floss, prevention from caries and periodontal diseases, the scaling, and the oral health care for the elderly. The investigation showed that there are needs so great and so urgent for dentists to work hard on.

Diversity-oriented synthesis (DOS) aims to efficiently generate collections of small molecules with diverse appendages, functional groups, stereochemistry and skeletons, thus yielding diverse biological activities capable of modulating a wide variety of biological processes. In this review, we discussed the common strategies employed in DOS with specific examples from recent literature, including reagent-based approach, substrate-based approach, build-couple-pair strategy and privileged substructure-based DOS. The application of some DOS libraries in drug discovery is also presented.

Farnesoid X receptor (FXR) belongs to the nuclear receptor superfamily. It is highly related to the formation of metabolic syndrome and the glucose homeostasis, and therefore represents an important drug target against metabolic diseases and diabetes. In recent years, great progress has been made in the agonists, antagonists, and crystal structures of FXR. The diverse FXR ligands and their structure-activity relationship are reviewed in this article. The advances in the crystal structures of FXR in complex with different ligands are also introduced.

Objective To investigate the immunomodulation of lower polypeptide from sea cucumber in mice.Methods Effects of polypeptide from sea cucumber on the immunity were studied by the observation of the serum hemolysins level(HC_(50)),the plaque-forming cell (PFC),the phagocytosis of the phagocytes and the activities of NK cells.Results To compare experiment groups with control group,the enhancement facilitation of HC_(50),PFC,phagocytosis ability of macrophage and activity of NK cell was observed.Conclusion The results indicated that polypeptide from sea cucumber has the function of immunomodulation in mice.

Objective: To investigate influence of isometric exercise (IE) training on number of endothelial progenitor cells (EPCs) and level of vascular endothelial growth factor (VEGF) of circulating blood in patients with coronary chronic total occlusion (CTO). Methods: A total of 20 CTO patients were divided into training group (n=10) and control group (n=10). Both groups received routine medication for three months, training group also received three-month IE training (maximal handgrip was used to induce maximum IE of upper limb muscles, leading to temporary physiological ischemia of skeletal muscle),while control group remained sedentary without exercise training. Flow cytometry was used to measure number of blood EPCs, and enzyme linked immunosorbent assay (ELISA) was used to measure serum concentration of VEGF. Results: Before treatment, the differences of levels of blood EPCs and VEGF between two groups were no significant（P>0.05）. Compared with before treatment, there were significant increase in blood number of EPCs [(0.028±0.009)% vs. (0.044±0.016)%] and VEGF concentration [(65.3±15.1) pg/ml vs. (98.5±17.4)pg/ml] after three-month treatment in training group (P=0.015, P<0.01), and they were significantly higher than those of control group after treatment. Compared with before treatment, there were no significant difference in blood number of EPCs and concentration of VEGF after treatment in control group, P>0.05. The blood numbers of EPCs were positively correlated with VEGF concentration in training group and control group (r=0.727, r=0.785, P<0.05 both). Conclusions: Isometric exercise training can increase blood number of EPCs and VEGF concentration in coronary CTO patients, which may contribute to collateral angiogenesis in remote ischemic myocardium.

