, degradation behavior of Z-ligustilide and its degradation products stored at room temperature under direct sunlight were investigated and structure elucidated by HPLC-UV, UPLC-QTOF-MS and NMR. Z-ligustilide degradation and total five degradation products were generated and detected. Two degradation products were unequivocally identified as senkyunolide I and senkyunolide H by comparison with reference compounds. Another two degradation products were further isolated by semi-preparative HPLC and structure elucidated as (E)-6, 7-trans-dihydroxyligustilide and (Z)-6, 7-epoxyligustilide by 1H and 13C NMR, respectively. The degradation pathways of Z-ligustilide were finally proposed. Oxidation, hydrolysis and isomerization are the major degradation reactions.
4-Butyrolactone ; analogs & derivatives ; isolation & purification ; metabolism ; Benzofurans ; metabolism ; Chromatography, High Pressure Liquid ; Hydrolysis ; Ligusticum ; chemistry ; Magnetic Resonance Spectroscopy ; Metabolic Networks and Pathways ; Oxidation-Reduction ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

BACKGROUNDT-SPOT.TB is a novel test for tuberculosis infection with higher sensitivity and specificity than the traditional tuberculin skin test (TST). However, there are no longitudinal data in the literature evaluating T-SPOT.TB for Mycobacterium tuberculosis in patients with acquired immune deficiency syndrome (AIDS) on highly active antiretroviral therapy (HAART). The objective of this study was to assess the value of T-SPOT.TB longitudinally in AIDS patients on HAART without prophylaxis for tuberculosis.

METHODSA prospective observational study was conducted in 50 AIDS patients on HAART. None of the subjects had evidence of active tuberculosis. T-SPOT.TB, a T-cell-based interferon gamma released assay, was performed at the onset of the study and repeated 24 months thereafter. Subjects were evaluated every 6 months during the 36-month follow-up.

RESULTSTwenty-one (42%) AIDS patients on HAART tested positive by T-SPOT.TB (95%CI 28.3% - 55.7%). The pooled spot-forming cells of early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) peptides were 68/million peripheral blood mononuclear cell (PBMC) (interquartile range 44 - 220). The average number of CD4 cells in subjects was (305 +/- 152) cells/microl, and there was no significant difference in T-SPOT.TB response rates between subjects with CD4 cell counts < 200 cells/microl (7/15 (46.7%), 95%CI 21.5% - 71.9%) and those with CD4 cell counts >/= 200 cells/microl (14/35 (40.0%), 95%CI 23.8% - 56.2%, P = 0.662). In the 32 subjects who completed the 24-month follow-up, 10 underwent T-SPOT.TB reversion, one had T-SPOT.TB conversion, six remained positive and 15 remained negative. None of them advanced to active tuberculosis during the 36-month follow-up.

CONCLUSIONThe inactive status of tuberculosis infection may be maintained for a long period in AIDS patients on HAART.

Acquired Immunodeficiency Syndrome ; drug therapy ; immunology ; microbiology ; Adult ; Antiretroviral Therapy, Highly Active ; Female ; Humans ; Interferon-gamma ; secretion ; Male ; Middle Aged ; Mycobacterium tuberculosis ; pathogenicity ; Prospective Studies ; Tuberculosis ; diagnosis ; immunology

OBJECTIVETo investigate the clinical characteristics of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients in China.

METHODSTotally 143 HIV/AIDS patients who were first diagnosed in Peking Union Medical College Hospital form January 1988 to April 2006 were enrolled in this study. Clinical characteristics were retrospectively analyzed.

RESULTSAmong 143 HIV/ AIDS patients, 57 patients had no clinical symptoms and were confirmed by routine examinations; 86 patients had clinical symptoms, including fever (n = 50), weight loss (n = 18), and discomforts involving respiratory system (n = 34), gastrointestinal system (n = 16), and derma and mucosa (n = 17). Opportunistic infections (OIs) such as pneumocystis jiroveci pneumonia (PCP) (n = 27), oropharyngeal candidiasis (n = 16), tuberculosis (n = 15) , and cytomegalovirus (CMV) infection (n = 9) were also observed in patients whose CD4 + T cell counts were less than 200/mm3. Most CMV infection and cryptococcal meningitis occurred in patients whose CD4 + T cell counts were less than 100/mm3. CD4 + T cell count was negatively correlated with plasma viral load (r = -0.420, P = 0.001).

CONCLUSIONSFever, dyspnea, and weight loss are the most common symptoms in the patients of this study. The respiratory system, gastrointestinal system, derma and mucosa are the most commonly affected areas by OIs, and PCP is the most common OI. The occurrence of OIs corelates with CD4 + T cell count.

