Hemorrhagic shock (HS) often renders patients more susceptible to lung injury by priming for an exaggerated response to a second infectious stimulus. Acute lung injury (ALI) is a major component of multiple organ dysfunction syndrome following HS and regularly serves as a major cause of patient mortality. The lung vascular endothelium is an active organ that has a central role in the development of ALI through synthesizing and releasing of a number of inflammatory mediators. Cell pyroptosis is a caspase-1-dependent regulated cell death, which features rapid plasma membrane rupture and release of proinflammatory intracellular contents. In this study, we demonstrated an important role of HS in priming for LPS-induced lung endothelial cell (EC) pyroptosis. We showed that LPS through TLR4 activates Nlrp3 (NACHT, LRR, and PYD domains containing protein 3) inflammasome in mouse lung vascular EC, and subsequently induces caspase-1 activation. However, HS induced release of high-mobility group box 1 (HMGB1), which acting through the receptor for advanced glycation end products initiates EC endocytosis of HMGB1, and subsequently triggers a cascade of molecular events, including cathepsin B release from ruptured lysosomes followed by pyroptosome formation and caspase-1 activation. These HS-induced events enhance LPS-induced EC pyroptosis. We further showed that lung vascular EC pyroptosis significantly exaggerates lung inflammation and injury. The present study explores a novel mechanism underlying HS-primed ALI and thus presents a potential therapeutic target for post-HS ALI.

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Background and aims. To determine whether reduction of CA125 levels is a predictive factor for cytoreduction to no visible residual disease (NVRD) and chemotherapeutic sensitivity in advanced epithelial ovarian carcinoma (EOC), primary carcinoma of fallopian tube and peritoneal carcinoma patients who received neoadjuvant chemotherapy followed by interval debulking surgery (NAC-IDS).Methods. This was a single-team-based study of advanced EOC, primary carcinoma of fallopian tube and peritoneal carcinoma patients diagnosed between 1996 and 2015 at Peking Union Medical College Hospital. Patients were treated with NAC-IDS by one gynecologic oncologist. Demographic data, CA125 levels, radiographic data, and chemotherapy and surgical-pathologic information were obtained. Univariate and multivariate analyses were performed to evaluate variables associated with optimal cytoreduction to NVRD and chemotherapy-sensitivity.Results. One hundred and eighteen patients met the study inclusion criteria. Thirty-seven (31.4%) patients underwent resection to NVRD. The median serum CA125 level at presentation and before IDS was 1814.5 U/ml and 205.9 U/ml, respectively. In the univariate analysis, histology, a preoperative CA125 of ≤200 U/ml and a >80% reduction of CA125 between presentation and IDS were significantly associated with the likelihood of NVRD (P=0.014, 0.000, 0.000, respectively). Multivariate analysis revealed that, of the various CA125 parameters tested, preoperative CA125 ≤200 U/ml was the only independent predictor of NVRD (odds ratio 3.667, 95% confidence interval 1.337-10.057; P=0.012). Preoperative CA125 ≤200 U/ml was also significantly associated with chemotherapy-sensitive disease in the univariate analysis (P=0.037).Conclusions. EOC patients who received NAC-IDS and had a preoperative CA125 level of ≤200 U/ml were highly likely to be cytoreduced to NVRD and to exhibit chemotherapeutic sensitivity.

Our results demonstrated that IL-11 contributed to the obtain of resistance to chemotherapy drugs through gp130/JAK/STAT3/Bcl2 pathway, and targeting the IL-11 signaling pathway induced by fibroblasts might be a promising strategy to overcome the multi-drugs resistant cancer in clinic.

Our findings identified VAMP8 as a novel oncogene by promoting cell proliferation and therapeutic resistance in glioma. Targeting VAMP8 may serve as a potential therapeutic regimen for the treatment of glioma.

Glioma is the most malignant brain tumor and glioblastoma (GBM) is the most aggressive type. The involvement of N-myc (and STAT) interactor (NMI) in tumorigenesis was sporadically reported but far from elucidation. This study aims to investigate roles of NMI in human glioma. Three independent cohorts, the Chinese tissue microarray (TMA) cohort (N = 209), the Repository for Molecular Brain Neoplasia Data (Rembrandt) cohort (N = 371) and The Cancer Genome Atlas (TCGA) cohort (N = 528 or 396) were employed. Transcriptional or protein levels of NMI expression were significantly increased according to tumor grade in all three cohorts. High expression of NMI predicted significantly unfavorable clinical outcome for GBM patients, which was further determined as an independent prognostic factor. Additionally, expression and prognostic value of NMI were associated with molecular features of GBM including PTEN deletion and EGFR amplification in TCGA cohort. Furthermore, overexpression or depletion of NMI revealed its regulation on G1/S progression and cell proliferation (both in vitro and in vivo), and this effect was partially dependent on STAT1, which interacted with and was regulated by NMI. These data demonstrate that NMI may serve as a novel prognostic biomarker and a potential therapeutic target for glioblastoma.

Pulmonary emphysema (PE) has been demonstrated to have a high prevalence in patients with locally advanced non-small cell lung cancer (NSCLC). A total of 153 patients with locally advanced NSCLC were enrolled in this study to investigate the association between PE and radiation pneumonitis (RP) after definitive thoracic radiation therapy (TRT). The incidence of RP in Grade 2, 3 and 5 were 11.1%, 9.8% and 0.7%, respectively. Univariate analysis revealed that age, PE, forced vital capacity (FVC), arterial partial pressure of oxygen (PO2) and mean lung dose (MLD) were significantly associated with the risk of Grade ≥2 or Grade ≥3 RP in patients with squamous cell carcinoma (SCC, P < 0.05). Logistic analysis demonstrated that PE was an independent risk factor of RP in SCC (P < 0.05). Receiver operating characteristics (ROC) analysis revealed that the combination of age, PE, FVC, PO2 and MLD had a higher value to predict RP in SCC (AUC = 0.856 in Grade ≥2 RP and 0.882 in Grade ≥3 RP, respectively). Kaplan-Meier analysis revealed that the more severe the PE, the higher the incidence of RP in SCC. Our results revealed that PE was a high risk factor for locally advanced NSCLC patients followed definitive TRT, especially for SCC patients.