Ambient fine particulate matter (PM) has been associated with impaired lung function, but the effect of temperature on lung function and the potential interaction effect between PM and temperature remain uncertain. To estimate the short-term effects of PM2.5 combined with temperature on lung function, we measured the daily peak expiratory flow (PEF) in a panel of 37 healthy college students in four different seasons. Meanwhile, we also monitored daily concentrations of indoor and outdoor PM2.5 (particulate matter with an aerodynamic diameter ≤2.5 μm), ambient temperature and relative humidity of the study area, where the study participants lived and attended school. Associations of air pollutants and temperature with lung function were assessed by generalized estimating equations (GEEs). A 10 μg/m3 increase of indoor PM2.5 was associated with a change of −2.09 L/min in evening PEF (95%CI: −3.73 L/min–−0.51 L/min) after adjusting for season, height, gender, temperature and relative humidity. The changes of −2.17 L/min (95%CI: −3.81 L/min– −0.52 L/min) and −2.18 L/min (95%CI: −3.96 L/min–−0.41 L/min) in evening PEF were also observed after adjusting for outdoor SO2 and NO2 measured by Environmental Monitoring Center 3 kilometers away, respectively. An increase in ambient temperature was found to be associated with a decrease in lung function and our results revealed a small but significant antagonistic interactive effect between PM2.5 and temperature. Our findings suggest that ambient PM2.5 has an acute adverse effect on lung function in young healthy adults, and that temperature also plays an important role.
college students; particulate matter; temperature; lung function; GEE
The reduced graphene oxide/silver nanotriangle (rGO/AgNT) composite sol was prepared by the reduction of silver ions with sodium borohydride in the presence of H2O2 and sodium citrate. In the nanosol substrate, the molecular probe of acridine red (AR) exhibited a weak surface-enhanced Raman scattering (SERS) peak at 1506 cm−1 due to its interaction with the rGO of rGO/AgNT. Upon addition of dopamine (DA), the competitive adsorption between DA and AR with the rGO took place, and the AR molecules were adsorbed on the AgNT aggregates with a strong SERS peak at 1506 cm−1 that caused the SERS peak increase. The increased SERS intensity is linear to the DA concentration in the range of 2.5–500 μmol/L. This new analytical system was investigated by SERS, fluorescence, absorption, transmission electron microscope (TEM), and scanning electron microscope (SEM) techniques, and a SERS quantitative analysis method for DA was established, using AR as a label-free molecular probe.
rGO/AgNT; Dopamine; Acridine red; Label-free; SERS
To investigate the association of the interleukin-1β (IL-1β) (3953/4) C→T polymorphism with chronic periodontitis (CP) in Asians.
Material and methods
Systematic searches of electronic databases and hand searching of references were performed, including PubMed, Embase, the Cochrane Library, and the Chinese National Knowledge Infrastructure (CNKI). Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the associations. Publication bias was tested by Egger's test. Sensitivity analysis was conducted by limiting the meta-analysis studies conforming to Hardy-Weinberg equilibrium (HWE). Data analyses were carried out using RevMan 6.0.
A meta-analysis was performed on 20 published case-control studies, including 1,656 CP cases and 1,498 healthy controls. The pooled OR was 1.60 (95% CI = 1.02–2.52, p = 0.04) for the T allele carriers (TT + CT) compared with CC and 1.60 (95% CI = 1.06–2.42, p = 0.02) for T vs. C. Subgroup analysis by country revealed significant risks of CP among Indians carrying the T allele (TT vs. CC: OR = 3.88, 95% CI = 1.77–8.50, p = 0.0007).
The analysis showed that IL-1β (3953/4) C→T polymorphism probably increases the risk of CP in Asians, and the IL-1β+3954 TT genotype may be associated with a strongly increased risk of CP in Indians, but not in Chinese.
polymorphism; interleukin-1; chronic periodontitis; meta-analysis; Asians
The prevalence of obesity among children and adolescents has been rapidly rising in Mainland China in recent decades, both in urban and rural areas. There is an urgent need to develop effective interventions to prevent childhood obesity. Limited rigid data regarding children and adolescent overweight prevention in China are available. A national random controlled school-based obesity intervention program was developed in the mainland of China.
