选择性支气管动脉插管转铁蛋白受体单克隆抗体灌注治疗中晚期肺癌(附68例临床报告)

本文对68例中晚期肺癌进行选择性支气管动脉插管采用转铁蛋白受体单克隆抗体与表阿霉素、顺伯等药物制成偶联物灌注。结果显示,肿瘤明显消退24例(35.2％),部分消退36例(52.5％),无变化8例(12.3％),总有效率为87.7％。通过对支气管动脉插管,导向灌注疗法结果显示,本疗法优于周围静脉供药,且无严重并发症,副作用轻,不失为一种可供选择的治疗方法。     

Epidemiology and Outcome of Severe Sepsis and Septic Shock in Intensive Care Units in Mainland China

Introduction

Information about sepsis in mainland China remains scarce and incomplete. The purpose of this study was to describe the epidemiology and outcome of severe sepsis and septic shock in mixed ICU in mainland China, as well as the independent predictors of mortality.

Methods

We performed a 2-month prospective, observational cohort study in 22 closed multi-disciplinary intensive care units (ICUs). All admissions into those ICUs during the study period were screened and patients with severe sepsis or septic shock were included.

Results

A total of 484 patients, 37.3 per 100 ICU admissions were diagnosed with severe sepsis (n = 365) or septic shock (n = 119) according to clinical criteria and included into this study. The most frequent sites of infection were the lung and abdomen. The overall ICU and hospital mortality rates were 28.7% (n = 139) and 33.5% (n = 162), respectively. In multivariate analyses, APACHE II score (odds ratio[OR], 1.068; 95% confidential interval[CI], 1.027–1.109), presence of ARDS (OR, 2.676; 95%CI, 1.691–4.235), bloodstream infection (OR, 2.520; 95%CI, 1.142–5.564) and comorbidity of cancer (OR, 2.246; 95%CI, 1.141–4.420) were significantly associated with mortality.

Conclusions

Our results indicated that severe sepsis and septic shock were common complications in ICU patients and with high mortality in China, and can be of help to know more about severe sepsis and septic shock in China and to improve characterization and risk stratification in these patients.     

Albumin versus Other Fluids for Fluid Resuscitation in Patients with Sepsis: A Meta-Analysis

Background

Early fluid resuscitation is vital to patients with sepsis. However, the choice of fluid has been a hot topic of discussion. The objective of this study was to evaluate whether the use of albumin-containing fluids for resuscitation in patients with sepsis was associated with a decreased mortality rate.

Methods

We systematically searched PubMed, EMBASE and Cochrane library for eligible randomized controlled trials (RCTs) up to March 2014. The selection of eligible studies, assessment of methodological quality, and extraction of all relevant data were conducted by two authors independently.

Results

In total, 15 RCTs were eligible for analysis. After pooling the data, we found there was no significant effect of albumin-containing fluids on mortality in patients with sepsis of any severity (RR: 0.94, 95% CI: 0.87, 1.02 and RD: –0.01, 95% CI: –0.03, 0.01). The results were robust to subgroup analyses, sensitivity analyses and trial sequential analyses.

Conclusion

The present meta-analysis did not demonstrate significant advantage of using albumin-containing fluids for resuscitation in patients with sepsis of any severity. Given the cost-effectiveness of using albumin, crystalloids should be the first choice for fluid resuscitation in septic patients.     

Genetic diversity and population structure assessment of Chinese <Emphasis Type="Italic">Senna obtusifolia</Emphasis> L. by molecular markers and morphological traits of seed

