Role of international normalized ratio in nonpulmonary sepsis screening: An observational study.

BACKGROUND: Currently, there is a lack of sepsis screening tools that can be widely used worldwide. Pulmonary sepsis can be of sufficient concern to physicians due to their noticeable symptoms, which usually rely less on screening tools. AIM: To investigate the efficiency of the international normalized ratio (INR) for the early rapid recognition of adult nonpulmonary infectious sepsis. METHODS: This is a prospective observational study. A total of 108 sepsis patients and 106 nonsepsis patients were enrolled according to relevant inclusion and exclusion criteria. Commonly used clinical indicators, such as white blood cell, neutrophil count, lymphocyte count, neutrophil-lymphocyte count ratio (NLCR), platelets (PLT), prothrombin time, INR, activated partial thromboplastin time, and quick Sequential "Sepsis-related" Organ Failure Assessment (qSOFA) scores were recorded within 24 h after admission. The diagnostic performances of these clinical indicators were analyzed and compared through multivariate logistic regression analysis, Spearman correlation, and receiver operating characteristic curve analysis. RESULTS: The INR value of the sepsis group was significantly higher than that of the nonsepsis group. INR has superior diagnostic efficacy for sepsis, with an area under the curve value of 0.918, when those preexisting diseases which significantly affect coagulation function were excluded. The diagnostic efficacy of the INR was more significant than that of NLCR, PLT, and qSOFA (P < 0.05). Moreover, INR levels of 1.17, 1.20, and 1.22 could be used to categorize the relative risk of nonpulmonary infections sepsis into three categories: low, medium and high risk, respectively. CONCLUSION: The INR is a promising and easily available biomarker for diagnosis, and it can be used as one of the indicators for early screening of adult nonpulmonary infectious sepsis. When its value is higher than the optimal cutoff value (1.22), high vigilance is required for adult nonpulmonary infectious sepsis.

Inflammatory bowel disease in Chinese children: a multicenter analysis over a decade from Shanghai.

BACKGROUND: The purpose was to estimate the incidence and characteristics of childhood inflammatory bowel disease (IBD) during 2000-2010 in Shanghai, China. METHODS: IBD patients between the ages of 0 and 18 years old were identified by survey of computerized medical information. Relevant data were extracted from their corresponding medical records. RESULTS: A total of 153 IBD cases were included in the study. Among them, 107 were males and 46 were females (male/female ratio, 2.3:1.0). Eighty-two had Crohn's disease (CD) and 71 had ulcerative colitis (UC). The peak prevalence of IBD was observed in the 10-14-year-old age group. The annual incidence of IBD in the 0 to 14 years age group of Shanghai residents steadily increased from 2000 to 2010. The most common symptoms of IBD were diarrhea (68.6%), bloody stool (68.6%), and abdominal pain (61.4%). More CD than UC patients had anemia and raised erythrocyte sedimentation rate and C-reactive protein levels. Ileocolonic type disease was more common in CD patients, and left-side colon involvement was more common in UC. Of all CD patients, 33 had mild active disease and 49 had moderate/severe disease. In UC patients, 34 were mild and 37 were moderate/severe disease. CONCLUSIONS: This retrospective, multicenter hospital-based study over a decade shows a steadily increasing trend of childhood IBD in China. This suggests a need for population-based epidemiological studies to explore the risk factors.

Myeloid dendritic cells loaded with dendritic tandem multiple antigenic telomerase reverse transcriptase (hTERT) epitope peptides: a potentially promising tumor vaccine.

Human telomerase reverse transcriptase (hTERT) has been identified as an ideal tumor-associated antigen (TAA). Use of a synthetic hTERT epitope peptide to pulse dendritic cells can induce autologous T cell anti-tumor immune responses, but such responses induced by a single epitope peptide have been shown to be weak and a narrow-spectrum. Here, we designed dendritic tandem multiple antigenic peptides (MAPs) containing the following three hTERT epitope peptides: I540, V461 and L766, which are HLA-A*02-, HLA-A*24- and HLA-RDB1*04/11/15-restricted, respectively. The MAPs and their three single-epitope peptides were obtained through solid-phase synthesis. Healthy volunteers that were HLA-A*02(+)/HLA-DRB1*04(+) and HLA-A*24(+)/HLA-DRB1*15(+) were recruited. Myeloid dendritic cells were isolated by magnetic activated cell sorting and were divided into a MAP-stimulated group (MAP-DC), a group in which the three epitope peptides were mixed and used to stimulate the DCs (MixP-DC) and a no peptide-stimulated group (NoP-DC, control group). All of the DCs were cultured in serum-free medium, pulsed with the corresponding peptides on the 3rd, 5th and 7th days, and co-cultured with autologous lymphocytes when they were mature. The related cytokines were measured via ELISA. The killing effects of cytotoxic T lymphocytes (CTLs) on SW480/A549 tumor cells expressing HLA-A*02(+), HepG2/SMMC-7721 cells expressing HLA-A*24(+) and SKOV3 cells negative for HLA-A*02/A*24 were detected by flow cytometry. Our results indicated that the CTLs induced by the MAP-DCs had the greatest anti-tumor effect. Therefore, the dendritic tandem multiple antigenic hTERT epitope peptides combined with MDCs may represent a powerful, broad-spectrum anti-tumor vaccine.

