Cuproptosis, a recently identified form of regulated cell death triggered by excess intracellular copper, has emerged as a promising cytotoxic strategy for cancer therapy. However, the therapeutic efficacy of copper ionophores such as elesclomol (ES) is often hindered by cellular copper homeostasis mechanisms that limit copper influx and cuproptosis induction. To address this challenge, we developed a nanoagent utilizing outer membrane vesicle (OMV) derived from Akkermansia muciniphila (Akk) for co-delivery of antioxidant 1 copper chaperone (Atox1)-targeting siRNA and ES (siAtox1/ES@OMV) to tumors. In vitro, we demonstrated that Atox1 knockdown via siRNA significantly disrupted copper export mechanisms, resulting in elevated intracellular copper levels. Simultaneously, ES facilitated efficient copper influx and mitochondrial transport, leading to Fe-S cluster depletion, increased proteotoxic stress, and robust cuproptosis. In vivo, siAtox1/ES@OMV achieved targeted tumor delivery and induced pronounced cuproptosis. Furthermore, leveraging the immunomodulatory properties of OMVs, siAtox1/ES@OMV promoted T-cell infiltration and the activation of tumor-reactive cytotoxic T cells, enhancing tumor immune responses. The combination of siAtox1/ES-induced cuproptosis and immunogenic cell death synergistically suppressed tumor growth in both subcutaneous breast cancer and orthotopic rectal cancer mouse models. This study highlights the potential of integrating copper homeostasis disruption with a copper ionophore using an immunomodulatory OMV-based vector, offering a promising combinatorial strategy for cancer therapy.

Objective To analyze antimicrobial resistance of clinically isolated Burkholderia cepacia (B.cepacia),and provide evidence for clinical rational antimicrobial use.Methods B.cepacia isolated from clinical specimens between January 2013 and December 2014 were analyzed retrospectively,antimicrobial susceptibility results were statistically analyzed.Results A total of 98 isolates of B.cepacia between January 2013 and December 2014 were isolated,the main specimen was sputum(n =86,87.76 ％),the main department distribution was intensive care unit(n =46,46.94％),resistance rate of B.cepacia to ticarcillin / clavulanic acid was highest(73.47％),resistance rates to piperacillin / tazobactam and cefoperazone / sulbactam were both 16.33％,resistance rate to minocycline was the lowest(5.10％).Conclusion Infection caused by B.cepacia is high,prevention and control of healthcare-associated infection should be strengthened,early etiological examination should be performed,antimicrobial treatment should be combined with antimicrobial susceptibility results.

Objective To investigate the demand of patients with coronary heart disease (CHD) for transitional care service in a tertiary hospital of Shaanxi,in order to provide more reasonable and effective transitional care service measures for patients.Methods A total of 721 patients with CHD (two days before their discharge) in a tertiary hospital of Shaanxi were selected from May to October 2015,and were investigated by using self-designed transitional care questionnaire.Results There were 50.3% of patients with CHD willing to accept the transitional care service and only 0.8% of them not willing to receive the transitional care service. There were 51.2% of the patients willing to accept the telephone follow-up from the ward,and 60.5% of them willing to get other transitional care services,including the guidance of self-monitoring vital signs, guidance of diet and moderate exercise,guidance of disease recurrence prevention,attentions of life work after discharge,and first-aid knowledge. There were 88.8% of the patients using the mobile phone as the main communication tools. There were 34.4% of patients who need the telephone follow-up from the ward and 35% of them willing to receive text message alerts for one month. There were 53.7% of the patients who can accept the cost of transitional care service less than 10 yuan per time,and 50.3% of them who can accept the cost less than 30 yuan per hour.Conclusions The patients with CHD have great demands for the transitional care service. The transitional care should be established and developed according to patients′ demand after discharge,so as to meet discharged patients′ demand for transitional care.

Objective To evaluate the value of pre-S1 Ag in combined detection of hepatitis B virus. Methods 288 patients' serums with chronicity type B hepatitis (CHB)were collected when they had been detected with HBV-DNA,HBVM or ALT/AST,and then ELISA assay were applied to detect pre-S1Ag. Results A total of 288 patients ,including 175 males and 113 females( their meso-age is 36.89 years old) were recruited into this study. 161 patients were pre-S1 Ag positive(68.4%), 197 patients' HBV DNA contents exceeded 5.0E + 2 copy/ml(55.9%) ,71patients were H BeAg positive (24.6%), 186 patients were HBeAg negative (64.58%). The rate of 64 patients' ALT and AST exceeded 0. 84, and their' ALT exceeded 40 u/ml ( 22. 2% ). 60 patients' AST exceeded 50 u/ml (20. 8% ). These patients were divided into pre-S1 Ag positive group and pre-S1 Ag group. In pre-S1 Ag positive group, 124 patients' HBV DNA contents exceeded 5.0E + 2 copy/ml( 62.9% ), 118 patients were HBeAg negative (59.8%). When HBV DNA content was less than 5.0E+2 copy/ml,pre-S1 Ag positive rate was 35.2% and pre-S1 Ag negative rate was 63.6%. when HBV DNA content was less than 5.0E + 3 copy/ml, pre-S1 Ag positive rate was 56.9% and pre-S1 Ag negative rate was 81.7%. When HBV DNA content exceeded 5.0E + 5 copy/ml but less than 5.0E + 8 copy/ml ,pre-S1 Ag positive rate was 33% and pre-S1 Ag negative rate was 14.3% ,so two groups had significant difference. Conclusion Pre-S1 Ag positive and HBeAg negative in the CHB patients serums signify virus replication,and it can help us decide prognosis.

Objective To observe the effects of Pinggan Jiangya Capsule on renin activity (RA) and angiotensinⅡ (AngⅡ) of spontaneously hypertensive rats. Methods Pinggan Jiangya Capsule was administered to male SHRs as treatment group (n=10), and equal volume of normal saline was administered to normal control WKY rats group(n=10) or SHR as model group(n=10) respectively for 12 weeks intragastrically. RA and AngⅡ level were measured by radio-immunoassay. Results The blood pressure decreased significantly after treatment with Pinggan Jiangya Capsule for 12 weeks(P

Objective:To observe the effect of anti-lymphocyte globulin(ALG)combined with cyclosporin A(CsA)in treatment of severe aplastic anemia(SAA).Methods:Forty-three patients with SAA received ALG [15mg/(kg?d)once a day for5d],CsA [5mg/(kg?d)for6months]and androgen(80mg,tid)for more than6months.Results:After6months,the blood corpuscle counts of patients increased(P