Circular DNAzyme-Switched CRISPR/Cas12a Assay for Electrochemiluminescent Response of Demethylase Activity.

DNA nanostructure provides powerful tools for DNA demethylase activity detection, but its stability has been significantly challenged. By virtue of circular DNA with resistance to exonuclease degradation, herein, the circular DNAzyme duplex with artificial methylated modification was constructed to identify the target and output the DNA activators to drive the CRISPR/Cas12a, constructing an "on-off-on" electrochemiluminescence (ECL) biosensor for monitoring the activity of the O6-methylguanine-DNA methyltransferase (MGMT). Specifically, the circular DNAzyme duplex consisted of the chimeric RNA-DNA substrate ring with double activator sequences and two single-stranded DNAzymes, whose catalytic domains were premodified with the methyl groups. When the MGMT was present, the methylated DNAzymes were repaired and restored the catalytic activity to cleave the chimeric RNA-DNA substrates, followed by the output of DNA activators to initiate the CRISPR/Cas12a. Subsequently, the ECL signals of silver nanoparticle-modified SnO2 nanospheres (Ag@SnO2) were recovered by releasing the ferrocene-labeled quenching probes (Fc-DNA) from the electrode surface because of the trans-cleavage activity of CRISPR/Cas12a, thus achieving the specific and sensitive ECL detection of MGMT from 2.5 × 10-4 to 2.5 × 102 ng/mL with a low limit (9.69 × 10-5 ng/mL). This strategy affords novel ideas and insights into research on how to project stable nucleic acid probes to detect DNA demethylases beyond traditional methods.

Pyrenecarboxaldehyde@Graphene Oxide Acted as a Highly Efficient ECL Emitter and Target-Triggered the Recyclable Cascade System as an Amplifier for Ultrasensitive APE1 Activity Detection.

Herein, pyrenecarboxaldehyde@graphene oxide (Pyc@GO) sheets with highly efficient electrochemiluminescence (ECL) as emitters were prepared by a noncovalent combination to develop a neoteric ECL biosensing platform for the ultrasensitive assessment of human apurinic/apyrimidinic endonuclease1 (APE1) activity. Impressively, the pyrenecarboxaldehyde (Pyc) molecules were able to form stable polar functional groups on the surface of GO sheets through the noncovalent π-π stacking mechanism to prevent intermolecular restacking and simultaneously generate Pyc@GO sheets. Compared with the tightly packed PAH nanocrystals, the Pyc@GO sheets significantly reduced internal filtering effects and diminished nonactivated emitters to enhance ECL intensity and achieve strong ECL emission. Furthermore, the APE1-activated initiators could trigger the recyclable cascade amplified system based on the synergistic cross-activation between catalytic hairpin assembly (CHA) and DNAzyme, which improved the signal amplification and transduction ability. Consequently, the developed ECL platform for the detection of APE1 activity displayed exceptional sensitivity with a low detection limit of 4.6 × 10-9 U·mL-1 ranging from 10-8 to 10-2 U·mL-1. Therefore, the proposed strategy holds great promise for the future development of sensitive and reliable biosensing platforms for the detection of various biomarkers.

Rapid classification of whole milk powder and skimmed milk powder by laser-induced breakdown spectroscopy combined with feature processing method and logistic regression.

Whole milk powder and skimmed milk powder are suitable for different groups of people due to their differences in composition. Therefore, a rapid classification method for whole milk powder and skimmed milk powder is urgently needed. In this paper, a novel strategy based on laser-induced breakdown spectroscopy (LIBS) and feature processing methods combined with logistic regression (LR) was constructed for the classification of milk powder. A LR classification model based on mini-batch gradient descent (MGD) was employed first. As indicated by the research results, the accuracy of the MGD-LR model for the milk powder samples in the test set is 96.33% and the modeling time is 33.07 s. The modeling efficiency is low and needs to be improved. Principal components analysis (PCA) and mutual information (MI) were used as feature processing methods to reduce the high dimensional LIBS data into fewer features for improving the modeling efficiency of the classification model. The research results indicate that the accuracy of the PCA-MGD-LR model and the MI-MGD-LR model for the test set of milk powder samples was 99.33% and 99.67%, respectively. Compared with MGD-LR model, the modeling efficiency of PCA-MGD-LR and MI-MGD-LR models has increased by 89.7% and 74.8%, respectively. The results fully demonstrate the feasibility of rapid milk powder classification based on LIBS and feature processing methods combined with LR, and it will provide a new technology for the identification and classification of milk powder.

