Dihydroartemisinin inhibits plasmid transfer in drug-resistant Escherichia coli via limiting energy supply.

Conjugative transfer of antibiotic resistance genes (ARGs) by plasmids is an important route for ARG dissemination. An increasing number of antibiotic and nonantibiotic compounds have been reported to aid the spread of ARGs, highlighting potential challenges for controlling this type of horizontal transfer. Development of conjugation inhibitors that block or delay the transfer of ARG-bearing plasmids is a promising strategy to control the propagation of antibiotic resistance. Although such inhibitors are rare, they typically exhibit relatively high toxicity and low efficacy in vivo and their mechanisms of action are inadequately understood. Here, we studied the effects of dihydroartemisinin (DHA), an artemisinin derivative used to treat malaria, on conjugation. DHA inhibited the conjugation of the IncI2 and IncX4 plasmids carrying the mobile colistin resistance gene ( mcr-1) by more than 160-fold in vitro in Escherichia coli, and more than two-fold (IncI2 plasmid) in vivo in a mouse model. It also suppressed the transfer of the IncX3 plasmid carrying the carbapenem resistance gene bla NDM-5 by more than two-fold in vitro. Detection of intracellular adenosine triphosphate (ATP) and proton motive force (PMF), in combination with transcriptomic and metabolomic analyses, revealed that DHA impaired the function of the electron transport chain (ETC) by inhibiting the tricarboxylic acid (TCA) cycle pathway, thereby disrupting PMF and limiting the availability of intracellular ATP for plasmid conjugative transfer. Furthermore, expression levels of genes related to conjugation and pilus generation were significantly down-regulated during DHA exposure, indicating that the transfer apparatus for conjugation may be inhibited. Our findings provide new insights into the control of antibiotic resistance and the potential use of DHA.

[The Research on Measurement System and Method of Tissue Optical Parameters with Wide Spectra Based on Double-Integrating-Spheres].

The measurement of tissue optical parameters is the focusing research content of Biomedical Photonics. The optical properties of human tissue are closely related to the physiological and pathological state. In recent years, the tissue imaging diagnosis and non-invasive detection of componentsbecome the hot research topics, applying the tissue optical properties especially the absorption and scattering properties. These provide the basis for the study of optical imaging and the spectrum detection of body composition etc. The Double-Integrating-Spheres (DIS) method can measure the absorption coefficient, scattering coefficient and so on in vitro tissuesimultaneously. It has the advantages of accurate, rapid, large applicable scope. The method applya standard method for measuring the optical parameters. This paper build the wide spectrum measurement system of optical parameters based on DIS and super continuum lasers. Then we analyze the transfer function, error sources and the best measuring conditions of the system. Finally we establish the correction forward model based on BP-MCML and the inverse algorithm of the optical parameters based on L-M algorithm. The optical parameters of intralipid solution in the wavelength range of 1,100~1,400 nm are measured. The experiment results show that the improved inverse algorithm is accurate. The multiple measurements standard deviation is within 3%. Compared the results of scattering coefficient and absorption coefficient at different wavelengths to the results of other research groups, the deviation is less than 3.4%.

EGFR mutations and clinical outcomes of chemotherapy for advanced non-small cell lung cancer: a meta-analysis.

BACKGROUND: This meta-analysis was performed to assess whether epidermal growth factor receptor (EGFR) mutation status was associated with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy. METHOD: We systematically identified eligible articles investigating the effects of chemotherapy in patients with NSCLC stratified by EGFR mutation status. The summary risk ratio (RR) for ORR and hazard ratios (HRs) for both PFS and OS were calculated using the inverse variance formula of meta-analysis. RESULTS: Identification for the current meta-analysis: 5 prospective studies (n=875) and 18 retrospective studies (n=1934) for ORR; 2 prospective studies (n=434) and 10 retrospective studies (n=947) for PFS; 2 prospective studies (n=438) and 7 retrospective studies (n=711) for OS. The ORR was significantly higher in patients with EGFR mutations in prospective studies (RR=1.42; 95% confidence interval [CI], 1.16-1.74; P=0.001), but not in retrospective studies (RR=1.12; 95% CI, 0.96-1.32; P=0.146). There was no obvious association between EGFR mutations and PFS both in prospective (HR=0.84; 95% CI: 0.65-1.09; P=0.197) and retrospective (HR=1.02; 95% CI: 0.87-1.18; P=0.838) studies. Association between EGFR mutations and OS was also not seen in prospective studies (HR=0.74; 95% CI: 0.27-2.05; P=0.566), but was seen in retrospective studies (HR=0.48; 95% CI: 0.33-0.72; P<0.001; I(2)=75.9%; P<0.001) with significant heterogeneity. CONCLUSION: EGFR mutations in advanced NSCLC may be associated with higher ORRs to chemotherapy, but may have nothing to do with PFS and OS. Further prospective studies are required to identify the influence of EGFR mutations on chemotherapy effects in advanced NSCLC.

[Efficacy and safety of low-frequency rotary magnetic fields in the treatment of patients with advanced malignant tumors].

OBJECTIVE: To investigate the clinical efficacy and safety of low-frequency rotary magnetic fields in the treatment of patients with advanced malignant tumors. METHODS: 137 patients with advanced malignant tumors were exposed to 400 r/min, 0.4 T low-frequency rotary magnetic fields. An area including the primary tumor, local metastasis and metastatic lymph nodes was exposed daily, 2 hours per day for 30~50 days (average time of 42 days). RESULTS: All of the 137 patients completed the low-frequency rotary magnetic field treatment. There were 28 cases with complete response, 54 cases with partial response, and the clinical benefit rate was 59.9%. The tumor type, initial KPS and QOL showed statistical significance in the clinical benefit rate (P < 0.05). The median overall survival was 12 months, and the 1-year, 2-year and 3-year survival rates were 47.0%, 11.8%, 3.4%, respectively. The tumor type, initial KPS and QOL were identified by univariate log-rank test as significant prognostic factors for overall survival (P < 0.05). Multivariate analysis showed that the initial QOL was an independent prognostic factors (P = 0.037) . During the treatment, asthenia and local pain were observed in 11 patients, and 6 patients had mild tachycardia (increased 3 to 5/min) and/or temperature elevation (0.5 to 1.0°C). All above symptoms disappeared spontaneously. No treatment-related death was observed. CONCLUSIONS: Low-frequency rotary magnetic fields is an effective and safe method in the treatment of patients with advanced malignant tumors, and may prolong survival significantly.

[Human hnRNP I prokaryotic expression and preliminary application.].

AIM: To express recombinant protein hnRNP I with prokaryotic expression system and assess the presence of autoantibodies against hnRNP I in systemic sclerosis (SSc) as well as other CTD. METHODS: Human hnRNP I gene was amplified by RT-PCR from HeLa cells and cloned into pET-30a vector , then pET-30a-hnRNP I plasmid was transferred into E.coli BL21 (DE3) to express recombinant protein. The sera from patients including SSc, SLE, SS, MCTD, UCTD, RA and controls were detected by ELISA with the purified recombinant hnRNP I protein. RESULTS: The recombinant protein was highly expressed in E.coli BL21(DE3) and specially reacted with clinically diagnosed SSc patients's serum. The result suggested that the autoantibodies against hnRNP I had higher positive ratio(48.72%) in SSc than other serum of AID and control. CONCLUSION: Human hnRNP I protein was successfully expressed in prokaryotic expression system. The purified hnRNP I protein can be used to diagnosis of SSc.