The study was designed as a national multi-centered cluster randomized controlled trial involving more than 70,000 children and adolescents aged 7–18 years from 7 provinces in China. In each center, about 12–16 primary and secondary schools, with totally at least 10000 participants were randomly selected (Primary: Secondary = 1:1). All of the selected schools were randomly allocated to either intervention or control group (Intervention: Control = 1:1).The multi-components school-based and family-involved scheme was conducted within the intervention group for 9 month, while students in the control group followed their usual health practice. The intervention consisted of four components: a) Create supportive school and family environment, b) Health lifestyles education and related compulsory physical activities, c) Instruct and promote school physical education, d) Self-monitor obesity related behaviors. Four types of outcomes including anthropometric, behavioral, blood chemical and physical fitness were measured to assess the effectiveness of the intervention program.
This is the first and largest multi-centered school-based obesity intervention program with the consideration of geographical and social-demographic characteristics of the rapidly increased obesity prevalence of Chinese children and adolescent. The intervention is based on Social Cognitive Theory and Social-Ecological Model of Health, and follows a stepwise approach guided by PRECEDE-PROCEED (P-P) Model and Intervention Map. The results of and lesson learned from this study will help guide future school-based national childhood obesity prevention programs in Mainland China.
January 22, 2015; Registration number: NCT02343588
Chinese children and adolescent; School-based obesity intervention; Multi-centered randomized controlled trial
Interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) have important functions in injury and repair processes of glomerular intrinsic cells. A study was conducted to analyze the urinary VEGF/creatinine (CR) and IL-6/CR levels in simple hematuria patients after excluding the interference of creatinine. We aimed to investigate the function and relationships of the above indices in the glomerular pathological injury process, and to elaborate the values of urinary VEGF and IL-6 changes in the diagnosis of asymptomatic hematuria or hematuria with proteinuria.
A total of 121 renal hematuria patients diagnosed by clinical and laboratory tests were included as research subjects. The midstream fresh morning urine was collected on the day renal biopsy was performed.
The IL-6/CR value of the group III was significantly greater than in group I (Z=−2.478, P<0.05), with a statistically significant difference between these 2 groups. The VEGF/CR value of group III was significantly greater than in group II (P<0.01). Compared with group I, the VEGF/CR of group III was significantly greater (Z=−4.65, P<0.01), with a statistically significant difference.
The VEGF/CR and IL-6/CR values in simple hematuria patients were positively correlated with glomerular pathological injury scores. VEGF/CR and IL-6/CR might be used as biological diagnostic indicators in determining the extent of simple hematuria glomerular injury.
Cytokine Receptor gp130; Kidney Glomerulus; Vascular Endothelial Growth Factor A; Hematuria
Milk fat globules memebrane (MFGM)-enriched proteomes from Holstein, Jersey, yak, buffalo, goat, camel, horse, and human were extracted and identified by an iTRAQ quantification proteomic approach. Proteomes data were analyzed by bioinformatic and multivariate statistical analysis and used to present the characteristic traits of the MFGM proteins among the studied mammals. The data of this study are also related to the research article “Proteomic characterization and comparison of mammalian milk fat globule proteomes by iTRAQ analysis” in the Journal of Proteomics .
No studies have been reported on children obesity prevalence of Guangzhou, one of the most urbanized areas in China. This study tracks the secular trends of obesity prevalence of children.
The data were derived from the surveys on students’ constitution and health carried out by government. Randomly, 3832 students in 2007, 13141 in 2008, 14052 in 2009, 13750 in 2010, and 15225 in 2011, aged 7-12 years, from urban primary school were examined. Anthropometric parameters were measured in all students.
The mean of body mass index increased significantly from 16.6 in 2008 to 16.8 in 2011 in the total group of children, and the total prevalence of overweight and obesity increased from 9.4 and 6.2 to 10.5 and 7.5 from 2007 to 2011, respectively. The minimum value of the mean body mass index and the overweight and obesity prevalence in the total age group all appeared in 2008. The prevalence of overweight and obesity in males was significantly higher than that in females in each year among the 5 years.
