BGB-A445, a novel non-ligand-blocking agonistic anti-OX40 antibody, exhibits superior immune activation and antitumor effects in preclinical models / 医学前沿

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.

Research on constructing ICU nursing sensitivity quality index system based on evidence-based and"three-dimensional quality structure"model / 中国实用护理杂志

Objective To use the "three-dimensional quality structure" model as a theoretical basis, based on multiple evidence-based evidence, to construct ICU nursing sensitivity quality indicators, and to provide reference for the evaluation and monitoring of ICU department nursing safety quality. Methods Evidence-based and Delphi methods were used to complete 3 rounds of inquiry among 27 experts to obtain consensus opinions of experts and to determine nursing quality indicators. Results Of the 30 articles included, 17 wereⅢA, 10 wereⅣA, 2 wereⅤA, and 1 wasⅤB. According to the"three-dimensional structure theory"model, the included indicators were sorted out and a total of 12 items were obtained. The effective recovery rate of 3 rounds of questionnaires was 96.6％, 100.0％, and 96.4％. The authoritative coefficients were 0.899, 0.895, and 0.909, and the coordination coefficients of the first, second, and third indexes were 0.340, 0.379, and 0.403, respectively,with significance (P<0.01). The final ICU nursing sensitivity quality indicator consists of 3 first-level indicators, 15 second-level indicators and 69 third-level indicators. The selection of indicators at all levels gradually converges. Conclusions The established ICU nursing sensitivity quality index accords with the principle of scientificity and practicality, and can be used for ICU department nursing quality assessment.

Mechanistic studies of the transport of peimine in the Caco-2 cell model

Fritillaria thunbergii Miq. has been widely used in traditional Chinese medicine for its expectorant, antitussive, antiinflammatory and analgesic properties. Moreover, modern pharmacological studies have demonstrated that F. thunbergii Miq. has efficacy in the treatment of leukemia and cancers of the liver and cervix. Although the alkaloid, peimine, is largely responsible for these pharmacological effects, it has very low oral bioavailability. The aim of this study was to investigate the intestinal absorption of peimine in Caco-2 cell monolayers. Having demonstrated that peimine is non-toxic to Caco-2 cells at concentrations <200 μmol/L, the effect of peimine concentration, pH, temperature, efflux transport protein inhibitors and EDTA-Na2 on peimine transport were studied. The results show that peimine transport is concentration-dependent; that at pH 6.0 and 7.4, the P app(AP-BL) of peimine is not significantly different but the P app(BL-AP)) is; that both P app(AP-BL) and P app(BL-AP) at 4 °C are significantly higher than their corresponding values at 37 °C; that the P-glycoprotein (P-gp) inhibitors, verapamil and cyclosporin A, increase absorption of peimine; and that EDTA-Na2 has no discernible effect. In summary, the results demonstrate that the intestinal absorption of peimine across Caco-2 cell monolayers involves active transport and that peimine is a substrate of P-gp.

Study on the Residual Characteristics of Pesticide and Heavy Metals in Panax notoginseng / 中国药房

OBJECTIVE:To know the residual characteristics of organochlorine pesticides and 5 kinds of heavy metals (Cu, As,Cd,Hg and Pb) in Panax notoginseng. METHODS:P. notoginseng samples with 3 years were collected from Baiyi Town, Songming County and Liushao Township,Xundian County of Yunnan Province in Apr. 2013. 60 strains of P. notoginseng and 1 kg rhizosphere soil samples were also collected. The organochlorine pesticide residues and 5 kinds of heavy metals on its various parts and soil samples were detected. Pesticide residues determination method in Chinese Pharmacopoeia(2010 edition,volumeⅠ)was conducted to determine the organochlorine pesticides and 5 kinds of heavy metals (Cu,As,Cd,Hg and Pb). RESULTS:There was pentachloronitrobenzene in different parts of P. notoginseng from Baiyi Town,Songming County,and the contents were root bark>fibrous≥notches>ribs>leaves;there were pentachloronitrobenzene only in the root bark and fibrous of P. notoginseng from Liushao Township,Xundian County,and the contents were root bark>fibrous. No Hg was detected in any part of P. notoginseng samples,and the other heavy metals were highest in root bark;As and Pb were relatively high in soil,the contents of As and Pb in samples were far lower than in soil. CONCLUSIONS:The contents of pesticide residues and heavy metals in different parts of P. notoginseng are different,and those in root bark are relatively high. P. notoginseng sample contains organochlorine pesticides, which is mainly pentachloronitrobenzene;P. notoginseng sample has relatively strong accumulation of Cd.

Nursing of patients with AIDS complicated with tuberculosis and penicilliosis marneffei / 中国实用护理杂志

Objective To improve the degree of acquaintance of nursing of AIDS complicated with tu-berculosis(TB)and pencilliosis marneffei (PSM) through analysis of the clinical data of patients with these three diseases. Methods The clinical characteristics, treament and nursing care of 26 patients with AIDS compli-cated with TB and PSM were analyzed and summarized. Results 5 patients cured,13 patients turned better,8 cases died. The survival patients did not relapse after 6 to 30 months of follow- up. Conclusions The clinic presence of AIDS complicated with TB and PSM is complex and not specific, and the nursing care is difficult. We should monitor the state of illness carefully, make diagnosis and give treatment and meticulous nursing care as soon as possible to improve the prognosis.