Objective To explore the risk factors affecting the prognosis of sepsis patients progressing to chronic critical illness (CCI), and to construct and validate a Nomogram model for predicting in-hospital mortality risk. Methods Patients who met the criteria for sepsis progressing to CCI were selected from the Medical Information Mart for Intensive Care Ⅳ (MIMIC-Ⅳ) database in the United States as the research objects. Clinical materials of patients were collected retrospectively, and a total of 928 patients were included. The patients were randomly divided into modeling group (n=649) and validation group (n=279) at a ratio of 7 to 3; the patients were also divided into survival group and mortality group based on in-hospital mortality. Univariate and multivariate Logistic regression analyses were performed on the modeling group based on the outcomes; a Nomogram model for predicting in-hospital mortality in sepsis patients progressing to CCI was constructed based on independent risk factors; the discrimination and calibration of the Nomogram model were evaluated by the concordance index and calibration curve, and then validated by the validation group. Results Among the 928 sepsis patients progressing to CCI, 723 cases were in survival group and 205 cases in mortality group, with an in-hospital mortality rate of 22.1%. Age (OR=1.021, 95%CI, 1.007 to 1.036, P=0.004), body mass (OR=0.988, 95%CI, 0.979 to 0.997, P=0.016), the Acute Physiological Score Ⅲ (APS Ⅲ) score (OR=1.013, 95%CI, 1.004 to 1.023, P=0.004), blood alkaline phosphatase (OR=1.002, 95%CI, 1.000 to 1.003, P=0.023), continuous renal replacement therapy (CRRT) duration (OR=1.065, 95%CI, 1.023 to 1.108, P=0.002), and mechanical ventilation duration (OR=1.117, 95%CI, 1.056 to 1.184, P < 0.001) were identified as independent influencing factors for in-hospital mortality in sepsis patients progressing to CCI. A prediction model was constructed based on these risk factors, and the concordance index analysis showed that the concordance index was 0.75 (95%CI, 0.70 to 0.80) in the modeling group and 0.74 (95%CI, 0.68 to 0.81) in the validation group. The calibration curves of both themodeling group and the validation group were close to the standard curve. Conclusion Nomogram model constructed based on the 6 indicators including age, body mass, blood alkaline phosphatase, APS Ⅲ score, CRRT, and mechanical ventilation duration has good discrimination and calibration for predicting the mortality risk of sepsis patients progressing to CCI, which is helpful for clinicians to assess patient's prognosis.

ONYX-015 and H101 are E1B 55-kDa protein-deficient replicating C group adenoviruses that are currently in clinical trials as antitumor agents. However, their application in cancer gene therapy is limited by the native tropism of C group adenoviruses. This is in part due to low expression of the C group adenovirus receptor (coxsackievirus-adenovirus receptor, CAR) on malignant tumors. An H101-based chimeric virus vector containing sequences encoding the Ad35 fiber domain instead of the Ad5 fiber (H101-F35) was constructed. This modification allowed infection of tumor cells through CD46, a membrane protein over-expressed on tumors. The CAR and CD46 RNA expression was evaluated by RT-PCR method. H101-F35 conferred a stronger cytocidal effect than H101 and ONYX-015 in tumor cell lines that lacked CAR expression (MDA-MB-435 and MCF-7), while the cytocidal effect of H101-35, H101 and ONYX-015 was similar in high-level CAR expressing cancer cell lines (A549, NCI-H446, Hep3B, LNCaP, ZR-75-30 and Bcap-37). In an MDA-MB-435 xenograft mouse tumor model, tumor growth in mice receiving H101-F35 was significantly inhibited compared with mice injected with H101. These results suggest that the chimeric oncolytic adenovirus H101-F35 vector might be a useful candidate for gene therapy of cancer.

AIM: To examine the change of serum tumor necrosis factor-? (TNF-?), nitric oxide (NO) in patient with congestive heart failure (CHF) and the effect of angiotensin Ⅱ (AngⅡ), valsartan on TNF-? and NO production in culture peripheral blood mononuclear cells (PBMC), to assess the relationship between the renin-angiotensin system and cytokines. METHODS: Venous blood of both healthy volunteers (n=12) and patients with CHF (n=16) were collected. Serum TNF-? and NO were examined. Peripheral blood mononuclear cells (PBMC) were obtained from both the control and the patients groups and cultured with AngⅡ at concentrations of 0, 0.01, 0.1, 1 ?mol/L, respectively. AngⅡ at concentration of 0.1 ?mol/L combined with 0.1 ?mol/L of valsartan was also used. After 24 h incubation, the contents of TNF-? and NO in the culture supernatants were measured. RESULTS: Serum TNF-? and NO production in CHF group were significantly higher than that in control group (P0.05) were observed. AngⅡ stimulated TNF-? and NO release from PBMC of patients with CHF and normal person, which was inhibited by valsartan. CONCLUSIONS: AngⅡ obviously increases TNF-? and NO production from PBMC, which indicates there is relationship between the renin-angiotensin system and TNF-?, NO. The fact that valsartan inhibits TNF-? production may be one of the mechanisms in treating CHF.