Although the prevalence of children obesity in Guangzhou in 2011 is still lower than the average values of Chinese large coastal cities, a significant increase was found in their prevalence from 2007 to 2011 and the total obesity prevalence of children is even higher than that of adolescent. Furthermore, we found that the minimum value of overweight and obesity prevalence of the total group and almost all gender-specific age groups appeared in 2008.
Body mass index; Children; Overweight; Obesity; Secular trend
It has been reported that red blood cell width (RDW) is a marker associated with the presence and adverse outcomes of various diseases. However, no data are available on the correlation of RDW with presence, stage, and grade in patients with renal cell carcinoma (RCC) yet. By retrospectively analyzing clinical and laboratory data at baseline of histologically confirmed RCC cases and controls, the present study demonstrated that the RDW values were significantly higher in patients with RCC than those in controls, and the baseline RDW value was independently associated with the presence of RCC. Besides, the data revealed a positive association between RCC stage and grade and the level of RDW. These findings may have important clinical implications due to future application using a RDW value in predicting RCC.
The choice of surgical or conservative treatment for patients with spontaneous intracerebral hemorrhage is controversial. Some minimally invasive treatments have been applied to hematoma evacuation and could improve prognosis to some extent. Up to now, studies on minimally invasive surgery for patients with spontaneous intracerebral hemorrhage are still insufficient.
The MISTICH is a multi-center, prospective, randomized, assessor-blinded, parallel group, controlled clinical trial. 2448 eligible patients will be assigned to neuroendoscopy group, stereotactic aspiration group and craniotomy group randomly. Patients will receive the corresponding surgery based on the result of randomization. Surgeries will be performed by well-trained surgeons and standard medical treatment will be given to all patients. Patients will be followed up at 7 days, 30 days, and 6 months. The primary outcome of this study is unfavorable outcome at 6 months. Secondary outcomes include: mortality at 30 days and 6 months after surgery; neurological functional status of 6 months after surgery; complications including rebleeding, ischemic stroke and intracranial infection; days of hospitalization.
The MISTICH trial is a randomized controlled trial designed to determine whether minimally invasive surgeries could improve the prognosis for patients with spontaneous intracerebral hemorrhage compared with craniotomy. (ChiCTR-TRC-12002026. Registered 23 March 2012).
Intracerebral hemorrhage; Minimally invasive surgical treatment; Craniotomy; Neuroendoscope; Stereotactic aspiration
The age-related loss of anti-oxidant defense reduces recovery from myocardial ischemia/reperfusion injury (MI/R) in aged people. Our previous data showed that inactivation of thioredoxin (Trx) was involved in enhanced aging MI/R injury. Thioredoxin reductase (TrxR), the enzyme known to regulate Trx, is less efficient with age. The aim of the current study was to determine why TrxR activity was reduced and whether reduced TrxR activity contributed to enhanced aging MI/R injury. Both Trx and TrxR activity were decreased in the aging heart, and this difference was further amplified after MI/R. However, MI/R injury did not change TrxR expression between young and aging rats. Increased nitrogen oxide (NOx) but decreased nitric oxide (NO) bioavailability (decreased phosphorylated vasodilator-stimulated phosphoprotein) was observed in aging hearts. Peroxynitrite (ONOO−) was increased in aging hearts and was further amplified after MI/R. TrxR nitration in young and aging hearts was detected by immunoprecipitation (anti-nitrotyrosine) followed by immunoblotting (anti-TrxR). Compared with young hearts, TrxR nitration was increased in the aging hearts, and this was further intensified after MI/R. The ONOO− decomposition catalyst (FeTMPyp) reduced TrxR nitration and increased TrxR and Trx activity. More importantly, FeTMPyp attenuated the MI/R injury in aging hearts as evidenced by decreased caspase-3 and malondialdehyde (MDA) concentration and increased cardiac function. Increased ONOO− nitrated TrxR in the aging heart as a post-translational modification, which may be related to the enhanced MI/R injury of aging rats. Interventions that inhibit nitration and restore TrxR activity might be a therapy for attenuating enhanced MI/R injury in aging heart.
Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are evolutionarily conserved machines that couple their folding/assembly to membrane fusion. However, it is unclear how these processes are regulated and function. To determine these mechanisms, we characterized the folding energy and kinetics of four representative SNARE complexes at a single-molecule level using high-resolution optical tweezers. We found that all SNARE complexes assemble by the same step-wise zippering mechanism: slow N-terminal domain (NTD) association, a pause in a force-dependent half-zippered intermediate, and fast C-terminal domain (CTD) zippering. The energy release from CTD zippering differs for yeast (13 kBT) and neuronal SNARE complexes (27 kBT), and is concentrated at the C-terminal part of CTD zippering. Thus, SNARE complexes share a conserved zippering pathway and polarized energy release to efficiently drive membrane fusion, but generate different amounts of zippering energy to regulate fusion kinetics.
Many processes in living things need molecules to be transported within, or between, cells. For example, damaged or waste molecules are transported within a cell to structures that can break the molecules down, while nerve impulses are transmitted from one neuron to the next via the release of signaling molecules.
Cells—and the compartments within cells—are surrounded by membranes that act as barriers to certain molecules. Vesicles are small, membrane-enclosed packages that are used to transport molecules between different membranes; and in order to release its cargo, a vesicle must fuse with its target membrane. To fuse like this, the forces that act to push membranes away from one another need to be overcome. Proteins called SNARES, which are embedded in both membranes, are the molecular engines that power the fusion process. Once the SNARE proteins from the vesicle and the target membrane bind, they assemble into a more compact complex that pulls the two membranes close together and allows fusion to take place.
The final shape of an assembled SNARE complex is essentially the same for all SNARE complexes; however, it is not known whether all of these complexes fold using the same method. Now Zorman et al. have used optical tweezers—an instrument that uses a highly focused laser beam to hold and manipulate microscopic objects—to observe the folding and unfolding of four different types of SNARE complex. All four SNARE complexes followed the same step-by-step process: the leading ends of the SNARE proteins slowly bound to each other; the process paused; then the rest of the proteins rapidly ‘zippered’ together.
Zorman et al. revealed that, although the steps in the processes were the same, the energy released in the last step was different when different complexes assembled. This suggests that the energy released by the ‘zippering’ of different SNARE proteins is optimized to match the required speed of different membrane fusion events. Furthermore, Zorman et al. propose that the reason why the majority of energy is released in the later stages of complex assembly is because this is when the repulsion between the two membranes is strongest.
The discoveries of Zorman et al. will now aid future efforts aimed at understanding better how the numerous other proteins that interact with SNARE proteins regulate the process of membrane fusion.
SNAREs; optical tweezers; protein folding; membrane fusion; SNARE assembly; energy landscape; E. coli
Declined vasorelaxation function in aging resistance arteries is responsible for aging-related multiple organ dysfunctions. The aim of the present study is to explore the role of peroxynitrite (ONOO-) in aging resistance arterial vasorelaxation dysfunction and the possible mechanism. In the present study, young (3–4 months olds) and aging (20 months olds) male SD rats were randomized to receive vehicle (Saline) or FeTMPyP (ONOO- scavenger) for 2 weeks. The vasorelaxation of resistance arteries was determined in vitro; NOx level was tested by a colorimetric assay; the expression of nitrotyrosine (NT), soluble Guanylate Cyclase (sGC), vasodilator-stimulated phosphoprotein (VASP), phosphorylated VASP (P-VASP) and cGMP in resistance arteries were detected by immunohistochemical staining. In the present study, endothelium-dependent dilation in aging resistance arteries was lower than in those from young rats (young vs. aging: 68.0%±4.5% vs. 50.4%±2.9%, P<0.01). And the endothelium-independent dilation remained constant. Compared with young rats, aging increased nitrative stress in resistance arteries, evidenced by elevated NOx production in serum (5.3±1.0 nmol/ml vs. 3.3±1.4 nmol/ml, P<0.05) and increased NT expression (P<0.05). ONOO- was responsible for the vasorelaxation dysfunction, evidenced by normalized vasorelaxation after inhibit ONOO- or its sources (P<0.05) and suppressed NT expression after FeTMPyP treatment (P<0.05). The expression of sGC was not significantly different between young and aging resistance arteries, but the cGMP level and P-VASP/VASP ratio (biochemical marker of NO-sGC-cGKs signaling) decreased, which was reversed by FeTMPyP treatment in vivo (P<0.05). The present study suggested that ONOO- mediated the decline of endothelium-dependent vasorelaxation of aging resistance arteries by induction of the NO-sGC-cGKs pathway dysfunction.
