ObjectiveTo investigate the efficacy and safety of porcine large intestine-processed Dahuang Pill （肠制大黄丸） in the treatment of type 2 diabetes mellitus （T2DM） complicated by chronic constipation. MethodsA total of 80 patients with T2DM complicated by chronic constipation were enrolled and randomly divided into a control group and a treatment group， with 40 cases in each group. All patients received routine basic treatment. The control group was treated with oral lactulose solution 10 ml once daily， while the treatment group was administered with oral porcine large intestine-processed Dahuang Pill 3 g once daily. The treatment course was 4 weeks for both groups. The primary outcome was the score of the Wexner Constipation Scale score. The secondary outcomes included fasting blood glucose （FBG）， 2-hour postprandial blood glucose （2 hPG）， glycated hemoglobin A1c （HbA1c）， Patient Assessment of Constipation Quality of Life （PAC-QOL） score， traditional Chinese medicine （TCM） syndrome score， and clinical effective rate before and after treatment. TCM syndrome efficacy was evaluated in both groups after treatment， and safety was assessed simultaneously. ResultsSeventy-five subjects completed the study， including 37 in the treatment group and 38 in the control group. After treatment， the Wexner Constipation Scale score， FBG， 2 hPG， HbA1c， PAC-QOL score and TCM syndrome score all significantly decreased in both groups （P＜0.01）. In intergroup comparison， the treatment group showed significantly superior improvements in the Wexner Constipation Scale score， FBG， HbA1c， PAC-QOL score and TCM syndrome score relative to the control group （P＜0.05 or P＜0.01）. No significant difference in 2 hPG was observed between groups （P＞0.05）. The total clinical effective rate of TCM syndrome efficacy was 91.89%（34/37）in the treatment group， which was higher than 63.16%（24/38） in the control group. No adverse events occurred in either group， and all safety indicators were within the normal range. ConclusionPorcine large intestine-processed Dahuang Pill can effectively relieve clinical symptoms， synergistically improve glucose metabolism and quality of life in patients with T2DM complicated by chronic constipation， which possesses good clinical safety.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

Objective:To assess the clinical value of helium-free magnetocardiography(MCG) in the diagnosis of coronary artery disease(CAD).Methods:A total of 213 patients with suspected CAD undergoing MCG in Beijing Anzhen Hospital were enrolled in the study. All patients underwent coronary CT angiography/invasive coronary angiography(CCTA/ICA) within 48 hours after MCG scanning. The parameters of MCG, including magnetic field multipolarization, magnetic field unipolarization, T-wave flattened, change in magnetic field distribution at TT segment, abnormal T-peak amplitude ration of maximum to minimum, significant movement of poles, magnetic field angle deviation and abnormal distribution of positive pole were used for the evaluation of the stenosis of coronary arteries.Results:Among 213 patients, MCG scanning was completed in 193 cases(90.6%), while 20 cases were excluded for various reasons. The CCTA/ICA results were taken as gold standard, the total coincidence rate of MCG with the degree of stenosis was 88.60%(95% CI: 83.25%-92.72%), the sensitivity and specificity of MCG in the diagnosis of CAD was 89.63%(95% CI: 83.21%-94.21%) and 88.23%(95% CI:78.12%-94.78%), respectively; the positive and negative predictive value were 93.80%(95% CI:88.72%-96.68%) and 81.08%(95% CI:72.15%-87.64%), respectively. Conclusion:MCG is highly accurate in the diagnosis of CAD, it may be widely used clinically as an non-invasive method free of radiation or contrast agent.

Objective To prepare a recombinant pneumococcal surface protein A clade 4 ( PspA4) and to analyze its immunogenicity.Methods The gene encoding PspA4 protein was synthesized and inserted into pET-20b to construct the recombinant expression plasmid.The transformed E.coli strains carrying expression plasmid were induced to express PspA4 protein.ELISA was performed to analyze the ti-ters of PspA4-specific IgG in a mouse model.Results The recombinant PspA4 protein of high purity ( 90%) was successfully prepared.The titers of PspA4-specific antibody in mice received PspA4 immuniza-tion were 106 times higher than those of the blank control group, suggesting that the expressed PspA4 protein had the advantage of high immunogenicity.Conclusion This study suggested that the PspA4 protein might be used as one of the candidate protein for the development of pneumovax and laid a foundation for further in-vestigation on pneumococcal protein based vaccine.

BACKGROUNDGlucosylceramide synthase (GCS), an enzyme responsible for ceramide glycosylation, plays an important role in multidrug resistance (MDR) in some tumors in vitro; however, its expression and clinicopathological significance in non-small cell lung cancer (NSCLC) remains unclear.

METHODSWe evaluated GCS expression in 116 paired tumor and adjacent non-cancerous tissues and 50 frozen tissues from patients with NSCLC using immunohistochemistry and western blotting, and explored the correlation between GCS and NSCLC clinicopathological characteristics and prognosis. We observed the association between GCS and the MDR proteins P-glycoprotein (P-gp) and lung resistance-related protein (LRP) to determine the link between GCS and MDR at the histological level.

RESULTSGCS expression was significantly upregulated in NSCLC tumors compared with non-cancerous tissue. There was high GCS expression in 75/116 tumor specimens (64.7%) and 16/116 non-cancerous specimens (13.8%). High GCS expression was significantly associated with poor differentiation (P = 0.01), lymph node metastasis (P = 0.004), recurrence/distant metastasis (P = 0.006), and chemotherapy resistance (P = 0.025). Multivariate analysis demonstrated that GCS immunopositivity was an independent risk factor for survival (P = 0.018). P-gp was expressed in 80/116 tumors (69.0%) and in 12/116 non-cancerous tissue specimens (10.3%; P = 0.001); LRP was expressed in 85/116 tumors (73.3%) and 19/116 non-cancerous tissue specimens (16.4%; P = 0.001). Importantly, the results demonstrated that increased GCS expression in NSCLC cancer specimens correlated with increased expression of P-gp and LRP, molecules known to stimulate cancer cell MDR (r = 0.612 and 0.503, P = 0.01 and 0.035, respectively).

CONCLUSIONGCS upregulation might contribute to the development of NSCLC and could be a useful prognostic indicator and chemoresistance predictor for NSCLC patients.

ATP Binding Cassette Transporter, Sub-Family B ; genetics ; metabolism ; Adult ; Aged ; Blotting, Western ; Carcinoma, Non-Small-Cell Lung ; enzymology ; pathology ; Drug Resistance, Multiple ; Female ; Glucosyltransferases ; genetics ; metabolism ; Humans ; Immunohistochemistry ; Male ; Middle Aged

A total of 59 untreated asthmatics and 47 healthy control subjects were recruited from Qianfoshan Hospital of Shandong Province from May 2011 to April 2012.Compared with healthy control subjects,the levels of IL-25 in induced sputum and eosinophils,IgE,interleukin-4 (IL-4) and interleukin25 (IL-25) in serum samples of asthmatics were significantly higher while the level of interferon-gamma (IFN-γ) were much lower.However,after inhaled glucocorticoid treatment,the levels of eosinophils,IL-4 and IL-25 decreased and IFN-γ significantly increased,while the level of IgE showed no significant changes.It was also found the expression of IL-25 was markedly positively correlated with the levels of eosinophils and IL-4 in serum and markedly negatively correlated with the levels of IFN-γ and had no relatio.