The prognostic value of phosphatidylinositol-4,5-bisphosphate 3-kinase,catalytic subunit alpha (PIK3CA) in patients with esophageal squamous cell carcinoma (ESCC) is controversial.We aimed to investigate the prognostic significance of PIK3CA mutation in patients with ESCC.EMBASE,PubMed,and Web of Science databases were systematically searched from inception through Oct.3,2016.The hazard ratios (HRs) and 95％ confidence intervals (CI) were calculated using a random effects model for overall survival (OS) and disease-free survival (DFS).Seven studies enrolling 1505 patients were eligible for inclusion of the current meta-analysis.Results revealed that PIK3CA mutation was not significantly associated with OS (HR:0.90,95％ CI:0.63-1.30,P=0.591),with a significant heterogeneity (I2=65.7％,P=0.012).Additionally,subgroup analyses were further conducted according to various variables,such as types of specimen,the sample size,technique and statistical methodology.All results suggested that no significant relationship was found between PIK3CA mutation and OS in patients with ESCC.For DFS,there was no significant association between PIK3CA mutation and DFS in patients with ESCC (HR:1.00,95％ CI=0.47-2.11,P=0.993,I2=73.7％).Publication bias was not present and the results of sensitivity analysis were very stable in the current meta-analysis.Our findings suggest that PIK3CA mutation has no significant effects on OS and DFS in ESCC patients.More well-designed prospective studies with better methodology for PIK3CA assessment are required to clarify the prognostic significance of PIK3CA mutation in ESCC patients.

OBJECTIVETo observe the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in the unstable plaque of patients with acute coronary syndrome (ACS), and the impact of leukotriene B4 (LTB4) on the EMMPRIN expression in macrophages.

METHODSThe EMMPRIN expression was detected by immunohistochemistry in 11 unstable plaques from patients with ACS. Protein expression of EMMPRIN was evaluated by Western blot on macrophages differentiated from THP-1 which were stimulated with LTB4 in the absence or presence of LTB4 antagonist U75302. There are 8 study groups: 1-THP-1, 2-8-the macrophages derived from THP-1, 2-6-macrophages were stimulated by LTB4 (0, 10(-10), 10(-9), 10(-8) and 10(-7) mol/L) for 24 h, 7-8-the macrophages were pretreated by 10(-6) mol/L or 10(-7) mol/L U75302 2 h before the LTB4 (10(-7) mol/L) stimulation.

RESULTSAbundant EMMPRIN expression was detected in macrophages and smooth muscle cells of unstable plaques from ACS patients. As to the THP-1 derived macrophages, EMMPRIN expression was significantly upregulated in a concentration-dependent manner in LTB4 stimulated groups, which was significantly higher in group 3-6 than in the THP-1 group (group 1) and macrophages group (group 2) (all P < 0.05) and pretreatment with U75302 significantly reduced the LTB4 induced upregulation of EMMPRIN in a dose-dependent manner (P < 0.05).

CONCLUSIONEMMPRIN expression is enhanced in macrophages and smooth muscle cells on unstable coronary artery plaques from ACS patients. LTB4 could stimulate EMMPRIN expression on THP-1 derived macrophages suggesting that LTB4 and EMMPRIN might be both involved in the formation and progression of unstable plaques, future studies are warranted to explore if LTB4 and EMMPRIN antagonists are effective or not for treating patients with ACS.

Acute Coronary Syndrome ; metabolism ; pathology ; Basigin ; metabolism ; Cell Line ; Humans ; Leukotriene B4 ; metabolism ; pharmacology ; Macrophages ; drug effects ; metabolism ; Myocytes, Smooth Muscle ; drug effects ; metabolism ; Plaque, Atherosclerotic ; metabolism

OBJECTIVE15-lipoxygenase (15-LO) is a prooxidant enzyme which is expressed in asthmatic lungs leading to formation of pro- and anti-inflammatory mediators. Gene expression profiling studies show the association between 15-LO and allergic asthma. This study was designed to observe the expression of 15-LO in lungs of asthmatic rats and examine the effects of dexamethasone on 15-lipoxygenase expression.