The epithelial-to-mesenchymal transition (EMT) is a key process in carcinogenesis, invasion, and metastasis of oral squamous cell carcinoma (OSCC). In our previous studies, we found that neuropilin-1 (NRP1) is overexpressed in tongue squamous cell carcinoma and that this overexpression is associated with cell migration and invasion. Nuclear factor-kappa B (NF-κB) plays an essential role both in the induction and the maintenance of EMT and tumor metastasis. Therefore, we hypothesized that NRP1 induces EMT, and that NRP1-induced migration and invasion may be an important mechanism for promoting invasion and metastasis of OSCC through NF-κB activation.
The variations in gene and protein expression and the changes in the biological behavior of OSCC cell lines transfected with a vector encoding NRP1, or the corresponding vector control, were evaluated. NRP1 overexpression promoted EMT and was associated with enhanced invasive and metastatic properties. Furthermore, the induction of EMT promoted the acquisition of some cancer stem cell (CSC)-like characteristics in OSCC cells. We addressed whether selective inhibition of NF-κB suppresses the NRP1-mediated EMT by treating cells with pyrrolidinedithiocarbamate ammonium (PDTC), an inhibitor of NF-κB. Immunohistochemical analysis of NRP1 in OSCC tissue samples further supported a key mediator role for NRP1 in tumor progression, lymph node metastasis, and indicated that NRP1 is a predictor for poor prognosis in OSCC patients.
Our results indicate that NRP1 may regulate the EMT process in OSCC cell lines through NF-κB activation, and that higher NRP1 expression levels are associated with lymph node metastasis and poor prognosis in OSCC patients. Further investigation of the role of NRP1 in tumorigenesis may help identify novel targets for the prevention and therapy of oral cancers.
Generalized two-dimensional correlation spectroscopy (2D COS) can be used to enhance spectral resolution in order to help differentiate highly overlapped spectral bands. Despite the numerous extensive 2D COS investigations, the origin of the 2D spectral resolution enhancement mechanism(s) are not completely understood. In the work here we studied the 2D COS of simulated spectra in order to develop new insights into the dependence of the 2D COS spectral features on the overlapping band separations, their intensities and bandwidths, and their band intensity change rates. We find that the features in the 2D COS maps that derive from overlapping bands are determined by the spectral normalized half-intensities and the total intensity changes of the correlated bands. We identify the conditions required to resolve overlapping bands. In particular, 2D COS peak resolution requires that the normalized half-intensities of a correlating band have amplitudes between the maxima and minima of the normalized half-intensities of the overlapping bands.
Two dimensional correlation spectroscopy; resolution enhancement; overlapping bands; normalized half-intensity
Hyperhomocysteinemia is strongly associated with cardiovascular diseases. Previous studies have shown that phytoestrogen α-zearalanol can protect cardiovascular system from hyperhomocysteinemia and ameliorate the level of plasma total homocysteine; however, the underlying mechanisms remain to be clarified. The aim of this research is to investigate the possible molecular mechanisms involved in ameliorating the level of plasma homocysteine by α-zearalanol. By the successfully established diet-induced hyperhomocysteinemia rat models, we found that, after α-zearalanol treatment, the activity of cystathionine β-synthase, the key enzyme in homocysteine metabolism, was significantly elevated and level of nitrative stress in liver was significantly reduced. In correlation with this, results also showed a decreased nitration level of cystathionine β-synthase in liver. Together data implied that alleviation of plasma homocysteine level by phytoestrogen α-zearalanol might be related to the reduction of cystathionine β-synthase nitration.
