Screening for anti-inflammatory components of Astragalus polysaccharide and metabolomics research based on molecular weight distribution / 药学学报

Molecular mass distribution of Astragalus polysaccharides is wide. Astragalus polysaccharides prepared by conventional water extraction and alcohol precipitation are mostly mixture of macromolecules. Although studies have shown that Astragalus polysaccharides have two-sided immunomodulation, the relationship between anti-inflammatory components and molecular mass distribution of Astragalus polysaccharides is not clear. Therefore, Astragalus polysaccharides were extracted by water extraction and alcohol precipitation. The relative molecular weight of them was determined by high performance gel permeation chromatography (HPGPC). Astragalus polysaccharides with different molecular weights were separated and prepared by membrane separation. RAW 264.7 cells were induced by lipopolysaccharide (LPS) to establish an inflammatory cell model in vitro and the anti-inflammatory polysaccharide were screened. The anti-inflammatory regulation mechanism of Astragalus polysaccharides was analyzed by the LC-MS/MS metabonomics technology. The results showed that APS was composed of APS-Ⅰ ( > 2 000 kDa) and APS-Ⅱ (10 kDa). APS-Ⅰ was composed of mannose, rhamnose, galacturonic acid, glucose, galactose, arabinose and the molar ratios of these monosaccharide of APS-I were 0.54∶0.26∶12.24∶17.24∶8.46∶1. APS-II was composed of rhamnose, galacturonic acid, glucose, galactose, arabinose and the molar ratios of these monosaccharide of APS-II were 0.26∶0.14∶24.04∶0.62∶1. APS-Ⅰ and APS-Ⅱ had no cell toxicity to RAW 264.7 macrophage in the range of 0-100 μg·mL-1. Compared with the model group, APS-I at a concentration of 0-100 μg·mL-1could significantly inhibit the secretion of NO and TNF-α by RAW 264.7, and can significantly promote the secretion of IL-10. APS-I had better anti-inflammatory activity than APS-II in vitro. The metabolomics results showed that 32 different metabolites were found between the model group and blank group; APS-I group can significantly callback 18 different metabolites; mainly related to arginine biosynthesis, arginine and proline metabolism, pyrimidine metabolism, citric acid cycle (TCA cycle), cysteine and methionine acid metabolism, tryptophan metabolism. This study found that APS-I had better anti-inflammatory activity than APS-II in vitro, and its mechanism may be closely related to amino acid metabolism and energy metabolism, which indicated the direction for further clarifying the pharmacodynamic material basis of Astragalus polysaccharides.

Comparison and Correlation of Magnetic Resonance Imaging and Clinical Severity in Nonhuman Immunodeficiency Virus Patients with Cryptococcal Infection of Central Nervous System / 中华医学杂志(英文版)

Background@#The incidence of cryptococcal meningitis among immunocompetent patients increases, especially in China and imaging plays an important role. The current study was to find the correlation between magnetic resonance imaging (MRI) manifestation and clinical severity in nonhuman immunodeficiency virus patients with cryptococcal infection of central nervous system (CNS).@*Methods@#A total of 65 patients with CNS cryptococcal infection from August 2014 to October 2016 were retrospectively included in this study. All the patients had MRI data and clinical data. The patients were divided into two groups according to whether the patients were confirmed with identifiable underlying disease. Comparison and correlation of MRI and clinical data in both groups were investigated using independent sample t- test, Chi-square test, Mann-Whitney test and Spearman rank correlation analysis.@*Results@#In all 65 patients, 41 cases (41/65, 63.1%; Group 1) had normal immunity and 24 cases (24/65, 36.9%; Group 2) had at least one identifiable underlying disease. Fever, higher percentage of neutrophil (NEUT) in white blood cell (WBC), and increased cell number of cerebral spinal fluid (CSF) were much common in patients with underlying disease (Group 1 vs. Group 2: Fever: 21/41 vs. 21/24, χ = 8.715, P = 0.003; NEUT in WBC: 73.15% vs. 79.60%, Z = -2.370, P = 0.018; cell number of CSF: 19 vs. 200, Z = -4.298, P < 0.001; respectively). Compared to the patients with normal immunity, the lesions are more common in the basal ganglia among patients with identifiable underlying disease (Group 1 vs. Group 2: 20/41 vs. 20/24, χ = 7.636, P = 0.006). The number of the involved brain areas in patients with identifiable underlying disease were well correlated with the number of cells and pressure of CSF (r = -0.472, P = 0.031; r = 0.779, P = 0.039; respectively).@*Conclusions@#With the increased number of the involved brain areas in patients with identifiable underlying disease, the body has lower immunity against the organism which might result in higher intracranial pressure and more severe clinical status.

