摘要：Immune evasion behavior and immunosuppressive characteristics of tumor extensively impedethe immune initiation effect of therapy triggered immunogeniccell death (ICD). In this work, a carrier-adjuvantedimmunostimulator (designated as CoCeC) is developed toboost photodynamic immunotherapy by downregulatingprogrammed death ligand 1 (PD-L1) and impairing adenosinetriphosphate (ATP) hydrolysis. Among these, the crosslinkedchitosan oligosaccharide is applied as the drug carrier fordelivery of Ce6 and Ceritinib, which also serves as an immuneadjuvant to downregulate PD-L1. Meanwhile, the robustphotodynamic therapy (PDT) of CoCeC exhibits lethal toxicityagainst tumor cells to induce ICD and release damage-associated molecular patterns (DAMPs), which can also impairATP hydrolysis by blocking CD39. In vitro and in vivo resultsdemonstrate the robust therapeutic efficacy of CoCeC tosuppress primary tumor growth and activate a superior immune elimination against lung metastasis by amplifying theimmune initiation of ICD with the assistance of immune *** work provides a self-adjuvanted strategy to enhance the immune response of therapy induced ICD, which ispromising to activate systemic antitumor immunity in consideration of the complicated immunosuppressive factors.

摘要：Cough is a defensive behavior that protects the respiratory system from infection and clears airway *** airflow dynamics have been analyzed by a variety of mathematical and experimental *** this paper,the cough airflow dynamics of 42 subjects were obtained and *** identification model based on piecewise Gauss function for cough airflow dynamics is proposed through the dimensionless method,which could achieve over 90%identification ***,an assisted cough system based on pneumatic flow servo system is *** vacuum situation and feedback control are used to increase the simulated peak cough flow rate,which are important for airway secretion clearance and to avoid airway collapse,*** simulated cough peak flow could reach 5 L/s without the external assistance such as manual pressing,patient cooperation and other ***,the backstepping control is developed to generate a simulated cough airflow that closely mimics the natural cough airflow of *** assisted cough system opens up wide opportunities of practical application in airway secretion clearance for critically ill patients with COVID 2019 and other pulmonary diseases.

摘要：New pH-responsive saccharide hydrogels were designed and prepared using curdlan derivatives（curdlan-Bochistidine, CUR-HIS）. The CUR-HIS hydrogels possessed highly porous structures. The swelling ratios of CUR-HIS hydrogels increased with the degree of substitution of Boc-histidine groups. And the addition of 0.5 mol/L Na Cl provoked a sharp reduction of swelling ratio of CUR-HIS hydrogels. Bovine serum albumin（BSA） can be efficiently encapsulated into CUR-HIS hydrogels. Moreover, the release profiles of BSA at different p H values from CUR-HIS hydrogels were significantly different. These hydrogels showed good biocompatibility in the cytotoxicity assays. The CUR-HIS hydrogels are of great potential in biomedical applications such as protein delivery systems.

摘要：Candida albicans （C. albicans） infection has a high mortality rate in immunocompromised patients. Owing to the inefficiency of the current diagnostic system and the absence of licensed vaccines against candidiasis, the prevention of C. albicans infection remains a challenge. C. albicans infection can be evaluated and prevented by the anti-secreted aspartyl proteinase 2 antibody （anti-Sap2 IgG） and Hsp90 antibody （anti-Hsp90 IgG）. In this study, to explore a new agent for the improvement of the diagnosis and the prevention of C. albicans infection, an engineered fd bacteriophage, which is considered a human-safe virus nanofiber, was designed and prepared with two epitopes that could induce and capture anti-Sap2 IgG and anti-Hsp90 IgG. The dual-display phage was employed as a novel capture probe to develop a new enzyme-linked immunosorbent assay （ELISA） method, which significantly improved the detection rate compared with those of the ELISA in which recombinant protein Sap2 was used as coating antigen to capture the spedfic antibodies （rSap2-ELISA） and the ELISA in which recombinant protein Hsp90 was used as coating antigen to capture the specific antibodies （rHsp90-ELISA）. In addition, the nanofibers acted as a potential vaccine to immunize mice, as well as recombinant proteins, more efficiently mediated humoral and cellular immune responses, decreased levels of C. albicans colonization, and increased the survival rates in C. albicans-infected mice. Therefore, the phage dual-display nanofiber has been shown to be a powerful bifunctional agent for protection against and sensitive detection of clinical infections, which has the potential to be widely used in the life sciences, clinical medicine, and environmental sciences.

摘要：Background Chronic obstructive pulmonary disease(COPD)is a severe public health *** smoke(CS)is a risk factor for COPD and lung *** underlying molecular mechanisms of CS-induced malignant transformation of bronchial epithelial cells remain *** this study,we describe a lung-on-a-chip to explore the possible mechanistic link between cigarette smoke extract(CSE)-associated COPD and lung *** An in vitro lung-on-a-chip model was used to simulate pulmonary epithelial cells and vascular endothelial cells with *** levels of IL-6 and TNF-αwere tested as indicators of inflammation using an enzyme-linked immune sorbent *** junction complex mRNA expression was detected with qRT-PCR as the index of epithelial-to-mesenchymal transition(EMT).The effects of CSE on the phosphorylation of signal transduction and transcriptional activator 3(STAT3)were detected by Western *** cytometry was performed to investigate the effects of this proto-oncogene on cell cycle *** Inflammation caused by CSE was achieved in a lung-on-a-chip model with a mimetic *** exposure induced the degradation of intercellular connections and triggered the EMT *** exposure also activated the phosphorylation of proto-oncogene STAT3,while these effects were inhibited with *** CSE exposure in the lung-on-a-chip model caused activation of STAT3 in epithelial cells and endothelial ***0152,an inhibitor of activated STAT3,could be a potential treatment for CS-associated COPD and lung cancer.