The collision avoidance warning system is an emerging technology designed to assist drivers in avoiding red-light running (RLR) collisions at intersections. The aim of this paper is to evaluate the effect of auditory warning information on collision avoidance behaviors in the RLR pre-crash scenarios and further to examine the casual relationships among the relevant factors. A driving-simulator-based experiment was designed and conducted with 50 participants. The data from the experiments were analyzed by approaches of ANOVA and structural equation modeling (SEM). The collisions avoidance related variables were measured in terms of brake reaction time (BRT), maximum deceleration and lane deviation in this study. It was found that the collision avoidance warning system can result in smaller collision rates compared to the without-warning condition and lead to shorter reaction times, larger maximum deceleration and less lane deviation. Furthermore, the SEM analysis illustrate that the audio warning information in fact has both direct and indirect effect on occurrence of collisions, and the indirect effect plays a more important role on collision avoidance than the direct effect. Essentially, the auditory warning information can assist drivers in detecting the RLR vehicles in a timely manner, thus providing drivers more adequate time and space to decelerate to avoid collisions with the conflicting vehicles.
red-light running; audio warning information; driving simulator; driving behavior; structural equation modeling
Forces hold everything together and determine its structure and dynamics. In
particular, tiny forces of 1-100 piconewtons govern the structures and dynamics
of biomacromolecules. These forces enable folding, assembly, conformational
fluctuations, or directional movements of biomacromolecules over sub-nanometer
to micron distances. Optical tweezers have become a revolutionary tool to probe
the forces, structures, and dynamics associated with biomacromolecules at a
single-molecule level with unprecedented resolution. In this review, we
introduce the basic principles of optical tweezers and their latest applications
in studies of protein folding and molecular motors. We describe the folding
dynamics of two strong coiled coil proteins, the GCN4-derived protein pIL and
the SNARE complex. Both complexes show multiple folding intermediates and
pathways. ATP-dependent chromatin remodeling complexes translocate DNA to
remodel chromatin structures. The detailed DNA translocation properties of such
molecular motors have recently been characterized by optical tweezers, which are
reviewed here. Finally, several future developments and applications of optical
tweezers are discussed. These past and future applications demonstrate the
unique advantages of high-resolution optical tweezers in quantitatively
characterizing complex multi-scale dynamics of biomacromolecules.
optical tweezers; single-molecule manipulation; protein folding; molecular motors; DNA translocation; SNARE proteins
Subarachnoid hemorrhage is a common and dangerous disease with an unfavorable prognosis. Patients with poor-grade subarachnoid hemorrhage (Hunt & Hess Grades 4–5) are unconscious on admission. Because of the high mortality and disability rate associated with poor-grade subarachnoid hemorrhage, it is often treated conservatively. Timing of surgery for poor-grade aneurysmal subarachnoid hemorrhage is still controversial, therefore this study aims to identify the optimal time to operate on patients admitted in poor clinical condition.
Ninety-nine patients meeting the inclusion criteria were randomly assigned into three treatment groups. The early surgery group received operation within 3 days after onset of subarachnoid hemorrhage (day of SAH = day 1); the intermediate surgery group received operation from days 4 to 7, and surgery was performed on the late surgery group after day 7. Follow-up was performed 1, 3, and 6 months after aneurysm clipping. Primary indicators of outcome included the Extended Glasgow Outcome Scale and the Modified Rankin Scale, while secondary indicators of outcome were assessed using the Barthel Index and mortality.
This is the first prospective, single-center, observer-blinded, randomized controlled trial to elucidate optimal timing for surgery in poor-grade subarachnoid hemorrhage patients. The results of this study will be used to direct decisions of surgical intervention in poor-grade subarachnoid hemorrhage, thus improving clinical outcomes for patients.