Inhibition of Combination of Icaritin and Doxorubicin on Human Osteosarcoma MG-63 Cells in vitro / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the inhibition and molecular mechanism of icaritin (ICT) combined doxorubicin (DOX) on human osteosarcoma MG-63 cells in vitro.</p><p><b>METHODS</b>The control group, ICT groups (10, 20, 40, 80, and 160 µmol/L), DOX groups (1, 2, 4, 8, and 16 µg/mL), and combination groups (20 µmol/ L ICT +1 µg/mL DOX, 20 µmol/L ICT +2 µg/mL DOX, 20 µmol/L ICT +4 µg/mL DOX, 40 µmol/L ICT +1 µg/mL DOX, 40 µmol/L ICT +2 µg/mL DOX, 40 µmol/L ICT +4 µg/mL DOX, 80 µmol/L ICT +1 µg/mL DOX, 80 µmol/L ICT +2 µg/mL DOX, 80 µmol/L ICT +4 µg/mL DOX) were set up. Human osteosarcoma MG-63 cells were respectively cultured and their effects on morphological changes were observed using inverted phase contrast microscope after 24-and 48-h intervention. The cell proliferation inhibition rate of each group was de- termined using CCK-8, and IC50 calculated. The MG-63 apoptosis rate was detected using Annexin V-FITC/ PI double dye flow cytometry. Expression levels of bcl-2, caspase-3, and p21 were detected using RT-PCR.</p><p><b>RESULTS</b>ICT and DOX could obviously inhibit the proliferation of MG-63 cell. Along with ICT concentration increasing from 10 µmol/L to 160 µmol/L, the cell proliferation inhibition rate also increased gradually from 9.67% ± 3.62% to 89.18% ± 9.66%. The IC50 was 46.93 µmol/L and 3.87 µg/mL respectively. ICT and DOX could cause either early or late stage apoptosis, down-regulate Bcl-2 gene expression, and up-regulate gene expressions of Caspase-3 and p21 respectively (P < 0.05). Aforesaid changes were more obviously seen in combination groups than in lCT groups and DOX groups (P < 0.05).</p><p><b>CONCLUSION</b>CT combined DOX had additive or synergistic inhibition effect for the proliferation of osteosarcoma MG-63 cells, which might be related with regulating gene expressions of bcl-2, caspase-3, and p21.</p>

