[The predictive factors and unfavourable prognostic factors of interstitial lung disease in patients with polymyositis/dermatomyositis].

OBJECTIVE: To analyze the predictive factors and the unfavourable prognostic factors of interstitial lung disease (ILD) in patients with polymyositis (PM)/dermatomyositis (DM). METHODS: The clinical data were collected from 87 inpatients with DM or PM, who were admitted to Shanghai Changhai Hospital from January 1997 to November 2006. The patients were divided into an ILD group and a non-ILD group. The clinical feature, incidence and prognosis of ILD were retrospectively analyzed. The clinical and laboratory data were analyzed by using the SPSS 13.0 software. The t-test and rank-sum test were used, depending on the measurement data. The enumeration data were analyzed with chi-square test. Logistic regression and Kaplan-Meier survival curve were used to analyze the correlative and prognostic factors of interstitial lung disease (ILD) in patients with PM/DM. RESULTS: The incidence and mortality of ILD in PM/DM patients were 46% (40/87) and 40% (16/40), respectively. Compared with the non-ILD group, the age in the ILD group was markedly older [(54 +/- 13) years vs (45 +/- 18) years], and the percentages of fever (21/40 vs 7/47, chi2 = 14.00, P < 0.01), dysphagia (16/40 vs 8/47, chi2 = 5.71, P < 0.05), arthralgia (26/40 vs 9/47, chi2 = 18.89, P<0.01), Gottron's rash (14/40 vs 2/47, chi2 = 13.61, P <0.01) and heart impairment (26/40 vs 14/47, chi2 = 10.28, P <0.01) were significantly higher in the ILD group. The levels ofLDH [(472 +/- 285) IU vs (310 +/- 238) IU, t =2.86, P<0.01], ESR [(44 +/- 24) mm/1 h vs (26 +/- 24) mm/l h, t = 3.19, P <0.01] and immunoglobulin G [(18 +/- 9) g/L vs (14 +/- 5) g/L, t = 2.31, P <0.05] were statistically different between the two groups. By multivariate nonparametric logistic regression analysis, Gottron's rash, arthralgia, fever, and > or = 40 years of age were identified as predictors with relative risk ratio of 12.048, 7.812, 6.329 and 5.236 respectively. The unfavourable prognostic factors of ILD were Gottron' s rash (chi2 = 5.35, P <0.05), cardiac impairment (chi2 = 5.68, P < 0.05) and pulmonary fibrosis (chi2 = 5.42, P <0.05) by survival analysis. CONCLUSION: The occurrence of ILD in PM/ DM patients was closely correlated to Gottron's rash, age > or = 40 years, arthralgia and fever. Gottron's rash, heart impairment and pulmonary fibrosis were poor prognosis factors of PM/DM patients complicated with ILD.

A bispecific enediyne-energized fusion protein targeting both epidermal growth factor receptor and insulin-like growth factor 1 receptor showing enhanced antitumor efficacy against non-small cell lung cancer.

Epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF-1R) both overexpressed on non-small cell lung cancer (NSCLC) and are known cooperatively to promote tumor progression and drug resistance. This study was to construct a novel bispecific fusion protein EGF-IGF-LDP-AE consisting of EGFR and IGF-IR specific ligands (EGF and IGF-1) and lidamycin, an enediyne antibiotic with potent antitumor activity, and investigate its antitumor efficacy against NSCLC. Binding and internalization assays showed that EGF-IGF-LDP protein could bind to NSCLC cells with high affinity and then internalized into cells with higher efficiency than that of monospecific proteins. In vitro, the enediyne-energized analogue of bispecific fusion protein (EGF-IGF-LDP-AE) displayed extremely potent cytotoxicity to NSCLC cell lines with IC50<10-11 mol/L. Moreover, the bispecific protein EGF-IGF-LDP-AE was more cytotoxic than monospecific proteins (EGF-LDP-AE and LDP-IGF-AE) and lidamycin. In vivo, EGF-IGF-LDP-AE markedly inhibited the growth of A549 xenografts, and the efficacy was more potent than that of lidamycin and monospecific counterparts. EGF-IGF-LDP-AE caused significant cell cycle arrest and it also induced cell apoptosis in a dosage-dependent manner. Pretreatment with EGF-IGF-LDP-AE inhibited EGF-, IGF-stimulated EGFR and IGF-1R phosphorylation, and blocked two main downstream signaling molecules AKT and ERK activation. These data suggested that EGF-LDP-IGF-AE protein would be a promising targeted agent for NSCLC patients with EGFR and/or IGF-1R overexpression.