Chinese Clinical Trial Registry: ChiCTR-TRC-12002917
Timing of surgery; Poor-grade; Subarachnoid hemorrhage; ICP; Prognosis
SNARE proteins drive membrane fusion by assembling into a four-helix bundle in a zippering process. Here we used optical tweezers to observe in real time a long-sought SNARE assembly intermediate in which only the membrane-distal N-terminal half of the bundle is assembled. Our finding supports the zippering hypothesis, but suggests that zippering proceeds through three sequential binary switches, not continuously, in the N- and C-terminal halves of the bundle and the linker domain. The half-zippered intermediate was stabilized by externally applied force which mimicked the repulsion between apposed membranes being forced to fuse. This intermediate then rapidly and forcefully zippered, delivering free energy of 36 kBT to mediate fusion.
Renal hematuria is caused by glomerular disease. Under pathological conditions, the distribution of interleukin-6 (IL-6) in kidney tissue is abnormal and urinary IL-6 levels are increased. Abnormal IL-6 secretion promotes the hyperplasia of mesangial cells and matrix and, thus, affects the permeability of the glomerular filtration membrane. Therefore, the detection of urinary IL-6 levels in patients with renal hematuria is beneficial for disease evaluation. A total of 82 patients with primary renal hematuria were divided into group 1 (UPr/24 h < 150 mg; pure hematuria group), group 2 (150 mg ≤ UPr/24 h ≤ 1,000 mg) and group 3 (UPr/24 h > 1,000 mg). A total of 30 normal individuals were selected as the controls. The urinary IL-6 levels were detected by the enzyme-linked immunosorbent assay (ELISA) method and a renal biopsy was conducted. The urinary IL-6 levels and renal pathological damage scores in groups 1 and 2 were significantly reduced compared with those in group 3, (P<0.001 and 0.01, respectively), with no significant difference between groups 1 and 2 (P>0.05). The correlation coefficient (r) of urinary IL-6 with 24 h urinary protein (UPr/24 h) in groups 1, 2 and 3 was 0.017, 0.045 and 0.747, respectively, and that of urinary IL-6 with renal pathological damage score was 0.627, 0.199 and 0.119, respectively. The UPr/24 h was significantly correlated with IL-6 level (r=0.7320, P<0.000). In group 1, the urinary IL-6 levels were correlated with the degree of renal pathological damage. A positive correlation was observed between urinary IL-6 levels and UPr/24 h.
interleukin-6; renal hematuria; 24 h urinary protein
CD and UV resonance Raman measurements surprisingly find that the charge screening of even 2 M concentrations of NaCl and KCl do not alter the unfolded PPII and 2.51-helix conformations of poly-L-glutamate. These salts appear to be excluded from the region between the side chain charges and the peptide backbone. Furthermore, no direct ion pairing occurs between these salts and the side chain carboxylates.
poly-L-glutamate; PPII; 2.51-helix; salt exclusion; UV resonance Raman
We used 204 nm excitation UV Resonance Raman (UVRR) spectroscopy to examine the effects of NaClO4 on the conformation of poly–L–lysine (PLL). The presence of NaClO4 induces the formation of α–helix, π–helix/bulge and turn conformations. The dependence of the AmIII3 frequency on the peptide Ψ Ramachandran angle allows us to experimentally determine the conformational population distributions and the energy landscape of PLL along the Ramachandran Ψ angle. We also used UVRR to measure the NaClO4 concentration dependence of PLL amide hydrogen exchange kinetics. Exchange rates were determined by fitting the D2O exchanging PLL UVRR AmII′ band time evolution. Hydrogen exchange is slowed at high NaClO4 concentrations. The PLL AmII′ band exchange kinetics at 0.0, 0.2 and 0.35 M NaClO4 can be fit by single exponentials, but the AmII′ band kinetics of PLL at 0.8 M NaClO4 requires a double exponential fit. The exchange rates for the extended conformations were monitored by measuring the Cα–H band kinetics. These kinetics are identical to those of the AmII′ band until 0.8 M NaClO4 whereupon the extended conformation exchange becomes clearly faster than that of the α–helix–like conformations. Our results indicate that ClO4− binds to the PLL backbone to protect it from OH− exchange catalysis. In addition, ClO4− binding also slows the conformational exchange between the extended and α–helix–like conformations, probably by increasing the activation barriers for conformational interchanges.