Objective: To explore the influence of public physical education curriculum integrated with physical fitness training on college students’ physical health,and to provide a reference for improving physical health of college students. Methods: A total of 280 freshmen from 6 classes in Qiqihar Medical University were selected, and all the participants were divided into two groups (3 classes in each group). The control group (n=132) received regular public physical education curriculum. The experimental group (n=148) received physical fitness training in addition on the public physical education curriculum. The experiment lasted for one semester. Physical fitness of the two groups of college students were tested, and the changes of physical health of the two groups before and after the experiment were compared. Results: The qualified rate of physical health assessment before the experiment was close to that of the two groups (χ2=0.24，P>0.05). Compared with that before the experiment, the qualified rate of physical health assessment after the experiment in the experimental group was significantly higher than that in the control group (χ2=22.52，12.39，P<0.05). The scores of physical health assessment of boys and girls in the experimental group after the experiment were significantly higher than those before the experiment (boys:t=6.87,7.99,8.05,5.02,6.94,10.05; girls:t=5.88,6.32,7.08,9.84,6.17,4.06,P<0.05). The test results of vital capacity, 50-meter running, sitting forward bending, standing long jump, pull-up and 1 000-meter running in the experimental group were significantly better than those in the control group(t=7.26,4.30,8.07,2.34,8.31,4.20,P<0.05). After the experiment, the test scores of vital capacities, 50-metre running, sitting forward bending, standing long jump, sit-up and 800-metre running in the experimental group were significantly better than those in the control group (t=8.64,5.81,5.53,22.27,9.60,13.06,P<0.05). Conclusion Integrating physical fitness training in college public physical education curriculum can help improve the physique health level of college students, actively reform public physical education curriculum in colleges and universities, and explore the curriculum model suitable for the actual situation of each school is an important way to improve the physique health level of college students.

Abstract: Upon monitoring cytoplasmic aberrant double-stranded DNA, cGAS-STING signaling pathway induces the expression of type I interferons and pro-inflammatory cytokines, which activates the host immune response and enhances anti-tumor immune response and resistance to pathogen infection. However, sustained activation of the cGAS-STING signaling pathway drives diseases such as autoimmune diseases, aging-associated inflammation, and neurodegenerative pathologies. Herein, we describe the mechanism by which cGAS-STING signaling pathway participates in regulating the development of various immune-related diseases, with a particular review of the research and development progress of STING agonists, cGAS inhibitors, and STING inhibitors, aiming to provide some theoretical reference for the future development of cGAS-STING modulators.

OBJECTIVETo investigate the effects of intragastric administration of human interferon-α (hIFN-α)-transformed Bifidobacterium on immune functions of mice.

METHODSThe E.coli-Bifidobacterium shuttle expression vector containing hIFN-α gene was constructed and transformed into Bifidobacterium. The hIFN-α-transformed Bifidobacterium suspension (1010 /ml) was prepared after induction with 0.2% L-arabinose for hIFN-α expression and administered intragastrically in male Balb/C mice at the dose of 0.1 ml every other day for 2 weeks, with the mice receiving empty vector-transformed Bifidobacteria as the negative control and those having an equal volume of saline as the blank control. The percentages of mononuclear cell subsets in the thymus, spleen and blood were detected in the mice by flow cytometry, and the serum levels of IL-4, IL-12, IFN-γ and TNF-α were assayed using mouse cytokine FlowCytomix Kit.

RESULTSThe percentages of CD3⁺CD8⁺ and CD4⁺CD8⁺ cells in the thymus, CD3⁺CD4⁺, CD3⁺CD8⁺ and CD4⁺CD8⁺ cells in the spleen, and CD3⁺CD8⁺ cells in the blood all increased significantly in IFN group as compared with those in the negative and blank control groups (P<0.01 or 0.05). The serum level of IFN-γ also increased significantly (P<0.05) while IL-4 level remained unchanged in IFN group compared with those in the two groups.

CONCLUSIONIntragastric administration of hIFN-α-transformed Bifidobacterium promotes lymphocyte proliferation and maturation and increases the serum levels of Th1 cytokines in mice.

Animals ; Bifidobacterium ; Cell Proliferation ; Genetic Vectors ; Humans ; Interferon-alpha ; pharmacology ; Interferon-gamma ; blood ; Interleukin-12 ; blood ; Interleukin-4 ; blood ; Lymphocyte Activation ; drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins ; pharmacology ; Spleen ; cytology ; Th1 Cells ; cytology ; Thymus Gland ; cytology ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo explore the differences in sensitivity to rapamycin of five esophageal squamous cell carcinoma cell lines with different differentiation and the changes of sensitivity of the cells after siRNA-interfered expression of p70S6K.