Target-Driven Annular DNA Walker Coupled with Electrochemiluminescent Silicon Quantum Dots for APE1 Bioanalysis.

Functional DNA walkers with substantial nanostructures have been extensively investigated; however, their stability still faces challenges when exposed to diverse nuclease in clinical biological samples, resulting in the unreliability of actual assessment. This work proposed a target-driven annular DNA walker with enhanced stability enabling the sensitive and reliable response to different concentrations of apurinic/apyrimidinic endonuclease 1 (APE1), by preparing silicon quantum dots (SiQDs) as electrochemiluminescence (ECL) emitters. Specifically, the SiQDs showed significant strong and stable ECL signals by purifying the microenvironment of SiQDs through the dialysis removal of the gel-like layers surrounding the SiQDs. The relative standard deviation (RSD) of their ECL signal had been improved 16.59 times under consecutive scanning compared to that of SiQDs without dialysis, demonstrating a significant improvement in ECL stability. Subsequently, in the presence of APE1, the designed annular DNA walker was activated to move along the numerous quenching probes within the continuous cross-based DNA orbits, which were immobilized to the SiQD-modified electrode, providing ECL readout signals. The linear range of this ECL biosensor was 1.0 × 10-13 U·µL-1 to 1.0 × 10-7 U·µL-1, and the limit of detection (LOD) was as low as 1.766 × 10-14 U·µL-1. This work provides a novel structure of a DNA walker with nuclease resistance for clinical sample detection and designs a new strategy for synthesizing SiQDs with favorable ECL performance, tremendously expanding the ECL application of SiQDs.

In Situ Rapid Analysis of Squalene, Tocopherols, and Sterols in Walnut Oils Based on Supercritical Fluid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry.

Quantification of liposoluble micronutrients in large-scale vegetable oil samples is urgently needed, because their health benefits are increasingly emphasized. However, current analytical methods are limited to either labor-intensive preparation processes or time-consuming chromatography separation. In this work, an online oil matrix separation strategy for direct, rapid, and simultaneous determination of squalene, tocopherols, and phytosterols in walnut oil (WO) was developed on the basis of the lipid class separation mode of supercritical fluid chromatography. A single run was completed in 13 min containing 6 min of column cleaning and balancing. Satisfactory limit of detections (0.05-0.20 ng/mL), limit of quantifications (0.15-0.45 ng/mL), recoveries (70.61-101.44%), and matrix effects (78.43-91.62%) were achieved, indicating the reliability of this method. In addition, eight sterol esters were identified in WO, which have not previously been reported. The proposed method was applied to characterize the liposoluble micronutrient profile of WO samples obtained from different walnut cultivars, geographical origins, and processes.

Accuracy of Mean Value of Central Venous Pressure from Monitor Digital Display: Influence of Amplitude of Central Venous Pressure during Respiration.