[Chemical composition and daily variation of melt water during ablation season in monsoonal temperate Glacier region: a case study of Baishui Glacier No. 1].

Melt water samples collected continuously from 29 August to 3 September 2009 in the Baishui Glacier No. 1 at elevation of 4750 m were analyzed for pH, conductivity, delta18O and inorganic ions. The results showed that the pH had obvious diurnal variations and was increased slightly by the influence of precipitation. The dissolution of alkaline soluble salts in the dust was the main reason for the increase of melt water conductivity; the value of delta18O was relatively low in strong ablation period and high in slight ablation period. Different from other research areas, the concentrations of Na+, K+, which were influenced by lithological and marine water vapor, were higher than that of Mg2+ in the study area; HCO3- and Ca2+ accounted for more than 80% of total ions in snow and ice melt water, indicating that the ions mainly came from limestone and the melt water was a typical carbonate solution; The content of melt water had an obvious daily change with temperature change, but the response amplitudes were different; Monsoon transport, local rock lithology, human industrial and agricultural activities were the main sources of inorganic ions and the deciding factors of the ion composition in the Baishui Glacier No. 1.

[Antibacterial activity of recombinant thanatin expressed by E.coli ER2566].

OBJECTIVE: To express antibacterial peptide thanatin in the prokaryotic expression system and test its antibacterial activity. METHODS: The DNA sequence coding for the 21 peptides of thanatin was synthesized using the preferred genetic codes of E. coli, cloned into pTYB11 plasmid, and transformed into E.coli ER2566. The expression of thanatin fused with intein was induced by IPTG in E.coli, and intein-thanatin specifically bound to the column through intein tag was cleaved overnight at 4 degrees celsius; in DTT/cysteine buffer. RESULTS: The cleaved thanatin was eluted with a protein concentration of 245 microg/ml in the first 4 ml. The purified thanatin had showed strong antibacterial activities against G- bacteria such as Shigella flexneri, Klebsiella pneumoniae, Shigella snnei, Escherichia coli O157, toxin producing Escherichia coli, Pseudomonas aeruginosa, and fungi such as Candida albicans, with especial potency in killing drug-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa, and extended-spectrum beta-lactamases (ESBL)-producing E.coli. Eighty strains of drug-resistant (ESBL-producing) and 30 strains of sensitive E. coli were used for anti-bacterial assay, and no significant differences in the antibacterial activity of thanatin were found between the sensitive and drug-resistant E. coli (P>0.05). CONCLUSION: The recombinant thanatin obtained shows strong antibacterial activity against drug-resistant and sensitive bacteria, and can be a potential substitute for routine antibiotics in the treatment of G- bacterial infections.

Report of two Chinese families and a review of Mainland Chinese CADASIL patients.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebrovascular disease caused by a mutation of the NOTCH3 gene. The clinical information of two CADASIL families was studied and mutation analysis of the NOTCH3 gene was performed by DNA direct sequencing. Published studies of Mainland Chinese CADASIL patients were reviewed and reanalyzed. The patients in the two families showed migraine with aura, stroke and cognitive decline. Cranial MRI revealed subcortical white matter infarcts and leukoencephalopathy. Two previously reported mutations of the NOTCH3 gene, c.397C>T and c.268C>T, were identified and cosegregated with the disease. The main clinical features, cranial MRI and pathological changes in Mainland Chinese CADASIL patients were similar to those in other regions. The frequency of migraine may be lower than that in Europe, but similar to that in Asia. Eight different NOTCH3 gene mutations were reported among Mainland Chinese CADASIL patients; of these, the c.322C>T mutation has not been reported in other regions. This study supports that the clinical features of Mainland Chinese CADASIL patients are similar to those seen in other regions and that exon 3 and exon 4 of the NOTCH3 gene are the mutation hotspots in Mainland Chinese CADASIL patients.