METHODSEffects of rapamycin on proliferation of ESCC cell lines with different differentiation, EC9706, TE-1, Eca109, KYSE790 and KYSE450 cells, were investigated using cell counting kit 8 (CCK-8) assay, and according to the above results, the EC9706 cells non-sensitive to rapamycin were chosen to be transfected with p70S6K-siRNA. The changes in sensitivity of cells to rapamycin were measured in vitro and in vivo using CCK-8 kit, flow cytometry and tumor formation in nude mice.

RESULTSCCK-8 results showed that all the five cell line cells were sensitive to low concentration of rapamycin (<100 nmol/L), but TE-1 and EC9706 cells, which were with poor differentiation, showed resistance to high concentration of rapamycin. After EC9706 cells were treated with 50, 100, 200, 500 and 1 000 nmol/L rapamycin and p70S6K-siRNA, the proliferation rates of EC9706 cells were (48.67 ± 1.68)%, (15.45 ± 1.54)%, (14.00 ± 0.91)%, (10.97 ± 0.72)% and (2.70 ± 0.32)%, respectively, and were significantly lower than that of cells treated with 50, 100, 200, 500 and 1 000 nmol/L rapamycin and control siRNA [(74.53 ± 1.71)%, (68.27 ± 1.35)%, (71.74 ± 2.44)%, (76.23 ± 1.02)% and (80.21 ± 2.77)%] (P<0.05 for all). The results of flow cytometry showed that the ratios of cells in G1 phase of the p70S6K-siRNA, rapamycin and p70S6K-siRNA+ rapamycin groups were (53.82 ± 1.78)%, (57.87 ± 4.01)% and (73.73 ± 3.68)%, respectively, significantly higher than that in the control group (46.09 ± 2.31)% (P<0.05 for all). The results of tumor formation test in vivo showed that the inhibitory effect of rapamycin on tumor growth was stronger after the cells were transfected with p70S6K-siRNA, and the inhibition rate was 96.5%.

CONCLUSIONESCC cells with different differentiation have different sensitivity to rapamycin, and p70S6K-siRNA can improve the sensitivity of cells to rapamycin in vitro and in vivo.

Animals ; Antibiotics, Antineoplastic ; pharmacology ; Carcinoma, Squamous Cell ; drug therapy ; metabolism ; pathology ; Cell Differentiation ; Cell Line, Tumor ; Cell Proliferation ; Esophageal Neoplasms ; drug therapy ; metabolism ; pathology ; Humans ; Mice ; Mice, Nude ; RNA, Small Interfering ; Ribosomal Protein S6 Kinases, 70-kDa ; genetics ; metabolism ; Signal Transduction ; Sirolimus ; pharmacology ; Transfection

Objective To conclude the clinical features and treatments of adult cryptococcal meningoencephalitis (CM) patients.Methods Retrospective analysis of epidemiological characteristics,clinical features,treatments and prognoses of 94 adult CM patients,admitted to our hospital from July 1,1998 to June 30,2013,was performed.Cox regression analysis was performed to explore the influencing factors of survival time.Results CM was common in male adult patients who were younger than 60 years old.Nonspecific symptoms,such as headache and fever,were found most frequently.The most common risk factor was chronic usage of corticosteroid and/or immunosuppressants.The increased cerebrospinal fluid (CSF) pressure (＞180 mmH2O) was noted in 81 patients (86.17％),increased CSF protein level(＞0.45 g/L) was noted in 69 patients (73.40％) and decreased CSF glucose level (＜2.25 mmol/L) was noted in 54 patients (57.45％).The ratio of CSF glucose/blood glucose was associated to survival time of adult CM patients (P=0.011,OR=0.119).Conclusions CM should be considered when the adult patients have sub-acute or chronic headache and/or fever,with obviously increased CSF pressure,decreased CSF glucose level and non-specific EEG features.More attention should be called for the patients with decreased ratio of CSF glucose/blood glucose.