Background A simple measurement of central venous pressure (CVP)-mean by the digital monitor display has become increasingly popular. However, the agreement between CVP-mean and CVP-end (a standard method of CVP measurement by analyzing the waveform at end-expiration) is not well determined. This study was designed to identify the relationship between CVP-mean and CVP-end in critically ill patients and to introduce a new parameter of CVP amplitude (ΔCVP= CVPmax - CVPmin) during the respiratory period to identify the agreement/disagreement between CVP-mean and CVP-end.Methods In total, 291 patients were included in the study. CVP-mean and CVP-end were obtained simultaneously from each patient. CVP measurement difference (|CVP-mean - CVP-end|) was defined as the difference between CVP-mean and CVP-end. The ΔCVP was calculated as the difference between the peak (CVPmax) and the nadir value (CVPmin) during the respiratory cycle, which was automatically recorded on the monitor screen. Subjects with |CVP-mean - CVP-end|≥ 2 mmHg were divided into the inconsistent group, while subjects with |CVP-mean - CVP-end| < 2 mmHg were divided into the consistent group.Results ΔCVP was significantly higher in the inconsistent group [7.17(2.77) vs.5.24(2.18), P<0.001] than that in the consistent group. There was a significantly positive relationship between ΔCVP and |CVP-mean - CVP-end| (r=0.283, P <0.0001). Bland-Altman plot showed the bias was -0.61 mmHg with a wide 95% limit of agreement (-3.34, 2.10) of CVP-end and CVP-mean. The area under the receiver operating characteristic curves (AUC) of ΔCVP for predicting |CVP-mean - CVP-end| ≥ 2 mmHg was 0.709. With a high diagnostic specificity, using ΔCVP<3 to detect |CVP-mean - CVP-end| lower than 2mmHg (consistent measurement) resulted in a sensitivity of 22.37% and a specificity of 93.06%. Using ΔCVP>8 to detect |CVP-mean - CVP-end| >8 mmHg (inconsistent measurement) resulted in a sensitivity of 31.94% and a specificity of 91.32%.Conclusions CVP-end and CVP-mean have statistical discrepancies in specific clinical scenarios. ΔCVP during the respiratory period is related to the variation of the two CVP methods. A high ΔCVP indicates a poor agreement between these two methods, whereas a low ΔCVP indicates a good agreement between these two methods.

Detection of walnut oil adulterated with high-linoleic acid vegetable oils using triacylglycerol pseudotargeted method based on SFC-QTOF-MS.

Authentication of walnut oil (WO) is challenging due to the adulteration of high-linoleic acid vegetable oils (HLOs) with similar fatty acid composition. To allow the discrimination of WO adulteration, a rapid, sensitive and stable scanning method based on supercritical fluid chromatography quadrupole time-of-flight mass spectrometry (SFC-QTOF-MS) was established to profile 59 potential triacylglycerol (TAGs) in HLOs samples within 10 min. Limit of quantitation of the proposed method is 0.002 µg mL-1 and the relative standard deviations range from 0.7% to 12.0%. TAGs profiles of WO samples from various varieties, geography origins, ripeness, and processing methods were used to construct orthogonal partial least squares-discriminant analysis (OPLS-DA) and OPLS models that were highly accurate in both qualitative and quantitative prediction at adulteration levels as low as 5% (w/w). This study advances the TAGs analysis to characterize vegetable oils and holds promise as an efficient method for oil authentication.

A convenient and economical strategy for multiple-target electrochemiluminescence detection using peroxydisulfate solution.

As various aptasensors are adopted in clinical diagnosis, the development of convenient multiple-target determination is a field of ever-increasing interests. Herein, a label-free and amplified electrochemiluminescence (ECL) sensing platform was constructed to detect multiple targets of hemin, glucose and thrombin (TB) using peroxydisulfate (S2O82-) solution, which was one of the most convenient and economical ECL systems. It was worth mentioning that the target-induced bi-enzyme cascade catalysis reaction was developed to increase the ECL response strongly of S2O82- solution due to the production of (1O2)2* from the inter-reaction between reactive oxygen species (ROS) and sulfate radical (SO4•-). Specifically, with the layer-by-layer assembly of multi-walled carbon nanotubes (MWCNTs), glucose oxidase (GOx) and gold nanoparticles (AuNPs) as the interface, the guanine-rich (G-rich) thrombin aptamer (TBA) was anchored for hemin (target 1) detection, due to the electrocatalysis of hemin/G-quadruplex as a horseradish peroxidase mimicking DNAzyme (HRP-DNAzyme) towards dissolved oxygen for ROS generation. Second, in the presence of glucose (target 2), the ECL intensity was improved because glucose was the substrate of the bi-enzyme cascade catalysis reaction. Third, when TB (target 3) was sequentially incubated based on the above-mentioned aptasensor, the bi-enzyme catalysis was inhibited to decrease the ECL signal, due to the steric hindrance effect of the TB protein. As a result, the aptasensor achieved the nanomolar detection for hemin (3.33 nM), the micromolar detection for glucose (0.33 µM) and the femtomolar detection for TB (3.33 fM), respectively.