Clinicopathologic correlation between CD4-positive T lymphocyte counts and superficial lymphadenopathy in HIV-positive/AIDS patients / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the clinicopathological correlation between CD4(+) T lymphocyte count and superficial lymphadenopathy HIV/AIDS patients.</p><p><b>METHODS</b>A total of 1066 HIV/AIDS patients were included in this study. The incidence of superficial lymphadenopathy, peripheral blood CD4(+) T lymphocyte counts and histological features of superficial lymphadenopathy were analyzed.</p><p><b>RESULTS</b>Among 1066 patients, 126 cases (11.8%) presented with superficial lymphadenopathy. Of the 126 cases, there were 69 cases with CD4(+) T lymphocyte counts < 100/µl and clinical diagnoses including tuberculosis (37 cases), reactive hyperplasia (8 cases), AIDS-related lymphadenopathy (18 cases), penicillium diseases (12 cases), fungal infection (5 cases) and non-tuberculous mycobacterial infection (1 case). Twenty-six cases had CD4(+) T lymphocyte counts between 100/µl to 200/µl and clinical diagnosis including tuberculosis (12 cases), reactive hyperplasia (8 cases), AIDS-related lymphadenopathy(6 cases), penicillium disease (2 cases) and non-Hodgkin lymphoma (1 case). Twenty-nine cases had CD4(+) T lymphocyte counts > 200/µl and clinical diagnoses including tuberculosis (11 cases), reactive hyperplasia (12 cases), AIDS-related lymphadenopathy (3 cases), Penicillium diseases (1 case) and non-Hodgkin lymphoma (4 cases). The CD4(+) T lymphocyte counts among patients with tuberculosis, AIDS-related lymphadenopathy and Penicillium diseases were significantly different (χ(2) = 8.861, P = 0.012). A significant correlation between the incidence of superficial lymphadenopathy and CD4(+) T lymphocyte counts was found (χ(2) = 375.41, P = 0.000).</p><p><b>CONCLUSIONS</b>The most common cause of superficial lymphadenopathy in HIV/AIDS patients is tuberculosis, followed by lymph node reactive hyperplasia, AIDS-related lymphadenopathy and Penicillium disease. Low CD4(+) T lymphocyte count correlates with an increased incidence of superficial lymphadenopathy and the risk of opportunity infection. Therefore, determination of peripheral blood CD4(+) T lymphocyte count should become an integral marker for the early diagnosis and treatment of superficial lymphadenopathy in HIV/AIDS patients.</p>

Clinical analysis of 108 cases with adenocarcinoma Barretts's esophagus / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the prognostic factors and to analyze the efficacy of chemotherapy and/or radiotherapy for Barrett's esophageal adenocarcinoma after radical surgical resection.</p><p><b>METHODS</b>The clinical data of 108 patients with adenocarcinoma Barrett's esophagus picking out from 783 esophageal adenocarcinoma patients surgically treated between June 1978 to June 2001 in the Shandong Provincial Hospital and Shandong Qianfoshan Hospital were analyzed retrospectively. 60Co gamma-irradiation or 6MVX-ray with conventional fraction were used for radiotherapy with a total volume dosage of 55-70 Gy. The chemotherapy was either FAM (iv infusion of 5-Fu 500 mg, d1-d5; ADM 50 mg d1; MMC 12 mg, d1) or CMF regimen (iv infusion of CTX 800 mg d1, d8; MTX 30 mg d1; 5-Fu 500 mg, d1-d5) for 4-6 cycles. The Kaplan-Meier amalysis was used to estimate the survival rate. Log rank test was used for comparison of the survival difference among different groups.</p><p><b>RESULTS</b>In this series, 76 of 92 patients who underwent radical surgical resection received postoperative radiotherapy alone, and 16 received radiotherapy plus chemotherapy. Twelve of the other 16 patients who underwent palliative surgical resection received chemotherapy plus radiotherapy, the remaining 4 patients died of operative complications during surgery. The overall 1-, 3- and 5-year survival rate of this series was 81.5%, 51.9% and 22.2%, respectively. In the radical resection group, it was 15.8% for the patients received radiotherapy alone versus 75.0% for those treated by chemotherapy plus radiotherapy. The 5-year survival rate was 33.3% for the patients without extra-esophageal infiltration and 33.3% for the patients without lymph node metastasis, respectively. However, it was only 9.1% for the patients with extra-esophageal infiltration and 14.3% for those with lymph node metastasis, respectively. For the patients who had palliative surgical resection, though they received chemotherapy plus radiotherapy postoperatively, none of them survived longer than 5-year. Statistically significant difference among these groups was demonstrated by Log rank test (P < 0.05).</p><p><b>CONCLUSION</b>Chemotherapy plus radiotherapy after radical surgical resection may improve the survival of patients with adenocarcinoma in Barrett's esophagus adenocarcinoma patient. The pathological stage, extra-esophageal infiltration, lymph node metastasis and postoperative chemotherapy plus radiotherapy are important prognostic factors.</p>