AIDS-Related Opportunistic Infections ; immunology ; Acquired Immunodeficiency Syndrome ; complications ; Adolescent ; Adult ; Aged ; CD4 Lymphocyte Count ; China ; Dyspnea ; etiology ; Emaciation ; etiology ; Female ; Fever ; etiology ; HIV Infections ; complications ; Humans ; Male ; Middle Aged ; Pneumonia, Pneumocystis ; immunology ; Retrospective Studies

Objective: To observe the preventive and therapeutic effect of Huanglian Ejiao Tang on myocardial injury induced by anthracycline chemotherapeutic drugs in all kinds of cancer patients undergoing chemotherapy. Method:We chosen all kinds of cancer patients with combined use of anthracycline chemotherapy drugs in our hospital, 21 days as one cycle. The cardiac toxicity reaction was observed after three continuous chemotherapy cycles. A total of 64 patients who met the dialectical criteria of "imbalance between heart-Yang and kidney-Yin" were randomly divided into treatment group (32 cases) and control group (32 cases). Patients in treatment group were treated with Chinese medicine Huanglian Ejiao Tang based on original chemotherapy regimen, adding and subtracting Chinese medical materials according to the symptoms. Patients in control group continued to maintain the original chemotherapy regimen, and both two groups of patients continued to receive 3 cycles of continuous chemotherapy. By comparing the cardiac function classification and cardiac function tolerance between the 3 cycles and 6 cycles of two groups of patients after chemotherapy; changes of echocardiography index, QTc interval, creatine kinase isoenzyme (CK-MB), Myoglobin (MYO), cardiac troponin I (cTNI)and nitrogenous terminal-pro-brain natriuretic peptide(NT-pro-BNP) concentration value were compared between two groups; and the concentrations of adrenaline (E), norepinephrine (NE) and angiotensin Ⅱ(AngⅡ) were observed and compared; meanwhile, the correlation analysis was carried out at the same time. Result:After 6 cycles of chemotherapy in Chinese medicine treatment group, degree of cardiac function classification and the 6 minute walking heart function tolerance were significantly better than those at the 3 cycles of chemotherapy (P<0.05), but there was no significant change in control group; the concentrations of CK-MB, cTNI, MYO and NT-pro-BNP in treatment group were significantly lower than those in control group(P<0.05), and the electrocardiogram QTc interval in the treatment group was significantly lower than that in the control group (P<0.05); echocardiography indexes E/A ratio and left ventricular ejective fraction (LVEF) value in the treatment group were significantly higher than those in control group (P<0.05). There were no significant changes in left ventricular end-systolic diameter (LVDd) and left ventricular end-systolic diameter (LVDs) between the treatment and the control group. After 3 cycles and 6 cycles of chemotherapy, the blood NE,E and AngⅡ concentrations in the treatment group were significantly lower than those in the control group (P<0.05). There were positive linear correlation in concentration changes of blood NE, E and AngⅡ as well as the concentration changes of CK-MB, cTNI, MYO and NT-pro-BNP between 3 cycles and 6 cycles after chemotherapy. After 6 cycles of chemotherapy, the incidence of cardiovascular events in the treatment group was significantly lower than that in the 3 cycles of chemotherapy, while the incidence in control group was increased. Conclusion:Huanglian Ejiao Tang can reduce the excitability of the symppthetic nervous system (SNS) and renin-angiotensin system(RAS) in human body and inhibit the release level of NE, E and AngⅡ by effect of "invigorating the kidney and clearing the heart". It has a certain preventive and treatment effect on the cardiac toxicity of patients with the cumulative use of anthracycline chemotherapy. To a certain extent, it can inhibit myocardial injury, improve cardiac function and reduce the incidence of cardiovascular events.

OBJECTIVE: To explore the impact of induction treatment response on the prognosis of pediatric core binding factor-acute myeloid leukemia (CBF-AML). METHODS: The result of induce reaction and survival data of 157 pediatric CBF-AML patients in our hospital from September 2008 to December 2018 were retrospectively analyzed．The survival rate of the patients with different degrees of morphological remission after induction chemotherapy was comparative analyzed. RESULTS: Among the 157 children with CBF-AML, 113 (72.4%) patients achieved morphologic leukemia-free state (MLFS) after the first course of induction chemotherapy, 153 (98.1%) patients achieved MLFS after the second course of induction chemotherapy. The 5-year event-free survival (EFS) rate and 5-year overall survival (OS) rate of patients with non-remission (NR) status after the first course of induction of chemotherapy was significantly lower than the patients achieved MLFS and the patients achieved partial remission (PR). The 5-year EFS rate and 5-year OS rate of the patients with PR status after the second course of induction chemotherapy were lower than the patients achieved MLFS, but the difference was not statistically significant. Multivariable analyze showed that NR after the first course of induction chemotherapy and myeloid sarcoma were the independent risk factors affecting EFS of the patients. There were six patients with NR status after the first course of induction chemotherapy, in which all of them harbored t(8;21), three of them with sex chromosome deletion, two of them with myeloid sarcoma. CONCLUSION NR status after the first course of induction chemotherapy was the independent risk factor affecting EFS and OS of CBF-AML patients, it can be taken as an indicator for higher risk stratification. PR status after the first course of induction chemotherapy may not be used as a diagnostic criterion for primary drug resistance.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child ; Core Binding Factors ; Disease-Free Survival ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute/drug therapy* ; Prognosis ; Remission Induction ; Retrospective Studies

