ApoE has been reported to be associated with tumorigenesis and tumor progression. In this study, we explored the potential diagnostic and prognostic role of serum ApoE in breast cancer patients. Subject cohorts consisted of 152 normal healthy controls female and 257 breast cancer cases. Serum levels of ApoE were determined with turbidimetric immunoassay. The serum levels of ApoE were significantly elevated in breast cancer patients compared with normal healthy controls (45.82 ± 13.96 mg/L vs. 33.61 ± 6.44 mg/L, respectively, P < 0.0001) and also significantly associated with TNM stage and lymph nodes status (all P < 0.05). Area under receiver operating characteristic curve for serum ApoE discriminate breast cancer patients from controls was 0.786 with specificity of 0.974 and sensitivity of 0.541, the cut-off value of ApoE was 43.15 mg/L. Kaplan-Meier log rank analysis showed that the high serum ApoE group (serum ApoE ≥ 43.15 mg/L) had a poorer progression-free survival and overall survival compared with low serum ApoE group (serum ApoE < 43.15 mg/L) (all P < 0.05). In addition, univariate and multivariate Cox regression analysis displayed serum ApoE as an independent risk factor of breast cancer patients prognosis (all P < 0.05). Serum ApoE played a role as serological biomarkers that indicated diagnostic and prognostic evaluation in breast cancer patients.

Background Bloodstream infection (BSI) caused by carbapenem resistant Klebsiella pneumoniae (CRKP), especially in elderly patients, results in higher morbidity and mortality. The purpose of this study was to assess risk factors associated with CRKP BSI and short-term mortality among elderly patients in China. Methods In this retrospective cohort study, we enrolled 252 inpatients aged ≥ 65 years with BSI caused by KP from January 2011 to December 2020 in China. Data regarding demographic, microbiological characteristics, and clinical outcome were collected. Result Among the 252 BSI patients, there were 29 patients (11.5%) caused by CRKP and 223 patients (88.5%) by carbapenem-susceptible KP (CSKP). The overall 28-day mortality rate of elderly patients with a KP BSI episode was 10.7% (27/252), of which CRKP BSI patients (14 / 29, 48.3%) were significantly higher than CSKP patients (13 / 223, 5.83%) (P < 0.001). Hypertension (OR: 13.789, [95% CI: 3.883–48.969], P < 0.001), exposure to carbapenems (OR: 8.073, [95% CI: 2.066–31.537], P = 0.003), and ICU stay (OR: 11.180, [95% CI: 2.663–46.933], P = 0.001) were found to be associated with the development of CRKP BSI in elderly patients. A multivariate analysis showed that isolation of CRKP (OR 2.881, 95% CI 1.228–6.756, P = 0.015) and KP isolated in ICU (OR 11.731, 95% CI 4.226–32.563, P < 0.001) were independent risk factors for 28-day mortality of KP BSI. Conclusion In elderly patients, hypertension, exposure to carbapenems and ICU stay were associated with the development of CRKP BSI. Active screening of CRKP for the high-risk populations, especially elderly patients, is significant for early detection and successful management of CRKP infection.

Nasopharyngeal carcinoma (NPC) and Epstein–Barr virus (EBV)–associated gastric carcinoma (EBVaGC) are two major EBV-associated epithelial malignancies, both of which are characterized by the infiltration of a large number of lymphocytes, including natural killer (NK) cells. Although NK cells can prevent the development of EBV-associated epithelial malignancies, EBV-infected tumor cells often develop resistance to surveillance by NK cells. Elucidating the interactions between NK cells and EBV-infected tumor cells will facilitate the development of more effective NK-mediated therapies for treating EBV-associated malignancies. Here we investigated the cytotoxic function of NK cells in EBV-associated epithelial malignancies and discovered that EBV infection-induced upregulation of F3 expression correlates with NK-cell dysfunction in NPC and EBVaGC. The subsequent inhibitory effect of F3-mediated platelet aggregation on NK-cell function was verified in vitro and in vivo. Mechanistically, EBV latent membrane protein 2A (LMP2A) mediated upregulation of F3 through the PI3K/AKT signaling pathway. In an NPC xenograft mouse model, inhibition of F3 restored the antitumor function of NK cells and showed therapeutic efficacy when administered with NK-cell transfer. On the basis of these findings, EBV infection induces F3-mediated platelet aggregation that inhibits the antitumor function of NK cells, providing a rationale for developing and combining NK-cell–based therapies with F3 inhibitors to treat EBV-associated epithelial malignancies. Significance: This study reveals a mechanism by which EBV-associated epithelial malignancies escape NK-cell–mediated immune surveillance, providing a new target for improving NK-cell immunotherapy.

Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV)-associated epithelial malignancy characterized by the presence of prominent infiltration of lymphocytes, including natural killer (NK) cells. Although NK cells can directly target EBV-infected tumor cells without restriction by the MHC, EBV+ NPC cells often develop resistance mechanisms that allow them to evade immune surveillance by NK cells. Elucidating the mechanisms involved in EBV-induced NK-cell dysfunction will contribute to the design of novel NK cell–based immunotherapies to treat NPC. Herein, we confirmed that the cytotoxic function of NK cells was impaired in EBV-positive NPC tissues and found that EBV infection–induced expression of B7-H3 in NPC negatively correlated with NK-cell function. The inhibitory effect of EBV+ tumor expression of B7-H3 on NK-cell function was clarified in vitro and in vivo. Mechanistically, activation of the PI3K/AKT/mTOR signaling pathway via EBV latent membrane protein 1 (LMP1) was responsible for EBV infection–induced upregulation of B7-H3 expression. In an NPC xenograft mouse model with adoptive transfer of primary NK cells, deletion of B7-H3 on tumor cells in combination with anti–PD-L1 treatment restored NK cell–mediated antitumor activity and significantly improved the antitumor efficacy of NK cells. Based on our findings, we conclude that EBV infection can inhibit NK cell–mediated antitumor function by inducing upregulation of B7-H3 expression and provide a rationale for NK cell–based immunotherapies in combination of PD-L1 blockade and overcoming the immunosuppression of B7-H3 to treat EBV-associated NPC.

Background Streptomyces cacaoi , Gram-positive, branched, filamentous bacillus forms without fragmentation, are saprophytic soil organisms rarely known to cause invasive infections other than mycetoma. Here we describe a case of chronic suppurative otitis media caused by Streptomyces cacaoi in a patient with hyperlipidemia in China. Case presentation A 62-year-old female patient with hyperlipidemia suffered chronic suppurative otitis media caused by Streptomyces cacaoi . She had a favorable outcome with a 4-week course of ofloxacin ear drops. Conclusions Streptomyces cacaoi is rarely reported to cause human infection. The introduction of molecular techniques improves the ability to identify rare species such as Streptomyces considerably. We report the case improve our ability to identify this pathogen and expand the range of known bacterial causes of human infection.