Hath1 inhibits proliferation of colon cancer cells probably through up-regulating expression of Muc2 and p27 and down-regulating expression of cyclin D1.

Previous studies showed that Math1 homologous to human Hath1 can cause mouse goblet cells to differentiate. In this context it is important that the majority of colon cancers have few goblet cells. In the present study, the potential role of Hath1 in colon carcinogenesis was investigated. Sections of paraffin-embedded tissues were used to investigate the goblet cell population of normal colon mucosa, mucosa adjacent colon cancer and colon cancer samples from 48 patients. Hath1 and Muc2 expression in these samples were tested by immunohistochemistry, quantitative real-time reverse transcription -PCR and Western blotting. After the recombinant plasmid, pcDNA3.1(+)-Hath1 had been transfected into HT29 colon cancer cells, three clones were selected randomly to test the levels of Hath1 mRNA, Muc2 mRNA, Hath1, Muc2, cyclin D1 and p27 by quantitative real-time reverse transcription-PCR and Western blotting. Moreover, the proliferative ability of HT29 cells introduced with Hath1 was assessed by means of colony formation assay and xenografting. Expression of Hath1, Muc2, cyclin D1 and p27 in the xenograft tumors was also detected by Western blotting. No goblet cells were to be found in colon cancer and levels of Hath1 mRNA and Hath1, Muc2 mRNA and Muc2 were significantly down-regulated. Hath1 could decrease cyclin D1, increase p27 and Muc2 in HT29 cells and inhibit their proliferation. Hath1 may be an anti-oncogene in colon carcinogenesis.

[CTLs induced by hTERT-related multiepitope peptide-sensitived mDCs specifically kill HLA-A24+ tumor cells].

AIM: To study the antigen specific anti-tumor effect of cytotoxic T lymphocytes(CTLs), which was induced by human telomerase reverse transcriptase (hTERT)-related multiple epitope peptides impulsed myeloid dendritic cells(mDCs), against human leukocyte antigen (HLA)-A24(+) tumor cells. METHODS: Four branches of multiple antigen peptides (MAPs) of hTERT epitopes and three separate peptides were solid-phase artificially synthesized, phlebotomize peripheral blood from HLA-A24(+) healthy volunteers, sorted the blood through MACS MicroBeads and cultured mDCs, Nylon fiber column purified T lymphocytes, mDCs impulsed with each type of peptides were co-cultured with T lymphocytes to induce CTLs specifically killing effect, and the resultant CTLs were used as effector cells, SMMC-7721 with hTERT and HLA-A24 positive and SKOV3 which are hTERT-positive but HLA-A24-negative tumor cells were used as target cells. The level of human IL-12, TNF-α in the culture supernatant was determined by ELISA. Flow cytometry assay was used to assess the killing ability of CTLs against tumor cells. RESULTS: MAPs of hTERT epitopes including I540 (ILAKFLHWL), V461 (VYGFVRACL), L766 (LTDLQPYMRQFVAHL) and three separate peptides could impulse mDCs and then induce CTLs to specifically kill SMMC-7721, CTLs induced by MAPs had stronger cytotoxic effect compared with three separate peptides mixed(P < 0.05). CONCLUSION: mDCs-impulsed with hTERT-associated MAPs can induce production and proliferation of allogenic CTLs, which show antigen specific anti-tumor effect against HLA-A24(+) tumor cells. This result has significantly meaning in tumor immunotherapy.

Delayed administration of D-Ala2-D-Leu5-enkephalin, a delta-opioid receptor agonist, improves survival in a rat model of sepsis.

Sepsis is the major cause of death in intensive care units, despite enormous efforts in the development of antimicrobial therapies. Sepsis is mediated by early [e.g., tumor necrosis factor (TNF)-α and interleukin (IL)-1ß] and late [e.g., high-mobility group box 1 protein (HMGB1)] proinflammatory cytokines. HMGB1, which is secreted into extracellular milieu by activated macrophages or passively released by destroyed macrophages, stimulates intensive inflammatory responses. D-Ala2-D-Leu5-enkephalin (DADLE), a synthetic δ-opioid receptor agonist, has been shown to protect rats from sepsis. Here we elucidated the mechanism for protective effect of DADLE against sepsis. Sepsis was established in Sprague-Dawley rats by means of cecal ligation and puncture (CLP). In this model, the serum levels of TNF-α and IL-1ß were increased after 2-3 h, while those of HMGB1 were increased after 18 h. Administration of DADLE (5 mg/kg) concurrently with CLP improved survival, which was associated with the decreases in the serum levels of TNF-α, IL-1ß and HMGB1. Importantly, DADLE administrated 4 h after CLP showed comparable protective effect as the concurrent administration, with decreased serum HMGB1 levels. Moreover, peritoneal macrophages isolated from rats were challenged with lipopolysaccharide (LPS). Concurrent or delayed DADLE administration at 10(-6) M suppressed the LPS-induced cell death. DADLE also suppressed the release of HMGB1 from macrophages that was induced by LPS, TNF-α or interferon-γ. In conclusion, DADLE protects rats from sepsis probably by decreasing the serum level of HMGB1. We propose DADLE as a candidate for septic shock therapy, even if it is administered after the onset of sepsis.