Investigating the impact of oral health on pregnancy and offspring outcomes: protocol for the Lifetime Impact of ORal heAlth (LIORA) cohort study.

INTRODUCTION: Oral health is a fundamental component of well-being, and is closely associated with overall health and quality of life. Oral health may also affect the next generation. The children of mothers with poor oral health are likely to also have poor oral health as they go through life. We aim to investigate associations between maternal oral health and general health, pregnancy outcomes, offspring oral health and offspring general health. METHODS AND ANALYSIS: The Lifetime Impact of Oral Health study is a prospective, observational cohort study being done at a single centre in Chongqing, China. A total of 1000 pregnant women will be recruited in their first trimester (11-14 weeks gestation). After obtaining informed consent, general and oral health assessments will be undertaken. Maternal lifestyle, demographic data and biospecimens (blood, hair, urine, nail clippings, saliva, dental plaque, buccal, vaginal and anal swabs) will be collected. Pregnancy outcomes will be recorded at the time of delivery. Cord blood and placenta samples will be collected. The offspring will be followed up for general and oral health examinations, neurodevelopmental assessments and biospecimen (dental plaque, saliva, buccal swabs, exfoliated primary dentition, urine, hair, nail clippings) collection until they are 15 years old. Biological samples will undergo comprehensive metabolomic, microbiome and epigenome analyses. Associations between maternal oral health and general health, pregnancy outcomes, offspring oral health and offspring general health will be investigated and the underlying mechanisms explored. ETHICS AND DISSEMINATION: This project has been approved by the Research Ethics Committee of the Affiliated Hospital of Stomatology of Chongqing Medical University (CQHS-REC-2021 LSNo.23). Participants will be required to provide informed consent to participate in the study. Dissemination of findings will take the form of publications in peer-reviewed journals and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2100046898.

Programmable Y-Shaped Probes with Proximity Bivalent Recognition for Rapid Electrochemiluminescence Response of Acute Myocardial Infarction.

Herein, an exogenous luminophore-free and disposable electrochemiluminescence (ECL) biosensor was established for rapid response of acute myocardial infarction (AMI) using programmable Y-shaped probes (Y-probes) with proximity bivalent recognition. Specifically, the indium tin oxide thin film coated glass electrode (ITO) was modified with urchin-like porous TiO2 microspheres (pTiO2 MSs), which could achieve strong and stable ECL in S2O82- solution due to the dual promoting effect of the coreaction accelerator pTiO2 MSs, exhibiting 2.7-fold higher ECL intensity in comparison with that of bare ITO. Moreover, the Y-probes as bivalent recognition elements containing two kinds of cardiac troponin I (cTnI, a biomarker of AMI) aptamers and a linker labeled with ferrocene (L-Fc) were designed to export a "signal off" mode. When the target cTnI was in the proximity of the Y-probes, the L-Fc was separated from the electrode surface due to the proximity recognition of cTnI and its aptamers, achieving the highly effective recovery of ECL, which allowed for a much more rapid detection of cTnI than the sandwich-type immunoassay. As a proof of concept, an exogenous luminophore-free and disposable ECL platform for rapid and sensitive monitoring of cTnI was obtained and displayed a desired linear range from 100 fg mL-1 to 100 ng mL-1 with a limit of detection (LOD) of 30.1 fg mL-1, which can be ingeniously expanded as a portable home tester with ECL biosensors developments.

