Ventilator-associated pneumonia (VAP) is the most common hospital acquired infection,which increases the burden of patients significantly.Early diagnosis and effective prevention are important for VAP management.The guidelines for diaguosis,prevention and treatment of ventilator-associated pneumonia was issued by Chinese Society of Critical Care Medicine Chinese Medical Association in 2013.This article reviews the new progress of the diagnosis,treatment and prevention of VAP after the guideline was published.

Objective To explore the effects of fibroblast transdifferentiation for myofibroblast (MFB) in the pathogenesis of systemic sclerosis (SSc) and to explore the antifibrotic mechanism of interferon γ (IFN-γ) in SSc.Methods The fibroblasts derived from the skin lesions of SSc patients and healthy adult controls were cultured in vitro and the MFB proportion in fibroblasts was examined by qualitative and quantitative α-smooth muscle actin (α-SMA) detection.By adding IFN-γ to the culture system with several doses,the influence on fibroblast proliferation and transdifferentiation for MFB in SSc was observed with MTT and enzyme linked immunosorbent assay (ELISA) respectively.Differences in the means of two independent samples were tested by Student' t-test.The means among multiple independent samples were com-pared by ANOVA.Results The means of positive α-SMA in SSc fibroblasts were higher than those in the controls (P＜0.01).With extended culture time,α-SMA levels of the two groups all increased gradually (P＜ 0.01 all),but there were higher α-SMA levels in SSc fibroblasts (24 h:130±19,48 h:183±21,72 h:249± 22) than those in controls (24 h:98±21,48 h:143±16,72 h:174±19) (P＜0.05 all).Although fibroblast proliferation and α-SMA levels were not influenced after adding of IFN-γ 10 U/ml (P＞0.05 all),but IFN-γ at concentration of 100 U/ml and 1000 U/ml could obviously repress fibroblast proliferation and α-SMA levels (P＜0.05 all),and 1000 U/ml had the strongest inhibiting effect at 24,48,72 h.Conclusion The fibroblasts in the skin of SSc patients have a strong potency to transdifferentiate to MFB.Early appropviate dose of IFN-γ could repress fibroblast proliferation and transdifferentiation in SSc.

Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and pathologically proven chronic inflammation of airway,pulmonary parenchyma and pulmonary blood vessels.It is divided into stable COPD and acute exacerbation of COPD (AECOPD).As a comprehensive intervention,pulmonary rehabilitation has remarkable therapeutic effect on stable COPD.At present,the effect of pulmonary rehabilitation of COPD has been widely confirmed.We will briefly review the research progress on pulmonary rehabilitation of AECOPD in recent years.

Objective: To investigate human epidermal growth factor 2 (HER2) gene status and in situ mRNA expression in breast cancers with immunohistochemistry(IHC) 1+ , and to reveal HER2 positive rate in these patients to provide reference data for obtaining precise HER2 results and modifying relevant clinical strategy to breast cancer. Methods: Sixty-five IHC 1+ formalin-fixed and paraffin-embedded samples of invasive breast carcinoma of no special type (IBC-NST) were collected by surgical operation at Peking Union Medical College Hospital during 2011 to 2013. HER2 status and in situ mRNA expression were tested by fluorescence in situ hybridization (FISH) and RNAscope, respectively, by using tissue microarray. Metastatic lymph node was re-tested by FISH if HER2 status was equivocal or negative and with high expression of mRNA in the primary lesion. Results: Four of 65 samples (6.2%) were FISH positive, which included 2 cases of HER2/CEP17>2 and average HER2 copy number>4 and 2 cases of HER2/CEP17<2 and average HER2 copy number>6. In the 4 samples of HER2 positive, 2 patients showed high in situ mRNA expression (3 scores by RNAscope), 2 patients showed moderate in situ mRNA expression (2 scores by RNAscope). In addition, 3 specimens with HER2/CEP17>2 and average HER2 copy number<4 were found in all patients, which included 2 cases of high in situ mRNA expression (3 and 4 scores by RNAscope) and 1 cases of moderate in situ mRNA expression (2 scores by RNAscope). There was no significant association between HER2 status or mRNA expression and clinicopathological characteristics, including tumor size, histopathological differentiation, lymph node metastasis and lymphovascular invasion (P>0.05). Conclusions A small number of HER2 IHC 1+ patients exist mRNA expression by using FISH method, which suggested that these patients might benefit from anti-HER2 therapy potentially. Since the importance for patients with breast cancers to develop diagnostic and therapeutic strategies from accurate molecular typing, further studies based on a larger cohort are needed to validate our findings.

Pharmaconutrients refer to macronutrients,micronutrients,microecologics,and nucleotides.Informed by large randomized clinical trials,people have become increasingly prudent in using pharmaconutrients.Critically-ill neurological patients are intensive care patients who have neurological impairment,and therefore command extra caution in using pharmaconutrients.This article reviews the latest studies on the use of pharmaconutrients in this group of patients.

T cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer immunotherapy. Emerging evidence has shown that interferon-gamma (IFNγ) could enhance CXCL9 secretion from macrophages to recruit T cells, but Siglec15 expressed on TAMs can attenuate T cell proliferation. Therefore, targeted regulation of macrophage function could be a promising strategy to enhance cancer immunotherapy via concurrently promoting the infiltration and proliferation of T cells in tumor tissues. We herein developed reduction-responsive nanoparticles (NPs) made with poly (disulfide amide) (PDSA) and lipid-poly (ethylene glycol) (lipid-PEG) for systemic delivery of Siglec15 siRNA (siSiglec15) and IFNγ for enhanced cancer immunotherapy. After intravenous administration, these cargo-loaded could highly accumulate in the tumor tissues and be efficiently internalized by tumor-associated macrophages (TAMs). With the highly concentrated glutathione (GSH) in the cytoplasm to destroy the nanostructure, the loaded IFNγ and siSiglec15 could be rapidly released, which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for T cell infiltration and silence Siglec15 expression to promote T cell proliferation, leading to significant inhibition of hepatocellular carcinoma (HCC) growth when combining with the immune checkpoint inhibitor. The strategy developed herein could be used as an effective tool to enhance cancer immunotherapy.