Objective:To explore the effect of Huangjingwan （HW） on the expressions of Wnt/β-catenin signal pathway-associated proteins in the hippocampus of mice with Alzheimer's disease （AD） induced by D-galactose and okadaic acid with learning and memory disorders， as well as its mechanism. Method:After subcutaneous injection with 1.0% D-galactose （0.14 g·kg^-1·d^-1） into the back and neck of mice for 4 weeks， the right ventricle of mice was injected with 2 μL（75 ng） of okadaic acid for one time to make AD model， and the successfully modeled AD mice were selected by Morris water maze. Then， the selected AD mice were randomly divided into AD model group， memantine group （1.3×10^-3 g·kg^-1·d^-1） and HW group （2.5 g·kg^-1·d^-1）. In addition， the sham model control group and the normal control group were set up. At the same time， 2 μL normal saline was injected into the right ventricle of mouse in the sham model control group as the modeling control. Two weeks after molding， the mice in the two experimental drug groups were given the corresponding dose of the experimental drug by gavage for 4 weeks. In addition， after 2 weeks of AD modeling， mice in sham model control group and AD model group were intragastrically administrated with the same amount of normal saline daily for 4 weeks. There was no special treatment in the normal control group. At the end of gavage， the shuttle experiment was performed to detect the differences in learning and memory levels of mice in each group. The changes of β-catenin and GSK-3β positive neurons in CA1 area of hippocampus in each group were tested by immunohistochemistry. Quantitative real-time polymerase chain reaction （Real-time PCR） was used to measure the mRNA expressions of GSK-3β， β-catenin and CyclinD₁ in hippocampus of mice in each group. The Western blot was used to detect the expressions of total GSK-3β （t-GSK-3β）， phosphorylation of GSK-3β at Ser9 （p-Ser9-GSK-3β）， phosphorylation of GSK-3β at Tyr216 （p-Tyr216-GSK-3β）， total β-catenin （t-β-catenin）， phosphorylation of β-catenin （p-β-catenin） and CyclinD₁ proteins in hippocampus of mice in each group. Result:Compared with the normal control group， mice in AD model group showed an obvious dementia state， which was characterized by significant declines in learning and memory ability， the number of β-catenin immunoreactive neurons in hippocampal CA1 area， the mRNA and protein expressions of t-β-catenin and CyclinD₁， the protein expressions of p-Ser9-GSK-3β， and the ratio of p-Ser9-GSK-3β/t-GSK-3β and p-Tyr216-GSK-3β/t-GSK-3β in hippocampal region （P<0.01）， and significant increases in the number of GSK-3β immunoreactive neurons in hippocampal CA1 area， the mRNA and protein expressions of t-GSK-3β， the protein expressions of p-Tyr216-GSK-3β and p-β-catenin， the ratio of p-β-catenin/t-β-catenin in hippocampal region （P<0.01 respectively）. Compared with the AD model group， the dementia symptoms of mice in HW group were significantly alleviated， and the number of β-catenin immunoreactive neurons in hippocampal CA1 area， the mRNA and protein expressions of t-β-catenin and CyclinD₁， the protein level of p-Ser9-GSK-3β， the ratio of p-Ser9-GSK-3β/t-GSK-3β in hippocampal region were all significantly increased （P<0.01 respectively）， whereas the number of GSK-3β immunoreactive neurons in hippocampal CA1 area， the mRNA and protein expressions of t-GSK-3β， the proteins expressions of p-Tyr216-GSK-3β and p-β-catenin， the ratio of p-β-catenin/t-β-catenin in hippocampal region were all significantly decreased （P<0.01 respectively）， but the ratio of p-Tyr216-GSK-3β/t-GSK-3β has no significant statistical difference. Conclusion:HW shows the role of AD treatment， which can down-regulate the expression of GSK-3β in the hippocampus of AD mice and reduce its protein activity， and up-regulate the expression of β-catenin as well as increase its protein activity， so as to enhance the expression of downstream CyclinD₁ and promote the transcription of the target genes. Its mechanism may be related to the activation of Wnt/β-catenin signal pathway.