MicroRNA-Triggered Deconstruction of Field-Free Spherical Nucleic Acid as an Electrochemiluminescence Biosensing Switch.

Herein, a new field-free and highly ordered spherical nucleic acid (SNA) nanostructure was self-assembled directly by ferrocene (Fc)-labeled DNA tweezers and DNA linkers based on the Watson-Crick base pairing rule, which was employed as an electrochemiluminescence (ECL) quenching switch with improved recognition efficiency due to the high local concentration of the ordered nanostructure. Moreover, with a collaborative strategy combined with the advantages of both self-accelerated approach and pore confinement-enhanced ECL effect, the mesoporous silica nanospheres (mSiO2 NSs) were prepared to be filled with rubrene (Rub) as ECL emitters and Pt nanoparticles (PtNPs) as coreaction accelerators (Rub-Pt@mSiO2 NSs), which demonstrated high ECL response in the aqueous media (dissolved O2 as coreactant). When the SNA nanostructure was immobilized on the Rub-Pt@mSiO2 NSs-modified electrode, it presented a "signal off" state owing to the quenching effect of the Fc molecules. As a proof of concept, the SNA-based ECL switch platform was applied in the detection of microRNA let-7b (let-7b). Impressively, in the presence of the target let-7b, a deconstruction of the SNA nanostructure was actuated, causing the Fc to leave the electrode surface and achieved an extremely high ECL recovery ("signal on" state). Hence, a sensitive determination for let-7b was realized with a low detection limit of 1.8 aM ranging from 10 aM to 1 nM by employing the Rub-Pt@mSiO2 NSs-based ECL platform combined with the target-triggered SNA deconstruction, which also offered an ingenious method for the further applications of biomarker analyses.

An Affinity-Enhanced DNA Intercalator with Intense ECL Embedded in DNA Hydrogel for Biosensing Applications.

Herein, an amphiphilic perylene derivative (denoted as PTC-DEDA) was explored as DNA intercalators endowed with an enhanced affinity and intense electrochemiluminescence (ECL) to construct a target-induced DNA hydrogel biosensing platform for the sensitive detection of microRNA let-7a (miRNA let-7a). Specifically, the DNA hydrogel with numerous dendritic DNA structures was in situ generated via a target-induced nonlinear hybrid chain reaction in the presence of miRNA let-7a, which possessed a large loading capacity to entrap massive DNA intercalators. Then, the PTC-DEDA with positive charges could easily intercalate into the DNA grooves due to the inherent amphipathic structure, achieving a strong ECL signal. Using the proposed PTC-DEDA as both DNA intercalators and ECL emitters, the DNA hydrogel biosensing platform exhibited a high stability and an excellent sensitivity for miRNA let-7a, with a desirable linear range (10 fM to 10 nM) and a low detection limit (1.49 fM). Significantly, the work provides a potential alternative to develop simple and high-efficiency ECL platforms for biochemical analysis applications.

Association of Ang-2, vWF, and EVLWI with risk of mortality in sepsis patients with concomitant ARDS: A retrospective study.