Senna obtusifolia L. is an important medicinal plant in Asia. This study was the first report on the genetic diversity and population structure of S. obtusifolia which were collected from 47 geographic populations widespread in China. Inter-Simple Sequence Repeat (ISSR) and Start Codon Target Polymorphism (SCoT) combined with seeds morphological traits were used to investigate the relationship of 47 populations. 11 ISSR primers yielded 98 polymorphic bands with 81.67% polymorphism. 24 SCoT primers yielded 267 polymorphic bands with 89.59% polymorphism. The number of allele (Na), the number of effective allele (Ne), Nei’s diversity index (H), and Shannon’s information index (I) reflected a high level of genetic diversity of S. obtusifolia species. The greatest genetic distance (G _D) existed between Southwest and Northwest (0.4022_ISSR/0.5019_SCoT), while the Eastern and Northern showed the least genetic distance (0.1751_ISSR/0.2186_SCoT). The genetic differentiation (Gst) was 0.4875_ISSR/0.4434_SCoT, and the gene flow (Nm) was 0.5256_ISSR/0.6275_SCoT, which indicated that gene exchange among four regions was limited. 47 samples were divided into four clusters mainly according to their geographic distribution through clustering and structure analysis. The analysis on the combined data of ISSR and SCoT showed more reliable and superior results than single analysis of ISSR and SCoT. This study explored the effectiveness of ISSR and SCoT markers to evaluate the genetic diversity and population structure of S. obtusifolia and provided useful information for S. obtusifolia germplasm research and breeding program.     

Heme Oxygenase-2 Suppress TNF-α and IL6 Expression via TLR4/MyD88-Dependent Signaling Pathway in Mouse Cerebral Vascular Endothelial Cells

Heme oxygenase (HO) represents an intrinsic antiinflammatory system based on its ability to inhibit expression of proinflammatory cytokines. The constitutive isoform heme oxygenase-2 (HO-2) has high expression and activity in cerebral microvascular endothelial cells (CMVEC). This study was undertaken to evaluate the role of HO-2 in regulation of TLR4/MyD88-dependent signaling and to study the effect of HO-2 on the expression and secretion of the proinflammatory cytokines tumor necrosis factor α (TNF-α) and Interleukin-6 (IL6) in CMVEC. HO-2 short hairpin RNA (shRNA) and HO-2 overexpression plasmids were used to observe the effect of HO-2 on proinflammatory cytokines in CMVEC in vitro, and the results showed that the messenger RNA (mRNA) and protein levels of TNF-α and IL6 were increased and decreased, respectively, compared with control groups. LPS-stimulated TNF-α and IL6 mRNA and protein were also reduced in CMVEC treated with an inhibitor of TLR4 signaling, CLI-095, or HO-2 overexpression. CLI-095 and HO-2 overexpression both reduced TLR4 expression in CMVEC, and HO-2 shRNA blocked these effects of CLI-095. CLI-095 and HO-2 overexpression potently suppressed TLR4/MyD88-dependent proinflammatory cytokine expression in CMVEC. These results suggest that HO-2 plays an important role in protecting CMVEC against cytokine-mediated inflammation.     

Derivation of Mouse Haploid Trophoblast Stem Cells

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Biodegradation kinetics of microcystins-LR crude extract by Lysinibacillus boronitolerans strain CQ5

As the most common variant of microcystins (MCs), microcystin-LR (MCLR) is a kind of toxins produced by some species of harmful cyanobacteria and more and more attention has been paid to it. Biodegradation has been extensively investigated and recognized to be a cost-efficient and environmentally benign method for MC clean-up. In order to further research the growth characteristics of strain and the biodegradation characteristics of MCLR, it is necessary to use the dynamic mathematical models as powerful and useful tools. In this study, strain CQ5 was screened and identified by morphological observation, physiological and biochemical tests, and 16S rDNA sequence analysis. The kinetic models of cell growth and MCLR degradation were established with the Gompertz model and revised Monod kinetic model. The results showed that strain CQ5 had the closest phylogenetic similarity to Lysinibacillus boronitolerans (T-10a, AB199591) in the phylogenetic tree, with 99% bootstrap support. Strain CQ5 could utilize MCLR as the carbon and nitrogen source for growth. When the initial pH value was 7 and the inoculation amount was 3%, strain CQ5 grew well in MSM, in which the MCLR crude extract was used as the carbon and nitrogen source of strain CQ5. Within 244 h, the MCLR concentration changed from 14.12 to 1.57 μg/L and its degradation rate could reach 88.88%. The growth curve fitted with the Gompertz growth model (Nt = 1.3119 * exp(−0.1237 * exp(−6.6341t)), R2 > 0.99). The process of MCLR degradation agreed with the first-order reaction kinetic equation (lnS = 2.64764 − 0.01537t, R2 > 0.99). The linkage relationship between MCLR concentration, cell density, and MCLR degradation rate was consistent with the revised Monod equation (V = 0.342S, R2 > 0.97) at low substrate concentration, where Vmax/ Ks was 0.342. The dynamic relationship in which strain CQ5 degraded MCLR and used it as the carbon and nitrogen source to promote its own growth could be explained by the equation S = 14.12 e− 0.342 Nt (N = 1.08). The growth of strain CQ5 and MCLR concentration in degradation system could be simulated and predicted by the dynamic mathematical models in this study. And the predicted results were very consistent. These results could provide theoretical reference for studying the mechanism of MCLR biodegradation and promote the engineering application of strain CQ5.     