METHODSTwenty-seven male Sprague-Dawley (SD) rats were randomly divided into three groups: control, asthma and dexamethasone (DXM) intervention. An asthma model was prepared by sensitization and challenging with ovalbumin. The production of 15-LO in lung tissue homogenates was measured using ELISA.The expression of 15-LO mRNA in lungs was determined by reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSThe levels of 15-LO mRNA and protein in the asthma group (0.51 ± 0.14 and 2080 ± 73 μg/mL, respectively) were lower than those in the control group (0.76 ± 0.15 and 2472 ± 106 μg/mL, respectively; P<0.01). DXM intervention increased significantly the levels of 15-LO mRNA and protein (1.02 ± 0.34 and 2562 ± 218 μg/mL) compared with the asthma group (P<0.01).

CONCLUSIONSThe production of 15-LO in lung tissues is reduced in asthmatic rats. DXM can increase the expression of 15-LO in lung tissues and thus might provide anti-inflammatory effects in asthmatic rats.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Arachidonate 15-Lipoxygenase ; analysis ; genetics ; Asthma ; drug therapy ; enzymology ; Dexamethasone ; pharmacology ; Lung ; enzymology ; pathology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo Study T lymphocyte subsets, including T(H1) and T(H2) cells in peripheral blood mononuclear cells (PBMC) of children with mycoplasma pneumonia, understand immunopathogenesis and explore the possibility of immunotherapy of patients with mycoplasma pneumonia.

METHODSFresh peripheral blood samples of patients from two groups, group 1, mycoplasma pneumonia (MP) group (35 cases, 15 males and 20 females, age range 3 - 13 years, mean 9 years), and control group consisted of 28 healthy children (14 males and 14 females, age range 3 - 12 years, mean 7 years) were treated and run through the flow cytometry. The data were obtained by using Simultest IMK-Lymphocyte software and the percentage of CD(3)(+), CD(3)(+)CD(4)(+), CD(3)(+)CD(8)(+), CD(3)(-)CD(19)(+) and CD(3)(-)CD(16 + 56)(+) cells were counted. The percentage of T(H1) and T(H2) cells were gained through determination of intracellular cytokines IFN-gamma or IL-4 in CD(4)(+) cells by flow cytometry. The 35 patients with MP were hospitalized at our hospital. In addition to fever and cough, all the patents had abnormal X-ray findings and/or moist rale on auscultation of the lungs. The IgM antibody to Mycoplasma pneumoniae was positive in each patient. Immunoglobulins were measured, and PPD skin tests were performed in 30 out of the 35 patients with MP. T test and rank sum test by SPSS FOR WINDOWS 10.0 was used for statistical analysis.

RESULTSThe percentage of CD(3)(+) and CD(4)(+) T lymphocyte was 68.00 +/- 6.66 and 37.86 +/- 5.84, respectively, in MP group, and 63.71 +/- 7.92 and 34.54 +/- 6.23 in control group (P < 0.05). The percentage of T(H1) cells was 14.13 +/- 8.46 in patients and 20.77 +/- 6.89 in normal control group (P = 0.001). The percentage of NK cells was 15.57 +/- 12.16 and 20.39 +/- 9.64 in MP and control group (P < 0.01). The ratio of T(H1)/T(H2) in MP group was lower than that in control group (P < 0.05). However the percentage of CD(8), T(H2), B cells and CD(4)/CD(8) had no difference between the MP and control groups. The levels of IgG, IgA, and IgM in serum were normal in most of patients except for a few patients who had elevated IgA and IgM levels. The PPD skin tests were negative in 30 out of 35 patients.

CONCLUSIONIn this study a higher percentage of CD(3)(+), CD(4)(+) T lymphocyte and lower percentage of T(H1), NK cells in PBMC of patients with mycoplasma pneumonia were found. The ratio of T(H1) and T(H2) cells in patients was also lower. None of thirty patients had positive PPD skin tests. Unbalanced cell-mediated immunity with a tendency toward T(H2) existed in patients with MP. Therefore, immunomodulators may be useful in treatment of mycoplasma pneumonia.