BACKGROUND/PURPOSE: This study aimed to determine the potential effects of angiopoietin-2 (Ang-2), von Willebrand factor (vWF), and extravascular lung water index (EVLWI) on the risk of mortality in sepsis patients with concomitant acute respiratory distress syndrome (ARDS). METHODS: This retrospective study recruited 41 sepsis patients with concomitant ARDS from January 2015 to June 2018. Data of Ang-2 and vWF levels, EVLWI, and sequential organ failure assessment scores were collected at 0, 24, and 48 h after admission to the hospital. RESULTS: The length of intensive care unit stay (P = 0.041) and Acute Physiology and Chronic Health Evaluation-2 (APACHE II) score (P = 0.003) were associated with the risk of mortality. Furthermore, increased Ang-2 levels and EVLWI at 24 h and 48 h were associated with an increased risk of mortality. Moreover, the APACHE II score at hospital admission significantly predicted the risk of mortality (area under the curve [AUC], 0.834; 95% confidence interval [CI], 0.665-0.983). Finally, the models containing a combination of Ang-2 level and EVLWI at 24 h (AUC, 0.908; 95% CI, 0.774-0.996) and Ang-2 level and EVLWI at 48 h (AUC, 0.981; 95% CI, 0.817-1.000) had high diagnostic values for predicting risk of mortality. CONCLUSION: The study findings indicate that Ang-2 levels and EVLWI at 24 h and 48 h after admission are significantly associated with the risk of mortality.

Phosphoproteomic Analysis of Paper Mulberry Reveals Phosphorylation Functions in Chilling Tolerance.

Paper mulberry is a valuable woody species with a good chilling tolerance. In this study, phosphoproteomic analysis, physiological measurement, and mRNA quantification were employed to explore the molecular mechanism of chilling (4 °C) tolerance in paper mulberry. After chilling for 6 h, 427 significantly changed phosphoproteins were detected in paper mulberry seedlings without obvious physiological injury. When obvious physiological injury occurred after chilling for 48 h, a total of 611 phosphoproteins were found to be significantly changed at the phosphorylation level. Several protein kinases, especially CKII, were possibly responsible for these changes according to conserved sequence analysis. The results of Gene Ontology analysis showed that phosphoproteins were mainly responsible for signal transduction, protein modification, and translation during chilling. Additionally, transport and cellular component organization were enriched after chilling for 6 and 48 h, respectively. On the basis of the protein-protein interaction network analysis, a protein kinase and phosphatases hub protein (P1959) were found to be involved in cross-talk between Ca2+, BR, ABA, and ethylene-mediated signaling pathways. We also highlighted the phosphorylation of BpSIZ1 and BpICE1 possibly impacted on the CBF/DREB-responsive pathway. From these results, we developed a schematic for the chilling tolerance mechanism at phosphorylation level.

The effect of variable arterial transducer level on the accuracy of pulse contour waveform-derived measurements in critically ill patients.

We know that a 10 cm departure from the reference level of pressure transducer position is equal to a 7.5 mmHg change of invasive hemodynamic pressure monitoring in a fluid-filled system. However, the relationship between the site level of a variable arterial pressure transducer and the pulse contour-derived parameters has yet to be established in critically ill patients. Moreover, the related quantitative analysis has never been investigated. Forty-two critically ill patients requiring PiCCO-Plus cardiac output monitoring were prospectively studied. The phlebostatic axis was defined as the zero reference level; the arterial pressure transducer was then vertically adjusted to different positions (+5, +10, +15, +20, -20, -15, -10, -5 cm) of departure from the zero reference site. The pulse contour waveform-derived parameters were recorded at each position. Elevation of the pressure transducer caused significantly positive changes in the continuous cardiac index (+CCI), stroke volume index (+SVI), and stroke volume variation (+SVV), and negative changes in the rate of left ventricular pressure rise during systole (-dP/dtmax), the systemic vascular resistance index (-SVRI), and vice versa. At the 5 cm position, the SVRI changes reached statistical significance with error. At the 10 cm position, the changes in CCI and dP/dtmax reached statistical significance with error, while the change in SVV reached statistical significance at 15 cm. The change rate of CCI was more than 5 % at the 15 cm position and approximately 10 % at the 20 cm position. On average, for every centimeter change of the transducer, there was a corresponding 0.014 L/min/m(2) CCI change and 0.36 % change rate, a 1.41 mmHg/s dP/dtmax change and 0.13 % change rate, and a 25 dyne/s/cm(5) SVRI change and 1.2 % change rate. The variation of arterial transducer position can result in inaccurate measurement of pulse contour waveform-derived parameters, especially when the transducer's vertical distance is more than 10 cm from the phlebostatic axis. These findings have clinical implications for continuous hemodynamic monitoring.