Conformational distribution; Energy landscape; Conformational dynamics; Salt binding
The previous meta-analysis on the use of endothelin-receptor antagonists (ETRAs) to treat aneurysmal subarachnoid hemorrhage (SAH) has become outdated due to recently published phase 3 clinical trials. An up-to-date meta-analysis is needed to provide the best available evidence for the efficacy of ETRAs for aneurysmal SAH.
We performed a systematic review and meta-analysis of published randomized controlled trials that investigate efficacy of ETRAs in patients with aneurysmal SAH. Mortality, unfavorable outcome, delayed ischemic neurological deficit (DIND), delayed cerebral infarction (DCI), angiographic vasospasm and adverse events were analyzed. Meta-analysis was performed in terms of the risk ratio (RR) and 95% confidence interval (CI).
Five eligible studies were reviewed and analyzed, involving 2,595 patients. The pooled RRs of mortality and unfavorable outcome after SAH were 1.03 (95% CI = 0.77 to 1.36) and 1.07 (95% CI = 0.93 to 1.22), respectively. The pooled RRs were 0.87 (95% CI = 0.74 to 1.03) for DCI, 0.77 (95% CI = 0.66 to 0.90) for DIND, and 0.66 (95% CI = 0.57 to 0.77) for angiographic vasospasm. There were significant increases in lung complications (RR = 1.80, 95% CI = 1.55 to 2.09), hypotension (RR = 2.42, 95% CI = 1.78 to 3.29) and anemia (RR = 1.47, 95% CI = 1.19 to 1.83) in patients administered ETRAs.
There is no evidence that ETRAs could benefit clinical outcome in patients with SAH. Owing to the increased adverse events, further clinical trials of ETRAs in SAH patients should be more carefully formulated and designed. The present results also suggest that DCI may be a better outcome measure than vasospasm and DIND in SAH clinical trials and observational studies.
Recently, a multicenter randomized controlled trial (RCT) by Cooper and colleagues indicated that decompressive craniectomy (DC) may be associated with a worse functional outcome in patients with diffuse traumatic brain injury (TBI), although DC can immediately and constantly reduce intracranial pressure (ICP). As this trial is well planned and of high quality, the unexpected result is meaningful. However, the evidence of the study is insufficient and the effect of DC in severe TBI is still uncertain. Additional multicenter RCTs are necessary to provide class I evidence on the role of DC in the treatment of refractory raised ICP after severe TBI.
We used 204 nm excitation UV Resonance Raman (UVRR) spectroscopy to examine the role of side chain electrostatic interactions in determining the conformation of poly-L-lysine (PLL). We examined the pH and ionic strength dependence of the UVRR. The pH dependence of PLL UVRR spectra between pH 7.1 and 11.7 cannot be described by a two-state model, but requires at least one additional state. The AmIII3 region fitting with pH 7.1 and 11.7 basis spectra reveals a small pH induced decrease in the relative fraction of the 2.51-helix conformation compared to the PPII conformation. We performed a 2D general correlation analysis on the PLL pH dependence UVRR spectra. The asynchronous spectrum shows enhanced spectral resolution. The 2D asynchronous spectrum reveals multiple components in the Cα-H b band and the AmII band whose origins are unclear. The cross peaks in the 2D asynchronous spectrum between the AmIII band and the other bands reveals that increasing pH induces three new structures: π-helix, α-helix and some turn structure. We find that 2.5 M NaCl does not change the equilibrium between the PPII and 2.51-helix conformations by screening sidechain electrostatic repulsion. The result indicates that NaCl does not penetrate the region between the sidechain and the peptide backbone. We also compared PLL conformations induced by high pH to that induced by 0.8 M ClO4−. Both conditions induce α-helix-like conformations. 0.8 M ClO4− induces 6% more α-helix-like conformations than at pH 12.4. Higher pH gives rise to longer α-helices and less turn structures.