Adolescent ; CD3 Complex ; blood ; CD4 Antigens ; blood ; CD8 Antigens ; blood ; Child ; Child, Preschool ; Female ; Flow Cytometry ; Humans ; Immunoglobulins ; blood ; Male ; Pneumonia, Mycoplasma ; blood ; immunology ; T-Lymphocyte Subsets ; cytology ; immunology ; Th1 Cells ; immunology ; Th2 Cells ; immunology

OBJECTIVETo study the role of urotension-II in serum and bronchoalveolar lavage fluid (BALF) in the process of airway remodelling in asthmatic rats.

METHODSThirty-two male Sprague-Dawley (SD) rats were randomly divided into normal control and 2-week, 4-week and 8-week asthmatic groups (OVA inhalation of 2, 4 and 8 weeks respectively). Rats were sensitized and challenged by OVA to establish a model of asthma. The bronchial wall thickness and the airway smooth muscle thickness were measured by image analysis system. The urotension-II contents in serum and BALF were determined using ELISA.

RESULTSThe bronchial wall thickness and the airway smooth muscle thickness in the three asthmatic groups significantly increased compared with those in the normal control group (P<0.01). The urotension-II contents in serum and BALF in the three asthmatic groups also increased significantly compared with those in the normal control group (P<0.01). The urotension-II contents in serum and BALF in the 8-week asthmatic group were the highest, followed by the 4-week and the 2-week asthmatic groups (P<0.01). BALF urotension-II contents were positively correlated with the bronchial wall thickness and the airway smooth muscle thickness as well as serum U-II contents in the four groups.

CONCLUSIONSThe urotension-II contents in serum and BALF in the process of airway remodeling increase in asthmatic rats. The changes in serum and BALF urotension-II contents may be associated with airway remodeling in asthmatic rats.

Airway Remodeling ; Animals ; Asthma ; metabolism ; pathology ; Bronchi ; pathology ; Bronchoalveolar Lavage Fluid ; chemistry ; Male ; Muscle, Smooth ; pathology ; Rats ; Rats, Sprague-Dawley ; Urotensins ; analysis ; blood

BACKGROUNDAmyloid β(1-42) (Aβ(42)) peptide vaccination has been proved to be effective in reducing amyloid burden in brain and improving cognitive function in Alzheimer's disease (AD) mouse models. But the phase II trial of Aβ(42) peptide vaccine was halted because of T cell-mediated meningoencephalitis. In this study, a DNA vaccine, p(Aβ(3-10))(10)-CpG, was constructed to test whether it would induce predominant T(H)2 immune response upon immunization of BALB/c mice.

METHODSBALB/c mice were vaccinated intramuscularly with p(Aβ(3-10))(10)-CpG plasmids. Aβ(42) peptide, pcDNA3.1(+) empty vector and PBS were injected to the control groups. Expression of interesting gene in injected muscle was identified by immunohistochemistry. Anti-Aβ antibody titers, isotype profiles as well as cytokines in ex vivo splenocytes culture supernatants were analyzed by enzyme-linked immunosorbent assay (ELISA).

RESULTSP(Aβ(3-10))(10)-CpG plasmid was expressed in muscle after injection detected by immunohistochemistry. The p(Aβ(3-10))(10)-CpG vaccine induced high titers of anti-Aβ antibodies in BALB/c mice. And isotype of the antibodies was mainly IgG1, the IgG1/IgG2a ratio for the p(Aβ(3-10))(10)-CpG group was approximately 5 times greater than that for the Aβ(42) peptide group. Ex vivo cultured splenocytes isolated from mice immunized with p(Aβ(3-10))(10)-CpG exhibited high interleukin-4 response and low interleukin-γ (IFN-γ) response.

CONCLUSIONSImmunization with p(Aβ(3-10))(10)-CpG vaccine primarily induces a T(H)2 type of response, thus reduces the probability of inflammation. This p(Aβ(3-10))(10)-CpG vaccine possesses the basic factors required for a safe and effective AD vaccine.

Alzheimer Disease ; immunology ; therapy ; Amyloid beta-Peptides ; immunology ; Animals ; Cells, Cultured ; Enzyme-Linked Immunosorbent Assay ; Immunity, Humoral ; immunology ; Immunoglobulin G ; metabolism ; Immunohistochemistry ; Interferon-gamma ; metabolism ; Interleukin-4 ; metabolism ; Mice ; Mice, Inbred BALB C ; Muscles ; metabolism ; T-Lymphocytes ; immunology ; Vaccines, DNA ; therapeutic use

OBJECTIVETo investigate the clinical phenotype and genetic characteristics of an azoospermia patient with ring 22 chromosome syndrome.