New method for noninvasive quantification of central venous pressure by ultrasound.

BACKGROUND: The central venous pressure (CVP) is essential for assessing the cardiac preload and circulating blood volume in clinic. The invasive CVP measurement by central venous catheter has been reported with various complications. The aim of this study was to develop a new noninvasive method for quantification of CVP by ultrasound. METHODS AND RESULTS: Seventy-six patients who had their CVP monitored for intraoperative or postoperative management were recruited. By accurate location of the collapse point of the internal jugular vein and the center of the right atrium using ultrasound imaging, the height of the fluid column between those 2 points was measured as the noninvasive CVP (CVPn). A total of 118 measurements were performed and compared with the invasive CVP (CVPi). Linear correlation analysis revealed a significant correlation between CVPi and CVPn (preoperative measurements, r=0.90; P<0.01 and postoperative measurements, r=0.93; P<0.01). Bland-Altman plots showed a good agreement between CVPi and CVPn with the mean difference of 0.22 mm Hg (preoperative measurements) and -0.09 mm Hg (postoperative measurements), respectively. CONCLUSIONS: The new noninvasive CVP quantification method based on the location of both the collapse point of internal jugular vein and the center of right atrium by ultrasound could be used as a reliable approach for monitoring the hemodynamic status in clinic.

Prognostic value of ERCC1, RRM1, and TS proteins in patients with resected non-small cell lung cancer.

PURPOSE: Recent clinical trials showed that expression of excision repair cross-complementation group 1 (ERCC1), ribonucleotide reductase M1 (RRM1), and thymidylate synthase (TS) proteins was able to predict the effects of non-small cell lung cancer (NSCLC) to chemotherapy. However, it remains unknown whether the adjuvant chemotherapy based on expression of the three proteins has survival significance in Chinese NSCLC patients. METHODS: We investigated 128 Chinese patients receiving chemotherapy after tumor resection for expression of these proteins using immunohistochemistry. Based on protein expression, patients were assigned to two groups for different adjuvant chemotherapy regimes. The disease-free survival (DFS) data were collected and analyzed using Kaplan-Meier curves and Cox models. RESULTS: We found that DFS of these patients with carboplatin and a third-generation agent (gemcitabine or pemetrexed) stratified by protein expression showed no statistical difference between individual treatment versus non-individuation treatment analyzed using Kaplan-Meier method (P = 0.143, median 23.9 vs. 30.8 months). Furthermore, the multivariate analysis showed that histology and tumor stages were independent predictors for DFS in these patients. CONCLUSIONS: The results suggest that chemotherapy based on ERCC1, RRM1, and TS expression did not have significant impact on DFS of patients with resection of NSCLC.

Unilateral intramuscular needling can improve ankle dorsiflexor strength and muscle activation in both legs.

BACKGROUND/OBJECTIVE: The aim of this study was to determine whether unilateral manual needling at nonacupoints could result in bilateral strength gain similar to that found in electroacupuncture at specific acupoints. METHODS: Fifty healthy male volunteers with an age range of 19-27 years were recruited and randomly allocated into five groups: (1) manual acupuncture and (2) electroacupuncture at two acupoints (ST-36 and ST-39); (3) manual acupuncture and (4) electroacupuncture at two nonacupoints on the tibialis anterior muscle; and (5) control group. The intervention groups received needling in each session on the right leg for 15 minutes in Week 1, 20 minutes in Week 2, and 30 minutes in Weeks 3-8, three sessions per week. The maximal isometric ankle dorsiflexion strength and muscle activation (as determined by twitch interpolation) of both legs were assessed pre, post, 2 weeks post, and 3 weeks post the experimental period. RESULTS: Mixed models (linear) with repeated-measures analysis identified significant strength gains (p < 0.01) after the intervention period in both limbs, while no significant differences were detected between the intervention groups and between the two legs, and no change was found in the control group. A significant improvement in muscle activation (p < 0.01) was also observed in both legs in the intervention groups. CONCLUSION: It was concluded that both unilateral manual and electric needling caused significant bilateral strength gain, and this effect was not specific to the selected acupoints or electric stimulation. The strength gain was sustained for at least 3 weeks after the 8-week intervention.

