Glucose oxidase (GOx) is regarded as an ideal endogenous natural enzyme for tumor starvation therapy and photothermal therapy (PTT) is a promising strategy for the ablation of primary tumor. In this work, Cu-doped cobalt oxide and porous carbon nanocomposites (CuCo­(O)@PCNs) were synthesized from double-layered ZIF-8@ZIF-67 and GOx was loaded in the porous carbon to form a CuCo­(O)/GOx@PCNs hybrid nanozyme. CuCo­(O) was characterized as the Cu0.3Co2.7O4 phase through X-ray diffraction analysis and it can react with H2O2 to generate O2 and alleviate tumor hypoxia, resulting in the recovered enzymatic activity of GOx and the enhanced starvation therapy. The porous nanocarbon can ablate the primary tumor because of its high photothermal conversion efficiency of 40.04%. The three-in-one functions of oxygen supply, glucose consumption, and photothermal conversion were realized in the ZIFs-derived CuCo­(O)/GOx@PCNs nanozyme and the starvation therapy effect was improved by PTT and oxygen supplement. Furthermore, the inhibition effect of CuCo­(O)/GOx@PCNs on metastatic tumor is similar to combined therapy of the nanozyme and the immune checkpoint-blocking antibody, α-PD-1. The related antitumor immune mechanism was studied through the analysis of immune-related proinflammatory cytokines and the activated T cells. This work may provide new ideas for the development and application of the ZIFs-derived hybrid nanozyme in tumor therapy and the CuCo­(O)/GOx@PCNs nanozyme may be a promising alternative to immune checkpoint inhibitors.

Introduction. Contamination of specimens and overuse of broad spectrum antibiotics contribute to false positives and false negatives, respectively. Therefore, useful and applicable biomarkers of bacteremia are still required. Hypothesis/Gap Statement. IL-6 can be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection. Aim. We aimed to evaluate the diagnostic efficiency of neutrophil/lymphocyte ratio (NLR), procalcitonin (PCT) and interleukin-6 (IL-6) in discriminating Gram-negative (G−) bacteria from Gram-positive (G+) bacteria and fungi in febrile patients. Methodology. A total of 567 patients with fever were evaluated. Serum levels of IL-6, PCT, NLR and CRP were compared among a G− group (n=188), a G+ group (n=168), a fungal group (n=38) and a culture negative group (n=173). Sensitivity, specificity, Yuden’s index and area under the Receiver operating characteristic (ROC) curve (AUC) were obtained to analyse the diagnostic abilities of these biomarkers in discriminating bloodstream infection caused by different pathogens. Results. Serum IL-6 and PCT in the G− group increased significantly when compared with both the G+ group and fungal group (P <0.05). AUC of IL-6 (0.767, 95 % CI:0.725–0.805) is higher than AUC of PCT (0.751, 95 % CI:0.708–0.796) in discriminating the G− group from G+ group. When discriminating the G− group from fungal group, the AUC of IL-6 (0.695, 95 % CI:0.651–0.747) with a cut-off value of 464.3 pg ml−1 was also higher than the AUC of PCT (0.630, 95 % CI:0.585–0.688) with a cut-off value of 0.68 ng ml−1. Additionally, AUC of NLR (0.685, 95 % CI:0.646–0.727) in discriminating the fungal group from G+ group at the cut-off value of 9.03, was higher than AUC of IL-6, PCT and CRP. Conclusion. This study suggests that IL-6 could be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection. In addition, NLR is valuable to discriminate fungal infections from Gram-positive infections in febrile patients with a bloodstream infection.

Objective: Gastric cancer (GC) is a gastrointestinal tumor. This study is aimed to explore the regulatory mechanism of long non-coding RNA BLACAT1 (BLACAT1)/microRNA-149-5p (miR-149-5p)/KIF2A cascade on GC. Methods: The expression of BLACAT1, miR-149-5p and KIF2A in GC was detected by qRT-PCR. The proliferation, migration and invasion of GC cells in vitro were analyzed by MTT, wound-healing and transwell assay, respectively. The xenograft tumor model was constructed in nude mice to confirm the inhibition effect of BLACAT1 knockdown on GC in vivo. Then, dual-luciferase reporter assay was used to detect the interactions among BLACAT1, miR-149-5p and KIF2A. Western blot assay was performed to determine the protein expression of KIF2A. Results: The expression of BLACAT1 and KIF2A was up-regulated in GC, but miR-149-5p expression was down-regulated. Silencing of BLACAT1 retarded the proliferation, migration and invasion of GC cells in vitro and the growth of tumor xenograft in vivo. Moreover, BLACAT1 acted as the molecular sponge of miR-149-5p to up-regulate KIF2A expression. At last, feedback experiments suggested that BLACAT1 accelerated the proliferation, migration and invasion of GC cells by regulating miR-149-5p/KIF2A axis. Conclusion: BLACAT1 facilitated the tumorigenesis of GC through regulating miR-149-5p/KIF2A axis, which indicated BLACAT1/miR-149-5p/KIF2A cascade may be a new therapeutic target.

Rationale:Currently, fistucolysis helps to establish intestinal nutrition and succus entericus reinfusion in the case of controllable mature high-output enterocutaneous fistula. However, if the tube cannot reach the distal limb of a fistula, fistuloclysis is not achieved. We proposed a strategy to establish succus entericus reinfusion for intractable intestinal fistula through percutaneous enterostomy.Patient concerns:A 43-year-old man was transferred to our facility for postoperative enterocutaneous fistulae, sepsis, malnutrition, and electrolyte and fluid imbalance. The contrast X-ray demonstrated the breakdown of the primary anastomosis, with fistula output ranging from 1500 to 2000 mL/d, despite the administration of medications to reduce gastrointestinal secretions.Diagnoses:The patient was diagnosed with high-output anastomosis fistula by gastrointestinal radiography.Interventions:We used percutaneous enterostomy to establish fistuloclysis.Outcomes:Fistuloclysis was established by percutaneous enterostomy successfully. No complications were found during the past 4-month follow-up after percutaneous enterostomy. He is waiting for reconstruction surgery after 6 months’ enteral nutrition (EN).Lessons:Fistuloclysis-assisted EN, if used appropriately, avoids the complications of long-term parenteral nutrition (PN) and may promote faster fistula healing.