METHODSWe analyzed the clinical data of an azoospermia patient with ring 22 chromosome syndrome and reviewed relevant literature.

RESULTSThe patient was a short 29-year-old male, with bilateral testes small in size and soft in texture. Seminal examination indicated azoospermia. Chromosome analysis showed the karyotype of the patient to be 46, XY, r (22) (p11, q25). The level of testosterone was low, and the testicular tissue was brittle and easy to break. Pathological microscopy revealed reduced number of Sertoli cells and germ cells in the seminiferous tubules and thinner layers of cells. All the germ cells were spermatogonia. Neither spermatocytes nor sperm cells were found, which suggested complete spermatogenic failure. Mild interstitial fibrosis was visible in part of the seminiferous tubule walls.

CONCLUSIONPatients with ring 22 chromosome syndrome usually represent normal clinical phenotypes. However, this kind of genetic abnormality often induces severe testicular damage and spermatogenic arrest, which may result in azoospermia.

Adult ; Azoospermia ; etiology ; genetics ; Chromosomes, Human, Pair 22 ; Humans ; Male ; Oligospermia ; Ring Chromosomes ; Spermatogenesis ; Spermatogonia ; Syndrome

The combination of field surveys and field interviews were conducted in Beijing Shunyi district Traditional Chinese medicine (TCM) hospital to investigate the work situation and find the effectiveness and the existing problems of the hospital after accepting the unified management, technical support, talent support, teaching and scientific research support from a 3As hospital. After trusteeship, the business volume of Shunyi District TCM hospital has increased,the level of scientific research and education have improved,and the service capacity of traditional Chinese medicine has been enhanced. But it is necessary to coordinate trusteeship funds, clear responsibility and power, strengthen the construction of hospital informatization, unified the use of hospital preparations and to improve the hospital trusteeship model.

Eucommiae Folium(EF),a traditional Chinese medicine,has been used to treat secondary hypertension,including renal hypertension and salt-sensitive hypertension,as well as hypertension caused by thoracic aortic endothelial dysfunction,a high-fat diet,and oxidized low-density lipoprotein.The antihyperten-sive components of EF are divided into four categories:flavonoids,iridoids,lignans,and phenyl-propanoids,such as chlorogenic acid,geniposide acid and pinoresinol diglucoside.EF regulates the occurrence and development of hypertension by regulating biological processes,such as inhibiting inflammation,regulating the nitric oxide synthase pathway,reducing oxidative stress levels,regulating endothelial vasoactive factors,and lowering blood pressure.However,its molecular antihypertensive mechanisms are still unclear and require further investigation.In this review,by consulting the relevant literature on the antihypertensive effects of EF and using network pharmacology,we summarized the active ingredients and pharmacological mechanisms of EF in the treatment of hypertension to clarify how EF is associated with secondary hypertension,the related components,and underlying mechanisms.The results of the network pharmacology analysis indicated that EF treats hypertension through a multi-component,multi-target and multi-pathway mechanism.In particular,we discussed the role of EF tar-gets in the treatment of hypertension,including epithelial sodium channel,heat shock protein70,rho-associated protein kinase 1,catalase,and superoxide dismutase.The relevant signal transduction path-ways,the ras homolog family member A(RhoA)/Rho-associated protein kinase(ROCK)and nicotinamide adenine dinucleotide phosphate(NADPH)oxidase/eNOS/NO/Ca2+pathways,are also discussed.

Pancreatic cancer is a highly malignant tumor with a poor prognosis. It is very hard to treat pancreatic cancers for their high heterogeneity, complex tumor microenvironment, and drug resistance. Currently, gemcitabine plus nab-paclitaxel, capecitabine and FOLFIRINOX are standard chemotherapy for resectable or advanced metastatic pancreatic cancer. Considering the limited efficacy and toxic side effects of chemotherapy, targeted and immune drugs have gradually attracted attention and made some progress. In this article, we systematically reviewed the chemotherapeutic drugs, targets and related targeted drugs, and immunotherapy drugs for pancreatic cancer.