A multi-center, randomized, single-blind, controlled clinical study on the efficacy of composite sophora colon-soluble capsules in treating ulcerative colitis.

OBJECTIVE: To evaluate the safety and efficacy of composite sophora colon-soluble capsule (CSCC) in treating ulcerative colitis (UC) of the damp-heat accumulation syndrome pattern (DHAS) and to prepare a basis for a phase III clinical trial. METHODS: A multi-center, randomized, single-blind, and positive drug parallel-controlled design was adopted. There were 126 patients of UC-DHAS stratified and assigned equally to three groups. Patients in two CSCC treated groups, Groups T1 and T2, were treated orally with high (six capsules, thrice a day) and low (four capsules, thrice a day) doses CSCC, and patients in the control group were treated orally with Mesalazine Enteric-coated Tablets (four tablets, thrice a day), respectively, all for eight weeks. The clinical efficacy and safety of treatments were evaluated through clinical symptom observations and colonoscopic examinations. RESULTS: (1) Full analysis set (FAS) and per-protocol set (PPS) analyses showed the comprehensive curative effect in Groups T1, T2, and the control group, obtaining the values of 85.7%, 92.9%, and 71.4% (P=0.330), and 89.5%, 92.7%, and 73.2% (P=0.552), respectively, demonstrating no statistical significance among the three groups. (2) FAS and PPS analysis showed the efficacy on membranous lesions in Groups T1, T2, and the control group, obtaining the values of 83.3%, 92.9%, and 73.8% (P=0.063), and 86.8%, 92.7%, and 75.6% (P=0.070), respectively, showing statistical insignificance among the three groups. (3) FAS analysis showed an efficacy tendency on improving tenesmus (P=0.056). No changes were found in improving the other symptoms, and statistical significance was not shown among the three groups (P>0.05). PPS analysis showed the efficacy on single item symptom in Groups T1, T2, and the control group was not statistically significant among the three groups (P=0.082). CONCLUSIONS: The comprehensive effect of CSCC in treating UC is basically equivalent to that of Mesalazine enteric-coated tablet; however, the tendency was shown to improve symptoms. Its efficacy could not be raised by increasing the dosage used. Therefore, the recommended dosage of CSCC is four capsules, three times a day.

Streptomyces plumbiresistens sp. nov., a lead-resistant actinomycete isolated from lead-polluted soil in north-west China.

The taxonomic position of an actinomycete isolated from a lead-polluted soil in Gansu province, north-west China, was determined by using a polyphasic approach. Chemical and morphological properties of the isolate, designated strain CCNWHX 13-160(T), were similar to those of streptomycetes. Analysis of the almost complete 16S rRNA gene sequence placed strain CCNWHX 13-160(T) in the genus Streptomyces where it formed a distinct phyletic line with recognized Streptomyces species. The strain was most similar to Streptomyces pseudovenezuelae NBRC 12904(T) (98.9 %) and Streptomyces resistomycificus NBRC 12814(T) (98.8 %). Furthermore, DNA-DNA hybridization studies between the novel isolate and these two strains showed relatedness values of 49.7+/-0.8 and 43.2+/-1.1 %, respectively. It is proposed that strain CCNWHX 13-160(T) (=ACCC 41207(T)=HAMBI 2991(T)) be classified as the type strain of a novel species in the genus Streptomyces, Streptomyces plumbiresistens sp. nov. The MIC of Pb(2+) for growth of strain CCNWHX 13-160(T) was 4.0 mM.