摘要：Organ-on-a-chip systems have been increasingly recognized as attractive platforms to assess toxicity and to develop new therapeutic ***,current organ-on-a-chip platforms are limited by a“single pot”design,which inevitably requires holistic analysis and limits parallel ***,we developed a digital organ-on-a-chip by combining a microwell array with cellular microspheres,which significantly increased the parallelism over traditional organ-on-a-chip for drug *** to 127 uniform liver cancer microspheres in this digital organ-on-a-chip format served as individual analytical units,allowing for analysis with high consistency and quick *** platform displayed evident anti-cancer efficacy at a concentration of 10μM for sorafenib,and had greater alignment than the“single pot”organ-on-a-chip with a previous in vivo *** addition,this digital organ-on-a-chip demonstrated the treatment efficacy of natural killer cell-derived extracellular vesicles for liver cancer at 50μg/*** successful development of this digital organ-on-a-chip platform provides high-parallelism and a low-variability analytical tool for toxicity assessment and the exploration of new anticancer modalities,thereby accelerating the joint endeavor to combat cancer.

摘要：背景:新加坡结核病控制中心——一个大规模的国家结核病人诊治中心。 目的:观察抗结核药物诱导性肝炎(DH)的发病率、临床经过、结局及在总体规划条件下与DH有关的危险因素。 设计:对1998年抗结核治疗的成年病人回顾性分析。 结果:1998年治疗的1036例病人中,共发生DH 55例。DH诊断的中位时间为38天。与DH显著有关的因素是基线转氨酶/胆红素异常(OR 2.1,95％CI1.1-4.3,P=0.02),>60岁(OR 1.97,95％CI1.14-3.34,P=0.01)及女性(OR 1.9,95％CI1.07-3.4,P=0.02)。而人种、自报的不同的饮酒量及体重均与叫发生无关。3例致死性肝炎均接受含PZA的方案。48例重新开始治疗者中45例完成治疗。再次建立结核治疗的中位时间为23天。 结论:抗结核药物诱导性肝炎的发生率为5.3％。与DH发生有关的危险因素为>60岁、基线转氨酶/胆红素异常及女性。

摘要：Objectives: To determine whether early treatment of cystic fibrosis made possible by diagnosis after newborn screening results in improved pulmonary outcomes in adolescence. Study design: Both screening (SG) and non-screening groups (NSG) comprised a cohort of children from Australia previously studied at 1, 5, and 10 years of age. The groups were compared on measures of clinical status obtained during their comprehensive annual review conducted at or near the 15th birthday of the subjects. Results: Data were collected on 48 of 57 original subjects in the NSG (7 had died; 2 were lost to follow-up) and 52 of 60 original subjects in the SG (4 had died; 2 transferred out of the country; 2 were lost to follow-up). Those dying in the SG were significantly older (by 48 months, P < .05) than those in the NSG. No statistically significant differences were found between the groups in nutritional status. However, subjects in the SG displayed statistically better total Shwachman-Kulczycki scores (7.0, P ≤ .05), chest x-ray scores (2.3, P ≤ .05) and lung function (forced expiratory volume in 1 second by 12.3% , P ≤ .01; forced vital capacity by 12.6% , P ≤ .01; and mean airflow by 23.3% , P ≤ .01). Conclusions: The previously observed advantage conferred by cystic fibrosis newborn screening on clinical outcomes in infancy and childhood is still apparent in adolescence.

摘要：背景:马来西亚,沙巴,Kota Kinabalu及其周边社区。 目的:了解影响抗结核化疗病人依从性的诸因素,以及他们的结核病知识水平及和DOTS管理的改进意见。 设计:对2000年8月至9月期间到诊所DOTS治疗的合作及不合作病人进行家庭访视。 结果:共访问了63例合作病人和23例不合作病人。对于不合作者,他们去治疗中心的花费(P<0.005)及旅途时间(P<0.005)均比合作者明显要多。交通费常常是不去治疗的主要原因。不合作病人中完成中等教育的多(P<0.05),并且有工作的也多(P<0.01)。更多的不合作者中其家庭成员曾患过本病(P<0.01)。有关结核病知识的得分,两组间无差别;但是,不合作病人大多认为,当症状消失后便可停止治疗(P<0.01)。很多病人(73％)认为,通过提供更多的结核病知识可改善DOTS管理体系。 结论:赴治疗中心的交通费、占用的时间及家庭成员曾患过结核病等因素对沙巴,Kota Kinabalu地区病人的DOTS依从性产生影响。病人愿意获得更多关于结核病的知识。

摘要：背景:有效的结核病(TB)控制需要对传染性结核病例进行及早诊断,这需要对所有有呼吸系统症状的患者进行早期的肺结核排查。目的:验证我们的假设:在结核病低发病率的欧洲国家,由于对细菌感染的患者优先使用抗生素治疗,导致结核病诊断延迟。设计:在一个独立的城市中心医院,对通过培养确诊的成年肺结核患者进行评价,研究抗生素治疗对症状改善和抗结核治疗起始时间的影响。结果:83例患者中,42例(51%)在诊断结核病之前使用了抗生素,其中20例(48%)患者症状得到改善,这与药物类别无关。虽然接受抗生素治疗的患者诊断周期的中位数延长(P=0.001),但对治疗结果并没有预测性提示。在94%的患者中,最初胸部X线提示有结核感染。结论:结核病诊断前的抗生素治疗,使患者遭受与诊断过程有关的治疗延误。为最大程度降低结核病传播,我们建议临床医生应将结核病包括在最初的鉴别诊断中,在诊断过程初期对有呼吸道症状的患者进行简单的结核病相关检查。