Associations of plasma high-sensitivity C-reactive protein concentrations with all-cause and cause-specific mortality among middle-aged and elderly individuals

Background

The plasma level of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is a strong predictor of disease development and premature mortality in the general population. Unhealthy lifestyle habits such as smoking or unhealthy eating is known to elevate the suPAR level. We aimed to investigate whether change in lifestyle habits impact on the suPAR level, and whether the resultant levels are associated with mortality.

Results

Paired suPAR measurements from baseline- and the 5-year visit of the population-based Inter99 study were compared with the habits of diet, smoking, alcohol consumption, and physical activity. Paired suPAR measurements for 3225 individuals were analyzed by linear regression, adjusted for demographics and lifestyle habits. Compared to individuals with a healthy lifestyle, an unhealthy diet, low physical activity, and daily smoking were associated with a 5.9, 12.8, and 17.6% higher 5-year suPAR, respectively. During 6.1 years of follow-up after the 5-year visit, 1.6% of those with a low suPAR (mean 2.93 ng/ml) died compared with 3.8% of individuals with a high suPAR (mean 4.73 ng/ml), P <  0.001. In Cox regression analysis, adjusted for demographics and lifestyle, the hazard ratio for mortality per 5-year suPAR doubling was 2.03 (95% CI: 1.22–3.37).

Conclusion

Lifestyle has a considerable impact on suPAR levels; the combination of unhealthy habits was associated with 44% higher 5-year suPAR values and the 5-year suPAR was a strong predictor of mortality. We propose suPAR as a candidate biomarker for lifestyle changes as well as the subsequent risk of mortality.

     

A novel vector for a rapid generation of fiber-mutant adenovirus based on one step ligation and quick screening of positive clones

The generation of fiber-modified adenoviral vector has proven difficult. In the paper, we developed a new system for rapid construction of fiber-modified adenoviral vector containing foreign peptides in the HI loop or C-terminal of the fiber knob. The new system was established through the following processes. First, a unique BamHI mutation was made in the genome of Ad5 without causing amino acid change. Second, two unique restriction enzymes BamHI and SfuI, both with sticky end, were introduced in the HI loop or C-terminal of Ad5 fiber knob. Third, a lacza expression cassette was placed between BamHI and SfuI sites for a quick identification of positive cloning based on white-blue color screening. This system allows generation of recombinant adenoviral vector by a single step, in vitro ligation followed by quick white-color positive clone screening. To prove the principle of the method, Ad5HI-RGD by modifying HI-loop of the fiber knob with RGD motif and Ad5Cter-PK7 by modifying C-terminal of the knob with poly-lysine (pK7) were successfully generated in vitro. Ad5 with a knob modified in the HI loop of the fiber with Tat-PTD, NGR or SIKVAV peptide were also successfully developed. The transduction of the modified viruses for Hela, U87 MG and MDA-MB-231 cells was investigated in vitro compared with unmodified Ad5. In conclusion, the new vector system allows for a rapid generation of fiber-mutant adenovirus and provides useful tool for gene function analysis and cancer gene therapy.     

Spatial phylogenetics of the Chinese angiosperm flora provides insights into endemism and conservation

The flora of China is well known for its high diversity and endemism. Identifying centers of endemism and designating conservation priorities are essential goals for biodiversity studies.However, there is no comprehensive study from a rigorous phylogenetic perspective to understand patterns of diversity and endemism and to guide biodiversity conservation in China. We conducted a spatial phylogenetic analysis of the Chinese angiosperm flora at the generic level to identify centers of neo-and pale...